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Neuroscience Publications Archive - December 2017

Weekly Scopus Report:

December 25, 2017

December 18, 2017

December 11, 2017

December 4, 2017

 

December 25, 2017

1) 

de Miranda Azevedo, R., Roest, A.M., Carney, R.M., Freedland, K.E., Lane, D.A., Parakh, K., de Jonge, P., Denollet, J.
Individual depressive symptoms and all-cause mortality In 6673 patients with myocardial infarction: Heterogeneity across age and sex subgroups
(2018) Journal of Affective Disorders, 228, pp. 178-185. 


Abstract
Background Depression predicts poor prognosis in patients with myocardial infarction (MI). However, individual depressive symptoms may have different prognostic value, and age and sex could be important effect modifiers. This study compared the prognostic value of individual depressive symptoms across age and sex subgroups in post-MI patients. Methods Individual patient-data were compiled for 6673 post-MI patients from seven studies. Depressive symptoms were measured with 10 items of the Beck Depression Inventory (BDI10). The endpoint was all-cause mortality (mean=3.8 years). Multilevel multivariable Cox regression analysis was used to estimate the mortality risk across age groups (≤55, 56–69 and ≥70 years) and sex for symptoms that potentially interacted with age and sex. Results At follow-up, 995 (15%) post-MI patients had died. BDI10 depression scores were associated with an increased mortality risk (HR:1.20;95%CI:1.11–1.28,p<.001). Negative self-image (HR:1.53;1.06–2.21;p=.022) and indecisiveness (HR:1.53;1.15–2.04;p=.003) were associated with increased mortality in men <55. Dissatisfaction was associated with increased mortality in men aged 56–69 (HR:1.35;1.07–1.71;p=. 011), and dissatisfaction (HR:1.34;1.10–1.63;p=.003) and fatigue (HR:1.45;1.20–1.74;p<.001) in men >70. Fatigue was associated with mortality in women aged 56–69 (HR:1.54;1.09–2.15;p=.012), and suicidal ideation in women aged >70 (HR:1.58;1.03–2.43;p=.037). Left-ventricular ejection fraction (LVEF) accounted for much of the associations in men ≤55 years and women ≥70 years. Limitations: Findings are sample-specific and need replication in future research; BDI10 items were derived from the original BDI assessment. Conclusions There is large heterogeneity in the prognostic value of individual depressive symptoms in post-MI patients across sex and age subgroups. LVEF partially explained the depression-prognosis association in specific subgroups. © 2017 Elsevier B.V.


Author Keywords
Depression;  Epidemiology;  Myocardial infarction


Document Type: Article
Source: Scopus

 

2) 

Schmidt, J.L., Tweten, D.J., Badachhape, A.A., Reiter, A.J., Okamoto, R.J., Garbow, J.R., Bayly, P.V.
Measurement of anisotropic mechanical properties in porcine brain white matter ex vivo using magnetic resonance elastography
(2018) Journal of the Mechanical Behavior of Biomedical Materials, 79, pp. 30-37. 


Abstract
The mechanical properties of brain tissue, particularly those of white matter (WM), need to be characterized accurately for use in finite element (FE) models of brain biomechanics and traumatic brain injury (TBI). Magnetic resonance elastography (MRE) is a powerful tool for non-invasive estimation of the mechanical properties of soft tissues. While several studies involving direct mechanical tests of brain tissue have shown mechanical anisotropy, most MRE studies of brain tissue assume an isotropic model. In this study, an incompressible transversely isotropic (TI) material model parameterized by minimum shear modulus (μ2), shear anisotropy parameter (?), and tensile anisotropy parameter (ζ) is applied to analyze MRE measurements of ex vivo porcine white matter (WM) brain tissue. To characterize shear anisotropy, “slow” (pure transverse) shear waves were propagated at 100, 200 and 300 Hz through sections of ex vivo brain tissue including both WM and gray matter (GM). Shear waves were found to propagate with elliptical fronts, consistent with TI material behavior. Shear wave fields were also analyzed within regions of interest (ROI) to find local shear wavelengths parallel and perpendicular to fiber orientation. FE simulations of a TI material with a range of plausible shear modulus (μ2) and shear anisotropy parameters (?) were run and the results were analyzed in the same fashion as the experimental case. Parameters of the FE simulations which most closely matched each experiment were taken to represent the mechanical properties of that particular sample. Using this approach, WM in the ex vivo porcine brain was found to be mildly anisotropic in shear with estimates of minimum shear modulus (actuation frequencies listed in parenthesis): μ2= 1.04 ± 0.12 kPa (at 100 Hz), μ2= 1.94 ± 0.29 kPa (at 200 Hz), and μ2= 2.88 ± 0.34 kPa (at 300 Hz) and corresponding shear anisotropy factors of ?= 0.27 ± 0.09 (at 100 Hz), ?= 0.29 ± 0.14 (at 200 Hz) and ?= 0.34 ± 0.13 (at 300 Hz). Future MRE studies will focus on tensile anisotropy, which will require both slow and fast shear waves for accurate estimation. © 2017 Elsevier Ltd


Author Keywords
Anisotropy;  MR elastography;  Shear waves;  Transversely isotropic material;  White matter brain tissue


Document Type: Article
Source: Scopus

 

3) 

Dryn, D., Luo, J., Melnyk, M., Zholos, A., Hu, H.
Inhalation anaesthetic isoflurane inhibits the muscarinic cation current and carbachol-induced gastrointestinal smooth muscle contractions
(2018) European Journal of Pharmacology, 820, pp. 39-44. 


Abstract
Gastrointestinal tract motility may be demoted significantly after surgery operations at least in part due to anaesthetic agents, but there is no comprehensive explanation of the molecular mechanism(s) of such adverse effects. Anesthetics are known to interact with various receptors and ion channels including several subtypes of transient receptor potential (TRP) channels. Two members of the canonical subfamily of TRP channels (TRPC), TRPC4 and TRPC6 are Ca2+-permeable cation channels involved in visceral smooth muscle contractility induced by acetylcholine, the primary excitatory neurotransmitter in the gut. In the present study, we aimed to study the effect of anesthetics on muscarinic receptor-mediated excitation and contraction of intestinal smooth muscle. Here we show that muscarinic cation current (mICAT) mediated by TRPC4 and TRPC6 channels in mouse ileal myocytes was strongly inhibited by isoflurane (0.5 mM), one of the most commonly used inhalation anesthetics. Carbachol-activated mICAT was reduced by 63 ± 11% (n = 5), while GTPγS-induced (to bypass muscarinic receptors) current was inhibited by 44 ± 9% (n = 6). Furthermore, carbachol-induced ileum and colon contractions were inhibited by isoflurane by about 30%. We discuss the main sites of isoflurane action, which appear to be G-proteins and muscarinic receptors, rather than TRPC4/6 channels. These results contribute to our better understanding of the signalling pathways affected by inhalation anesthetics, which may cause ileus, and thus may be important for the development of novel treatment strategies during postoperative recovery. © 2017 Elsevier B.V.


Author Keywords
G-proteins;  Gastrointestinal smooth muscles;  General anesthetics;  Isoflurane;  Muscarinic receptors;  TRP channels


Document Type: Article
Source: Scopus

 

4) 

Jin, H., Han, J., Resing, D., Liu, H., Yue, X., Miller, R.L., Schoch, K.M., Miller, T.M., Perlmutter, J.S., Egan, T.M., Tu, Z.
Synthesis and in vitro characterization of a P2X7 radioligand [123I]TZ6019 and its response to neuroinflammation in a mouse model of Alzheimer disease
(2018) European Journal of Pharmacology, 820, pp. 8-17. 


Abstract
The purinergic receptor P2X ligand-gated ion channel 7 (P2X7 receptor) is a promising imaging target to detect neuroinflammation. Herein, we report development of a potent iodinated radiotracer for P2X7 receptor, [123I]TZ6019. The radiosynthesis of [123I]TZ6019 was accomplished by allylic-tin precursor iodination using [123I]NaI with good radiochemical yield of 85% and high radiochemical purity of &gt; 99%. Human embryonic kidney 293 (HEK-293) cell line stably transfected with the human P2X7 receptor was used to characterize the binding affinity of TZ6019 by fluorescence, radioactive competitive, and saturation binding assays. A radioligand competitive binding assay with [123I]TZ6019 demonstrated that the nonradioactive compound TZ6019 has an IC50 value of 9.49 ± 1.4 nM, and the known P2X7 receptor compound GSK1482160 has an IC50 value of 4.30 ± 0.86 nM, consistent with previous reports. The radioligand saturation binding assay and competitive assay revealed that [123I]TZ6019 specifically bound to the human P2X7 receptor with high affinity (Ki = 6.3 ± 0.9 nM). In vitro autoradiography quantification with brain slices collected from 9-month old P301S tau transgenic mice along with wild type controls, revealed higher binding of [123I]TZ6019 (35% increase) in the brain of P301S transgenic mice (n = 3, p = 0.04) compared to wild type controls. The immunofluorescence microscopy confirmed that expression of P2X7 receptor was colocalized with astrocytes in the tauopathy P301S transgenic mice. [123I]TZ6019 has specific binding for P2X7 receptor and has great potential to be a radiotracer for screening new compounds and quantifying expression of P2X7 receptor in neuroinflammation related diseases. © 2017 Elsevier B.V.


Author Keywords
I-123;  Neuroinflammation;  P2X7 receptor;  P301S


Document Type: Article
Source: Scopus

 

5) 

Davoli, C.C., Bloesch, E.K., Abrams, R.A.
The power of the imagination to affect peripersonal space representations
(2017) Visual Cognition, pp. 1-11. Article in Press. 


Abstract
It is known that visual processing is altered for objects near the hands as well as for objects near the imagined position of the hands, indicating that the imagination can be used to remap peri-hand space. Little is known, however, about the physical conditions that allow for this remapping. In the present study, participants in one experiment performed visual searches through displays that were beyond reach while imagining that their hands were near the display. This imagined impossible posture slowed visual search rates, showing that imagination effectively remapped peri-hand space to be near the display. In another experiment, participants searched displays they were holding, but sometimes imagined their hands to be far away. This produced faster search rates, revealing a remapping of peri-hand space away from the monitor. The results provide new insights into the mechanisms involved in the representation of peri-hand space and about the power of imagined actions to influence body representations. © 2017 Informa UK Limited, trading as Taylor & Francis Group


Author Keywords
Embodied cognition;  motor imagery;  object processing;  peripersonal space;  visual attention


Document Type: Article in Press
Source: Scopus

 

6) 

Mulvahill, J.S., Nicol, G.E., Dixon, D., Lenze, E.J., Karp, J.F., Reynolds, C.F., III, Blumberger, D.M., Mulsant, B.H.
Effect of Metabolic Syndrome on Late-Life Depression: Associations with Disease Severity and Treatment Resistance
(2017) Journal of the American Geriatrics Society, 65 (12), pp. 2651-2658. 


Abstract
Background/Objectives: Metabolic syndrome (MetS) is the co-occurrence of obesity and metabolic derangements. Prior research implicates MetS in prolongation of the course of depression in older adults, but its effect on antidepressant response is unknown in this population. The objective was to determine whether MetS and related metabolic dyscrasias are associated with decreased rate of remission from depression in older adults treated pharmacologically for depression. Design: Secondary analysis of a randomized controlled trial. Setting: Three academic medical centers in North America. Participants: Adults aged 60 and older (mean age 69.1) with major depressive disorder (MDD) (N = 435). Intervention: Open-label, protocolized treatment with extended-release venlafaxine for 12 or more weeks. Measurements: Time to remission from depression, with remission defined as a Montgomery-Åsberg Depression Rating Scale (MADRS) score of 10 or less at last two visits. Results: Two hundred twenty-two participants (51%) met criteria for MetS at baseline; MetS was associated with greater severity (MADRS score) and chronicity of depression at baseline. Remission was achieved in 182 participants (42%). In the unadjusted analysis, MetS was associated with prolonged time to remission (hazard ratio for remission = 0.71, 95% confidence interval = 0.52–0.95), but this relationship was not significant in the adjusted model; greater number of MetS components and lower high-density lipoprotein cholesterol had similar effects. Only diastolic blood pressure (DBP) was a significant predictor of time to remission before and after adjustment, with higher DBP predicting longer time to remission. Insulin sensitivity did not predict time to remission. Conclusion: The presence of MetS in older adults with depression was associated with greater symptom severity and chronicity of depression, which appears to have accounted for the poorer antidepressant response observed in those with MetS. Additionally, our preliminary finding of an association between higher DBP and poorer antidepressant response bears further examination and replication. © 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society


Author Keywords
elderly;  late-life depression;  major depressive disorder;  metabolic syndrome;  venlafaxine


Document Type: Article
Source: Scopus

 

7) 

Zhang, J.
Always hard to absorb: Youngsters suicide from childhood adversity
(2017) Annals of Translational Medicine, 5 (24), art. no. 492, . 


Document Type: Editorial
Source: Scopus

 

8) 

Hill, P.L., Weston, S.J.
Evaluating eight-year trajectories for sense of purpose in the health and retirement study
(2017) Aging and Mental Health, pp. 1-5. Article in Press. 


Abstract
Objectives: Though cross-sectional research has suggested that sense of purpose declines into older adulthood, it remains unclear whether inter-individual variability occurs in these trajectories, and what factors predict these trajectories. The current study provides one of the first longitudinal investigations into how individuals’ sense of purpose fluctuates in older adulthood. Method: Participants from the Health and Retirement Study (n = 4,234, mean age = 65 years), completed assessments of sense of purpose over three years, along with multiple potential predictors (health, personality, demographics) at the start. Results: Second-order latent growth models demonstrated both mean-level declines on purpose over time, as well as the capacity for inter-individual variability in change patterns for retired adults. Among this cohort, health status, educational attainment, and marital status were significant predictors of purpose trajectories over time, though broad personality trait dimensions failed to uniquely predict change in sense of purpose. However, measurement invariance tests suggest that the scale did not operate similarly across work status groups. Conclusion: Findings advance the previous literature by demonstrating inter-individual variability in sense of purpose for those participants who had retired. Future research should consider that purpose inventories may operate differently for those in the workplace versus retired adults. © 2017 Informa UK Limited, trading as Taylor & Francis Group


Author Keywords
health;  longitudinal change;  personality;  Purpose in life;  retirement


Document Type: Article in Press
Source: Scopus

 

9) 

Hubbard, N.A., Turner, M.P., Ouyang, M., Himes, L., Thomas, B.P., Hutchison, J.L., Faghihahmadabadi, S., Davis, S.L., Strain, J.F., Spence, J., Krawczyk, D.C., Huang, H., Lu, H., Hart, J., Jr., Frohman, T.C., Frohman, E.M., Okuda, D.T., Rypma, B.
Calibrated imaging reveals altered grey matter metabolism related to white matter microstructure and symptom severity in multiple sclerosis
(2017) Human Brain Mapping, 38 (11), pp. 5375-5390. 


Abstract
Multiple sclerosis (MS) involves damage to white matter microstructures. This damage has been related to grey matter function as measured by standard, physiologically-nonspecific neuroimaging indices (i.e., blood-oxygen-level dependent signal [BOLD]). Here, we used calibrated functional magnetic resonance imaging and diffusion tensor imaging to examine the extent to which specific, evoked grey matter physiological processes were associated with white matter diffusion in MS. Evoked changes in BOLD, cerebral blood flow (CBF), and oxygen metabolism (CMRO2) were measured in visual cortex. Individual differences in the diffusion tensor measure, radial diffusivity, within occipital tracts were strongly associated with MS patients’ BOLD and CMRO2. However, these relationships were in opposite directions, complicating the interpretation of the relationship between BOLD and white matter microstructural damage in MS. CMRO2 was strongly associated with individual differences in patients’ fatigue and neurological disability, suggesting that alterations to evoked oxygen metabolic processes may be taken as a marker for primary symptoms of MS. This work demonstrates the first application of calibrated and diffusion imaging together and details the first application of calibrated functional MRI in a neurological population. Results lend support for neuroenergetic hypotheses of MS pathophysiology and provide an initial demonstration of the utility of evoked oxygen metabolism signals for neurology research. Hum Brain Mapp 38:5375–5390, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.


Author Keywords
blood flow and metabolism;  calibrated imaging;  diffusion tensor imaging;  multiple sclerosis;  white matter


Document Type: Article
Source: Scopus

 

10) 

Hawasli, A., Rutlin, J., Roland, J.L., Murphy, R., Song, S.-K., Leuthardt, E., Shimony, J., Ray, W.Z.
Spinal Cord Injury Disrupts Resting-State Networks in the Human Brain
(2017) Journal of Neurotrauma, . Article in Press. 


Abstract
Despite 253,000 spinal cord injury (SCI) patients in America, little is known about how SCI affects brain networks. Spinal magnetic resonance imaging (MRI) provides only structural information with no insight into functional connectivity. Resting-state functional MRI (RS-fMRI) quantifies network connectivity through the identification of resting-state networks (RSNs) and allows detection of functionally-relevant changes during disease. Given the robust network of spinal cord afferents to the brain, we hypothesized SCI produces meaningful changes in brain RSNs. RS-fMRIs and functional assessments were performed on 10 SCI subjects. Blood oxygen-dependent RS-fMRI sequences were acquired. Seed-based correlation mapping was performed using five RSNs: default-mode (DMN), dorsal-attention (DAN), salience (SAL), control (CON) and somatomotor (SMN). RSNs were compared to normal control subjects using false-discovery rate-corrected two-way t-tests. SCI reduced brain network connectivity within the SAL, SMN and DMN and disrupted anti-correlated connectivity between CON and SMN. When divided into separate cohorts, complete but not incomplete SCI disrupted connectivity within SAL, DAN, SMN and DMN and between CON and SMN. Finally, connectivity changed over time after SCI: primary motor cortex decreased connectivity with primary somatosensory cortex, visual cortex decreased connectivity with primary motor cortex and visual cortex decreased connectivity with sensory parietal cortex. These unique findings demonstrate the functional network plasticity that occurs in the brain as a result of injury to the spinal cord. Connectivity changes after SCI may serve as biomarkers to predict functional recovery following a SCI and guide future therapy. © Mary Ann Liebert, Inc.


Author Keywords
biomarkers;  MRI;  neuroplasticity;  Spinal Cord Injury


Document Type: Article in Press
Source: Scopus

 

December 18, 2017

1) 

Shepherd, A.J., Mohapatra, D.P.
Pharmacological validation of voluntary gait and mechanical sensitivity assays associated with inflammatory and neuropathic pain in mice
(2018) Neuropharmacology, 130, pp. 18-29. 


a Washington University Pain Center, St. Louis, MO, United States
b Department of Anesthesiology, St. Louis, MO, United States
c Center for the Investigation of Membrane Excitability Diseases, St. Louis, MO, United States
d Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, United States


Abstract
The urgent need for more effective analgesic treatment options has prompted a re-evaluation of the behavioral tests used to assess pain in pre-clinical research, with an emphasis on inclusion of more voluntary, un-evoked behavioral assessments of pain. In order to validate voluntary gait analysis and a voluntary mechanical conflict-avoidance assay, we tested mouse models of neuropathy (spared nerve injury) and inflammation (complete Freund's adjuvant) alongside reflexive measures of mechanical and thermal hypersensitivity. To establish whether the observed changes in behavioral responses were pain-related, known analgesics (buprenorphine, gabapentin, carprofen) were also administered. Spared nerve injury persistently altered several gait indices, whereas complete Freund's adjuvant caused only transient changes. Furthermore, known analgesics could not reverse these gait changes, despite demonstrating their previously established efficacy in reflexive measures of mechanical and thermal hypersensitivity. In contrast, the mechanical conflict-avoidance assay demonstrated aversion in mice with neuropathy and inflammation-induced hypersensitivity, which could both be reversed by analgesics. We conclude that voluntary gait changes in rodent neuropathic and inflammatory pain models are not necessarily indicative of pain-related adaptations. On the other hand, mechanical conflict-avoidance represents a valid operant assay for quantifying pain-related behaviors in mice that can be reversed by known analgesics. © 2017


Author Keywords
Catwalk;  Conflict-avoidance;  Gait;  Inflammatory pain;  Neuropathic pain

 

2) 

Zwemer, E., Bernson-Leung, M., Rea, C., Patel, A.A., Guerriero, R., Urion, D.K., Toomey, S.L.
Education on the Brain: A Partnership Between a Pediatric Primary Care Center and Neurology Residency
(2018) Clinical Pediatrics, 57 (1), pp. 46-51. 


a Department of Pediatrics, University of North Carolina School of Medicine, Chapel Hill, NC, United States
b Department of Neurology, Boston Children’s Hospital, Boston, MA, United States
c Harvard Medical School, Boston, MA, United States
d Department of Medicine, Boston Children’s Hospital, Boston, MA, United States
e Department of Neurology, St Louis Children’s Hospital, St Louis, MO, United States
f Washington University School of Medicine, St Louis, MO, United States


Abstract
The national shortage of pediatric neurologists is worsening, yet referral rates by pediatricians are high. Suboptimal training of pediatric residents in care of patients with neurologic disease may be a contributing factor. We formed a partnership between the Boston Children’s Primary Care at Longwood clinic and Child Neurology Residency Training Program. The educational intervention included lectures, observed neurologic examinations, in-person and virtual triage, and an electronic medical record–based consult system. Residents in other primary care clinics served as the comparison group. Intervention-group residents reported significantly improved confidence in diagnosis of chronic/recurrent headache, attention deficit hyperactivity disorder (ADHD), and developmental delay; initial management of ADHD and developmental delay; and secondary management of ADHD, developmental delay, and concussion/traumatic brain injury. Comparison-group residents reported significantly improved confidence only in diagnosis of developmental delay. Our multipronged intervention is a promising approach to improving pediatric resident training in pediatric neurology and may be generalizable to subspecialty collaborations for other residency programs. © 2017, © The Author(s) 2017.


Author Keywords
innovation;  medical education;  pediatric neurology;  resident training

 

3) 

Galgano, S., Viets, Z., Fowler, K., Gore, L., Thomas, J.V., McNamara, M., McConathy, J.
Practical Considerations for Clinical PET/MR Imaging
(2018) PET Clinics, 13 (1), pp. 97-112. 


a Department of Radiology, University of Alabama at Birmingham (UAB), 619 19th Street South, Birmingham, AL, United States
b Department of Radiology, Washington University in St Louis, 510 South Kingshighway Boulevard, St. Louis, MO, United States


Abstract
Clinical PET/MR imaging is currently performed at a number of centers around the world as part of routine standard of care. This article focuses on issues and considerations for a clinical PET/MR imaging program, focusing on routine standard-of-care studies. Although local factors influence how clinical PET/MR imaging is implemented, the approaches and considerations described here intend to apply to most clinical programs. PET/MR imaging provides many more options than PET/computed tomography with diagnostic advantages for certain clinical applications but with added complexity. A recurring theme is matching the PET/MR imaging protocol to the clinical application to balance diagnostic accuracy with efficiency. © 2017 Elsevier Inc.


