“Midfoot and ankle motion during heel rise and gait are related in people with diabetes and peripheral neuropathy” (2021) Gait and Posture
Midfoot and ankle motion during heel rise and gait are related in people with diabetes and peripheral neuropathy
(2021) Gait and Posture, 84, pp. 38-44.
Jeong, H.-J., Mueller, M.J., Zellers, J.A., Hastings, M.K.
Program in Physical Therapy, Washington University School of Medicine, St. Louis, Missouri. 4444 Forest Park Ave., St. Louis, MO 63108, United States
Abstract
Background: Midfoot and ankle movement dysfunction in people with diabetes mellitus and peripheral neuropathy (DMPN) is associated with midfoot deformity and increased plantar pressures during gait. If midfoot and ankle motion during heel rise and push-off of gait have similar mechanics, heel rise performance could be a clinically feasible way to identify abnormal midfoot and ankle function during gait. Research question: Is midfoot and ankle joint motion during a heel rise associated with midfoot and ankle motion at push-off during gait in people with DMPN? Methods: Sixty adults with DMPN completed double-limb heel rise, single-limb heel rise, and walking. A modified Oxford multi-segment foot model (forefoot, hindfoot, shank) was used to analyze midfoot (forefoot on hindfoot) and ankle (hindfoot on shank) sagittal angle during heel rise and gait. Pearson correlation was used to test the relationship between heel rise and gait kinematic variables (n = 60). Additionally, we classified 60 participants into two subgroups based on midfoot and ankle position at peak heel rise: midfoot and ankle dorsiflexed (dorsiflexed; n = 23) and midfoot and ankle plantarflexed (plantarflexed; n = 20). Movement trajectories of midfoot and ankle motion during single-limb heel rise and gait of the subgroups were examined. Results: Peak double-limb heel rise and gait midfoot and ankle angles were significantly correlated (r = 0.49 and r = 0.40, respectively). Peak single-limb heel rise and gait midfoot and ankle angles were significantly correlated (r = 0.63 and r = 0.54, respectively). The dorsiflexed subgroup, identified by heel rise performance showed greater midfoot and ankle dorsiflexion during gait compared to the plantarflexed subgroup (mean difference between subgroups: midfoot 3°, ankle 3°). Significance: People with DMPN who fail to plantarflex the midfoot and ankle during heel rise have difficulty plantarflexing the midfoot and ankle during gait. Utilizing a heel rise task may help identify midfoot and ankle dysfunction associated with gait in people with DMPN. © 2020 Elsevier B.V.
Author Keywords
Forefoot; Hindfoot; Kinematics; Plantarflexion; Walking
Funding details
National Institute of Diabetes and Digestive and Kidney DiseasesNIDDKF32 DK123916, R01 DK107809
Saint Louis UniversitySLU
Document Type: Article
Publication Stage: Final
Source: Scopus
“Decoding visual information from high-density diffuse optical tomography neuroimaging data” (2021) NeuroImage
Decoding visual information from high-density diffuse optical tomography neuroimaging data
(2021) NeuroImage, 226, art. no. 117516, .