Author Keywords
FDG-PET;  Oncologic imaging;  PET/MR imaging;  PET/MR imaging protocols;  Whole-body PET/MR imaging

 

4) 

Meinerz, K., Beeman, S.C., Duan, C., Bretthorst, G.L., Garbow, J.R., Ackerman, J.J.H.
Bayesian Modeling of NMR Data: Quantifying Longitudinal Relaxation in Vivo, and in Vitro with a Tissue-Water-Relaxation Mimic (Crosslinked Bovine Serum Albumin)
(2017) Applied Magnetic Resonance, pp. 1-22. Article in Press. 


a Department of Physics, Washington University, Saint Louis, MO, United States
b Department of Radiology, Washington University, Saint Louis, MO, United States
c Department of Chemistry, Washington University, Saint Louis, MO, United States
d Alvin J. Siteman Cancer Center, Washington University, Saint Louis, MO, United States
e Department of Internal Medicine, Washington University, Saint Louis, MO, United States


Abstract
Recently, a number of magnetic resonance imaging protocols have been reported that seek to exploit the effect of dissolved oxygen (O2, paramagnetic) on the longitudinal 1H relaxation of tissue water, thus providing image contrast related to tissue oxygen content. However, tissue water relaxation is dependent on a number of mechanisms and this raises the issue of how best to model the relaxation data. This problem, the model selection problem, occurs in many branches of science and is optimally addressed by Bayesian probability theory. High signal-to-noise, densely sampled, longitudinal 1H relaxation data were acquired from rat brain in vivo and from a cross-linked bovine serum albumin (xBSA) phantom, a sample that recapitulates the relaxation characteristics of tissue water in vivo. Bayesian-based model selection was applied to a cohort of five competing relaxation models: (1) monoexponential, (2) stretched-exponential, (3) biexponential, (4) Gaussian (normal) R1-distribution, and (5) gamma R1-distribution. Bayesian joint analysis of multiple replicate datasets revealed that water relaxation of both the xBSA phantom and in vivo rat brain was best described by a biexponential model, while xBSA relaxation datasets truncated to remove evidence of the fast relaxation component were best modeled as a stretched exponential. In all cases, estimated model parameters were compared to the commonly used monoexponential model. Reducing the sampling density of the relaxation data and adding Gaussian-distributed noise served to simulate cases in which the data are acquisition-time or signal-to-noise restricted, respectively. As expected, reducing either the number of data points or the signal-to-noise increases the uncertainty in estimated parameters and, ultimately, reduces support for more complex relaxation models. © 2017 Springer-Verlag GmbH Austria, part of Springer Nature

 

5) 

Kohan, E.M., Nemani, V.M., Hershman, S., Kang, D.G., Kelly, M.P.
Lumbar computed tomography scans are not appropriate surrogates for bone mineral density scans in primary adult spinal deformity
(2017) Neurosurgical Focus, 43 (6), art. no. E4, . 


a Department of Orthopedic Surgery, Washington University, St. Louis, MS, United States
b Raleigh Orthopaedic Clinic, Raleigh, NC, United States
c Department of Orthopaedic Surgery, Massachusetts General Hospital, Boston, MA, United States
d Madigan Army Medical Center, Tacoma, WA, United States


Abstract
OBJECTIVE The authors examined the correlation between lumbar spine CT Hounsfield unit (HU) measurements and bone mineral density measurements in an adult spinal deformity (ASD) population. METHODS Patients with ASD were identified in the records of a single institution. Lumbar CT scans were reviewed, and the mean HU measurements from L1-4 were recorded. Bone mineral density (BMD) was assessed using femoral neck and lumbar spine dual-energy x-ray absorptiometry (DEXA). The number of patients who met criteria for osteoporosis was determined for each imaging modality. RESULTS Forty-eight patients underwent both preoperative DEXA and CT scanning. Forty-three patients were female and 5 were male. Forty-seven patients were Caucasian and one was African American. The mean age of the patients was 62.1 years. Femoral neck DEXA was more likely to identify osteopenia (n = 26) than lumbar spine DEXA (n = 8) or lumbar CT HU measurements (n = 6) (p < 0.001). There was a low-moderate correlation between lumbar spine CT and lumbar spine DEXA (r = 0.463, p < 0.001), and there was poor correlation between lumbar spine CT and femoral neck DEXA (r = 0.303, p = 0.036). CONCLUSIONS Despite the opportunistic utility of lumbar spine CT HU measurements in identifying osteoporosis in patients undergoing single-level fusion, these measurements were not useful in this cohort of ASD patients. The correlation between femoral neck DEXA and HU measurements was poor. DEXA assessment of BMD in ASD patients is essential to optimize the care of these complicated cases. © AANS, 2017.


Author Keywords
Adult spinal deformity;  Bone mineral density;  Computed tomography;  Hounsfield units;  Osteoporosis

 

6) 

Boone, A.E., Morgan, K.A., Engsberg, J.R.
A new combined motor and cognitive strategy training intervention for stroke: Stakeholder perceptions
(2017) British Journal of Occupational Therapy, 80 (12), pp. 726-734. 


a Program in Occupational Therapy, Washington University School of Medicine, United States
b Programs in Occupational Therapy and Neurology, Washington University School of Medicine, United States
c Programs in Occupational Therapy, Neurosurgery, and Orthopedics, Washington University School of Medicine, United States


Abstract
Introduction: Hemiparesis affects about half of persons with chronic stroke and frequently leads to decreased participation in meaningful daily life activities. The purpose of this investigation was to evaluate the perceived acceptability and practicality feasibility of a complex intervention for addressing motor impairment and activity limitations post stroke. The newly developed intervention, Metacognitive Virtual Reality (MetacogVR), combines virtual reality technology to improve motor impairments with task-based, cognitive strategy training for meaningful transfer of skills. Method: Three separate focus groups were held with stakeholders including persons with stroke (n = 5), caregivers (n = 5), and occupational therapists (n = 5). Focus groups were audio recorded and transcribed. Data were analyzed using inductive content analysis. Results: Themes revealed stakeholder perceptions of the intervention as a cost-efficient and transportable intervention. The time commitment of the intervention was acknowledged as intense, but necessary for optimal improvements. Findings also included perceptions of the intervention as highly motivating and client-centered. Essential elements of guided discovery, cognitive strategies, and high repetitions were seen as facilitators of the intervention. Conclusion: Results indicate MetacogVR has positively perceived acceptability and practicality feasibility. Findings warrant further feasibility testing of MetacogVR prior to efficacy testing. © 2017, © The Author(s) 2017.


Author Keywords
Metacognition;  motor;  stroke

 

7) 

Vila, P.M., Townsend, M.E., Bhatt, N.K., Kao, W.K., Sinha, P., Neely, J.G.
The P Value Problem in Otolaryngology: Shifting to Effect Sizes and Confidence Intervals
(2017) Otolaryngology - Head and Neck Surgery (United States), 157 (6), pp. 1079-1080. 


Writing group, Department of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine in St Louis, St Louis, MO, United States

 

8) 

Valnegri, P., Huang, J., Yamada, T., Yang, Y., Mejia, L.A., Cho, H.Y., Oldenborg, A., Bonni, A.
RNF8/UBC13 ubiquitin signaling suppresses synapse formation in the mammalian brain
(2017) Nature Communications, 8 (1), art. no. 1271, . 


a Department of Neuroscience, Washington University School of Medicine, St. Louis, MO, United States
b Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan


Abstract
Although ubiquitin ligases have been implicated in autism, their roles and mechanisms in brain development remain incompletely understood. Here, we report that in vivo knockdown or conditional knockout of the autism-linked ubiquitin ligase RNF8 or associated ubiquitin-conjugating enzyme UBC13 in rodent cerebellar granule neurons robustly increases the number of parallel fiber presynaptic boutons and functional parallel fiber/Purkinje cell synapses. In contrast to the role of nuclear RNF8 in proliferating cells, RNF8 operates in the cytoplasm in neurons to suppress synapse differentiation in vivo. Proteomics analyses reveal that neuronal RNF8 interacts with the HECT domain protein HERC2 and scaffold protein NEURL4, and knockdown of HERC2 or NEURL4 phenocopies the inhibition of RNF8/UBC13 signaling on synapse differentiation. In behavior analyses, granule neuron-specific knockout of RNF8 or UBC13 impairs cerebellar-dependent learning. Our study defines RNF8 and UBC13 as components of a novel cytoplasmic ubiquitin-signaling network that suppresses synapse formation in the brain. © 2017 The Author(s).

 

9) 

Krauze, A., Attia, A., Braunstein, S., Chan, M., Combs, S., Fietkau, R., Fiveash, J., Flickinger, J., Grosu, A., Howard, S., Nieder, C., Niyazi, M., Rowe, L., Smart, D.D., Tsien, C., Camphausen, K.
Expert consensus on re-irradiation for recurrent glioma
(2017) Radiation Oncology, 12 (1), art. no. 194, . 


a National Cancer Institute NIH, Radiation Oncology Branch, Bethesda, MD, United States
b Vanderbilt University Medical Center, Department of Radiation Oncology, Nashville, TN, United States
c University of California, Department of Radiation Oncology, San Francisco, United States
d Department of Radiation Oncology, Wake Forest Baptist Medical Center, Winston-Salem, NC, United States
e Technical University of Munich (TUM), Department of Radiation Oncology, Munich, Germany
f Helmholtz Zentrum München, Institute of Innovative Radiotherapy (iRT), Department of Radiation Sciences (DRS), Neuherberg, Germany
g Deutsches Konsortium für Translationale Krebsforschung (DKTK), Partner Size, Munich, Germany
h Department of Radiotherapy Erlangen, Erlangen, Germany
i University of Alabama at Birmingham, Department of Radiation Oncology, Birmingham, AL, United States
j UPMC Presbyterian-Shadyside, Pittsburgh, PA, United States
k University of Freiburg, Department of Radiation Oncology, Freiburg, Germany
l University of Wisconsin, Department of Human Oncology, Madison, WI, United States
m Department of Oncology and Palliative Medicine, Hospital Trust, Bodø, Nordland, Norway
n University of Tromsø, Department of Clinical Medicine, Faculty of Health Sciences, Tromsø, Norway
o Department of Radiation Oncology, LMU Munich, Marchioninistr. 15, Munich, Germany
p German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany
q National Cancer Institute, NIH, Radiation Oncology Branch, Bethesda, MD, United States
r Washington University, Department of Radiation Oncology, St. Louis, MO, United States


Abstract
Purpose: To investigate radiation oncologists' opinions on important considerations to offering re-irradiation (re-RT) as a treatment option for recurrent glioma. Materials and methods: A survey was conducted with 13 radiation oncologists involved in the care of central nervous system tumor patients. The survey was comprised of 49 questions divided into 2 domains: a demographic section (10 questions) and a case section (5 re-RT cases with 5 to 6 questions representing one or several re-RT treatment dilemmas as may be encountered in the clinic). Respondents were asked to rate the relevance of various factors to offering re-RT, respond to the cases with a decision to offer re-RT vs. not, volume to be treated, margins to be employed, dose/fractionation suggested and any additional comments with respect to rationale in each scenario. Results: Sixty nine percent of responders have been practicing for greater than 10years and 61% have re-RT 20 to 100 patients to date, with 54% seeing 2-5 re-RT cases per month and retreating 1-2 patients per month. Recurrent tumor volume, time since previous radiation therapy, previously administered dose to organs at risk and patient performance status were rated by the majority of responders (85%, 92%, 77%, and 69% respectively) as extremely relevant or very relevant to offering re-RT as an option. Conclusion: The experts' practice of re-RT is still heterogeneous, reflecting the paucity of high-quality prospective data available for decision-making. Nevertheless, practicing radiation oncologists can support own decisions by referring to the cases found suitable for re-RT in this survey. © 2017 The Author(s).

 

10) 

Poorman, G.W., Passias, P.G., Horn, S.R., Frangella, N.J., Daniels, A.H., Hamilton, D.K., Kim, H., Sciubba, D., Diebo, B.G., Bortz, C.A., Segreto, F.A., Kelly, M.P., Smith, J.S., Neuman, B.J., Shaffrey, C.I., LaFage, V., LaFage, R., Ames, C.P., Hart, R., Mundis, G.M., Jr., Eastlack, R.
Despite worse baseline status depressed patients achieved outcomes similar to those in nondepressed patients after surgery for cervical deformity
(2017) Neurosurgical Focus, 43 (6), art. no. E10, . 


a Department of Orthopaedic Surgery, NYU Hospital for Joint Diseases, New York, NY, United States
b Department of Orthopaedic Surgery, Brown University Alpert Medical School, Providence, RI, United States
c Department of Neurologic Surgery, University of PittsburghPA, United States
d Department of Orthopaedic Surgery, Hospital for Special Surgery, New York, NY, United States
e Department of Neurologic Surgery, Johns Hopkins Medical Center, Baltimore, MD, United States
f Department of Orthopaedic Surgery, University Hospital of Brooklyn, New York, NY, United States
g Department of Orthopaedic Surgery, Washington University, St. Louis, MO, United States
h Department of Neurological Surgery, University of Virginia Health System, Charlottesville, VA, United States
i Department of Neurological Surgery, University of California, San Francisco, CA, United States
j Swedish Neuroscience Institute, Seattle, WA, United States
k San Diego Center for Spinal Disorders, La Jolla, CA, United States


Abstract
OBJECTIVE Depression and anxiety have been demonstrated to have negative impacts on outcomes after spine surgery. In patients with cervical deformity (CD), the psychological and physiological burdens of the disease may overlap without clear boundaries. While surgery has a proven record of bringing about significant pain relief and decreased disability, the impact of depression and anxiety on recovery from cervical deformity corrective surgery has not been previously reported on in the literature. The purpose of the present study was to determine the effect of depression and anxiety on patients' recovery from and improvement after CD surgery. METHODS The authors conducted a retrospective review of a prospective, multicenter CD database. Patients with a history of clinical depression, in addition to those with current self-reported anxiety or depression, were defined as depressed (D group). The D group was compared with nondepressed patients (ND group) with a similar baseline deformity determined by propensity score matching of the cervical sagittal vertical axis (cSVA). Baseline demographic, comorbidity, clinical, and radiographic data were compared among patients using t-tests. Improvement of symptoms was recorded at 3 months, 6 months, and 1 year postoperatively. All health-related quality of life (HRQOL) scores collected at these follow-up time points were compared using t-tests. RESULTS Sixty-six patients were matched for baseline radiographic parameters: 33 with a history of depression and/ or current depression, and 33 without. Depressed patients had similar age, sex, race, and radiographic alignment: cSVA, T-1 slope minus C2-7 lordosis, SVA, and T-1 pelvic angle (p > 0.05). Compared with nondepressed individuals, depressed patients had a higher incidence of osteoporosis (21.2% vs 3.2%, p = 0.028), rheumatoid arthritis (18.2% vs 3.2%, p = 0.012), and connective tissue disorders (18.2% vs 3.2%, p = 0.012). At baseline, the D group had greater neck pain (7.9 of 10 vs 6.6 on a Numeric Rating Scale [NRS], p = 0.015), lower mean EQ-5D scores (68.9 vs 74.7, p < 0.001), but similar Neck Disability Index (NDI) scores (57.5 vs 49.9, p = 0.063) and myelopathy scores (13.4 vs 13.9, p = 0.546). Surgeries performed in either group were similar in terms of number of levels fused, osteotomies performed, and correction achieved (baseline to 3-month measurements) (p < 0.05). At 3 months, EQ-5D scores remained lower in the D group (74.0 vs 78.2, p = 0.044), and NDI scores were similar (48.5 vs 39.0, p = 0.053). However, neck pain improved in the D group (NRS score of 5.0 vs 4.3, p = 0.331), and modified Japanese Orthopaedic Association (mJOA) scores remained similar (14.2 vs 15.0, p = 0.211). At 6 months and 1 year, all HRQOL scores were similar between the 2 cohorts. Oneyear measurements were as follows: NDI 39.7 vs 40.7 (p = 0.878), NRS neck pain score of 4.1 vs 5.0 (p = 0.326), EQ-5D score of 77.1 vs 78.2 (p = 0.646), and mJOA score of 14.0 vs 14.2 (p = 0.835). Anxiety/depression levels reported on the EQ-5D scale were significantly higher in the depressed cohort at baseline, 3 months, and 6 months (all p < 0.05), but were similar between groups at 1 year postoperatively (1.72 vs 1.53, p = 0.416). CONCLUSIONS Clinical depression was observed in many of the study patients with CD. After matching for baseline deformity, depression symptomology resulted in worse baseline EQ-5D and pain scores. Despite these baseline differences, both cohorts achieved similar results in all HRQOL assessments 6 months and 1 year postoperatively, demonstrating no clinical impact of depression on recovery up until 1 year after CD surgery. Thus, a history of depression does not appear to have an impact on recovery from CD surgery. © AANS, 2017.


Author Keywords
Cervical deformity;  Outcomes;  Spinal deformity;  Surgery

 

11) 

Bumpass, D.B., Lenke, L.G., Gum, J.L., Shaffrey, C.I., Smith, J.S., Ames, C.P., Bess, S., Neuman, B.J., Klineberg, E., Mundis, G.M., Jr., Schwab, F., Lafage, V., Kim, H.J., Burton, D.C., Kebaish, K.M., Hostin, R., Lafage, R., Kelly, M.P.
Male sex may not be associated with worse outcomes in primary all-posterior adult spinal deformity surgery: A multicenter analysis
(2017) Neurosurgical Focus, 43 (6), art. no. E9, . 


a Department of Orthopaedic Surgery, University of Arkansas for Medical Sciences, Little Rock, AR, United States
b Department of Orthopaedic Surgery, Columbia University, New York, NY, United States
c Department of Orthopaedic Surgery, Norton Leatherman Spine Center, Louisville, KY, United States
d Department of Neurological Surgery, University of Virginia, Charlottesville, VA, United States
e Department of Neurological Surgery, University of California, San Francisco, CA, United States
f Denver International Spine Center, Presbyterian St. Luke's/Rocky Mountain Hospital for Children, Denver, CO, United States
g Department of Orthopedic Surgery, Johns Hopkins University, Baltimore, MD, United States
h Department of Orthopedic Surgery, University of California, Davis, Sacramento, CA, United States
i San Diego Center for Spinal Disorders, San Diego, CA, United States
j Division of Spine Surgery, Hospital for Special Surgery, New York, NY, United States
k Department of Orthopedic Surgery, University of Kansas, Kansas City, KS, United States
l Baylor Scoliosis Center, Plano, TX, United States
m Department of Orthopaedic Surgery, Washington University in St. LouisMO, United States


Abstract
OBJECTIVE Adolescent spine deformity studies have shown that male patients require longer surgery and have greater estimated blood loss (EBL) and complications compared with female patients. No studies exist to support this relationship in adult spinal deformity (ASD). The purpose of this study was to investigate associations between sex and complications, deformity correction, and health-related quality of life (HRQOL) in patients with ASD. It was hypothesized that male ASD patients would have greater EBL, longer surgery, and more complications than female ASD patients. METHODS A multicenter ASD cohort was retrospectively queried for patients who underwent primary posterior-only instrumented fusions with a minimum of 5 levels fused. The minimum follow-up was 2 years. Primary outcomes were EBL, operative time, intra-, peri-, and postoperative complications, radiographic correction, and HRQOL outcomes (Oswestry Disability Index, SF-36, and Scoliosis Research Society-22r Questionnaire). Poisson multivariate regression was used to control for age, comorbidities, and levels fused. RESULTS Ninety male and 319 female patients met the inclusion criteria. Male patients had significantly greater mean EBL (2373 ml vs 1829 ml, p = 0.01). The mean operative time, transfusion requirements, and final radiographic measurements did not differ between sexes. Similarly, changes in HRQOL showed no significant differences. Finally, there were no sex differences in the incidence of complications (total, major, or minor) at any time point after controlling for age, body mass index, comorbidities, and levels fused. CONCLUSIONS Despite higher EBL, male ASD patients did not experience more complications or require less deformity correction at the 2-year follow-up. HRQOL scores similarly showed no sex differences. These findings differ from adolescent deformity studies, and surgeons can counsel patients that sex is unlikely to influence the outcomes and complication rates of primary all-posterior ASD surgery. © AANS, 2017.


Author Keywords
Adult spinal deformity;  Blood loss;  Complications;  Deformity correction;  Gender;  Health-related quality of life;  Patient-reported outcomes;  Sex

 

12) 

Ridge, P.G., Karch, C.M., Hsu, S., Arano, I., Teerlink, C.C., Ebbert, M.T.W., Gonzalez Murcia, J.D., Farnham, J.M., Damato, A.R., Allen, M., Wang, X., Harari, O., Fernandez, V.M., Guerreiro, R., Bras, J., Hardy, J., Munger, R., Norton, M., Sassi, C., Singleton, A., Younkin, S.G., Dickson, D.W., Golde, T.E., Price, N.D., Ertekin-Taner, N., Cruchaga, C., Goate, A.M., Corcoran, C., Tschanz, J.A., Cannon-Albright, L.A., Kauwe, J.S.K.
Linkage, whole genome sequence, and biological data implicate variants in RAB10 in Alzheimer's disease resilience
(2017) Genome Medicine, 9 (1), art. no. 100, . 


a Brigham Young University, Department of Biology, Provo, UT, United States
b Washington University School of Medicine, St. Louis, MO, United States
c University of Utah School of Medicine, Division of Genetic Epidemiology, Department of Internal Medicine, Salt Lake City, UT, United States
d Mayo Clinic, Department of Neuroscience, 4500 San Pablo Road, Jacksonville, FL, United States
e Mayo Clinic, Department of Neuroscience, Jacksonville, FL, United States
f Mayo Clinic, Department of Health Sciences Research, Jacksonville, FL, United States
g University College London, Department of Molecular Neuroscience, Institute of Neurology, London, United Kingdom
h Utah State University, Department of Nutrition, Dietetics, and Food Sciences, Logan, UT, United States
i Utah State University, Department of Family Consumer and Human Development, Logan, UT, United States
j National Institute on Aging, Bethesda, MD, United States
k Center for Translational Research in Neurodegenerative Disease, McKnight Brain Institute, University of Florida, Department of Neuroscience, Gainesville, FL, United States
l Institute for Systems Biology, 401 Terry Avenue N, Seattle, WA, United States
m Mayo Clinic, Departments of Neurology and Neuroscience, Jacksonville, FL, United States
n Icahn School of Medicine at Mount Sinai, Departments of Neuroscience, Genetics and Genomic Sciences, and Neurology, New York, NY, United States
o Utah State University, Department of Mathematics and Statistics, Logan, UT, United States
p Utah State University, Department of Psychology, Logan, UT, United States
q George E. Wahlen Department of Veterans Affairs Medical Center, Salt Lake City, UT, United States
r Brigham Young University, Departments of Biology and Neuroscience, Provo, UT, United States


Abstract
Background: While age and the APOE ε4 allele are major risk factors for Alzheimer's disease (AD), a small percentage of individuals with these risk factors exhibit AD resilience by living well beyond 75 years of age without any clinical symptoms of cognitive decline. Methods: We used over 200 "AD resilient" individuals and an innovative, pedigree-based approach to identify genetic variants that segregate with AD resilience. First, we performed linkage analyses in pedigrees with resilient individuals and a statistical excess of AD deaths. Second, we used whole genome sequences to identify candidate SNPs in significant linkage regions. Third, we replicated SNPs from the linkage peaks that reduced risk for AD in an independent dataset and in a gene-based test. Finally, we experimentally characterized replicated SNPs. Results: Rs142787485 in RAB10 confers significant protection against AD (p value = 0.0184, odds ratio = 0.5853). Moreover, we replicated this association in an independent series of unrelated individuals (p value = 0.028, odds ratio = 0.69) and used a gene-based test to confirm a role for RAB10 variants in modifying AD risk (p value = 0.002). Experimentally, we demonstrated that knockdown of RAB10 resulted in a significant decrease in Aβ42 (p value = 0.0003) and in the Aβ42/Aβ40 ratio (p value = 0.0001) in neuroblastoma cells. We also found that RAB10 expression is significantly elevated in human AD brains (p value = 0.04). Conclusions: Our results suggest that RAB10 could be a promising therapeutic target for AD prevention. In addition, our gene discovery approach can be expanded and adapted to other phenotypes, thus serving as a model for future efforts to identify rare variants for AD and other complex human diseases. © 2017 The Author(s).


Author Keywords
Alzheimer's disease;  Linkage analyses;  Protective variants;  Utah Population Database;  Whole genome sequencing

 

13) 

Chung, H.-K., Sjöström, T., Lee, H.-J., Lu, Y.-T., Tsuo, F.-Y., Chen, T.-S., Chang, C.-F., Juan, C.-H., Kuo, W.-J., Huang, C.-Y.
Why do irrelevant alternatives matter? An fMRI-TMS study of context-dependent preferences
(2017) Journal of Neuroscience, 37 (48), pp. 11647-11661. 


a Department of Psychology, New York University, New York, NY, United States
b Department of Economics, Rutgers University, New Brunswick, NJ, United States
c Institute of Neuroscience, National Yang-Ming University, Taipei, Taiwan
d Department of Economics, National Taiwan University, Taipei, Taiwan
e Department of Electrical Engineering, National Taiwan University, Taipei, Taiwan
f Department of Economics, Washington University in St. Louis, St. Louis, MO, United States
g Institute of Cognitive Neuroscience, National Central University, Taoyuan, Taiwan


Abstract
Both humans and animals are known to exhibit a violation of rationality known as “decoy effect”: introducing an irrelevant option (a decoy) can influence choices among other (relevant) options. Exactly how and why decoys trigger this effect is not known. It may be an example of fast heuristic decision-making, which is adaptive in natural environments, but may lead to biased choices in certain markets or experiments. We used fMRI and transcranial magnetic stimulation to investigate the neural underpinning of the decoy effect of both sexes. The left ventral striatum was more active when the chosen option dominated the decoy. This is consistent with the hypothesis that the presence of a decoy option influences the valuation of other options, making valuation context-dependent even when choices appear fully rational. Consistent with the idea that control is recruited to prevent heuristics from producing biased choices, the right inferior frontal gyrus, often implicated in inhibiting prepotent responses, connected more strongly with the striatum when subjects successfully overrode the decoy effect and made unbiased choices. This is further supported by our transcranial magnetic stimulation experiment: subjects whose right inferior frontal gyrus was temporarily disrupted made biased choices more often than a control group. Our results suggest that the neural basis of the decoy effect could be the context-dependent activation of the valuation area. But the differential connectivity from the frontal area may indicate how deliberate control monitors and corrects errors and biases in decision-making. © 2017 the authors.


Author Keywords
Context dependence;  Decoy effect;  Inhibitory control

 

14) 

Sun, W., Barbour, D.L.
Rate, not selectivity, determines neuronal population coding accuracy in auditory cortex
(2017) PLoS Biology, 15 (11), art. no. e2002459, . 


Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO, United States


Abstract
The notion that neurons with higher selectivity carry more information about external sensory inputs is widely accepted in neuroscience. High-selectivity neurons respond to a narrow range of sensory inputs, and thus would be considered highly informative by rejecting a large proportion of possible inputs. In auditory cortex, neuronal responses are less selective immediately after the onset of a sound and then become highly selective in the following sustained response epoch. These 2 temporal response epochs have thus been interpreted to encode first the presence and then the content of a sound input. Contrary to predictions from that prevailing theory, however, we found that the neural population conveys similar information about sound input across the 2 epochs in spite of the neuronal selectivity differences. The amount of information encoded turns out to be almost completely dependent upon the total number of population spikes in the read-out window for this system. Moreover, inhomogeneous Poisson spiking behavior is sufficient to account for this property. These results imply a novel principle of sensory encoding that is potentially shared widely among multiple sensory systems. © 2017 Sun, Barbour.

 

15) 

Fernández, M.V., Kim, J.H., Budde, J.P., Black, K., Medvedeva, A., Saef, B., Deming, Y., Del-Aguila, J., Ibañez, L., Dube, U., Harari, O., Norton, J., Chasse, R., Morris, J.C., Goate, A., NIA-LOAD family study group, NCRAD, Cruchaga, C.
Analysis of neurodegenerative Mendelian genes in clinically diagnosed Alzheimer Disease
(2017) PLoS Genetics, 13 (11), art. no. e1007045, . 


a Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States
b Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO, United States
c Department of Neurology, Dementia Center, Ilsan hospital, National Health Insurance Service, Goyang, South Korea
d Medical Scientist Training Program, Division of Biology and Biomedical sciences, School of Medicine, Washington University in Saint Louis, St. Louis, MO, United States
e Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO, United States
f Ronald M. Loeb Center for Alzheimer’s disease, Dept of Neuroscience, Icahn School of Medicine at Mount Sinai, ICAHN 10–52, New York, NY, United States


Abstract
Alzheimer disease (AD), Frontotemporal lobar degeneration (FTD), Amyotrophic lateral sclerosis (ALS) and Parkinson disease (PD) have a certain degree of clinical, pathological and molecular overlap. Previous studies indicate that causative mutations in AD and FTD/ALS genes can be found in clinical familial AD. We examined the presence of causative and low frequency coding variants in the AD, FTD, ALS and PD Mendelian genes, in over 450 families with clinical history of AD and over 11,710 sporadic cases and cognitive normal participants from North America. Known pathogenic mutations were found in 1.05% of the sporadic cases, in 0.69% of the cognitively normal participants and in 4.22% of the families. A trend towards enrichment, albeit non-significant, was observed for most AD, FTD and PD genes. Only PSEN1 and PINK1 showed consistent association with AD cases when we used ExAC as the control population. These results suggest that current study designs may contain heterogeneity and contamination of the control population, and that current statistical methods for the discovery of novel genes with real pathogenic variants in complex late onset diseases may be inadequate or underpowered to identify genes carrying pathogenic mutations. © 2017 Fernández et al.

 

16) 

Mehta, R.I., Perrin, R.J., Baldzizhar, R., Mehta, R.I.
Polymer coating embolism: Cause of cerebral vasculopathy and death following congenital heart repair in two infants
(2017) Journal of Neuropathology and Experimental Neurology, 76 (11), pp. 978-980. 


a Department of Radiology, West Virginia University, Morgantown, WA, United States
b Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, United States
c Department of Pathology and Laboratory Medicine, University of Rochester, Rochester, NY, United States
d Departments of Pathology and Laboratory Medicine and Neuroscience, University of Rochester, Rochester, NY, United States

 

17) 

Moulder, K.L., Besser, L.M., Beekly, D., Blennow, K., Kukull, W., Morris, J.C.
Factors Influencing Successful Lumbar Puncture in Alzheimer Research
(2017) Alzheimer Disease and Associated Disorders, 31 (4), pp. 287-294. 


a Department of Neurology, Knight Alzheimer Disease Research Center, Washington University, 4488 Forest Park Ave., St. Louis, MO, United States
b National Alzheimer's Coordinating Center, University of Washington, Seattle, WA, United States
c Department of Neuroscience and Physiology, Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, University of Gothenburg, Mölndal, Sweden


Abstract
Objective: Lumbar puncture (LP) is increasingly common in Alzheimer disease research; however, agreement to undergo LP varies. We sought to determine factors influencing LP consent at Alzheimer's Disease Centers (ADCs) in the United States. Methods: A 3-part survey was distributed to each ADC: (1) ADC LP Experience; (2) LP Requestor Experience; and (3) Patient LP Experience (both Initial and Follow-up). In all, 64 LP Requestor, 579 Patient/Initial, and 404 Patient/Follow-up surveys were collected. Logistic regression analyses with generalized estimating equations were used to assess factors associated with LP agreement and post-LP complications. Results: Asians and those viewing LP negatively were less likely to agree to LP. Three hundred fifty-two participants had an LP; LP headache occurred in 11.9% (blood patch required in 1.4%) and 9.9% reported other complications. Younger individuals, women, those diagnosed with mild cognitive impairment, use of a Quincke needle, =20mL cerebrospinal fluid drawn, and hemorrhage during LP were associated with LP headache. Use of gravity flow during LP was associated with fewer other complications (nausea, dizziness, vasovagal response, back pain, neck stiffness, and/or nerve root pain). Conclusions: LP in Alzheimer disease research is generally safe and well tolerated. Factors influencing LP agreement potentially could be studied to advance participant acceptance of the procedure. Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.


Author Keywords
Alzheimer disease;  biomarkers;  cerebrospinal fluid;  lumbar puncture;  post-LP complications;  post-LP headache

December 11, 2017

1) 

Rana, M., Cho, H.-J., Roy, T.K., Mirica, L.M., Sharma, A.K.
Azo-dyes based small bifunctional molecules for metal chelation and controlling amyloid formation
(2018) Inorganica Chimica Acta, 471, pp. 419-429. 


Abstract
Chemical tools are needed to discover new effective drugs for tackling multifaceted complex neurodegenerative diseases like Alzheimer's disease (AD). Multifunctional nature of two compounds, 5-((4-nitrophenyl)diazenyl)quinolin-8-ol (HL1) and 4-((4-nitrophenyl)diazenyl)benzene-1,3-diol (HL2) is reported w.r.t. their ability to bind Cu2+ ions and amyloid aggregates related to AD. HL1 and HL2 have half congo-red type azo-stilbene structural framework incorporated with metal chelating groups, designed to chelate metal ions from metal-amyloid species. Metal binding studies of HL1 and HL2 are established by the methods of Job's Plot, UV-vis spectra with metal ions and stability constant determination. In addition, their metal complexes are isolated, purity checked by elemental analysis, spectroscopically characterized and their structural analyses were obtained from DFT based calculations including binding energy determination. Chicken egg white Lysozyme (CEWL) was used as a model peptide for fibrillation studies. HL1 is found as an excellent colorimetric sensor for amyloid fibrils. Inhibitory effect of HL1 and HL2 and their isolated metal complexes L1-Cu and L2-Cu on CEWL fibrillation was studied using ThT and ANS fluorescence assay along with TEM imaging. In addition, the cell toxicity studies on these compounds suggest that although azo dyes may be non-toxic but having a nitro-substitution lead to significant cell toxicity. Overall, these results suggest that this new class of multifunctional small molecules can interact with amyloids as well as metal ions and could be potential anti-aggregation metal chelating agents. © 2017 Elsevier B.V.

 

2) 

Yap, M.H.W., Grabowska, M.J., Rohrscheib, C., Jeans, R., Troup, M., Paulk, A.C., Van Alphen, B., Shaw, P.J., Van Swinderen, B.
Oscillatory brain activity in spontaneous and induced sleep stages in flies
(2017) Nature Communications, 8 (1), art. no. 1815, . 


Abstract
Sleep is a dynamic process comprising multiple stages, each associated with distinct electrophysiological properties and potentially serving different functions. While these phenomena are well described in vertebrates, it is unclear if invertebrates have distinct sleep stages. We perform local field potential (LFP) recordings on flies spontaneously sleeping, and compare their brain activity to flies induced to sleep using either genetic activation of sleep-promoting circuitry or the GABAA agonist Gaboxadol. We find a transitional sleep stage associated with a 7-10 Hz oscillation in the central brain during spontaneous sleep. Oscillatory activity is also evident when we acutely activate sleep-promoting neurons in the dorsal fan-shaped body (dFB) of Drosophila. In contrast, sleep following Gaboxadol exposure is characterized by low-amplitude LFPs, during which dFB-induced effects are suppressed. Sleep in flies thus appears to involve at least two distinct stages: increased oscillatory activity, particularly during sleep induction, followed by desynchronized or decreased brain activity. © 2017 The Author(s).

 

3) 

Samineni, V.K., Mickle, A.D., Yoon, J., Grajales-Reyes, J.G., Pullen, M.Y., Crawford, K.E., Noh, K.N., Gereau, G.B., Vogt, S.K., Lai, H.H., Rogers, J.A., Gereau, R.W.
Optogenetic silencing of nociceptive primary afferents reduces evoked and ongoing bladder pain
(2017) Scientific Reports, 7 (1), art. no. 15865, . 


Abstract
Patients with interstitial cystitis/bladder pain syndrome (IC/BPS) suffer from chronic pain that severely affects quality of life. Although the underlying pathophysiology is not well understood, inhibition of bladder sensory afferents temporarily relieves pain. Here, we explored the possibility that optogenetic inhibition of nociceptive sensory afferents could be used to modulate bladder pain. The light-activated inhibitory proton pump Archaerhodopsin (Arch) was expressed under control of the sensory neuron-specific sodium channel (sns) gene to selectively silence these neurons. Optically silencing nociceptive sensory afferents significantly blunted the evoked visceromotor response to bladder distension and led to small but significant changes in bladder function. To study of the role of nociceptive sensory afferents in freely behaving mice, we developed a fully implantable, flexible, wirelessly powered optoelectronic system for the long-term manipulation of bladder afferent expressed opsins. We found that optogenetic inhibition of nociceptive sensory afferents reduced both ongoing pain and evoked cutaneous hypersensitivity in the context of cystitis, but had no effect in uninjured, naïve mice. These results suggest that selective optogenetic silencing of nociceptive bladder afferents may represent a potential future therapeutic strategy for the treatment of bladder pain. © 2017 The Author(s).

 

4) 

Lee, J.J., Khoury, N., Shackleford, A.M., Nelson, S., Herrera, H., Antenor-Dorsey, J.A., Semenkovich, K., Shimony, J.S., Powers, W.J., Cryer, P.E., Arbeláez, A.M.
Dissociation between hormonal counterregulatory responses and cerebral glucose metabolism during hypoglycemia
(2017) Diabetes, 66 (12), pp. 2964-2972. 


Abstract
Hypoglycemia is the most common complication of diabetes, causing morbidity and death. Recurrent hypoglycemia alters the cascade of physiological and behavioral responses that maintain euglycemia. The extent to which these responses are normally triggered by decreased wholebrain cerebral glucose metabolism (CMRglc) has not been resolved by previous studies. We measured plasma counterregulatory hormonal responses and whole-brain CMRglc (along with blood-to-brain glucose transport rates and brain glucose concentrations) with 1-[11C]-D-glucose positron emission tomography during hyperinsulinemic glucose clamps at nominal plasma glucose concentrations of 90, 75, 60, and 45 mg/dL (5.0, 4.2, 3.3, and 2.5 mmol/L) in 18 healthy young adults. Clear evidence of hypoglycemic physiological counterregulation was first demonstrated between 75 mg/dL (4.2 mmol/L) and 60 mg/dL (3.3 mmol/L) with increases in both plasma epinephrine (P = 0.01) and glucagon (P = 0.01). In contrast, there was no statistically significant change in CMRglc (P = 1.0) between 75 mg/dL (4.2 mmol/L) and 60 mg/dL (3.3 mmol/L), whereas CMRglc significantly decreased (P = 0.02) between 60 mg/dL (3.3 mmol/L) and 45 mg/dL (2.5 mmol/L). Therefore, the increased epinephrine and glucagon secretion with declining plasma glucose concentrations is not in response to a decrease in whole-brain CMRglc. © 2017 by the American Diabetes Association.

 

5) 

Wilcox, H.C., Fullerton, J.M., Glowinski, A.L., Benke, K., Kamali, M., Hulvershorn, L.A., Stapp, E.K., Edenberg, H.J., Roberts, G.M.P., Ghaziuddin, N., Fisher, C., Brucksch, C., Frankland, A., Toma, C., Shaw, A.D., Kastelic, E., Miller, L., McInnis, M.G., Mitchell, P.B., Nurnberger, J.I., Jr.
Traumatic Stress Interacts With Bipolar Disorder Genetic Risk to Increase Risk for Suicide Attempts
(2017) Journal of the American Academy of Child and Adolescent Psychiatry, 56 (12), pp. 1073-1080. 


Abstract
Objective Bipolar disorder (BD) is one of the most heritable psychiatric conditions and is associated with high suicide risk. To explore the reasons for this link, this study examined the interaction between traumatic stress and BD polygenic risk score in relation to suicidal ideation, suicide attempt, and nonsuicidal self-injury (NSSI) in adolescent and young adult offspring and relatives of persons with BD (BD-relatives) compared with adolescent and young adult offspring of individuals without psychiatric disorders (controls). Method Data were collected from 4 sites in the United States and 1 site in Australia from 2006 through 2012. Generalized estimating equation models were used to compare rates of ideation, attempts, and NSSI between BD-relatives (n = 307) and controls (n = 166) and to determine the contribution of demographic factors, traumatic stress exposure, lifetime mood or substance (alcohol/drug) use disorders, and BD polygenic risk score. Results After adjusting for demographic characteristics and mood and substance use disorders, BD-relatives were at increased risk for suicidal ideation and attempts but not for NSSI. Independent of BD-relative versus control status, demographic factors, or mood and substance use disorders, exposure to trauma within the past year (including bullying, sexual abuse, and domestic violence) was associated with suicide attempts (p =.014), and BD polygenic risk score was marginally associated with attempts (p =.061). Importantly, the interaction between BD polygenic risk score and traumatic event exposures was significantly associated with attempts, independent of demographics, relative versus control status, and mood and substance use disorders (p =.041). Conclusion BD-relatives are at increased risk for suicide attempts and ideation, especially if they are exposed to trauma and have evidence of increased genetic vulnerability. © 2017 American Academy of Child and Adolescent Psychiatry


Author Keywords
attempted;  bipolar disorder;  polygenic risk;  populations at risk;  suicide;  traumatic stress

 

6) 

Schwetye, K.E., Kansagra, A.P., McEachern, J., Schmidt, R.E., Gauvain, K., Dahiya, S.
Unusual high-grade features in pediatric diffuse leptomeningeal glioneuronal tumor: comparison with a typical low-grade example
(2017) Human Pathology, 70, pp. 105-112. 


Abstract
Diffuse leptomeningeal glioneuronal tumor, a recent addition to the World Health Organization classification system, typically presents in the pediatric population with signs and symptoms related to elevated intracranial pressure and imaging characteristics that may mimic infectious etiologies. The tumor is usually low grade and tends to harbor BRAF rearrangement/duplication in up to 75% of cases, BRAF V600E mutation in a smaller subset of cases, and loss of chromosomal arm 1p in approximately 50%-60% of cases, with ~20% of those showing loss of both 1p and 19q (codeletion). We report here 2 contrasting cases of diffuse leptomeningeal glioneuronal tumors, one with typical low-grade features and an indolent, although not benign, course, in which the disease is currently successfully managed by chemotherapy, and a second case with unusually high-grade features on initial presentation, including frank anaplasia and elevated mitotic index, in which the disease showed an initial response to chemoradiation but ultimately was fatal. © 2017 Elsevier Inc.


Author Keywords
Diffuse;  Glioneuronal;  Leptomeningeal;  Neuropathology;  Pediatric;  Tumor

 

7) 

Bui, Y., Pyc, M.A., Bailey, H.
When people’s judgments of learning (JOLs) are extremely accurate at predicting subsequent recall: the “Displaced-JOL effect”
(2017) Memory, pp. 1-13. Article in Press. 


Abstract
Judgments of learning (JOL) made after a delay more accurately predict subsequent recall than JOLs made immediately after learning. One explanation is that delayed JOLs involve retrieving information about the target item from secondary memory, whereas immediate JOLs involve retrieval from primary memory. One view of working memory claims that information in primary memory is displaced to secondary memory when attention is shifted to a secondary task. Thus, immediate JOLs might be as accurate as delayed JOLs if an intervening task displaces the target item from primary memory, requiring retrieval from secondary memory, prior to making the JOL. In four experiments, participants saw related word-pairs and made JOLs predicting later recall of the item. In Experiment 1, delayed JOLs were more accurate than JOLs made shortly after learning, regardless of whether a secondary task intervened between learning and JOL. In Experiments 2–4, the secondary task demands increased and JOLs made shortly after learning with an intervening task were just as accurate as delayed JOLs, and both were more accurate than immediate JOLs with no intervening task (Experiment 4). These results are consistent with a retrieval-based account of JOLs, and demonstrate that the “delayed-JOL effect” can be obtained without a long delay. © 2017 Informa UK Limited, trading as Taylor & Francis Group


Author Keywords
Judgments of learning;  metacognition;  primary memory;  secondary memory;  working memory

 

8) 

Stepanova, E.V., Strube, M.J.
Attractiveness as a Function of Skin Tone and Facial Features: Evidence from Categorization Studies
(2017) Journal of General Psychology, pp. 1-20. Article in Press. 


Abstract
Participants rated the attractiveness and racial typicality of male faces varying in their facial features from Afrocentric to Eurocentric and in skin tone from dark to light in two experiments. Experiment 1 provided evidence that facial features and skin tone have an interactive effect on perceptions of attractiveness and mixed-race faces are perceived as more attractive than single-race faces. Experiment 2 further confirmed that faces with medium levels of skin tone and facial features are perceived as more attractive than faces with extreme levels of these factors. Black phenotypes (combinations of dark skin tone and Afrocentric facial features) were rated as more attractive than White phenotypes (combinations of light skin tone and Eurocentric facial features); ambiguous faces (combinations of Afrocentric and Eurocentric physiognomy) with medium levels of skin tone were rated as the most attractive in Experiment 2. Perceptions of attractiveness were relatively independent of racial categorization in both experiments. © 2017 Taylor & Francis Group, LLC


Author Keywords
Attractiveness;  facial features;  mixed race;  race;  racial categorization;  skin tone

 

9) 

Ko, J.M., Tecson, K.M., Rashida, V.A., Sodhi, S., Saef, J., Mufti, M., White, K.S., Ludbrook, P.A., Cedars, A.M.
Clinical and Psychological Drivers of Perceived Health Status in Adults With Congenital Heart Disease
(2017) American Journal of Cardiology, . Article in Press. 


Abstract
The factors having the greatest impact on self-reported health status in adults with congenital heart disease (ACHD) remain incompletely studied. We conducted a single-site, cross-sectional study of ACHD patients followed at the Center for ACHD at Washington University School of Medicine, including retrospectively gathered clinical data and psychometric and health status assessments completed at the time of enrollment. To identify primary drivers of perceived health status, we investigated the impact of the demographic, clinical, and psychological variables on self-reported health status as assessed using the Rand 36-Item Short Form Health Survey. Variables with significant associations within each domain were considered jointly in multivariable models constructed via stepwise selection. There was domain-specific heterogeneity in the variables having the greatest effect on self-reported health status. Depression was responsible for the greatest amount of variability in health status in all domains except physical functioning. In the physical functioning domain, depression remained responsible for 5% of total variability, the third most significant variable in the model. In every domain, depression more strongly influenced health status than did any cardiac-specific variable. In conclusion, depression was responsible for a significant amount of heterogeneity in all domains of self-perceived health status. Psychological variables were better predictors of health status than clinical variables. © 2017 Elsevier Inc.

 

10) 

Hobson, B.A., Rowland, D.J., Supasai, S., Harvey, D.J., Lein, P.J., Garbow, J.R.
A magnetic resonance imaging study of early brain injury in a rat model of acute DFP intoxication
(2017) NeuroToxicology, . Article in Press. 


Abstract
Current treatments for seizures induced by organophosphates do not protect sufficiently against progressive neurodegeneration or delayed cognitive impairment. Developing more effective therapeutic approaches has been challenging because the pathogenesis of these delayed consequences is poorly defined. Using magnetic resonance imaging (MRI), we previously reported brain lesions that persist for months in a rat model of acute intoxication with the OP, diisopropylfluorophosphate (DFP). However, the early spatiotemporal progression of these lesions remains unknown. To address this data gap, we used in vivo MRI to longitudinally monitor brain lesions during the first 3 d following acute DFP intoxication. Adult male Sprague Dawley rats acutely intoxicated with DFP (4. mg/kg, sc) were MR imaged at 6, 12, 18, 24, 48, 72. h post-DFP, and their brains then taken for correlative histology to assess neurodegeneration using FluoroJade C (FJC) staining. Acute DFP intoxication elicited moderate-to-severe seizure activity. T2-weighted (T2w) anatomic imaging revealed prominent lesions within the thalamus, piriform cortex, cerebral cortex, hippocampus, corpus striatum, and substantia nigra that corresponded to neurodegeneration, evident as bands of FJC positive cells. Semi-quantitative assessment of lesion severity demonstrated significant regional variation in the onset and progression of injury, and suggested that lesion severity may be modulated by isoflurane anesthesia. These results imply that the timing of therapeutic intervention for attenuating brain injury following OP intoxication may be regionally dependent, and that longitudinal assessment of OP-induced damage by MRI may be a powerful tool for assessing therapeutic response. © 2017 Elsevier B.V.


Author Keywords
In vivo imaging;  Neuropathology;  Organophosphate;  Seizure;  T2-weighted MRI

 

11) 

Tayebi, N., Parisiadou, L., Berhe, B., Gonzalez, A.N., Serra-Vinardell, J., Tamargo, R.J., Maniwang, E., Sorrentino, Z., Fujiwara, H., Grey, R.J., Hassan, S., Blech-Hermoni, Y.N., Chen, C., McGlinchey, R., Makariou-Pikis, C., Brooks, M., Ginns, E.I., Ory, D.S., Giasson, B.I., Sidransky, E.
Glucocerebrosidase haploinsufficiency in A53T α-synuclein mice impacts disease onset and course
(2017) Molecular Genetics and Metabolism, . Article in Press. 