Tripathy, K.a , Markow, Z.E.a , Fishell, A.K.a , Sherafati, A.a , Burns-Yocum, T.M.a , Schroeder, M.L.a , Svoboda, A.M.a , Eggebrecht, A.T.a , Anastasio, M.A.b , Schlaggar, B.L.c , Culver, J.P.a
a Department of Radiology, Washington University School of Medicine, Couch Biomedical Research Building, 4515 McKinley Avenue, 2nd Floor, St. Louis, MO 63110, United States
b Department of Bioengineering, University of Illinois, Urbana-Champaign, IL, United States
c Kennedy Krieger Institute, Baltimore, MD, United States
Abstract
Background: Neural decoding could be useful in many ways, from serving as a neuroscience research tool to providing a means of augmented communication for patients with neurological conditions. However, applications of decoding are currently constrained by the limitations of traditional neuroimaging modalities. Electrocorticography requires invasive neurosurgery, magnetic resonance imaging (MRI) is too cumbersome for uses like daily communication, and alternatives like functional near-infrared spectroscopy (fNIRS) offer poor image quality. High-density diffuse optical tomography (HD-DOT) is an emerging modality that uses denser optode arrays than fNIRS to combine logistical advantages of optical neuroimaging with enhanced image quality. Despite the resulting promise of HD-DOT for facilitating field applications of neuroimaging, decoding of brain activity as measured by HD-DOT has yet to be evaluated. Objective: To assess the feasibility and performance of decoding with HD-DOT in visual cortex. Methods and Results: To establish the feasibility of decoding at the single-trial level with HD-DOT, a template matching strategy was used to decode visual stimulus position. A receiver operating characteristic (ROC) analysis was used to quantify the sensitivity, specificity, and reproducibility of binary visual decoding. Mean areas under the curve (AUCs) greater than 0.97 across 10 imaging sessions in a highly sampled participant were observed. ROC analyses of decoding across 5 participants established both reproducibility in multiple individuals and the feasibility of inter-individual decoding (mean AUCs > 0.7), although decoding performance varied between individuals. Phase-encoded checkerboard stimuli were used to assess more complex, non-binary decoding with HD-DOT. Across 3 highly sampled participants, the phase of a 60° wide checkerboard wedge rotating 10° per second through 360° was decoded with a within-participant error of 25.8±24.7°. Decoding between participants was also feasible based on permutation-based significance testing. Conclusions: Visual stimulus information can be decoded accurately, reproducibly, and across a range of detail (for both binary and non-binary outcomes) at the single-trial level (without needing to block-average test data) using HD-DOT data. These results lay the foundation for future studies of more complex decoding with HD-DOT and applications in clinical populations. © 2020
Author Keywords
Decoding; Functional neuroimaging; High-density diffuse optical tomography; Retinotopy
Funding details
James S. McDonnell FoundationJSMF
National Institutes of HealthNIHU01EB027005, R01NS090874
Document Type: Article
Publication Stage: Final
Source: Scopus
“Tobacco Use Is Associated with Readmission within 90 Days after Craniotomy” (2021) Clinical Neurology and Neurosurgery
Tobacco Use Is Associated with Readmission within 90 Days after Craniotomy
(2021) Clinical Neurology and Neurosurgery, 200, art. no. 106383, .
Connor, M.a , Bonney, P.A.b , Lamorie-Foote, K.c , Shkirkova, K.c , Rangwala, S.D.b , Ding, L.d , Attenello, F.J.b , Mack, W.J.b
a Department of Neurosurgery, Washington University School of Medicine, St. Louis, MO, United States
b Department of Neurological Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States
c Keck School of Medicine, University of Southern California, Los Angeles, CA, United States
d Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States
Abstract
Objective: Tobacco use increases morbidity and mortality following craniotomy. Readmission is an important hospital metric of patient outcomes and has been used to inform reimbursement. This study aims to determine if tobacco use is associated with readmission within 90 days of hospital discharge among patients undergoing elective craniotomy. Methods: The Nationwide Readmissions Database (NRD), a population-based, nationally representative database, was queried from 2010-2014. Patients undergoing craniotomy for benign or malignant tumors, vascular pathologies, and epilepsy were identified. Readmissions within 90 days of index hospitalization were characterized by admitting diagnoses. Tobacco use was defined by ICD-9 coding for active or prior use. Descriptive and multivariable regression analyses evaluated patient and hospital factors associated with readmission. Results: The study population included 77,903 patients treated with craniotomy. Of these, 17,674 (22.6%) were readmitted within 90 days. The most common reasons for readmission were post-operative infection (5.8%), septicemia (4.2%), pulmonary embolism (3.9%), and pneumonia (2.9%). Tobacco use was associated with a 7% increased likelihood of 90-day readmission (OR 1.07, 95% CI 1.03-1.11, p = 0.0008) after accounting for other patient-, disease-, and hospital-level factors in multivariate analysis. Conclusions: Tobacco use was associated with increased 90-day readmission in patients undergoing craniotomy. Recognizing tobacco use as a modifiable risk factor of readmission presents an opportunity to identify susceptible patients. © 2020 Elsevier B.V.