Abstract
Mutations in GBA1 encountered in Gaucher disease are a leading risk factor for Parkinson disease and associated Lewy body disorders. Many GBA1 mutation carriers, especially those with severe or null GBA1 alleles, have earlier and more progressive parkinsonism. To model the effect of partial glucocerebrosidase deficiency on neurological progression in vivo, mice with a human A53T α-synuclein (SNCA A53T) transgene were crossed with heterozygous null gba mice (gba +/-). Survival analysis of 84 mice showed that in gba +/-//SNCA A53T hemizygotes and homozygotes, the symptom onset was significantly earlier than in gba +/+ //SNCA A53T mice (p-values 0.023-0.0030), with exacerbated disease progression (p-value &lt;0.0001). Over-expression of SNCA A53T had no effect on glucocerebrosidase levels or activity. Immunoblotting demonstrated that gba haploinsufficiency did not lead to increased levels of either monomeric SNCA or insoluble high molecular weight SNCA in this model. Immunohistochemical analyses demonstrated that the abundance and distribution of SNCA pathology was also unaltered by gba haploinsufficiency. Thus, while the underlying mechanism is not clear, this model shows that gba deficiency impacts the age of onset and disease duration in aged SNCA A53T mice, providing a valuable resource to identify modifiers, pathways and possible moonlighting roles of glucocerebrosidase in Parkinson pathogenesis. © 2017.


Author Keywords
A-synuclein;  Aggregates;  Gaucher disease;  Glucocerebrosidase;  Mouse model;  Parkinson disease

 

December 4, 2017

1) 

Ziobrowski, H., Brewerton, T.D., Duncan, A.E.
Associations between ADHD and eating disorders in relation to comorbid psychiatric disorders in a nationally representative sample
(2018) Psychiatry Research, 260, pp. 53-59. 

DOI: 10.1016/j.psychres.2017.11.026


a Department of Epidemiology, Brown University School of Public Health, Providence, RI, United States
b Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, SC, United States
c George Warren Brown School of Social Work, Washington University in St. Louis, St. Louis, MO, United States
d Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States


Abstract
The objective of this study was to examine whether previously observed associations of attention-deficit/hyperactivity disorder (ADHD) with eating disorders (EDs) are at least partially attributable to other underlying psychopathology. Data came from 4719 participants aged 18–44 years in the National Comorbidity Survey Replication and the National Survey of American Life. DSM-IV diagnoses were assessed using the World Health Organization Composite International Diagnostic Interview. Multinomial logistic regression assessed associations between DSM-IV lifetime and past-12 month diagnoses of ADHD with EDs in unadjusted models and in models adjusted for demographic variables and other psychopathology. Lifetime ADHD was strongly and significantly associated with lifetime bulimia nervosa (BN), binge eating disorder (BED), and any ED in unadjusted models, but not with anorexia nervosa or subthreshold BED. After adjusting for demographic variables and psychiatric comorbidities, all associations of lifetime ADHD with EDs were substantially attenuated, and only the association of ADHD with BN remained statistically significant. Similar results were found using past-12 month diagnoses. These results suggest that previously observed associations of ADHD with EDs might be due – at least in part – to additional psychiatric disorders that are often comorbid with both ADHD and EDs. © 2017 Elsevier B.V.


Author Keywords
Anorexia nervosa;  Attention deficit hyperactivity disorder;  Binge eating;  Bulimia nervosa;  Comorbidity


Document Type: Article
Source: Scopus

 

2) 

Yee, D.M., Braver, T.S.
Interactions of motivation and cognitive control
(2018) Current Opinion in Behavioral Sciences, 19, pp. 83-90. 

DOI: 10.1016/j.cobeha.2017.11.009


Department of Psychological and Brain Sciences, Washington University in Saint Louis, United States


Abstract
There is general agreement that both motivation and cognitive control play critical roles in shaping goal-directed behavior, but only recently has scientific interest focused around the question of motivation–control interactions. Here we briefly survey this literature, organizing contemporary findings around three issues: (1) whether motivation preferentially impacts cognitive control processes, (2) the neural mechanisms that underlie motivation–cognition interactions, and (3) why motivation might be relevant for overcoming the costs of control. Dopamine (DA) is discussed as a key neuromodulator in these motivation–cognition interactions. We conclude by highlighting open issues, specifically Pavlovian versus instrumental control distinctions and effects of motivational valence and conflict, which could benefit from future research attention. © 2017 Elsevier Ltd


Document Type: Review
Source: Scopus

 

3) 

Ratajczyk, E., Ledzewicz, U., Leszczynski, M., Schattler, H.
Treatment of glioma with virotherapy and TNF-α inhibitors: Analysis as a dynamical system
(2018) Discrete and Continuous Dynamical Systems - Series B, 23 (1), pp. 425-441. 

DOI: 10.3934/dcdsb.2018029


a Institute of Mathematics, Lodz University of Technology, Lodz, Poland
b Dept. of Mathematics and Statistics, Southern Illinois University Edwardsville, Edwardsville, IL, United States
c Dept. of Electrical and Systems Engr., Washington University, St. Louis, MO, United States


Abstract
Oncolytic viruses are genetically altered replication-competent viruses which upon death of a cancer cell produce many new viruses that then infect neighboring tumor cells. A mathematical model for virotherapy of glioma is analyzed as a dynamical system for the case of constant viral infusions and TNF-α inhibitors. Aside from a tumor free equilibrium point, the system also has positive equilibrium point solutions. We investigate the number of equilibrium point solutions depending on the burst number, i.e., depending on the number of new viruses that are released from a dead cancer cell and then infect neighboring tumor cells. After a transcritical bifurcation with a positive equilibrium point solution, the tumor free equilibrium point becomes asymptotically stable and if the average viral load in the system lies above a threshold value related to the transcritical bifurcation parameter, the tumor size shrinks to zero exponentially. Other bifurcation events such as saddle-node and Hopf bifurcations are explored numerically.


Author Keywords
Cancer treatment;  Glioma;  Optimal control;  Saddle-node and Hopf bifurcations;  Trans-critical


Document Type: Conference Paper
Source: Scopus

 

4) 

Van Buren, D.J., Wilfley, D.E., Marcus, M.D., Anderson, B., Abramson, N.W., Berkowitz, R., Ievers-Landis, C., Trief, P., Yasuda, P., Hirst, K.
Depressive symptoms and glycemic control in youth with type 2 diabetes participating in the TODAY clinical trial
(2018) Diabetes Research and Clinical Practice, 135, pp. 85-87. 

DOI: 10.1016/j.diabres.2017.11.008


a Washington University School of Medicine, United States
b University of Pittsburgh School of Medicine, United States
c Baylor College of Medicine, United States
d Department of Pediatrics, University of Colorado School of Medicine, United States
e University of Pennsylvania, United States
f Case Western Reserve University School of Medicine, United States
g SUNY Upstate Medical University, United States
h Children's Hospital Los Angeles, United States
i George Washington University Biostatistics Center, United States


Abstract
The relationship between depressive symptoms and glycemic control in youth with type 2 diabetes was assessed at baseline (n = 682), 6, and/or 24 months (n = 576). Neither baseline nor persistence of depressive symptoms was significantly associated with maintenance of glycemic control. Nevertheless, depressive symptoms were common, suggesting the importance of repeated screening. © 2017 Elsevier B.V.


Author Keywords
Adolescent;  Depressive symptoms;  Type 2 diabetes


Document Type: Article
Source: Scopus

 

5) 

Wan, L., Jin, H., Liu, X.-Y., Jeffry, J., Barry, D.M., Shen, K.-F., Peng, J.-H., Liu, X.-T., Jin, J.-H., Sun, Y., Kim, R., Meng, Q.-T., Mo, P., Yin, J., Tao, A., Bardoni, R., Chen, Z.-F.
Distinct roles of NMB and GRP in itch transmission
(2017) Scientific Reports, 7 (1), art. no. 15466, . 

DOI: 10.1038/s41598-017-15756-0


a Center for the Study of Itch, Washington University, School of Medicine, St. Louis, MO, United States
b Department of Anesthesiology, Washington University, School of Medicine, St. Louis, MO, United States
c Department of Psychiatry, Washington University, School of Medicine, St. Louis, MO, United States
d Department of Developmental Biology, Washington University, School of Medicine, St. Louis, MO, United States
e Department of Pain Medicine, State Key Clinical Specialty in Pain Medicine, Guangzhou Medical University, Guangdong, China
f Guangdong Provincial Key Laboratory of Allergy and Clinical Immunology, State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangdong, China
g Department of Neurosurgery, Xinqiao Hospital, Medical University, Chongqing, China
h Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy
i Department of Anesthesiology, First Hospital of Yunnan Province, Kunming, Yunnan, China
j Department of Anesthesiology, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical, Beijing, China
k Department of Anesthesiology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China
l Department of Anesthesiology, Renmin Hospital, Wuhan University, Wuhan, Hubei, China
m Department of Anesthesiology, Southern Medical University, Foshan, Guangdong, China


Abstract
A key question in our understanding of itch coding mechanisms is whether itch is relayed by dedicated molecular and neuronal pathways. Previous studies suggested that gastrin-releasing peptide (GRP) is an itch-specific neurotransmitter. Neuromedin B (NMB) is a mammalian member of the bombesin family of peptides closely related to GRP, but its role in itch is unclear. Here, we show that itch deficits in mice lacking NMB or GRP are non-redundant and Nmb/Grp double KO (DKO) mice displayed additive deficits. Furthermore, both Nmb/Grp and Nmbr/Grpr DKO mice responded normally to a wide array of noxious stimuli. Ablation of NMBR neurons partially attenuated peripherally induced itch without compromising nociceptive processing. Importantly, electrophysiological studies suggested that GRPR neurons receive glutamatergic input from NMBR neurons. Thus, we propose that NMB and GRP may transmit discrete itch information and NMBR neurons are an integral part of neural circuits for itch in the spinal cord. © 2017 The Author(s).


Document Type: Article
Source: Scopus

 

6) 

McKay, V.R., Margaret Dolcini, M., Hoffer, L.D.
The dynamics of de-adoption: a case study of policy change, de-adoption, and replacement of an evidence-based HIV intervention
(2017) Translational Behavioral Medicine, 7 (4), pp. 821-831. 

DOI: 10.1007/s13142-017-0493-1


a Center for Mental Health Services Research, Brown School of Social Work, Washington University in St. Louis, St. Louis, MO, United States
b School of Social and Behavioral Health Sciences, College of Public Health and Human Sciences, Oregon State University, Corvallis, OR, United States
c Department of Anthropology, Case Western Reserve University, Cleveland, OH, United States


Abstract
Evidence-based intervention (EBI) de–adoption and its influence on public health organizations are largely unexplored within public health implementation research. However, a recent shift in support for HIV prevention EBIs by the Centers for Disease Control and Prevention provides an opportunity to explore EBI de–adoption. The current mixed-method study examines EBI de-adoption and the subsequent impact on a community-based organization (CBO) dedicated to HIV prevention. We conducted a case study with a CBO implementing RESPECT, an HIV prevention EBI, over 5 years (2010–2014), but then de­adopted the intervention. We collected archival data documenting RESPECT implementation and conducted two semi­structured interviews with RESPECT staff (N = 5). Using Fixsen and colleagues’ implementation framework, we developed a narrative of RESPECT implementation, delivery, and de­adoption and a thematic analysis to understand additional consequences of RESPECT de-adoption. Discontinuation of RESPECT activities unfolded in a process over time, requiring effort by RESPECT staff. RESPECT de­adoption had wide­reaching influences on individual staff, interactions between the staff and the community, the agency overall, and for implementation of future EBIs. We propose a revision of the implementation framework, incorporating EBI de­adoption as a phase of the implementation cycle. Furthermore, EBI de­adoption may have important, unintended consequences and can inform future HIV prevention strategies and guide research focusing on EBI de-adoption. © 2017, Society of Behavioral Medicine.


Author Keywords
Complex adaptive system;  De-adoption;  De-implementation;  Dissemination and implementation;  Evidence-based intervention;  HIV prevention


Document Type: Article
Source: Scopus

 

7) 

Wong, T.T.W., Zhang, R., Zhang, C., Hsu, H.-C., Maslov, K.I., Wang, L., Shi, J., Chen, R., Shung, K.K., Zhou, Q., Wang, L.V.
Label-free automated three-dimensional imaging of whole organs by microtomy-assisted photoacoustic microscopy
(2017) Nature Communications, 8 (1), art. no. 1386, . 

DOI: 10.1038/s41467-017-01649-3


a Caltech Optical Imaging Laboratory, Andrew and Peggy Cherng Department of Medical Engineering, Department of Electrical Engineering, California Institute of Technology, Pasadena, CA, United States
b Optical Imaging Laboratory, Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO, United States
c NIH Resource Center for Medical Ultrasonic Transducer Technology, Department of Biomedical Engineering, University of Southern California, Los Angeles, CA, United States
d Roski Eye Institute, Department of Ophthalmology and Biomedical Engineering, University of Southern California, Los Angeles, CA, United States
e Department of Mechanical and Biomedical Engineering, City University of Hong Kong, Hong Kong, Hong Kong


Abstract
Three-dimensional (3D) optical imaging of whole biological organs with microscopic resolution has remained a challenge. Most versions of such imaging techniques require special preparation of the tissue specimen. Here we demonstrate microtomy-assisted photoacoustic microscopy (mPAM) of mouse brains and other organs, which automatically acquires serial distortion-free and registration-free images with endogenous absorption contrasts. Without tissue staining or clearing, mPAM generates micrometer-resolution 3D images of paraffin- or agarose-embedded whole organs with high fidelity, achieved by label-free simultaneous sensing of DNA/RNA, hemoglobins, and lipids. mPAM provides histology-like imaging of cell nuclei, blood vessels, axons, and other anatomical structures, enabling the application of histopathological interpretation at the organelle level to analyze a whole organ. Its deep tissue imaging capability leads to less sectioning, resulting in negligible sectioning artifact. mPAM offers a new way to better understand complex biological organs. © 2017 The Author(s).


Document Type: Article
Source: Scopus

 

8) 

Levinson, C.A., Brosof, L.C., Ma, J., Fewell, L., Lenze, E.J.
Fear of food prospectively predicts drive for thinness in an eating disorder sample recently discharged from intensive treatment
(2017) Eating Behaviors, 27, pp. 45-51. 

DOI: 10.1016/j.eatbeh.2017.11.004


a University of Louisville, Department of Psychological & Brain Sciences, United States
b Washington University in St. Louis, Department of Psychiatry, United States


Abstract
Fears of food are common in individuals with eating disorders and contribute to the high relapse rates. However, it is unknown how fears of food contribute to eating disorder symptoms across time, potentially contributing to an increased likelihood of relapse. Participants diagnosed with an eating disorder (N = 168) who had recently completed intensive treatment were assessed after discharge and one month later regarding fear of food, eating disorder symptoms, anxiety sensitivity, and negative affect. Cross lagged path analysis was utilized to determine if fear of food predicted subsequent eating disorder symptoms one month later. Fear of food—specifically, anxiety about eating and feared concerns about eating—predicted drive for thinness, a core symptom domain of eating disorders. These relationships held while accounting for anxiety sensitivity and negative affect. There is a specific, direct relationship between anxiety about eating and feared concerns about eating and drive for thinness. Future research should test if interventions designed to target fear of food can decrease drive for thinness and thereby prevent relapse. © 2017 Elsevier Ltd


Author Keywords
Anorexia nervosa;  Anxiety;  Eating disorders;  Fear of food


Document Type: Article
Source: Scopus

 

9) 

Samineni, V.K., Mickle, A.D., Yoon, J., Grajales-Reyes, J.G., Pullen, M.Y., Crawford, K.E., Noh, K.N., Gereau, G.B., Vogt, S.K., Lai, H.H., Rogers, J.A., Gereau, R.W.
Optogenetic silencing of nociceptive primary afferents reduces evoked and ongoing bladder pain
(2017) Scientific Reports, 7 (1), art. no. 15865, . 

DOI: 10.1038/s41598-017-16129-3


a Washington University Pain Center, Department of Anesthesiology, St. Louis, MO, United States
b Washington University School of Medicine, 660 S. Euclid Ave, Box 8054, St. Louis, MO, United States
c Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, United States
d Washington University Department of Surgery, Division of Urologic Surgery, St. Louis, MO, United States
e Department of Civil and Environmental Engineering, Mechanical Engineering, Materials Science and Engineering, Northwestern University, Evanston, IL, United States
f Departments of Materials Science and Engineering, Biomed. Eng., Chem., Mech. Eng., Elec. Engineering and Computer Science, and Neurological Surgery, Center for Bio-Integrated Electronics, Simpson Querrey Institute for Nano/biotechnology, Northwestern University, Evanston, IL, United States


Abstract
Patients with interstitial cystitis/bladder pain syndrome (IC/BPS) suffer from chronic pain that severely affects quality of life. Although the underlying pathophysiology is not well understood, inhibition of bladder sensory afferents temporarily relieves pain. Here, we explored the possibility that optogenetic inhibition of nociceptive sensory afferents could be used to modulate bladder pain. The light-activated inhibitory proton pump Archaerhodopsin (Arch) was expressed under control of the sensory neuron-specific sodium channel (sns) gene to selectively silence these neurons. Optically silencing nociceptive sensory afferents significantly blunted the evoked visceromotor response to bladder distension and led to small but significant changes in bladder function. To study of the role of nociceptive sensory afferents in freely behaving mice, we developed a fully implantable, flexible, wirelessly powered optoelectronic system for the long-term manipulation of bladder afferent expressed opsins. We found that optogenetic inhibition of nociceptive sensory afferents reduced both ongoing pain and evoked cutaneous hypersensitivity in the context of cystitis, but had no effect in uninjured, naïve mice. These results suggest that selective optogenetic silencing of nociceptive bladder afferents may represent a potential future therapeutic strategy for the treatment of bladder pain. © 2017 The Author(s).


Document Type: Article
Source: Scopus

 

10) 

Balantekin, K.N., Hayes, J.F., Sheinbein, D.H., Kolko, R.P., Stein, R.I., Saelens, B.E., Hurst, K.T., Welch, R.R., Perri, M.G., Schechtman, K.B., Epstein, L.H., Wilfley, D.E.
Patterns of Eating Disorder Pathology are Associated with Weight Change in Family-Based Behavioral Obesity Treatment
(2017) Obesity, 25 (12), pp. 2115-2122. 

DOI: 10.1002/oby.22028


a Department of Exercise and Nutrition Sciences, University at Buffalo, Buffalo, NY, United States
b Department of Psychiatry, Washington University in St. Louis, St. Louis, MO, United States
c Department of Internal Medicine, Washington University in St. Louis, St. Louis, MO, United States
d Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, United States
e Seattle Children's Research Institute and the University of Washington, Seattle, WA, United States
f National Center for Weight and Wellness, Washington, DC, United States
g Department of Clinical and Health Professions, University of Florida, Gainesville, FL, United States
h Department of Biostatistics, Washington University in St. Louis, St. Louis, MO, United States
i Department of Pediatrics, University at Buffalo School of Medicine and Biomedical Sciences, Buffalo, NY, United States


Abstract
Objective: Children with overweight or obesity have elevated eating disorder (ED) pathology, which may increase their risk for clinical EDs. The current study identified patterns of ED pathology in children with overweight or obesity entering family-based behavioral weight loss treatment (FBT) and examined whether children with distinct patterns differed in their ED pathology and BMI z score (zBMI) change across FBT. Methods: Before participating in a 16-session FBT, children (N = 241) completed surveys or interviews assessing ED pathology (emotional eating, shape/weight/eating concerns, restraint, and loss of control [LOC]). Shape and weight concerns (SWC) and LOC were also assessed post treatment. Child height and weight were measured at baseline and post treatment. Latent class analysis identified patterns of ED pathology. Repeated-measures ANOVA examined changes in zBMI and ED pathology. Results: Four patterns of ED pathology were identified: low ED pathology, SWC, only loss of control, and high ED pathology. SWC decreased across treatment, with the highest decreases in patterns characterized by high SWC. All groups experienced significant decreases in zBMI; however, children with the highest ED pathology did not achieve clinically significant weight loss. Conclusions: ED pathology decreased after FBT, decreasing ED risk. While all children achieved zBMI reductions, further research is needed to enhance outcomes for children with high ED pathology. © 2017 The Obesity Society


Document Type: Article
Source: Scopus

 

11) 

Hou, P., Eldstrom, J., Shi, J., Zhong, L., McFarland, K., Gao, Y., Fedida, D., Cui, J.
Inactivation of KCNQ1 potassium channels reveals dynamic coupling between voltage sensing and pore opening
(2017) Nature Communications, 8 (1), art. no. 1730, . 

DOI: 10.1038/s41467-017-01911-8


a Department of Biomedical Engineering, Center for the Investigation of Membrane Excitability Diseases, Cardiac Bioelectricity and Arrhythmia Center, Washington University in St Louis, St Louis, MO, United States
b Department of Anesthesiology Pharmacology and Therapeutics, University of British Columbia, Vancouver, BC, Canada
c Tencent AI Lab, Shenzhen, China


Abstract
In voltage-activated ion channels, voltage sensor (VSD) activation induces pore opening via VSD-pore coupling. Previous studies show that the pore in KCNQ1 channels opens when the VSD activates to both intermediate and fully activated states, resulting in the intermediate open (IO) and activated open (AO) states, respectively. It is also well known that accompanying KCNQ1 channel opening, the ionic current is suppressed by a rapid process called inactivation. Here we show that inactivation of KCNQ1 channels derives from the different mechanisms of the VSD-pore coupling that lead to the IO and AO states, respectively. When the VSD activates from the intermediate state to the activated state, the VSD-pore coupling has less efficacy in opening the pore, producing inactivation. These results indicate that different mechanisms, other than the canonical VSD-pore coupling, are at work in voltage-dependent ion channel activation. © 2017 The Author(s).


Document Type: Article
Source: Scopus

 

12) 

Polimanti, R., Amstadter, A.B., Stein, M.B., Almli, L.M., Baker, D.G., Bierut, L.J., Bradley, B., Farrer, L.A., Johnson, E.O., King, A., Kranzler, H.R., Maihofer, A.X., Rice, J.P., Roberts, A.L., Saccone, N.L., Zhao, H., Liberzon, I., Nievergelt, C.M., Koenen, K.C., Gelernter, J., Duncan, L.E., Chen, C.-Y., Ratanatharathorn, A., Aiello, A.E., Ashley-Koch, A.E., Garrett, M.E., Hauser, M.A., Beckham, J.C., Kimbrel, N.A., Bisson, J., Dalvie, S., Galea, S., Gelernter, J.E., Guffanti, G., Ressler, K.J., Kessler, R.C., Koen, N., Stein, D.J., Logue, M.W., Miller, M.W., Martin, A.R., Morey, R.A., Nugent, N.R., Ripke, S., Smoller, J.W., Sumner, J.A., Uddin, M., Ursano, R.J., Wildman, D.E., Yehuda, R., Daly, M.J.
A putative causal relationship between genetically determined female body shape and posttraumatic stress disorder
(2017) Genome Medicine, 9 (1), art. no. 99, . 

DOI: 10.1186/s13073-017-0491-4


a Yale University School of Medicine and VA CT Healthcare Center, Department of Psychiatry, 116A2, 950 Campbell Avenue, West Haven, CT, United States
b Virginia Commonwealth University, Department of Psychiatry, Richmond, VA, United States
c University of California San Diego, Department of Psychiatry, La Jolla, CA, United States
d University of California San Diego, Department of Family Medicine and Public Health, La Jolla, CA, United States
e Veterans Affairs San Diego Healthcare System, Veterans Affairs Center of Excellence for Stress and Mental Health, La Jolla, CA, United States
f Emory University, Department of Psychiatry and Behavioral Sciences, Atlanta, GA, United States
g Washington University School of Medicine, Department of Psychiatry, St. Louis, MO, United States
h Atlanta VA Medical Center, Atlanta, GA, United States
i Boston University School of Medicine, Department of Medicine, Biomedical Genetics Division, Boston, MA, United States
j Fellow Program and Behavioral Health and Criminal Justice Division RTI International, Research Triangle Park, NC, United States
k University of Michigan, Department of Psychiatry, Ann Arbor, MI, United States
l University of Pennsylvania Perelman School of Medicine and VISN 4 MIRECC, Crescenz VAMC, Department of Psychiatry, Philadelphia, PA, United States
m Harvard T. H. Chan School of Public Health, Department of Environmental Health, Boston, MA, United States
n Washington University School of Medicine, Department of Genetics, St. Louis, MO, United States
o Yale University, Department of Biostatistics, New Haven, CT, United States
p VA Ann Arbor Health System, Ann Arbor, MI, United States
q Harvard University, Department of Psychiatry, Cambridge, MA, United States
r McLean Hospital, Department of Psychiatry, Belmont, MA, United States
s Harvard TH Chan School of Public Health, Department of Epidemiology, Boston, MA, United States
t Massachusetts General Hospital, Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, and Department of Psychiatry, Boston, MA, United States
u Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Boston, MA, United States
v Yale University School of Medicine, Departments of Neuroscience and of Genetics, New Haven, CT, United States
w Department of Psychiatry, Stanford University, Stanford, CA, United States
x The Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, United States
y Department of Epidemiology, Columbia University, New York, NY, United States
z Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, Chapel Hill, NC, United States
aa Department of Medicine, Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC, United States
ab Veterans Affairs San Diego Healthcare System, Veterans Affairs Center of Excellence for Stress and Mental Health, San Diego, CA, United States
ac Department of Psychiatry, University of California, San Diego, San Diego, CA, United States
ad Veterans Affairs Durham Healthcare System, Durham, NC, United States
ae Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, United States
af Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, United Kingdom
ag Division of Human Genetics, University of Cape Town, Cape Town, South Africa
ah Boston University School of Public Health, Boston, MA, United States
ai Department of Psychiatry, Yale University School of Medicine and VA CT Healthcare System, New Haven, CT, United States
aj RTI International, Research Triangle Park, NC, United States
ak Department of Health Care Policy, Harvard Medical School, Boston, MA, United States
al Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa
am MRC Unit on Anxiety and Stress Disorders, Groote Schuur Hospital, Cape Town, South Africa
an VA Boston Healthcare System, Jamaica Plain, MA, United States
ao Department of Medicine, Boston University School of Medicine, Boston, MA, United States
ap Durham VA Medical Center, Durham, NC, United States
aq Division of Behavioral Genetics, Department of Psychiatry, Rhode Island Hospital, Providence, RI, United States
ar Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, RI, United States
as Department of Psychiatry, Washington University, St Louis, MO, United States
at Department of Psychiatry and Psychotherapy, Charité, Campus Mitte, Berlin, Germany
au Department of Social and Behavioral Sciences, Harvard T. H. Chan School of Public Health, Cambridge, MA, United States
av Department of Genetics, Washington University, St Louis, MO, United States
aw Veterans Affairs San Diego Healthcare System, San Diego, CA, United States
ax Center for Cardiovascular Behavioral Health, Columbia University Medical Center, New York, NY, United States
ay Department of Psychology and Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL, United States
az Center for the Study of Traumatic Stress, Department of Psychiatry, Uniformed Services University of the Health Sciences, Bethesda, MD, United States
ba Department of Molecular and Integrative Physiology and Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL, United States
bb James J. Peters Bronx Veterans Affairs and Department of Psychiatry, Icahn School of Medicine at Mount Sinai, Bronx, NY, United States
bc Department of Neuroscience, Icahn School of Medicine at Mount Sinai, Bronx, NY, United States
bd Department of Epidemiology, Harvard T. H. Chan School of Public Health, Cambridge, MA, United States


Abstract
Background: The nature and underlying mechanisms of the observed increased vulnerability to posttraumatic stress disorder (PTSD) in women are unclear. Methods: We investigated the genetic overlap of PTSD with anthropometric traits and reproductive behaviors and functions in women. The analysis was conducted using female-specific summary statistics from large genome-wide association studies (GWAS) and a cohort of 3577 European American women (966 PTSD cases and 2611 trauma-exposed controls). We applied a high-resolution polygenic score approach and Mendelian randomization analysis to investigate genetic correlations and causal relationships. Results: We observed an inverse association of PTSD with genetically determined anthropometric traits related to body shape, independent of body mass index (BMI). The top association was related to BMI-adjusted waist circumference (WCadj; R = -0.079, P &lt; 0.001, Q = 0.011). We estimated a relative decrease of 64.6% (95% confidence interval = 27.5-82.7) in the risk of PTSD per 1-SD increase in WCadj. MR-Egger regression intercept analysis showed no evidence of pleiotropic effects in this association (Ppleiotropy = 0.979). We also observed associations of genetically determined WCadj with age at first sexual intercourse and number of sexual partners (P = 0.013 and P &lt; 0.001, respectively). Conclusions: There is a putative causal relationship between genetically determined female body shape and PTSD, which could be mediated by evolutionary mechanisms involved in human sexual behaviors. © 2017 The Author(s).


Author Keywords
Anthropometric traits;  Genetics;  Trauma;  Women


Document Type: Article
Source: Scopus

 

13) 

Tan, C.H., Fan, C.C., Mormino, E.C., Sugrue, L.P., Broce, I.J., Hess, C.P., Dillon, W.P., Bonham, L.W., Yokoyama, J.S., Karch, C.M., Brewer, J.B., Rabinovici, G.D., Miller, B.L., Schellenberg, G.D., Kauppi, K., Feldman, H.A., Holland, D., McEvoy, L.K., Hyman, B.T., Bennett, D.A., Andreassen, O.A., Dale, A.M., Desikan, R.S., For the Alzheimer's Disease Neuroimaging Initiative
Polygenic hazard score: an enrichment marker for Alzheimer’s associated amyloid and tau deposition
(2017) Acta Neuropathologica, pp. 1-9. Article in Press. 

DOI: 10.1007/s00401-017-1789-4


a Neuroradiology Section, Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA, United States
b Department of Cognitive Science, University of California, La Jolla, San Diego, CA, United States
c Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, United States
d Department of Neurology, University of California, San Francisco, San Francisco, CA, United States
e Department of Psychiatry, Washington University in St. Louis, St. Louis, MO, United States
f Department of Neurosciences, University of California, La Jolla, San Diego, CA, United States
g Department of Radiology, University of California, La Jolla, San Diego, CA, United States
h Shiley-Marcos Alzheimer’s Disease Research Center, University of California, La Jolla, San Diego, CA, United States
i Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, United States
j Department of Neurology, Massachusetts General Hospital, Boston, MA, United States
k Rush Alzheimer’s Disease Center, Rush University Medical Center, Chicago, IL, United States
l NORMENT Institute of Clinical Medicine, University of Oslo, Oslo, Norway
m Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway


Abstract
There is an urgent need for identifying nondemented individuals at the highest risk of progressing to Alzheimer’s disease (AD) dementia. Here, we evaluated whether a recently validated polygenic hazard score (PHS) can be integrated with known in vivo cerebrospinal fluid (CSF) or positron emission tomography (PET) biomarkers of amyloid, and CSF tau pathology to prospectively predict cognitive and clinical decline in 347 cognitive normal (CN; baseline age range = 59.7–90.1, 98.85% white) and 599 mild cognitively impaired (MCI; baseline age range = 54.4–91.4, 98.83% white) individuals from the Alzheimer’s Disease Neuroimaging Initiative 1, GO, and 2. We further investigated the association of PHS with post-mortem amyloid load and neurofibrillary tangles in the Religious Orders Study and Memory and Aging Project (ROSMAP) cohort (N = 485, age at death range = 71.3–108.3). In CN and MCI individuals, we found that amyloid and total tau positivity systematically varies as a function of PHS. For individuals in greater than the 50th percentile PHS, the positive predictive value for amyloid approached 100%; for individuals in less than the 25th percentile PHS, the negative predictive value for total tau approached 85%. High PHS individuals with amyloid and tau pathology showed the steepest longitudinal cognitive and clinical decline, even among APOE ε4 noncarriers. Among the CN subgroup, we similarly found that PHS was strongly associated with amyloid positivity and the combination of PHS and biomarker status significantly predicted longitudinal clinical progression. In the ROSMAP cohort, higher PHS was associated with higher post-mortem amyloid load and neurofibrillary tangles, even in APOE ε4 noncarriers. Together, our results show that even after accounting for APOE ε4 effects, PHS may be useful in MCI and preclinical AD therapeutic trials to enrich for biomarker-positive individuals at highest risk for short-term clinical progression. © 2017 Springer-Verlag GmbH Germany, part of Springer Nature


Author Keywords
Alzheimer’s disease;  Amyloid;  Polygenic risk;  Tau


Document Type: Article in Press
Source: Scopus

 

14) 

Aleem, A.W., Wilent, W.B., Narzikul, A.C., Kuntz, A.F., Chang, E.S., Williams, G.R., Abboud, J.A.
Incidence of peripheral nerve injury during shoulder arthroplasty when motor evoked potentials are monitored
(2017) Journal of Clinical Monitoring and Computing, pp. 1-10. Article in Press. 

DOI: 10.1007/s10877-017-0080-5


a Department of Orthopedic Surgery, Washington University in St. Louis, 660 S. Euclid Ave., Campus Box 8233, St. Louis, MO, United States
b The Rothman Institute at Thomas Jefferson University, Philadelphia, PA, United States
c SpecialtyCare, Nashville, TN, United States
d Department of Orthopaedic Surgery, University of Pennsylvania, Philadelphia, PA, United States
e Inova Health System, Fairfax, VA, United States


Abstract
To report the incidence of clinically detectable nerve injuries when utilizing transcranial electrical motor evoked potentials (MEPs) during shoulder arthroplasty. A retrospective review of patients undergoing shoulder arthroplasty with continuous IONM was performed. The criteria for nerve alerts was an 80% amplitude reduction in MEPs. The primary outcome measure was post-operative clinically detectable nerve deficit. An additional retrospective analysis on a subset of cases using an all-or-none (100% amplitude reduction) criterion applied to the deltoid was performed. Two hundred eighty four arthroplasty cases were included. There were no permanent post-operative nerve injuries and two transient nerve injuries (0.7%). MEP alerts occurred in 102 cases (36.2%). Nineteen (6.7%) cases did not have signals return above alert threshold at closure. These cases were significantly associated with post-operative nerve injury (p = 0.03). There were no false negatives, making sensitivity 100% and specificity was 93.9%. In the subset of cases in which an all-or-none criterion was retrospectively applied to just the deltoid, MEP alerts occurred in just 17.9% of cases; specificity improved to 98.0%. We conclude that utilization of the real-time diagnostic MEP data during shoulder arthroplasty aids surgeons in decision making regarding impending peripheral nerve injuries. © 2017 Springer Science+Business Media B.V., part of Springer Nature


Author Keywords
Intraoperative motor evoked potentials;  Nerve injury;  Peripheral nerve function;  Peripheral nerve monitoring;  Shoulder arthroplasty


Document Type: Article in Press
Source: Scopus

 

15) 

Ben-Shahar, Y.
Epigenetic switch turns on genetic behavioral variations
(2017) Proceedings of the National Academy of Sciences of the United States of America, 114 (47), pp. 12365-12367. 

DOI: 10.1073/pnas.1717376114


Department of Biology, Washington University in St. Louis, St. Louis, MO, United States


Document Type: Note
Source: Scopus

 

16) 

Sharma, A.K., Schultz, J.W., Prior, J.T., Rath, N.P., Mirica, L.M.
Coordination Chemistry of Bifunctional Chemical Agents Designed for Applications in 64Cu PET Imaging for Alzheimer's Disease
(2017) Inorganic Chemistry, 56 (22), pp. 13801-13814. 

DOI: 10.1021/acs.inorgchem.7b01883


a Department of Chemistry, Washington University, One Brookings Drive, St. Louis, MO, United States
b Department of Chemistry and Biochemistry, University of Missouri St. Louis, One University Boulevard, St. Louis, MO, United States


Abstract
Positron emission tomography (PET) is emerging as one of the most important diagnostic tools for brain imaging, yet the most commonly used radioisotopes in PET imaging, 11C and 18F, have short half-lives, and their usage is thus somewhat limited. By comparison, the 64Cu radionuclide has a half-life of 12.7 h, which is ideal for administering and imaging purposes. In spite of appreciable research efforts, high-affinity copper chelators suitable for brain imaging applications are still lacking. Herein, we present the synthesis and characterization of a series of bifunctional compounds (BFCs) based on macrocyclic 1,4,7-triazacyclononane and 2,11-diaza[3.3](2,6)pyridinophane ligand frameworks that exhibit a high affinity for Cu2+ ions. In addition, these BFCs contain a 2-phenylbenzothiazole fragment that is known to interact tightly with amyloid β fibrillar aggregates. Determination of the protonation constants (pKa values) and stability constants (log β values) of these BFCs, as well as characterization of the isolated copper complexes using X-ray crystallography, electron paramagnetic resonance spectroscopy, and electrochemical studies, suggests that these BFCs exhibit desirable properties for the development of novel 64Cu PET imaging agents for Alzheimer's disease. © 2017 American Chemical Society.


Document Type: Article
Source: Scopus

 

17) 

Fredericksen, J., Fabbre, V.
Down Syndrome and Alzheimer’s Disease: Issues and Implications for Social Work Practice
(2017) Journal of Gerontological Social Work, pp. 1-7. Article in Press. 

DOI: 10.1080/01634372.2017.1393480


George Warren Brown School of Social Work, Washington University, St. Louis, United States


Abstract
Owing to recent medical advancements, people with Down Syndrome (DS) are now able to live considerably longer lives and thus experience a variety of complex issues as they age. Alzheimer’s Disease (AD) frequently occurs in older adults who have DS, but few practice guidelines exist to inform social work practice with older adults who have this dual diagnosis. This commentary will highlight the connection between these two conditions within a neurobiological framework and discuss implications for practice based on the available literature on this intersection of ability status, cognitive status, and age. © 2017 Taylor & Francis Group, LLC


Author Keywords
Alzheimer’s Disease;  Down Syndrome;  Social Work Practice


Document Type: Article in Press
Source: Scopus

 

18) 

Spangler, S., Bruchas, M.R.
Tuning Biased GPCR Signaling for Physiological Gain
(2017) Cell, 171 (5), pp. 989-991. 

DOI: 10.1016/j.cell.2017.10.046


b Department of Neuroscience, Washington University School of Medicine, St. Louis, MO, United States
c Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States
d Division of Biology and Biomedical Sciences, Washington University School of Medicine, St. Louis, MO, United States
e Washington University Pain Center, Washington University School of Medicine, St. Louis, MO, United States


Abstract
Effective and safe doses of opiate painkillers, like morphine, can be limited by respiratory depression. Schmid et al. (2017) now present a quantitative method to design ligands and correlate GPCR signaling bias to the dose separation between therapeutic and adverse effects in animals. Effective and safe doses of opiate painkillers, like morphine, can be limited by respiratory depression. Schmid et al. (2017) now present a quantitative method to design ligands and correlate GPCR signaling bias to the dose separation between therapeutic and adverse effects in animals. © 2017 Elsevier Inc.


Document Type: Short Survey
Source: Scopus

 

19) 

Lin, A.J., Campian, J.L., Hui, C., Rudra, S., Rao, Y.J., Thotala, D., Hallahan, D., Huang, J.
Impact of concurrent versus adjuvant chemotherapy on the severity and duration of lymphopenia in glioma patients treated with radiation therapy
(2017) Journal of Neuro-Oncology, pp. 1-9. Article in Press. 

DOI: 10.1007/s11060-017-2668-5


a Department of Radiation Oncology, Center for Advanced Medicine, Washington University School of Medicine, 4921 Parkview Place, Campus Box #8224, St. Louis, MO, United States
b Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, MO, United States


Abstract
Prolonged severe lymphopenia has been shown to persist beyond a year in glioma patients after radiation therapy (RT) with concurrent and adjuvant chemotherapy. This study examines the differential impact of concurrent versus adjuvant chemotherapy on lymphopenia after RT. WHO grade II–III glioma patients who received RT with concurrent and/or adjuvant chemotherapy from 2007 to 2016 were retrospectively analyzed. Concurrent chemotherapy was temozolomide (TMZ), and adjuvant chemotherapy was either TMZ or procarbazine/lomustine/vincristine (PCV). Absolute lymphocyte count (ALC) was analyzed at baseline, 1.5, 3, 6, and 12 months after the start of RT. Univariable and multivariable logistic regression were used to identify the clinical variables in predicting acute or late lymphopenia. There were 151 patients with evaluable ALC: 91 received concurrent and adjuvant TMZ (CRT + ADJ), 32 received only concurrent TMZ (CRT), and 28 received only adjuvant TMZ or PCV (ADJ). There were 9 (10%) versus 6 (19%) versus 0 (0%) cases of grade 3 lymphopenia (ALC &lt; 500/mm3) at 6 weeks and 4 (6%) versus 0 (0%) versus 3 (17%) cases at 12 months in CRT + ADJ, CRT and ADJ groups, respectively. On multivariable analyses, concurrent chemotherapy (odds ratio [OR] 72.3, p &lt; 0.001), female sex (OR 10.8, p &lt; 0.001), and older age (OR 1.06, p = 0.002) were the most significant predictors for any grade ≥ 1 lymphopenia (ALC &lt; 1000/mm3) at 1.5 months. Older age (OR 1.08, p = 0.02) and duration of adjuvant chemotherapy (OR 1.19, p = 0.003) were significantly associated with grade ≥ 1 lymphopenia at 12 months. Thus, concurrent chemotherapy appears as the dominant contributor to the severity of acute lymphopenia after RT in WHO grade II–III glioma patients, and duration of adjuvant chemotherapy appears as the key factor to prolonged lymphopenia. © 2017 Springer Science+Business Media, LLC, part of Springer Nature


Author Keywords
Adjuvant chemotherapy;  Concurrent chemotherapy;  Glioma;  Lymphopenia;  Radiation therapy


Document Type: Article in Press
Source: Scopus

 

20) 

Kafashan, M.M., Ryu, S., Hargis, M.J., Laurido-Soto, O., Roberts, D.E., Thontakudi, A., Eisenman, L., Kummer, T.T., Ching, S.N.
EEG dynamical correlates of focal and diffuse causes of coma
(2017) BMC Neurology, 17 (1), art. no. 197, . 

DOI: 10.1186/s12883-017-0977-0


a Washington University in St. Louis, Department of Electrical and Systems Engineering, 1 Brookings Dr. Campus Box 1042, St. Louis, MO, United States
b Washington University School of Medicine, Department of Neurology, 660 S Euclid Ave. Campus Box 8111, St. Louis, MO, United States
c Washington University in St. Louis, Division of Biology and Biomedical Science, St. Louis, MO, United States
d Harvard Medical School, Boston, United States
e Department of Neurology, Novant Health Forsyth Medical Center, Winston-Salem, United States
f University of Rochester, Department of Neurology, Rochester, United States


Abstract
Background: Rapidly determining the causes of a depressed level of consciousness (DLOC) including coma is a common clinical challenge. Quantitative analysis of the electroencephalogram (EEG) has the potential to improve DLOC assessment by providing readily deployable, temporally detailed characterization of brain activity in such patients. While used commonly for seizure detection, EEG-based assessment of DLOC etiology is less well-established. As a first step towards etiological diagnosis, we sought to distinguish focal and diffuse causes of DLOC through assessment of temporal dynamics within EEG signals. Methods: We retrospectively analyzed EEG recordings from 40 patients with DLOC with consensus focal or diffuse culprit pathology. For each recording, we performed a suite of time-series analyses, then used a statistical framework to identify which analyses (features) could be used to distinguish between focal and diffuse cases. Results: Using cross-validation approaches, we identified several spectral and non-spectral EEG features that were significantly different between DLOC patients with focal vs. diffuse etiologies, enabling EEG-based classification with an accuracy of 76%. Conclusions: Our findings suggest that DLOC due to focal vs. diffuse injuries differ along several electrophysiological parameters. These results may form the basis of future classification strategies for DLOC and coma that are more etiologically-specific and therefore therapeutically-relevant. © 2017 The Author(s).


Author Keywords
Classification;  Coma;  Depressed level of consciousness;  Electroencephalogram


Document Type: Article
Source: Scopus

 

21) 

Kornfield, S.L., Kang-Yi, C.D., Mandell, D.S., Epperson, C.N.
Predictors and Patterns of Psychiatric Treatment Dropout During Pregnancy Among Low-Income Women
(2017) Maternal and Child Health Journal, pp. 1-11. Article in Press. 

DOI: 10.1007/s10995-017-2394-9


a Department of Psychiatry, School of Medicine, Washington University in St. Louis, 660 S. Euclid Ave., Campus Box 8134, St. Louis, MO, United States
b Department of Psychiatry, Penn Center for Women’s Behavioral Wellness, University of Pennsylvania Perelman School of Medicine, 3535 Market Street, 3rd Floor, Philadelphia, PA, United States
c University of Pennsylvania Center for Mental Health Policy and Services Research, 3535 Market Street, 3rd Floor, Philadelphia, PA, United States
d The Children’s Hospital of Philadelphia Center for Autism Research, University of Pennsylvania Center for Mental Health Policy and Services Research, 3535 Market Street, 3rd Floor, Philadelphia, PA, United States
e Penn PROMOTES Research on Sex and Gender in Health, Penn Center for Women’s Behavioral Wellness, University of Pennsylvania, 3535 Market Street, Philadelphia, PA, United States


Abstract
Objective This study compared psychiatric treatment discontinuation rates among pregnant women using psychotropic medications, outpatient psychotherapy, or both before conception. Methods Using data from Pennsylvania Medicaid Fee-For-Service and Managed Care Organization claims and Medicaid enrollment, 3030 women were identified who gave birth between 2007 and 2009, had ≥ 1 claim for psychiatric treatment during the 120 days prior to pregnancy, and were enrolled in Medicaid until they delivered. Kaplan–Meier and Cox regression analyses were used to estimate psychiatric treatment dropout rate during pregnancy and examine relationships between treatment dropout and age, race/ethnicity, and pre-pregnancy psychiatric diagnosis and treatment pattern. Results After the first trimester, the probability of discontinuing psychotropic medications was 83 versus 37.8% for cessation of psychotherapy among combined treatment users. Two or more psychotherapy sessions in the 4 months prior to pregnancy were associated with decreased psychotherapy dropout during pregnancy. Psychotherapy during pregnancy was associated with prenatal psychotropic medication adherence. Conclusions To retain women in treatment during pregnancy, when discontinuation from care is common, innovative models of care should consider type of pre-pregnancy mental healthcare and individual characteristics. © 2017 Springer Science+Business Media, LLC


Author Keywords
Maternal psychiatric disorders;  Prenatal mental health;  Psychiatric treatment dropout


Document Type: Article in Press
Source: Scopus

 

22) 

Lam Shin Cheung, V., Kim, A., Sahgal, A., Das, S.
Meningioma recurrence rates following treatment: a systematic analysis
(2017) Journal of Neuro-Oncology, pp. 1-11. Article in Press. 