Author Keywords
Complications; Craniotomy; Readmission; Smoking; Tobacco
Document Type: Article
Publication Stage: Final
Source: Scopus
“Neuroplastin Modulates Anti-inflammatory Effects of MANF” (2020) iScience
Neuroplastin Modulates Anti-inflammatory Effects of MANF
(2020) iScience, 23 (12), art. no. 101810, .
Yagi, T.a , Asada, R.a , Kanekura, K.c , Eesmaa, A.d , Lindahl, M.d , Saarma, M.d , Urano, F.a b
a Department of Medicine, Division of Endocrinology, Metabolism, and Lipid Research, Washington University School of Medicine, St. Louis, MO 63110, United States
b Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, United States
c Department of Molecular Pathology, Tokyo Medical University, Tokyo, 160-8402, Japan
d Institute of Biotechnology, HiLIFE, University of Helsinki, Viikinkaari 9, Helsinki, 00014, Finland
Abstract
Endoplasmic reticulum (ER) stress is known to induce pro-inflammatory response and ultimately leads to cell death. Mesencephalic astrocyte-derived neurotrophic factor (MANF) is an ER-localized protein whose expression and secretion is induced by ER stress and a crucial survival factor. However, the underlying mechanism of how MANF exerts its cytoprotective activity remains unclear due to the lack of knowledge of its receptor. Here we show that Neuroplastin (NPTN) is such a receptor for MANF. Biochemical analysis shows the physiological interaction between MANF and NPTN on the cell surface. Binding of MANF to NPTN mitigates the inflammatory response and apoptosis via suppression of NF-kβ signaling. Our results demonstrate that NPTN is a cell surface receptor for MANF, which modulates inflammatory responses and cell death, and that the MANF-NPTN survival signaling described here provides potential therapeutic targets for the treatment of ER stress-related disorders, including diabetes mellitus, neurodegeneration, retinal degeneration, and Wolfram syndrome. © 2020 The Authors
Biochemistry; Molecular Biology; Cell Biology © 2020 The Authors
Author Keywords
Biochemistry; Cell Biology; Molecular Biology
Document Type: Article
Publication Stage: Final
Source: Scopus
“A Recurrent Gain-of-Function Mutation in CLCN6, Encoding the ClC-6 Cl−/H+-Exchanger, Causes Early-Onset Neurodegeneration” (2020) American Journal of Human Genetics
A Recurrent Gain-of-Function Mutation in CLCN6, Encoding the ClC-6 Cl−/H+-Exchanger, Causes Early-Onset Neurodegeneration
(2020) American Journal of Human Genetics, 107 (6), pp. 1062-1077.
Polovitskaya, M.M.a b , Barbini, C.a b , Martinelli, D.c , Harms, F.L.d , Cole, F.S.e , Calligari, P.f , Bocchinfuso, G.f , Stella, L.f , Ciolfi, A.c , Niceta, M.c , Rizza, T.c , Shinawi, M.g , Sisco, K.g , Johannsen, J.h , Denecke, J.h , Carrozzo, R.c , Wegner, D.J.e , Kutsche, K.d , Tartaglia, M.c , Jentsch, T.J.a b i
a Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), Berlin, 13125, Germany
b Max-Delbrück-Centrum für Molekulare Medizin (MDC), Berlin, 13125, Germany
c Genetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, IRCCS, Rome, 00146, Italy
d Institute for Human Genetics, University Medical Center Hamburg-Eppendorf, Hamburg, 20246, Germany
e Division of Newborn Medicine, Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine, and St. Louis Children’s Hospital, St. Louis, MO 63110, United States