DOI: 10.1007/s11060-017-2659-6


a Department of Clinical Neurological Sciences, Western University and London Health Sciences Centre, London, ON, Canada
b Department of Neurosurgery, Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, United States
c Department of Radiation Oncology, Sunnybrook Hospital, Toronto, ON, Canada
d Keenan Research Centre and Division of Neurosurgery, St. Michael’s Hospital, Toronto, ON, Canada
e University of Toronto, Toronto, ON, Canada


Abstract
Recurrence rates of meningiomas have been widely reported in the literature, but it remains challenging for clinicians to predict recurrence rate depending on treatment, patient demographics and tumor characteristics. To address these needs, we performed a systematic analysis of the literature to determine the recurrence rate ranges of meningiomas following surgery or radiation. Our search yielded 13 studies that met all criteria for inclusion, allowing us to include 1539 patients in the assessment. Recurrence rates ranged from 0.00 to 2.36 per 100-person-years for WHO grade I meningiomas; and from 7.35 to 11.46 per 100-person-years for WHO grade II meningiomas. Our findings suggest that (1) reported recurrence rates are variable and complicated by the heterogeneity of study populations; (2) as expected, WHO grade II meningiomas generally have a higher recurrence rate than WHO grade I, when controlling for time of diagnosis (by employing person-years); and (3) there is a need for more rigorous reporting of recurrence rates, WHO grade, and Simpson grading for individual patients in order to determine a robust mean of recurrence across WHO grades. © 2017 Springer Science+Business Media, LLC


Author Keywords
Meningioma;  Microsurgery;  Radiation;  Recurrence


Document Type: Article in Press
Source: Scopus

 

23) 

Ibanez, L., Dube, U., Saef, B., Budde, J., Black, K., Medvedeva, A., Del-Aguila, J.L., Davis, A.A., Perlmutter, J.S., Harari, O., Benitez, B.A., Cruchaga, C.
Parkinson disease polygenic risk score is associated with Parkinson disease status and age at onset but not with alpha-synuclein cerebrospinal fluid levels
(2017) BMC Neurology, 17 (1), art. no. 198, . 

DOI: 10.1186/s12883-017-0978-z


a Washington University in Saint Louis, Department of Psychiatry, School of Medicine, Saint Louis, MO, United States
b Washington University in Saint Louis, Hope Center Program on Protein Aggregation and Neurodegeneration, Saint Louis, MO, United States
c Washington University in Saint Louis, Medical Scientist Training Program, School of Medicine, Saint Louis, MO, United States
d Washington University in St Louis, Department of Neurology, School of Medicine, Saint Louis, MO, United States
e Washington University in Saint Louis, Department of Medicine, School of Medicine, Saint Louis, MO, United States


Abstract
Background: The genetic architecture of Parkinson's Disease (PD) is complex and not completely understood. Multiple genetic studies to date have identified multiple causal genes and risk loci. Nevertheless, most of the expected genetic heritability remains unexplained. Polygenic risk scores (PRS) may provide greater statistical power and inform about the genetic architecture of multiple phenotypes. The aim of this study was to test the association between PRS and PD risk, age at onset and cerebrospinal fluid (CSF) biomarkers (α-synuclein, Aβ1-42, t-tau and p-tau). Methods: The weighted PRS was created using the genome-wide loci from Nalls et al., 2014 PD GWAs meta-analysis. The PRS was tested for association with PD status, age at onset and CSF biomarker levels in 829 cases and 432 controls of European ancestry. Results: The PRS was associated with PD status (p = 5.83×10-08) and age at onset (p = 5.70×10-07). The CSF t-tau levels showed a nominal association with the PRS (p = 0.02). However, CSF α-synuclein, amyloid beta and phosphorylated tau were not found to be associated with the PRS. Conclusion: Our study suggests that there is an overlap in the genetic architecture of PD risk and onset, although the different loci present different weights for those phenotypes. In our dataset we found a marginal association of the PRS with CSF t-tau but not with α-synuclein CSF levels, suggesting that the genetic architecture for the CSF biomarker levels is different from that of PD risk. © 2017 The Author(s).


Author Keywords
Age at onset;  Biomarkers;  Genetics;  Parkinson disease;  Polygenic risk score


Document Type: Article
Source: Scopus

 

24) 

Carlozzi, N.E., Hahn, E.A., Frank, S.A., Perlmutter, J.S., Downing, N.D., McCormack, M.K., Barton, S., Nance, M.A., Schilling, S.G., Hdqlife Site Investigators And Coordinators, Carlozzi, N., Dayalu, P., Schilling, S., Austin, A., Canter, M., Goodnight, S., Miner, J., Migliore, N., Paulsen, J., Downing, N., DeSoriano, I., Shadrick, C., Miller, A., Quaid, K., Wesson, M., Ross, C., Churchill, G., Ong, M.J., Perlman, S., Clemente, B., Fisher, A., Obialisi, G., Rosco, M., McCormack, M., Marin, H., Dicke, A., Perlmutter, J.S., Barton, S., Smith, S., Nance, M., Ede, P., Rao, S., Ahmed, A., Lengen, M., Mourany, L., Reece, C., Geschwind, M., Winer, J., Cella, D., Gershon, R., Hahn, E., Lai, J.-S.
A new measure for end of life planning, preparation, and preferences in Huntington disease: HDQLIFE end of life planning
(2017) Journal of Neurology, pp. 1-10. Article in Press. 

DOI: 10.1007/s00415-017-8677-7


a Department of Physical Medicine and Rehabilitation, University of Michigan, North Campus Research Complex, 2800 Plymouth Road, Building NCRC B14, Room G216, Ann Arbor, MI, United States
b Department of Medical Social Sciences, Northwestern University, Chicago, IL, United States
c Beth Israel Deaconess Medical Center, Boston, MA, United States
d Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
e Departments of Radiology and Neuroscience, Program in Occupational Therapy and Program in Physical Therapy, Washington University, St. Louis, MO, United States
f Forensic Health Care College of Nursing, Texas A&M University, College Station, TX, United States
g Department of Psychiatry, Rutgers University-Robert Wood Johnson Medical School, Brunswick, NJ, United States
h Piscataway and Department of Pathology, Rowan University-SOM, Stratford, NJ, United States
i Hennepin County Medical Center, Minneapolis, MN, United States
j Institute for Social Research, University of Michigan, Ann Arbor, MI, United States


Abstract
Background: Huntington disease is a fatal inherited neurodegenerative disease. Because the end result of Huntington disease is death due to Huntington disease-related causes, there is a need for better understanding and caring for individuals at their end of life. Aim: The purpose of this study was to develop a new measure to evaluate end of life planning. Design: We conducted qualitative focus groups, solicited expert input, and completed a literature review to develop a 16-item measure to evaluate important aspects of end of life planning for Huntington disease. Item response theory and differential item functioning analyses were utilized to examine the psychometric properties of items; exploratory factor analysis was used to establish meaningful subscales. Participants: Participants included 508 individuals with pre-manifest or manifest Huntington disease. Results: Item response theory supported the retention of all 16 items on the huntington disease quality of life (“HDQLIFE”) end of life planning measure. Exploratory factor analysis supported a four-factor structure: legal planning, financial planning, preferences for hospice care, and preferences for conditions (locations, surroundings, etc.) at the time of death. Although a handful of items exhibited some evidence of differential item functioning, these items were retained due to their relevant clinical content. The final 16-item scale includes an overall total score and four subscale scores that reflect the different end of life planning constructs. Conclusions: The 16-item HDQLIFE end of life planning measure demonstrates adequate psychometric properties; it may be a useful tool for clinicians to clarify patients’ preferences about end of life care. © 2017 Springer-Verlag GmbH Germany, part of Springer Nature


Author Keywords
End of life;  HDQLIFE;  HDQLIFE Site Investigators and Coordinators;  Health-related quality of life;  Huntington disease;  Patient-reported outcome (PRO)


Document Type: Article in Press
Source: Scopus

 

25) 

Lin, M., Liu, S.B., Genin, G.M., Zhu, Y., Shi, M., Ji, C., Li, A., Lu, T.J., Xu, F.
Melting Away Pain: Decay of Thermal Nociceptor Transduction during Heat-Induced Irreversible Desensitization of Ion Channels
(2017) ACS Biomaterials Science and Engineering, 3 (11), pp. 3029-3035. Cited 1 time.

DOI: 10.1021/acsbiomaterials.6b00789


a Key Laboratory of Biomedical Information Engineering, Ministry of Education, School of Life Science and Technology, College of Stomatology, Xi'An Jiaotong University, Xi'an, China
b Bioinspired Engineering and Biomechanics Center, College of Stomatology, Xi'An Jiaotong University, Xi'an, China
c Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'An Jiaotong University, Xi'an, China
d Department of Neurological Surgery, Washington University, School of Medicine, NSF Science and Technology Center for Engineering Mechanobiology, School of Engineering, Washington University, St. Louis, MO, United States
e Department of Acupuncture, Shaanxi Hospital of Traditional Chinese Medicine, Xi'an, China


Abstract
Thermal transient receptor potential channels play a key role in thermal sensation. Although predictive models exist for temperature-dependent transduction through these channels and for the associated sensations of pain, the ability to predict irreversible desensitization has been lacking. We explored the role of irreversible ion channel desensitization in pain sensation and hypothesized that desensitization of ion channels would follow the kinetics similar to the denaturation of catalytic enzymes. We therefore proposed a three-state model to simulate the kinetic of temperature-sensitive ion channels from the closed state through opening and irreversible thermal desensitization. We tested the model against data obtained in vivo from a feline model. The theoretical model predicts all experimental data with reasonable accuracy, and represents an important step toward the ability for understanding of the molecular basis of nociceptor signaling providing the possibility to design local anesthesia regimens and to the prediction of postoperative pain. © 2017 American Chemical Society.


Author Keywords
Irreversible desensitization;  Temperature-sensitive ion channels;  Thermal pain;  Trans-membrane ion transport


Document Type: Article
Source: Scopus

 

26) 

Mitra, A., Snyder, A.Z., Tagliazucchi, E., Laufs, H., Elison, J., Emerson, R.W., Shen, M.D., Wolff, J.J., Botteron, K.N., Dager, S., Estes, A.M., Evans, A., Gerig, G., Hazlett, H.C., Paterson, S.J., Schultz, R.T., Styner, M.A., Zwaigenbaum, L., Chappell, C., Estes, A., Shaw, D., Botteron, K., McKinstry, R., Constantino, J., Pruett, J., Schultz, R., Paterson, S., Evans, A.C., Collins, D.L., Pike, G.B., Fonov, V., Kostopoulos, P., Das, S., Styner, M., Gu, H., Schlaggar, B.L., Piven, J., Pruett, J.R., Jr., Raichle, M.
Resting-state fMRI in sleeping infants more closely resembles adult sleep than adult wakefulness
(2017) PLoS ONE, 12 (11), art. no. e0188122, . 

DOI: 10.1371/journal.pone.0188122


a Department of Radiology, Washington University School of Medicine, Saint Louis, MO, United States
b Department of Neurology, Washington University School of Medicine, Saint Louis, MO, United States
c Departamento de Fisica, Universidad de Buenos Aires, Buenos Aires, Argentina
d Department of Neurology, Christian-Albrechts-University, Kiel, Germany
e Institute of Child Development, University of Minnesota, Minneapolis, MN, United States
f Department of Psychiatry, University of North Carolina, Chapel Hill, NC, United States
g Department of Radiology, University of Washington, Seattle, WA, United States
h Department of Psychology, University of Washington, Seattle, WA, United States
i Montreal Neurological Institute, McGill University, Montreal, QC, Canada
j Department of Psychiatry, New York University, New York, NY, United States
k Department of Pediatrics, University of Pennsylvania, Philadelphia, PA, United States
l Department of Pediatrics, University of Alberta, Edmonton, AB, Canada
m Department of Psychiatry, Washington University School of Medicine, Saint Louis, MO, United States
n University of North Carolina, United States
o IBIS Network PI, United States
p University of Washington, United States
q Washington University, United States
r Children’s Hospital of Philadelphia, United States
s University of Alberta, Canada
t University of Minnesota, United States
u Data Coordinating Center, Montreal Neurological Institute, Canada
v Image Processing Core, New York University, United States
w University of North Carolina, United States
x Statistical Analysis Core, United States


Abstract
Resting state functional magnetic resonance imaging (rs-fMRI) in infants enables important studies of functional brain organization early in human development. However, rs-fMRI in infants has universally been obtained during sleep to reduce participant motion artifact, raising the question of whether differences in functional organization between awake adults and sleeping infants that are commonly attributed to development may instead derive, at least in part, from sleep. This question is especially important as rs-fMRI differences in adult wake vs. sleep are well documented. To investigate this question, we compared functional connectivity and BOLD signal propagation patterns in 6, 12, and 24 month old sleeping infants with patterns in adult wakefulness and non-REM sleep. We find that important functional connectivity features seen during infant sleep closely resemble those seen during adult sleep, including reduced default mode network functional connectivity. However, we also find differences between infant and adult sleep, especially in thalamic BOLD signal propagation patterns. These findings highlight the importance of considering sleep state when drawing developmental inferences in infant rs-fMRI. © 2017 Mitra et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Document Type: Article
Source: Scopus

 

27) 

Sahrmann, S., Azevedo, D.C., Dillen, L.V.
Diagnosis and treatment of movement system impairment syndromes
(2017) Brazilian Journal of Physical Therapy, 21 (6), pp. 391-399. 

DOI: 10.1016/j.bjpt.2017.08.001


a Washington University School of Medicine, Program in Physical Therapy, St. Louis, United States
b Universidade Cidade de São Paulo (UNICID), Masters and Doctoral Programs in Physical Therapy, São Paulo, SP, Brazil
c Pontifícia Universidade Católica de Minas Gerais (PUC-MG), Departamento de Fisioterapia, Belo Horizonte, MG, Brazil


Abstract
Background Diagnoses and treatments based on movement system impairment syndromes were developed to guide physical therapy treatment. Objectives This masterclass aims to describe the concepts on that are the basis of the syndromes and treatment and to provide the current research on movement system impairment syndromes. Results The conceptual basis of the movement system impairment syndromes is that sustained alignment in a non-ideal position and repeated movements in a specific direction are thought to be associated with several musculoskeletal conditions. Classification into movement system impairment syndromes and treatment has been described for all body regions. The classification involves interpreting data from standardized tests of alignments and movements. Treatment is based on correcting the impaired alignment and movement patterns as well as correcting the tissue adaptations associated with the impaired alignment and movement patterns. The reliability and validity of movement system impairment syndromes have been partially tested. Although several case reports involving treatment using the movement system impairment syndromes concept have been published, efficacy of treatment based on movement system impairment syndromes has not been tested in randomized controlled trials, except in people with chronic low back pain. © 2017 Associação Brasileira de Pesquisa e Pós-Graduação em Fisioterapia


Author Keywords
Classification;  Impairment;  Movement system;  Musculoskeletal;  Pain;  Rehabilitation


Document Type: Review
Source: Scopus

 

28) 

Karadaghy, O.A., Hong, H., Scott-Wittenborn, N., Sinha, P., Suko, J., Tait, S., Wamkpah, N.S., Kallogjeri, D., Piccirillo, J.F.
Reporting of effect size and confidence intervals in JAMA Otolaryngology-Head & Neck Surgery
(2017) JAMA Otolaryngology - Head and Neck Surgery, 143 (11), pp. 1075-1080. 

DOI: 10.1001/jamaoto.2017.1504


a University of Missouri, Kansas City School of Medicine, Kansas City, United States
b Department of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine in St Louis, St Louis, MO, United States


Abstract
IMPORTANCE: Effect sizes and confidence intervals (CIs) are critical for the interpretation of the results for any outcome of interest. OBJECTIVE: To evaluate the frequency of reporting effect sizes and CIs in the results of analytical studies. DESIGN, SETTING, AND PARTICIPANTS: Descriptive review of analytical studies published from January 2012 to December 2015 in JAMA Otolaryngology-Head & Neck Surgery. METHODS: A random sample of 121 articles was reviewed in this study. Descriptive studies were excluded from the analysis. Seven independent reviewers participated in the evaluation of the articles, with 2 reviewers assigned per article. The review process was standardized for each article; the Methods and Results sections were reviewed for the outcomes of interest. Descriptive statistics for each outcome were calculated and reported accordingly. MAIN OUTCOMES AND MEASURES: Primary outcomes of interest included the presence of effect size and associated CIs. Secondary outcomes of interest included a priori descriptions of statistical methodology, power analysis, and expectation of effect size. RESULTS: There were 107 articles included for analysis. The majority of the articles were retrospective cohort studies (n = 36 [36%]) followed by cross-sectional studies (n = 18 [17%]). A total of 58 articles (55%) reported an effect size for an outcome of interest. The most common effect size used was difference of mean, followed by odds ratio and correlation coefficient, which were reported 17 (16%), 15 (13%), and 12 times (11%), respectively. Confidence intervals were associated with 29 of these effect sizes (27%), and 9 of these articles (8%) included interpretation of the CI. A description of the statistical methodology was provided in 97 articles (91%), while 5 (5%) provided an a priori power analysis and 8 (7%) provided a description of expected effect size finding. CONCLUSIONS AND RELEVANCE: Improving results reporting is necessary to enhance the reader’s ability to interpret the results of any given study. This can only be achieved through increasing the reporting of effect sizes and CIs rather than relying on P values for both statistical significance and clinically meaningful results. © 2017 American Medical Association. All rights reserved.


Document Type: Article
Source: Scopus

 

29) 

Wenrich, K.A., Davidson, L.S., Uchanski, R.M.
Segmental and suprasegmental perception in children using hearing AIDS
(2017) Journal of the American Academy of Audiology, 28 (10), pp. 901-912. 

DOI: 10.3766/jaaa.16105


a Department of Otolaryngology, Washington University, School of Medicine, St. Louis, MO, United States
b Central Institute for the Deaf, St. Louis, MO, United States
c Program in Audiology and Communication Science, Washington University, School of Medicine, St. Louis, MO, United States


Abstract
Background: Suprasegmental perception (perception of stress, intonation, ‘‘how something is said’’ and ‘‘who says it’’) and segmental speech perception (perception of individual phonemes or perception of ‘‘what is said’’) are perceptual abilities that provide the foundation for the development of spoken language and effective communication. While there are numerous studies examining segmental perception in children with hearing aids (HAs), there are far fewer studies examining suprasegmental perception, especially for children with greater degrees of residual hearing. Examining the relation between acoustic hearing thresholds, and both segmental and suprasegmental perception for children with HAs, may ultimately enable better device recommendations (bilateral HAs, bimodal devices [one CI and one HA in opposite ears], bilateral CIs) for a particular degree of residual hearing. Examining both types of speech perception is important because segmental and suprasegmental cues are affected differentially by the type of hearing device(s) used (i.e., cochlear implant [CI] and/or HA). Additionally, suprathreshold measures, such as frequency resolution ability, may partially predict benefit from amplification and may assist audiologists in making hearing device recommendations. Purpose: The purpose of this study is to explore the relationship between audibility (via hearing thresholds and speech intelligibility indices), and segmental and suprasegmental speech perception for children with HAs. A secondary goal is to explore the relationships among frequency resolution ability (via spectral modulation detection [SMD] measures), segmental and suprasegmental speech perception, and receptive language in these same children. Research Design: A prospective cross-sectional design. Study Sample: Twenty-three children, ages 4 yr 11 mo to 11 yr 11 mo, participated in the study. Participants were recruited from pediatric clinic populations, oral schools for the deaf, and mainstream schools. Data Collection and Analysis: Audiological history and hearing device information were collected from participants and their families. Segmental and suprasegmental speech perception, SMD, and receptive vocabulary skills were assessed. Correlations were calculated to examine the significance (p, 0.05) of relations between audibility and outcome measures. Results: Measures of audibility and segmental speech perception are not significantly correlated, while low-frequency pure-tone average (unaided) is significantly correlated with suprasegmental speech perception. SMD is significantly correlated with all measures (measures of audibility, segmental and suprasegmental perception and vocabulary). Lastly, although age is not significantly correlated with measures of audibility, it is significantly correlated with all other outcome measures. Conclusions: The absence of a significant correlation between audibility and segmental speech perception might be attributed to overall audibility being maximized through well-fit HAs. The significant correlation between low-frequency unaided audibility and suprasegmental measures is likely due to the strong, predominantly low-frequency nature of suprasegmental acoustic properties. Frequency resolution ability, via SMD performance, is significantly correlated with all outcomes and requires further investigation; its significant correlation with vocabulary suggests that linguistic ability may be partially related to frequency resolution ability. Last, all of the outcome measures are significantly correlated with age, suggestive of developmental effects.


Author Keywords
Hearing AIDS;  Hearing loss;  Pediatric;  Spectral resolution;  Speech perception;  Suprasegmental


Document Type: Article
Source: Scopus

 

30) 

Flaherty, L.B., Wood, T., Cheng, A., Khan, A.R.
Pre-existing psychological depression confers increased risk of adverse cardiovascular outcomes following cardiac surgery: A systematic review and meta-analysis
(2017) Journal of Thoracic and Cardiovascular Surgery, 154 (5), pp. 1578-1586.e1. 

DOI: 10.1016/j.jtcvs.2017.06.052


a Department of Psychological and Brain Sciences, University of Louisville School of Arts and Sciences, Louisville, Ky, United States
b Division of Cardiovascular Medicine, University of Louisville School of Medicine, Louisville, Ky, United States
c Division of Cardiothoracic Surgery, Washington University School of Medicine, St Louis, Mo, United States


Document Type: Editorial
Source: Scopus

 

31) 

Schoppy, D.W., Rhoads, K.F., Ma, Y., Chen, M.M., Nussenbaum, B., Orosco, R.K., Rosenthal, E.L., Divi, V.
Measuring institutional quality in head and neck surgery using hospital-level data: Negative margin rates and neck dissection yield
(2017) JAMA Otolaryngology - Head and Neck Surgery, 143 (11), pp. 1111-1116. 

DOI: 10.1001/jamaoto.2017.1694


a Division of Head and Neck Surgery, Department of Otolaryngology, Stanford University School of Medicine, Stanford, Palo Alto, CA, United States
b Motility Doc, San Jose, CA, United States
c Division of Head and Neck Surgery, Department of Otolaryngology, Washington University School of Medicine in St Louis, St Louis, MO, United States


Abstract
IMPORTANCE: Negative margins and lymph node yields (LNY) of 18 or more from neck dissections in patients with head and neck squamous cell carcinomas (HNSCC) have been associated with improved patient survival. It is unclear whether these metrics can be used to identify hospitals with improved outcomes. OBJECTIVE: To determine whether 2 patient-level metrics would predict outcomes at the hospital level. DESIGN, SETTING, AND PARTICIPANTS: A retrospective review of records from the National Cancer Database (NCDB) was used to identify patients who underwent primary surgery and concurrent neck dissection for HNSCC between 2004 and 2013. The percentage of patients at each hospital with negative margins on primary resection and an LNY 18 or more from a neck dissection was quantified. Cox proportional hazard models were used to define the association between hospital performance on these metrics and overall survival. MAIN OUTCOMES AND MEASURES: Margin status and lymph node yield at hospital level. Overall survival (OS). RESULTS: We identified 1008 hospitals in the NCDB where 64 738 patients met inclusion criteria. Of the 64 738 participants, 45 170 (69.8%) were men and 19 568 (30.2%) were women. The mean SD age of included patients was 60.5 (12.0) years. Patients treated at hospitals attaining the combined metric of a 90% or higher negative margin rate and 80% or more of cases with LNYs of 18 or more experienced a significant reduction in mortality (hazard ratio [HR] 0.93; 95% CI, 0.89-0.98). This benefit in survival was independent of the patient-level improvement associated with negative margins (HR, 0.73; 95% CI, 0.71-0.76) and LNY of 18 or more (HR, 0.85; 95% CI, 0.83-0.88). Including these metrics in the model neutralized the association of traditional measures of hospital quality (volume and teaching status). CONCLUSIONS AND RELEVANCE: Treatment at hospitals that attain a high rate of negative margins and LNY of 18 or more is associated with improved survival in patients undergoing surgery for HNSCC. These surgical outcome measures predicted outcomes independent of traditional, but generally nonmodifiable characteristics. Tracking of these metrics may help identify high-quality centers and provide guidance for institution-level quality improvement. © 2017 American Medical Association. All rights reserved.


Document Type: Article
Source: Scopus

 

32) 

Wen, J., Yablonskiy, D.A., Salter, A., Cross, A.H.
Limbic system damage in MS: MRI assessment and correlations with clinical testing
(2017) PLoS ONE, 12 (11), art. no. e0187915, . 