f Department of Chemical Science and Technologies, University “Tor Vergata,”, Rome, 00133, Italy
g Division of Genetics and Genomic Medicine, Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine, and St. Louis Children’s Hospital, St. Louis, MO 63110, United States
h Children’s Hospital, University Medical Center Hamburg-Eppendorf, Hamburg, 20246, Germany
i NeuroCure Cluster of Excellence, Charité Universitätsmedizin, Berlin, 10117, Germany
Abstract
Dysfunction of the endolysosomal system is often associated with neurodegenerative disease because postmitotic neurons are particularly reliant on the elimination of intracellular aggregates. Adequate function of endosomes and lysosomes requires finely tuned luminal ion homeostasis and transmembrane ion fluxes. Endolysosomal CLC Cl−/H+ exchangers function as electric shunts for proton pumping and in luminal Cl− accumulation. We now report three unrelated children with severe neurodegenerative disease, who carry the same de novo c.1658A>G (p.Tyr553Cys) mutation in CLCN6, encoding the late endosomal Cl−/H+-exchanger ClC-6. Whereas Clcn6−/− mice have only mild neuronal lysosomal storage abnormalities, the affected individuals displayed severe developmental delay with pronounced generalized hypotonia, respiratory insufficiency, and variable neurodegeneration and diffusion restriction in cerebral peduncles, midbrain, and/or brainstem in MRI scans. The p.Tyr553Cys amino acid substitution strongly slowed ClC-6 gating and increased current amplitudes, particularly at the acidic pH of late endosomes. Transfection of ClC-6Tyr553Cys, but not ClC-6WT, generated giant LAMP1-positive vacuoles that were poorly acidified. Their generation strictly required ClC-6 ion transport, as shown by transport-deficient double mutants, and depended on Cl−/H+ exchange, as revealed by combination with the uncoupling p.Glu200Ala substitution. Transfection of either ClC-6Tyr553Cys/Glu200Ala or ClC-6Glu200Ala generated slightly enlarged vesicles, suggesting that p.Glu200Ala, previously associated with infantile spasms and microcephaly, is also pathogenic. Bafilomycin treatment abrogated vacuole generation, indicating that H+-driven Cl− accumulation osmotically drives vesicle enlargement. Our work establishes mutations in CLCN6 associated with neurological diseases, whose spectrum of clinical features depends on the differential impact of the allele on ClC-6 function. © 2020 American Society of Human Genetics
Author Keywords
anion/proton antiport; channelopathy; chloride channel; chloride/proton exchange; copper metabolism; gain of function; gating glutamate; luminal pH; neurogenic bladder; vacuole fusion
Funding details
National Human Genome Research InstituteNHGRIU01 HG010215
Fondazione Bambino Gesù
Faculty of Medicine, Prince of Songkla University
Universitätsklinikum Hamburg-EppendorfUKE
Deutsche ForschungsgemeinschaftDFGFOR 2652 (Je164/14-1, Exc257, KU 1240/10-1
CCR-2017-23669081
Document Type: Article
Publication Stage: Final
Source: Scopus
“Use of fast-sequence spine MRI in pediatric patients” (2020) Journal of Neurosurgery: Pediatrics
Use of fast-sequence spine MRI in pediatric patients
(2020) Journal of Neurosurgery: Pediatrics, 26 (6), pp. 676-681.