DOI: 10.1371/journal.pone.0187915


a Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO, United States
b Division of Biostatistics, Washington University School of Medicine, St. Louis, MO, United States
c Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States


Abstract
Volume loss in some limbic region structures has been observed in multiple sclerosis (MS) patients. However, in vivo evaluation of existing tissue cellular microstructure integrity has received less attention. The goal of studies reported here was to quantitatively assess loss of limbic system volumes and tissue integrity, and to evaluate associations of these measures with cognitive and physical dysfunction in MS patients. Thirty-one healthy controls (HC) and 80 MS patients, including 32 relapsing remitting (RRMS), 32 secondary progressive (SPMS) and 16 primary progressive (PPMS), participated in this study. Tissue cellular integrity was evaluated by means of recently introduced tissue-specific parameter R2t* that was calculated from multi-gradient-echo MRI signals using a recently developed method that separates R2t* from BOLD (blood oxygen level dependent) contributions to GRE signal decay rate constant (R2*), and accounting for physiological fluctuations and artifacts from background gradients. Volumes in limbic system regions, normalized to skull size (NV), were measured from standard MPRAGE images. MS patients had lower R2t* and smaller normalized volumes in the hippocampus, amygdala, and several other limbic system regions, compared to HC. Alterations in R2t* of several limbic system regions correlated with clinical and neurocognitive test scores in MS patients. In contrast, smaller normalized volumes in MS were only correlated with neurocognitive test scores in the hippocampus and amygdala. This study reports the novel finding that R2t*, a measure that estimates tissue integrity, is more sensitive to tissue damage in limbic system structures than is atrophy. R2t* measurements can serve as a biomarker that is distinct from and complementary to volume measurements. © 2017 Wen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Document Type: Article
Source: Scopus

 

33) 

Policeni, B., Corey, A.S., Burns, J., Conley, D.B., Crowley, R.W., Harvey, H.B., Hoang, J., Hunt, C.H., Jagadeesan, B.D., Juliano, A.F., Kennedy, T.A., Moonis, G., Pannell, J.S., Patel, N.D., Perlmutter, J.S., Rosenow, J.M., Schroeder, J.W., Whitehead, M.T., Cornelius, R.S.
ACR Appropriateness Criteria® Cranial Neuropathy
(2017) Journal of the American College of Radiology, 14 (11), pp. S406-S420. 

DOI: 10.1016/j.jacr.2017.08.035


a Principal Author and Panel Vice Chair, University of Iowa Hospitals and Clinics, Iowa City, Iowa, United States
b Panel Chair, Emory University, Atlanta, Georgia
c Montefiore Medical Center, Bronx, New York, United States
d Northwestern University Feinberg School of Medicine, American Academy of Otolaryngology-Head and Neck Surgery, Chicago, Illinois, United States
e Rush University Medical Center, neurosurgical consultant, Chicago, Illinois, United States
f Massachusetts General Hospital, Boston, Massachusetts, United States
g Duke University Medical Center, Durham, North Carolina, United States
h Mayo Clinic, Rochester, Minnesota, United States
i University of Minnesota, Minneapolis, Minnesota, United States
j Massachusetts Eye and Ear Infirmary, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States
k University of Wisconsin Hospital and Clinic, Madison, Wisconsin, United States
l Columbia University Medical Center, New York, New York, United States
m University of California San Diego Medical Center, San Diego, California, United States
n Fairfax Radiology Consultants PC, Fairfax, Virginia, United States
o Washington University School of Medicine, American Academy of Neurology, Saint Louis, Missouri, United States
p Northwestern University Feinberg School of Medicine, Chicago, Illinois neurosurgical consultant, United States
q Walter Reed National Military Medical Center, Bethesda, Maryland, United States
r Children's National Medical Center, Washington, District of Columbia, United States
s Specialty Chair, University of Cincinnati Medical Center, Cincinnati, Ohio, United States


Abstract
Evaluation of cranial neuropathy can be complex given the different pathway of each cranial nerve as well as the associated anatomic landmarks. Radiological evaluation requires imaging of the entire course of the nerve from its nucleus to the end organ. MRI is the modality of choice with CT playing a complementary role, particularly in the evaluation of the bone anatomy. Since neoplastic and inflammatory lesions are prevalent on the differential diagnosis, contrast enhanced studies are preferred when possible. The American College of Radiology Appropriateness Criteria are evidencebased guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment. © 2017 American College of Radiology


Author Keywords
Appropriate Use Criteria;  Appropriateness Criteria;  AUC;  Cranial nerves;  Cranial neuropathy;  CT;  MRI;  Skull base


Document Type: Article
Source: Scopus

 

34) 

Yang, G.J., Murray, J.D., Glasser, M., Pearlson, G.D., Krystal, J.H., Schleifer, C., Repovs, G., Anticevic, A.
Altered Global Signal Topography in Schizophrenia
(2017) Cerebral Cortex, 27 (11), pp. 5156-5169. 

DOI: 10.1093/cercor/bhw297


a Department of Psychiatry, Yale University School of Medicine, 300 George Street, New Haven, CT, United States
b Department of Neuroscience, Yale University School of Medicine, 333 Cedar Street, New Haven, CT, United States
c Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, Yale University, Department of Psychiatry, 34 Park St, New Haven, CT, United States
d Department of Neurobiology, Washington University School of Medicine, Saint Louis, MO, United States
e Olin Neuropsychiatry Research Center, Institute of Living, Hartford Hospital, 200 Retreat Avenue, Hartford, CT, United States
f NIAAA Center for the Translational Neuroscience of Alcoholism, New Haven, CT, United States
g Department of Psychology, University of Ljubljana, Ljubljana, Slovenia
h Department of Psychology, Yale University, 2 Hillhouse Avenue, New Haven, CT, United States


Abstract
Schizophrenia (SCZ) is a disabling neuropsychiatric disease associated with disruptions across distributed neural systems. Resting-state functional magnetic resonance imaging has identified extensive abnormalities in the blood-oxygen level-dependent signal in SCZ patients, including alterations in the average signal over the brain - i.e. The "global" signal (GS). It remains unknown, however, if these "global" alterations occur pervasively or follow a spatially preferential pattern. This study presents the first network-by-network quantification of GS topography in healthy subjects and SCZ patients. We observed a nonuniform GS contribution in healthy comparison subjects, whereby sensory areas exhibited the largest GS component. In SCZ patients, we identified preferential GS representation increases across association regions, while sensory regions showed preferential reductions. GS representation in sensory versus association cortices was strongly anti-correlated in healthy subjects. This anti-correlated relationship was markedly reduced in SCZ. Such shifts in GS topography may underlie profound alterations in neural information flow in SCZ, informing development of pharmacotherapies. © The Author 2016. Published by Oxford University Press. All rights reserved.


Author Keywords
association cortex;  default mode network;  frontoparietal control network;  resting state;  sensory cortex


Document Type: Article
Source: Scopus

 

35) 

Omar, M.H., Campbell, M.K., Xiao, X., Zhong, Q., Brunken, W.J., Miner, J.H., Greer, C.A., Koleske, A.J.
CNS Neurons Deposit Laminin α5 to Stabilize Synapses
(2017) Cell Reports, 21 (5), pp. 1281-1292. 

DOI: 10.1016/j.celrep.2017.10.028


a Interdepartmental Neuroscience Program, Yale University, New Haven, CT, United States
b Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, United States
c Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT, United States
d Department of Neuroscience, Yale University, New Haven, CT, United States
e Department of Neurosurgery, Yale University, New Haven, CT, United States
f Department of Ophthalmology, Upstate Medical University, Syracuse, NY, United States
g Division of Nephrology, Department of Medicine, Washington University School of Medicine, St. LouisMO, United States


Abstract
Synapses in the developing brain are structurally dynamic but become stable by early adulthood. We demonstrate here that an α5-subunit-containing laminin stabilizes synapses during this developmental transition. Hippocampal neurons deposit laminin α5 at synapses during adolescence as connections stabilize. Disruption of laminin α5 in neurons causes dramatic fluctuations in dendritic spine head size that can be rescued by exogenous α5-containing laminin. Conditional deletion of laminin α5 in vivo increases dendritic spine size and leads to an age-dependent loss of synapses accompanied by behavioral defects. Remaining synapses have larger postsynaptic densities and enhanced neurotransmission. Finally, we provide evidence that laminin α5 acts through an integrin α3β1-Abl2 kinase-p190RhoGAP signaling cascade and partners with laminin β2 to regulate dendritic spine density and behavior. Together, our results identify laminin α5 as a stabilizer of dendritic spines and synapses in the brain and elucidate key cellular and molecular mechanisms by which it acts. In the developing brain, synaptic structure transitions from dynamic to stable by early adulthood. Omar et al. identify a laminin molecule deposited at synapses in the brain that is essential for dendritic spine structural regulation and synapse stability between early postnatal development and adulthood. © 2017 The Author(s)


Author Keywords
adhesion;  ECM;  extracellular matrix;  Lama5;  Lamb2;  motility;  stability;  structural plasticity;  synapse loss;  synapse maturation


Document Type: Article
Source: Scopus

 

36) 

Hughes, M.E., Abruzzi, K.C., Allada, R., Anafi, R., Arpat, A.B., Asher, G., Baldi, P., de Bekker, C., Bell-Pedersen, D., Blau, J., Brown, S., Ceriani, M.F., Chen, Z., Chiu, J.C., Cox, J., Crowell, A.M., DeBruyne, J.P., Dijk, D.-J., DiTacchio, L., Doyle, F.J., Duffield, G.E., Dunlap, J.C., Eckel-Mahan, K., Esser, K.A., FitzGerald, G.A., Forger, D.B., Francey, L.J., Fu, Y.-H., Gachon, F., Gatfield, D., de Goede, P., Golden, S.S., Green, C., Harer, J., Harmer, S., Haspel, J., Hastings, M.H., Herzel, H., Herzog, E.D., Hoffmann, C., Hong, C., Hughey, J.J., Hurley, J.M., de la Iglesia, H.O., Johnson, C., Kay, S.A., Koike, N., Kornacker, K., Kramer, A., Lamia, K., Leise, T., Lewis, S.A., Li, J., Li, X., Liu, A.C., Loros, J.J., Martino, T.A., Menet, J.S., Merrow, M., Millar, A.J., Mockler, T., Naef, F., Nagoshi, E., Nitabach, M.N., Olmedo, M., Nusinow, D.A., Ptácek, L.J., Rand, D., Reddy, A.B., Robles, M.S., Roenneberg, T., Rosbash, M., Ruben, M.D., Rund, S.S.C., Sancar, A., Sassone-Corsi, P., Sehgal, A., Sherrill-Mix, S., Skene, D.J., Storch, K.-F., Takahashi, J.S., Ueda, H.R., Wang, H., Weitz, C., Westermark, P.O., Wijnen, H., Xu, Y., Wu, G., Yoo, S.-H., Young, M., Zhang, E.E., Zielinski, T., Hogenesch, J.B.
Guidelines for Genome-Scale Analysis of Biological Rhythms
(2017) Journal of Biological Rhythms, 32 (5), pp. 380-393. 

DOI: 10.1177/0748730417728663


a Division of Pulmonary and Critical Care Medicine, Washington University School of Medicine, St. Louis, MO, United States
b Department of Biology and Howard Hughes Medical Institute, Brandeis University, Waltham, MA, United States
c Department of Neurobiology, Northwestern University, Evanston, IL, United States
d Division of Sleep Medicine, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, United States
e Center for Integrative Genomics, Génopode University of Lausanne, Lausanne, Switzerland
f Vital-IT, Swiss Institute of Bioinformatics, Lausanne, Switzerland
g Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot, Israel
h Institute for Genomics and Bioinformatics, University of California, Irvine, United States
i Department of Biology, University of Central Florida, Orlando, United States
j Department of Biology, Texas A&M University, College Station, United States
k Department of Biology, New York University, New York, United States
l Institute of Pharmacology and Toxicology, University of Zürich, Switzerland
m Laboratorio de Genética del Comportamiento, Fundación Instituto Leloir, IIBBA-CONICET, Buenos Aires, Argentina
n Department of Biochemistry and Molecular Biology, University of Texas Health Science Center, Houston, United States
o Department of Entomology and Nematology, University of California, Davis, United States
p Computational Systems Biochemistry, Max-Planck Institute of Biochemistry, Martinsried, Germany
q Department of Molecular and Systems Biology, Geisel School of Medicine at Dartmouth, Hanover, NH, United States
r Department of Pharmacology and Toxicology, Morehouse School of Medicine, Atlanta, GA, United States
s Surrey Sleep Research Centre, University of Surrey, Guildford, United Kingdom
t The University of Kansas Medical Center, University of Kansas, Kansas City, United States
u John A. Paulson School of Engineering and Applied Sciences, Harvard University, Boston, MA, United States
v Department of Biological Sciences, Eck Institute for Global Health, University of Notre Dame, Notre Dame, IN, United States
w Institute of Molecular Medicine, McGovern Medical School, UT Health Houston, Houston, TX, United States
x Department of Physiology and Functional Genomics, University of Florida College of Medicine, Gainesville, United States
y Systems Pharmacology and Translational Therapeutics, University of Pennsylvania Perelman School of Medicine, Philadelphia, United States
z Department of Mathematics, University of Michigan, Ann Arbor, United States
aa Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, United States
ab Kavli Institute for Fundamental Neuroscience, Weill Institute of Neuroscience, Department of Neurology, University of California, San Francisco, United States
ac Department of Diabetes and Circadian Rhythms, Nestlé Institute of Health Sciences, Lausanne, Switzerland
ad Department of Endocrinology & Metabolism, Academic Medical Center, Amsterdam, Netherlands
ae Center for Circadian Biology, Division of Biological Sciences, University of California, San Diego, La Jolla, United States
af Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, United States
ag Department of Mathematics, Duke University, Durham, NC, United States
ah Department of Plant Biology, University of California, Davis, United States
ai Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom
aj Institute for Theoretical Biology, Charité-Universitätsmedizin Berlin, Germany
ak Department of Biology, Washington University, St. Louis, MO, United States
al Department of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, TN, United States
am Department of Biological Sciences, Rensselaer Polytechnic Institute, Troy, NY, United States
an Department of Biology, University of Washington, Seattle, United States
ao Department of Biological Sciences, Vanderbilt University, Nashville, TN, United States
ap Department of Cell and Molecular Biology, The Scripps Research Institute, University of California, San Diego, La Jolla, United States
aq Department of Physiology and Systems Bioscience, Kyoto Prefectural University of Medicine, Japan
ar Division of Sensory Biophysics, The Ohio State University, Columbus, United States
as Laboratory of Chronobiology, Charité Universitätsmedizin Berlin, Germany
at Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA, United States
au Department of Mathematics and Statistics, Amherst College, Amherst, MA, United States
av Department of Biology, University of Missouri–St. Louis, United States
aw Department of Cell Biology, College of Life Sciences, Wuhan University, China
ax Department of Biological Sciences, University of MemphisTN, United States
ay Department of Biochemistry and Cell Biology, Geisel School of Medicine at Dartmouth, Hanover, NH, United States
az Centre for Cardiovascular Investigations, Department of Biomedical Sciences, University of Guelph, Guelph, ON, Canada
ba Institute of Medical Psychology, Faculty of Medicine, LMU Munich, Germany
bb SynthSys and School of Biological Sciences, University of Edinburgh, United Kingdom
bc Donald Danforth Plant Science Center, St. Louis, MO, United States
bd The Institute of Bioengineering, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Switzerland
be Department of Genetics and Evolution, University of Geneva, Switzerland
bf Department of Cellular and Molecular Physiology, Department of Genetics, Kavli Institute for Neuroscience, Yale School of Medicine, New Haven, CT, United States
bg Department of Genetics, University of Seville, Spain
bh Department of Neurology, University of California, San Francisco, United States
bi Warwick Systems Biology and Mathematics Institute, University of Warwick, Conventry, United Kingdom
bj The Francis Crick Institute, London, United Kingdom
bk UCL Institute of Neurology, Queen Square, London, United Kingdom
bl Centre for Immunity, Infection and Evolution, University of Edinburgh, United Kingdom
bm Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, United States
bn Department of Biological Chemistry, Center for Epigenetics and Metabolism, University of California, Irvine, United States
bo Howard Hughes Medical Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, United States
bp Department of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, United States
bq Chronobiology, Faculty of Health and Medical Sciences, University of Surrey, Guildford, United Kingdom
br Department of Psychiatry, Douglas Mental Health University Institute, McGill University, Montreal, Canada
bs Howard Hughes Medical Institute, Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, United States
bt Department of Systems Pharmacology, Graduate School of Medicine, Tokyo, Japan
bu Japan Laboratory for Synthetic Biology, RIKEN Quantitative Biology Center, Osaka, Japan
bv Center for Circadian Clocks, Soochow University, Suzhou, Jiangsu, China
bw Department of Neurobiology, Harvard Medical School, Boston, MA, United States
bx Institute of Genetics and Biometry, Leibniz Institute for Farm Animal Biology, Dummerstorf, Germany
by Biological Sciences and Institute for Life Sciences, University of Southampton, United Kingdom
bz Cam-Su GRC, Soochow University, Suzhou, China
ca Laboratory of Genetics, Rockefeller University, New York, NY, United States
cb National Institute of Biological Sciences, Beijing, China


Abstract
Genome biology approaches have made enormous contributions to our understanding of biological rhythms, particularly in identifying outputs of the clock, including RNAs, proteins, and metabolites, whose abundance oscillates throughout the day. These methods hold significant promise for future discovery, particularly when combined with computational modeling. However, genome-scale experiments are costly and laborious, yielding “big data” that are conceptually and statistically difficult to analyze. There is no obvious consensus regarding design or analysis. Here we discuss the relevant technical considerations to generate reproducible, statistically sound, and broadly useful genome-scale data. Rather than suggest a set of rigid rules, we aim to codify principles by which investigators, reviewers, and readers of the primary literature can evaluate the suitability of different experimental designs for measuring different aspects of biological rhythms. We introduce CircaInSilico, a web-based application for generating synthetic genome biology data to benchmark statistical methods for studying biological rhythms. Finally, we discuss several unmet analytical needs, including applications to clinical medicine, and suggest productive avenues to address them. © 2017, © 2017 The Author(s).


Author Keywords
biostatistics;  ChIP-seq;  circadian rhythms;  computational biology;  diurnal rhythms;  functional genomics;  guidelines;  metabolomics;  proteomics;  RNA-seq;  systems biology


Document Type: Article
Source: Scopus

 

37) 

Barch, D.M., Albaugh, M.D., Avenevoli, S., Chang, L., Clark, D.B., Glantz, M.D., Hudziak, J.J., Jernigan, T.L., Tapert, S.F., Yurgelun-Todd, D., Alia-Klein, N., Potter, A.S., Paulus, M.P., Prouty, D., Zucker, R.A., Sher, K.J.
Demographic, physical and mental health assessments in the adolescent brain and cognitive development study: Rationale and description
(2017) Developmental Cognitive Neuroscience, . Article in Press. 

DOI: 10.1016/j.dcn.2017.10.010


a Departments of Psychological and Brain Sciences and Psychiatry, Washington University, Box 1125, One Brookings Drive, St. Louis, MO 63130, United States
b Department of Psychiatry, University of Vermont College of Medicine, Mail Stop 446 AR6, 1 South Prospect Street, Burlington, VT 05401, United States
c National Institute of Mental Health, National Institutes of Health, 6001 Executive Blvd, Bethesda, MD 20892, United States
d Chang Department of Radiology, University of Maryland School of Medicine, 419 W. Redwood Street, Suite 225, Baltimore, MD 21201, United States
e Department of Psychiatry, University of Pittsburgh, 3811 O'Hara Street, Pittsburgh, PA 15215, United States
f Department of Epidemiology, Services, and Prevention Research, National Institute on Drug Abuse, National Institutes of Health, Bethesda, MD 20892, United States
g Department of Psychiatry, University of Vermont College of Medicine, St. Joe's Room 3213, Box 364SJ, 1 South Prospect, Burlington, VT 05401, United States
h Departments of Cognitive Science, Psychiatry and Radiology, University of California at San Diego,9500 Gilman Drive(0603), La Jolla, CA 92093-0603, United States
i Department of Psychiatry, University of California at San Diego,9500 Gilman Drive(0603), La Jolla, CA 92093-0603, United States
j Department of Psychiatry, University of Utah School of Medicine, 501 Chipeta Way, Salt Lake City, UT 84108, United States
k Department of Psychiatry, Icahn School of Medicine at Mount Sinai, Friedman Brain Institute, 1470 Madison Avenue, New York, NY 10029, United States
l Department of Psychiatry, University of Vermont College of Medicine, 1 South Prospect Street Arnold 6, Burlington, VT 05401, United States
m Laureate Institute for Brain Research, 6655 South Yale Ave, Tulsa, OK 74136-3326, United States
n Center for Health Sciences, SRI International, 333 Ravenswood Avenue, Menlo Park, CA 94025, United States
o Department of Psychiatry and Addiction Center, University of Michigan, Rachel UpJohn Building, 4250 Plymouth Road, Ann Arbor, MI 48109-2700, United States
p Department of Psychological Sciences, University of Missouri, 200 South Seventh Street, Columbia, MO 65211, United States


Abstract
The Adolescent Brain and Cognitive Development (ABCD) Study incorporates a comprehensive range of measures assessing predictors and outcomes related to both mental and physical health across childhood and adolescence. The workgroup developed a battery that would assess a comprehensive range of domains that address study aims while minimizing participant and family burden. We review the major considerations that went into deciding what constructs to cover in the demographics, physical health and mental health domains, as well as the process of selecting measures, piloting and refining the originally proposed battery. We present a description of the baseline battery, as well as the six-month interim assessments and the one-year follow-up assessments. This battery includes assessments from the perspectives of both the parent and the target youth, as well as teacher reports. This battery will provide a foundational baseline assessment of the youth's current function so as to permit characterization of stability and change in key domains over time. The findings from this battery will also be utilized to identify both resilience markers that predict healthy development and risk factors for later adverse outcomes in physical health, mental health, and substance use and abuse. © 2017 The Authors.


Author Keywords
Assessment;  Mental health;  Physical health;  Psychopathology


Document Type: Article in Press
Source: Scopus

 

38) 

Kelly, D.L., Buchbinder, D., Duarte, R.F., Auletta, J.J., Bhatt, N., Byrne, M., DeFilipp, Z., Gabriel, M., Mahindra, A., Norkin, M., Schoemans, H., Shah, A.J., Ahmed, I., Atsuta, Y., Basak, G.W., Beattie, S., Bhella, S., Bredeson, C., Bunin, N., Dalal, J., Daly, A., Gajewski, J., Gale, R.P., Galvin, J., Hamadani, M., Hayashi, R.J., Adekola, K., Law, J., Lee, C.J., Liesveld, J., Malone, A.K., Nagler, A., Naik, S., Nishihori, T., Parsons, S.K., Scherwath, A., Schofield, H.-L., Soiffer, R., Szer, J., Twist, I., Warwick, A., Wirk, B.M., Yi, J., Battiwalla, M., Flowers, M.E., Savani, B., Shaw, B.E.
Neurocognitive Dysfunction in Hematopoietic Cell Transplant Recipients: Expert Review from the Late Effects and Quality of Life Working Committee of the Center for International Blood and Marrow Transplant Research and Complications and Quality of Life Working Party of the European Society for Blood and Marrow Transplantation
(2017) Biology of Blood and Marrow Transplantation, . Article in Press. 