Gewirtz, J.I.a , Skidmore, A.a , Smyth, M.D.a , Limbrick, D.D.a , Goyal, M.b , Shimony, J.S.b , McKinstry, R.C.b , Groves, M.L.c , Strahle, J.M.a
a Department of Neurological Surgery, Washington University, School of Medicine, St. Louis, MO, United States
b Mallinckrodt Institute of Radiology, Washington University, School of Medicine, St. Louis, MO, United States
c Department of Neurosurgery, Johns Hopkins School of Medicine, Baltimore, MD, United States
Abstract
OBJECTIVE The immediate and long-term risk of anesthesia in the pediatric population is controversial. Traditional spine MRI protocols require the patient to remain still during the examination, and in young children this frequently results in the need for sedation administration. The authors’ goal was to develop an abbreviated spine MRI protocol to reduce sedation administration in young patients undergoing spine MRI. METHODS After IRB approval, the medical records of all pediatric patients who underwent a fast spine MRI protocol between 2017 and 2019 were reviewed. The protocol consisted of T2-weighted half-Fourier acquisition single-shot turbo spin echo, T1-weighted turbo spin echo, and T2-weighted STIR sequences acquired in the sagittal plane. The total acquisition time was 2 minutes with no single sequence acquisition longer than 60 seconds. Interpretability of the scans was assessed in accordance with the radiology report in conjunction with the neurosurgeon’s clinical notes. RESULTS A total of 47 fast spine MRI sessions were performed in 45 patients. The median age at the time of the MRI was 2.4 years (25th-75th quartile, 1.1-4.3 years; range 0.16-18.58 years). The most common indication for imaging was to rule out or follow a known syrinx (n = 30), followed by the need to rule out or follow known spinal dysraphism (n = 22). There were no uninterpretable or unusable scans. Eight of 47 scans were noted to have moderate motion artifact limitations with respect to the quality of the scan. Seven patients underwent a subsequent MRI with a sedated standard spine protocol within 1 year from the fast scan, which confirmed the findings on the fast MRI protocol with no new findings identified. CONCLUSIONS The authors report the first pediatric series of a fast spine MRI protocol for use in young patients. The protocol does not require sedation and is able to identify and monitor syrinx, spinal dysraphism, and potentially other intraspinal anomalies. © 2020 American Association of Neurological Surgeons. All rights reserved.
Author Keywords
Fast sequence; MRI; Sedation; Spine
Funding details
Doris Duke Charitable FoundationDDCF
Eunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNICHD
Intellectual and Developmental Disabilities Research CenterIDDRC
National Institutes of HealthNIHU54 HD087011
Document Type: Conference Paper
Publication Stage: Final
Source: Scopus
“Indian medicinal herbs and formulations for Alzheimer’s disease, from traditional knowledge to scientific assessment” (2020) Brain Sciences
Indian medicinal herbs and formulations for Alzheimer’s disease, from traditional knowledge to scientific assessment
(2020) Brain Sciences, 10 (12), art. no. 964, pp. 1-31.
Mehla, J.a , Gupta, P.b , Pahuja, M.c , Diwan, D.a , Diksha, D.b
a Department of Neurological Surgery, Washington University School of Medicine, St. Louis, MO 63110, United States
b Department of Pharmacology, All India Institute of Medical Sciences, New Delhi, 110029, India
c Division of Basic Medical Sciences, Indian Council of Medical Research, Ministry of Health and Family Welfare, Government of India, V. Ramalingaswamy Bhawan, New Delhi, 110029, India
Abstract
Cognitive impairment, associated with ageing, stress, hypertension and various neurodegenerative disorders including Parkinson’s disease and epilepsy, is a major health issue. The present review focuses on Alzheimer’s disease (AD), since it is the most important cause of cognitive impairment. It is characterized by progressive memory loss, language deficits, depression, agitation, mood disturbances and psychosis. Although the hallmarks of AD are cholinergic dysfunction, β-amyloid plaques and neurofibrillary tangle formation, it is also associated with derangement of other neurotransmitters, elevated levels of advanced glycation end products, oxidative damage, neuroinflammation, genetic and environmental factors. On one hand, this complex etiopathology makes a response to commonly used drugs such as donepezil, rivastigmine, galantamine and memantine less predictable and often unsatisfactory. On the other hand, it supports the use of herbal medicines due to their nonspecific antioxidant and anti-inflammatory activity and specific cholinesterase inhibitory activity. The popularity of herbal medicines is also increasing due to their perceived effectiveness, safety and affordability. In the present article, the experimental and clinical evidence have been reviewed for various Indian herbal medicines such as Centella asiatica, Bacopa monnieri, Curcuma longa, Clitoria ternatea, Withania somnifera, Celastrus paniculatus, Evolvulus alsinoides, Desmodium gangeticum, Eclipta alba, Moringa oleifera and Convolvulus pluricaulis, which have shown potential in cognitive impairment. Some commonly available herbal formulations for memory impairment in India have also been reviewed. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.