DOI: 10.1016/j.bbmt.2017.09.004


a Shands HealthCare and University of Florida, Gainesville, Florida
b Divsison of Pediatrics Hematology, Children's Hospital of Orange County, Orange, California
c University Hospital Puerta de Hierro, Madrid, Spain
d Blood and Marrow Transplant Program and Host Defense Program, Division of Hematology, Nationwide Children's Hospital, Columbus, Ohio
e Blood and Marrow Transplant Program and Host Defense Program, Division of Oncology, Nationwide Children's Hospital, Columbus, Ohio
f Blood and Marrow Transplant Program and Host Defense Program, Division of Bone Marrow Transplant and Infectious Diseases, Nationwide Children's Hospital, Columbus, Ohio
g Center for International Blood and Marrow Transplant Research, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin
h Vanderbilt University Medical Center, Nashville, Tennessee
i Blood and Marrow Transplant Program, Massachusetts General Hospital, Boston, Massachusetts
j The Children's Hospital at Westmead, New South Wales, Australia
k Scripps Blood and Marrow Transplant Program, La Jolla, California
l University Hospital of Leuven, Leuven, Belgium
m Division of Stem Cell Transplantation and Regenerative Medicine, Lucille Packard Children's Hospital, Stanford School of Medicine, Palo Alto, California
n Division of Pediatric Hem/Onc/BMT, Children's Mercy Kansas City, Kansas City, Missouri
o UMKC School of Medicine, Kansas City, Missouri
p Japanese Data Center for Hematopoietic Cell Transplantation, Nagoya, Japan
q Nagoya University Graduate School of Medicine, Nagoya, Japan
r Medical University of Warsaw, Warsaw, Poland
s Department of Psychosocial Oncology and Rehabilitation, Tom Baker Cancer Centre, Calgary, Alberta, Canada
t Ottawa Hospital Blood and Marrow Transplant Program and the Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
u Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
v Case Western Reserve School of Medicine, Cleveland, Ohio
w Rainbow Babies and Children's Hospital, Cleveland, Ohio
x Oregon Health and Science University, Portland, Oregon
y Division of Experimental Medicine, Department of Medicine, Imperial College London, Hematology Research Centre, London, United Kingdom
z Department of Medicine, University of Illinois at Chicago, Chicago, Illinois
aa Division of Pediatric Hematology/Oncology, Department of Pediatrics, Washington University School of Medicine in St. Louis, St. Louis, Missouri
ab Tufts University Medical Center, Boston, Massachusetts
ac Utah Blood and Marrow Transplant Program Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah
ad Department of Medicine, University of Rochester Medical Center, Rochester, New York
ae Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York
af Hematology Division and BMT, Chaim Sheba Medical Center, Tel Hashomer, Israel
ag Tel Aviv University, Tel Aviv, Israel
ah Texas Transplant Institute, San Antonino, Texas
ai Department of Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida
aj Department of Medical Psychology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
ak Pennsylvania State University, University Park, Pennsylvania
al Dana Farber Cancer Institute, Boston, Massachusetts
am Department Clinical Haematology and Bone Marrow Transplantation, Royal Melbourne Hospital, Victoria, Australia
an Department of Pediatrics, Uniformed Services University of the Health Sciences, Bethesda, Maryland
ao Division of Bone Marrow Transplant, Seattle Cancer Care Alliance, Seattle, Washington
ap Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington
aq Hematopoietic Transplantation Section, Hematology Branch, National Heart, Lung, and Blood Institute, Bethesda, Maryland


Abstract
Hematopoietic cell transplantation (HCT) is a potentially curative treatment for children and adults with malignant and nonmalignant diseases. Despite increasing survival rates, long-term morbidity after HCT is substantial. Neurocognitive dysfunction is a serious cause of morbidity, yet little is known about neurocognitive dysfunction after HCT. To address this gap, collaborative efforts of the Center for International Blood and Marrow Transplant Research and the European Society for Blood and Marrow Transplantation undertook an expert review of neurocognitive dysfunction after HCT. In this review we define what constitutes neurocognitive dysfunction, characterize its risk factors and sequelae, describe tools and methods to assess neurocognitive function in HCT recipients, and discuss possible interventions for HCT patients with this condition. This review aims to help clinicians understand the scope of this health-related problem, highlight its impact on well-being of survivors, and help determine factors that may improve identification of patients at risk for declines in cognitive functioning after HCT. In particular, we review strategies for preventing and treating neurocognitive dysfunction in HCT patients. Finally, we highlight the need for well-designed studies to develop and test interventions aimed at preventing and improving neurocognitive dysfunction and its sequelae after HCT. © 2017 The American Society for Blood and Marrow Transplantation.


Author Keywords
Bone marrow transplantation;  Cognition;  Cognitive function;  Hematology oncology;  Hematopoietic cell transplantation;  Neurocognitive dysfunction


Document Type: Article in Press
Source: Scopus

 

39) 

Martin, T., Smith, A., Breatnach, C.R., Kent, E., Shanahan, I., Boyle, M., Levy, P.T., Franklin, O., El-Khuffash, A.
Infants Born with Down Syndrome: Burden of Disease in the Early Neonatal Period
(2017) Journal of Pediatrics, . Article in Press. 

DOI: 10.1016/j.jpeds.2017.09.046


a Department of Neonatology, The Rotunda Hospital, Dublin, Ireland
b Department of Obstetrics and Gynecology, Royal College of Surgeons in Ireland, Dublin, Ireland
c Department of Pediatrics, Washington University School of Medicine, St Louis, MO
d Goryeb Children's Hospital, Atlantic Health System, Morristown, NJ
e Department of Pediatric Cardiology, Our Lady's Children's Hospital, Dublin, Ireland
f School of Medicine (Department of Pediatrics), Royal College of Surgeons in Ireland, Dublin, Ireland


Abstract
Objective: To evaluate the incidence of direct admission of infants with Down syndrome to the postnatal ward (well newborn nursery) vs the neonatal intensive care unit (NICU), and to describe the incidence of congenital heart disease (CHD) and pulmonary hypertension (PH). Study design: This retrospective cohort study of Down syndrome used the maternal/infant database (2011-2016) at the Rotunda Hospital in Dublin, Ireland. Admission location, early neonatal morbidities, outcomes, and duration of stay were evaluated and regression analyses were conducted to identify risk factors associated with morbidity and mortality. Results: Of the 121 infants with Down syndrome, 54 (45%) were initially admitted to the postnatal ward, but 38 (70%) were later admitted to the NICU. Low oxygen saturation profile was the most common cause for the initial and subsequent admission to the NICU. Sixty-six percent of the infants (80/121) had CHD, 34% (41/121) had PH, and 6% died. Risk factors independently associated with primary NICU admission included antenatal diagnosis of Down syndrome, presence of CHD, PH, and the need for ventilation. Conclusions: Infants with Down syndrome initially admitted to the postnatal ward have a high likelihood of requiring NICU admission. Overall, high rates of neonatal morbidity were noted, including rates of PH that were higher than previously reported. Proper screening of all infants with Down syndrome for CHD and PH is recommended to facilitate timely diagnoses and potentially shorten the duration of the hospital stay. © 2017 Elsevier Inc.


Author Keywords
Admission;  Down syndrome;  Morbidity;  Mortality;  Neonatal intensive care unit;  Pulmonary hypertension


Document Type: Article in Press
Source: Scopus

 

40) 

Poldrack, R.A., Monahan, J., Imrey, P.B., Reyna, V., Raichle, M.E., Faigman, D., Buckholtz, J.W.
Predicting Violent Behavior: What Can Neuroscience Add?
(2017) Trends in Cognitive Sciences, . Article in Press. 

DOI: 10.1016/j.tics.2017.11.003


a Department of Psychology, Stanford University, Stanford, CA, USA
b School of Law, University of Virginia, Charlottesville, VA, USA
c Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH, USA
d Human Neuroscience Institute, Cornell University, Ithaca, NY, USA
e Mallinckrodt Institute of Radiology, Washington University School of Medicine, St Louis, MO, USA
f University of California Hastings College of the Law, San Francisco, CA, USA
g Department of Psychology, Harvard University, Cambridge, MA, USA


Abstract
The ability to accurately predict violence and other forms of serious antisocial behavior would provide important societal benefits, and there is substantial enthusiasm for the potential predictive accuracy of neuroimaging techniques. Here, we review the current status of violence prediction using actuarial and clinical methods, and assess the current state of neuroprediction. We then outline several questions that need to be addressed by future studies of neuroprediction if neuroimaging and other neuroscientific markers are to be successfully translated into public policy. Violent behavior is a costly large-scale societal problem.There is growing interest in using neuroscience data to assess risk for future violent behavior, but the utility of neuroscience for violence risk assessment remains to be established.We review what is currently known about the underlying neurobiological mechanisms of violence, and evaluate recent neuroprediction efforts.Finally, we outline a set of practices for enhancing the validity and reliability of future risk assessment based on neuroscientific measures. © 2017 Elsevier Ltd.


Author Keywords
Crime;  Machine learning;  Neuroimaging;  Predictive modeling;  Violence


Document Type: Article in Press
Source: Scopus

 

41) 

Mauro, A., Savarino, E., De Bortoli, N., Tolone, S., Pugliese, D., Franchina, M., Gyawali, C.P., Penagini, R.
Optimal number of multiple rapid swallows needed during high-resolution esophageal manometry for accurate prediction of contraction reserve
(2017) Neurogastroenterology and Motility, . Article in Press. 

DOI: 10.1111/nmo.13253


a Department of Pathophysiology and Transplantation, Università degli Studi di Milano - Italy Gastroenterology and Endoscopy Unit, Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico Milan Italy
b Division of Gastroenterology Department of Surgery, Oncology and Gastroenterology University of Padua Padua Italy
c Division of Gastroenterology Department of Translational Research and New Technology in Medicine and Surgery University of Pisa Cisanello Hospital Pisa Italy
d Division of General and Bariatric Surgery Department of Surgery Second University of Naples Naples Italy
e Division of Gastroenterology Washington University School of Medicine St. Louis Missouri


Abstract
Background: Multiple rapid swallows (MRS) is a provocative test for assessment of contraction reserve, however reproducibility on repetitive MRS is incompletely understood. Our aim was to determine the optimal number of MRS sequences for consistent assessment of contraction reserve. Methods: One hundred and fifty-nine consecutive patients (79 IEM and 80 normal motility) who underwent high-resolution manometers were enrolled. Ten single swallows (SS) and 10 MRS were performed. Gold standard for evaluation of the contraction reserve was the ratio between the mean DCI of 10 MRS and the mean DCI of 10 SS (MRS/SS DCI ratio). Rates of false negatives and false positives were calculated for increasing numbers of MRS sequences, using either mean DCI or the MRS with the highest DCI. Key Results: According to the gold standard, 50 IEM and 50 normal motility patients had contraction reserve. With progressively increasing numbers of MRS sequences, contraction reserve was detected using mean MRS DCI within three and four MRS sequences in IEM and normal motility respectively, whereas two and three MRS sequences were needed using the MRS sequence with the highest DCI. False positives were much higher with highest DCI method compared with mean DCI, (22% vs 9% respectively in IEM; 24% vs 9% in normal motility) when three MRS sequences were considered. Conclusions & Inferences: At least three MRS are needed to reliably assess contraction reserve. The mean DCI of the three MRS sequences is the best variable to utilize as evidence of contraction reserve. © 2017 John Wiley & Sons Ltd.


Author Keywords
Contraction reserve;  High resolution manometry;  Ineffective esophageal motility;  Multiple rapid swallows


Document Type: Article in Press
Source: Scopus

 

42) 

Waldron, M., Watkins, N.K., Bucholz, K.K., Madden, P.A.F., Heath, A.C.
Interactive Effects of Maternal Alcohol Problems and Parental Separation on Timing of Daughter's First Drink
(2017) Alcoholism: Clinical and Experimental Research, . Article in Press. 

DOI: 10.1111/acer.13537


a Department of Counseling and Educational Psychology Indiana University Bloomington, Indiana
b Midwest Alcoholism Research Center and Family Research Center Department of Psychiatry Washington University School of Medicine St. Louis, Missouri


Abstract
Background: Few studies examine risk to offspring who experience both parental alcohol problems and parental separation and still fewer consider gender of the affected parent. We examined interactive effects of maternal versus paternal alcohol problems and parental separation on timing of first alcoholic drink in daughters. Methods: Data were drawn from a sample of 3,539 European (or other) ancestry (EA) and 611 African ancestry (AA) female twins born between 1975 and 1985, median age 15 at first assessment. Cox proportional hazards regression models were estimated predicting age at first full drink from parental history of alcohol problems (mother only, father only, or both parents), parental separation during childhood, and the interaction of parental alcohol problems and parental separation. Cox models were estimated without and with adjustment for correlated risk factors, separately for EA and AA twins. Results: For both EA and AA twins, a significant interaction between parental separation and mother-only alcohol problems was observed, suggesting reduced risk of drinking associated with mother-only alcohol problems in separated versus intact families. Conclusions: Findings highlight parental separation as an important moderator of risk to children of mothers who have a history of problem drinking, with interactive effects observed consistently across racial group. To identify underlying processes, additional research is needed with more detailed characterization of separated families where mother only has a history of alcohol problems. © 2017 Research Society on Alcoholism.


Author Keywords
Onset of Alcohol Use;  Parental Alcohol Problems;  Parental Separation or Divorce


Document Type: Article in Press
Source: Scopus

 

43) 

Tayebi, N., Parisiadou, L., Berhe, B., Gonzalez, A.N., Serra-Vinardell, J., Tamargo, R.J., Maniwang, E., Sorrentino, Z., Fujiwara, H., Grey, R.J., Hassan, S., Blech-Hermoni, Y.N., Chen, C., McGlinchey, R., Makariou-Pikis, C., Brooks, M., Ginns, E.I., Ory, D.S., Giasson, B.I., Sidransky, E.
Glucocerebrosidase haploinsufficiency in A53T α-synuclein mice impacts disease onset and course
(2017) Molecular Genetics and Metabolism, . Article in Press. 

DOI: 10.1016/j.ymgme.2017.11.001


a Medical Genetics Branch, NHGRI, NIH, Bethesda, MD, USA
b Department of Pharmacology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
c Department of Neuroscience, Center for Translational Research in Neurodegenerative Disease, College of Medicine, University of Florida, Gainesville, FL, USA
d Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA
e Laboratory of Protein Conformation and Dynamics, NHLBI, NIH, Bethesda, MD. USA
f Lysosomal Disorders Treatment and Research Program, University of Massachusetts Medical School, Worcester, MA, USA


Abstract
Mutations in GBA1 encountered in Gaucher disease are a leading risk factor for Parkinson disease and associated Lewy body disorders. Many GBA1 mutation carriers, especially those with severe or null GBA1 alleles, have earlier and more progressive parkinsonism. To model the effect of partial glucocerebrosidase deficiency on neurological progression in vivo, mice with a human A53T α-synuclein (SNCA A53T) transgene were crossed with heterozygous null gba mice (gba +/-). Survival analysis of 84 mice showed that in gba +/-//SNCA A53T hemizygotes and homozygotes, the symptom onset was significantly earlier than in gba +/+ //SNCA A53T mice (p-values 0.023-0.0030), with exacerbated disease progression (p-value &lt;0.0001). Over-expression of SNCA A53T had no effect on glucocerebrosidase levels or activity. Immunoblotting demonstrated that gba haploinsufficiency did not lead to increased levels of either monomeric SNCA or insoluble high molecular weight SNCA in this model. Immunohistochemical analyses demonstrated that the abundance and distribution of SNCA pathology was also unaltered by gba haploinsufficiency. Thus, while the underlying mechanism is not clear, this model shows that gba deficiency impacts the age of onset and disease duration in aged SNCA A53T mice, providing a valuable resource to identify modifiers, pathways and possible moonlighting roles of glucocerebrosidase in Parkinson pathogenesis. © 2017.


Author Keywords
A-synuclein;  Aggregates;  Gaucher disease;  Glucocerebrosidase;  Mouse model;  Parkinson disease


Document Type: Article in Press
Source: Scopus

 

44) 

Roostaei, T., Felsky, D., Nazeri, A., De Jager, P.L., Schneider, J.A., Bennett, D.A., Voineskos, A.N.
Genetic influence of plasma homocysteine on Alzheimer's disease
(2017) Neurobiology of Aging, . Article in Press. 

DOI: 10.1016/j.neurobiolaging.2017.09.033


a Kimel Family Translational Imaging-Genetics Laboratory, Research Imaging Centre, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada
b Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada
c Cell Circuits Program, Broad Institute, Cambridge, MA, USA
d Center for Translational and Computational Neuroimmunology, Department of Neurology, Columbia University Medical Center, New York, NY, USA
e Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO, USA
f Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA
g Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA
h Department of Pathology, Rush University Medical Center, Chicago, IL, USA
i Underserved Populations Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada


Abstract
Observational studies have consistently reported elevated plasma homocysteine as a risk factor for Alzheimer's disease (AD). However, results from clinical trials of homocysteine-lowering treatments are inconsistent. This discrepancy may be explained by a lack of causal association between homocysteine and AD. Mendelian randomization studies have the potential to provide insight into the causality of this association through studying the effect of genetic predisposition to high homocysteine on AD. Our analyses using summarized (n = 54,162) and individual participant (n = 6987) data from Caucasian participants did not show an effect of plasma homocysteine genetic risk on susceptibility to AD. Although with smaller sample sizes, further subanalyses also did not support an effect of genetically determined plasma homocysteine on cognitive impairment and decline, beta-amyloid and tau pathology and gray matter atrophy in AD. However, we found associations with tau tangle burden (n = 251) and gray matter atrophy (n = 605) in cognitively normal elderly. Our results do not support a causal association between elevated homocysteine and risk, severity, and progression of AD. However, the relationship between genetically determined homocysteine and brain pathology in cognitively normal elderly requires further exploration. © 2017 Elsevier Inc.


Author Keywords
Aging;  Alzheimer's disease;  Causal association;  Mendelian randomization;  Plasma homocysteine;  Polygenic score


Document Type: Article in Press
Source: Scopus

 

45) 

Aung, W.Y., Massoumzadeh, P., Najmi, S., Salter, A., Heaps, J., Benzinger, T.L.S., Mar, S.
Diffusion Tensor Imaging as a Biomarker to Differentiate Acute Disseminated Encephalomyelitis From Multiple Sclerosis at First Demyelination
(2017) Pediatric Neurology, . Article in Press. 

DOI: 10.1016/j.pediatrneurol.2017.09.016


a M.D. Degree Program, Saint Louis University School of Medicine, St. Louis, Missouri
b Department of Radiology, Washington University School of Medicine, St. Louis, Missouri
c Department of Neurology, Tabriz University of Medical Science, Tabriz, Iran
d Division of Biostatistics, Washington University School of Medicine, St. Louis, Missouri
e Missouri Institute of Mental Health, University of Missouri-Saint Louis, St. Louis, Missouri
f Department of Pediatric and Developmental Neurology, Washington University School of Medicine, St. Louis, Missouri


Abstract
Background: There are no clinical features or biomarkers that can reliably differentiate acute disseminated encephalomyelitis from multiple sclerosis at the first demyelination attack. Consequently, a final diagnosis is sometimes delayed by months and years of follow-up. Early treatment for multiple sclerosis is recommended to reduce long-term disability. Therefore, we intend to explore neuroimaging biomarkers that can reliably distinguish between the two diagnoses. Methods: We reviewed prospectively collected clinical, standard MRI and diffusion tensor imaging data of 12 pediatric patients who presented with acute demyelination with and without encephalopathy. Patients were followed for an average of 6.5 years to determine the accuracy of final diagnosis. Final diagnosis was determined using 2013 International Pediatric MS Study Group criteria. Control subjects consisted of four age-matched healthy individuals for each patient. Results: The study population consisted of six patients with central nervous system demyelination with encephalopathy with a presumed diagnosis of acute disseminated encephalomyelitis and six without encephalopathy with a presumed diagnosis of multiple sclerosis or clinically isolated syndrome at high risk for multiple sclerosis. During follow-up, two patients with initial diagnosis of acute disseminated encephalomyelitis were later diagnosed with multiple sclerosis. Diffusion tensor imaging region of interest analysis of baseline scans showed differences between final diagnosis of multiple sclerosis and acute disseminated encephalomyelitis patients, whereby low fractional anisotropy and high radial diffusivity occurred in multiple sclerosis patients compared with acute disseminated encephalomyelitis patients and the age-matched controls. Conclusions: Fractional anisotropy and radial diffusivity measures may have the potential to serve as biomarkers for distinguishing acute disseminated encephalomyelitis from multiple sclerosis at the onset. © 2017 Elsevier Inc.


Author Keywords
Acute disseminated encephalomyelitis;  DTI;  Multiple sclerosis;  Neuroimaging biomarker


Document Type: Article in Press
Source: Scopus

 

46) 

Grajales-Reyes, J.G., García-González, A., María-Ríos, J.C., Grajales-Reyes, G.E., Delgado-Vélez, M., Báez-Pagán, C.A., Quesada, O., Gómez, C.M., Lasalde-Dominicci, J.A.
A Panel of Slow-Channel Syndrome Mice Reveals a Unique Locomotor Behavioral Signature
(2017) Journal of Neuromuscular Diseases, 4 (4), pp. 341-347. 

DOI: 10.3233/JND-170226


a Department of Biology, University of Puerto Rico, Río Piedras Campus, PO Box 23360, San Juan, PR, United States
b Department of Chemistry, University of Puerto Rico, Río Piedras Campus, San Juan, PR, United States
c Department of Physical Sciences, University of Puerto Rico, Río Piedras Campus, San Juan, PR, United States
d Department of Neurology, University of Chicago, Chicago, IL, United States
e Washington University School of Medicine in St Louis, Medical ScientistTraining Program (MSTP), MSTP-Box 8226, 660 Euclid Avenue, St. Louis, MO, United States
f University of Massachusetts Medical School, Medical Scientist Training Program (MSTP), 55 Lake Ave North, Worcester, MA, United States
g University of Puerto Rico, Medical Sciences Campus, B. 365067, San Juan, PR, Puerto Rico
h Molecular Sciences Research Center, University of Puerto Rico, 1390 Ponce de León Avenue, San Juan, PR, Puerto Rico
i University of Puerto Rico, Physical Sciences Department, P.O. BOX 23323, San Juan, PR, Puerto Rico


Abstract
Muscle nicotinic acetylcholine receptor (nAChR) mutations can lead to altered channel kinetics and neuromuscular junction degeneration, a neurodegenerative disorder collectively known as slow-channel syndrome (SCS). A multivariate analysis using running wheels was used to generate activity profiles for a variety of SCS models, uncovering unique locomotor patterns for the different nAChR mutants. Particularly, the αL251T and ?L269F mutations exhibit decreased event distance, duration, and velocity over a period of 24 hours. Our approach suggests a robust relationship between the pathophysiology of SCS and locomotor activity. © 2017 - IOS Press and the authors. All rights reserved.


Author Keywords
acetylcholine;  Congenital myasthenia;  locomotor activity;  mice;  motor endplate;  myalgia;  neuromuscular junction (NMJ);  nicotinic acetylcholine receptor (nAChR);  running


Document Type: Article
Source: Scopus

 

47) 

Scott-Wittenborn, N., Jackson, R.S.
Intraoperative imaging during minimally invasive transoral robotic surgery using near-infrared light
(2017) American Journal of Otolaryngology - Head and Neck Medicine and Surgery, . Article in Press. 

DOI: 10.1016/j.amjoto.2017.09.001


Department of Otolaryngology, Head and Neck Surgery, Washington University School of Medicine, St. Louis, MO, United States


Abstract
Purpose: The purpose of this study was to determine if the use of the FIREFLY imaging system could be an asset in transoral robotic surgery (TORS) for oropharyngeal squamous cell carcinoma (OPSCC). The system uses indocyanine green dye (ICG), which fluoresces when illuminated by near-infrared light from the Da Vinci robot. The system may improve visualization of tumor margins, highlight important vascular structures, and help identify the location of tumors and unknown primary head and neck cancers. Methods: Six patients with OPSCC were enrolled in the study. Two of these cases were unknown primaries, one was base of tongue, and three were palatine tonsils. Each patient was given two 3. ml doses of ICG, one at the beginning of the surgical case and one during resection of the tumor. The oropharynx was then visualized using the near-infrared light of the Da Vinci robot for a minute after injection. Results: The FIREFLY system was unable to detect gross tumors, positive margins, unknown primaries, or vascular structures in any of the six subjects in the study. In addition, there were no adverse events or side effects in any of the subjects. Conclusion: The use of the FIREFLY system with indocyanine green fluorescence did not identify tumor boundaries, unknown primary head and neck cancers, or vascular structures in the oropharynx. © 2017 Elsevier Inc.


Author Keywords
Da Vinci;  FIREFLY;  Indocyanine green;  Oropharyngeal squamous cell carcinoma;  Transoral robotic surgery


Document Type: Article in Press
Source: Scopus