Author Keywords
Alzheimer’s disease; Cognitive impairment; Complimentary and alternative medicine; Herbal medicine; Memory
Document Type: Review
Publication Stage: Final
Source: Scopus
“Frequency and Risk Factors of Acute Kidney Injury During Diabetic Ketoacidosis in Children and Association With Neurocognitive Outcomes” (2020) JAMA Network Open
Frequency and Risk Factors of Acute Kidney Injury During Diabetic Ketoacidosis in Children and Association With Neurocognitive Outcomes
(2020) JAMA Network Open, 3 (12), p. e2025481.
Myers, S.R.a b , Glaser, N.S.c , Trainor, J.L.d e , Nigrovic, L.E.f g , Garro, A.h i , Tzimenatos, L.j , Quayle, K.S.k l , Kwok, M.Y.m n , Rewers, A.o p , Stoner, M.J.q r , Schunk, J.E.s , McManemy, J.K.t u , Brown, K.M.v w , DePiero, A.D.x y , Olsen, C.S.s , Casper, T.C.s , Ghetti, S.z , Kuppermann, N.c j , Pediatric Emergency Care Applied Research Network (PECARN) DKA FLUID Study Groupaa
a Division of Emergency Medicine, Children’s Hospital of Philadelphia, Philadelphia, PA, United States
b Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States
c Department of Pediatrics, University of California, Davis School of Medicine, Sacramento, Mexico
d Division of Emergency Medicine, Ann and Robert H. Lurie Children’s Hospital, Chicago, IL, Mexico
e Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, IL, Mexico
f Division of Emergency Medicine, Boston Children’s Hospital, Boston, MA
g Department of Pediatrics, Harvard Medical School, Boston, MA
h Department of Emergency Medicine, Rhode Island Hospital, Providence, United States
i Department of Pediatrics, Warren Alpert Medical School, Brown University, Providence, RI, United States
j Department of Emergency Medicine, University of California, Davis School of Medicine, Sacramento, Mexico
k Division of Emergency Medicine, St Louis Children’s Hospital, St Louis, MO, United States
l Department of Pediatrics, Washington University School of Medicine in St Louis, St Louis, MO, United States
m Division of Emergency Medicine, NewYork-Presbyterian Morgan Stanley Children’s HospitalNY
n Department of Pediatrics, Columbia University College of Physicians and SurgeonsNY
o Division of Emergency Medicine, Colorado Children’s Hospital, Denver, United States
p Department of Pediatrics, University of Colorado-Denver School of Medicine, Aurora, United States
q Division of Emergency Medicine, Nationwide Children’s Hospital, Columbus, OH, United States
r Department of Pediatrics, Ohio State University College of Medicine, Columbus, United States
s Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, United States
t Division of Emergency Medicine, Texas Children’s Hospital, Houston
u Department of Pediatrics, Baylor College of Medicine, Houston, TX
v Division of Emergency Medicine, Children’s National Medical Center, Washington, District of Columbia
w Department of Pediatrics, George Washington School of Medicine and Health Sciences, Washington, District of Columbia
x Division of Emergency Medicine, Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE, United States
y Department of Pediatrics, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA, United States
z Department of Psychology, UC Davis Health, University of California School of Medicine, Sacramento, Mexico
Abstract
Importance: Acute kidney injury (AKI) occurs commonly during diabetic ketoacidosis (DKA) in children, but the underlying mechanisms and associations are unclear. Objective: To investigate risk factors for AKI and its association with neurocognitive outcomes in pediatric DKA. Design, Setting, and Participants: This cohort study was a secondary analysis of data from the Pediatric Emergency Care Applied Research Network Fluid Therapies Under Investigation in DKA Study, a prospective, multicenter, randomized clinical trial comparing fluid protocols for pediatric DKA in 13 US hospitals. Included DKA episodes occurred among children age younger than 18 years with blood glucose 300 mg/dL or greater and venous pH less than 7.25 or serum bicarbonate level less than 15 mEq/L. Exposures: DKA requiring intravenous insulin therapy. Main Outcomes and Measures: AKI occurrence and stage were assessed using serum creatinine measurements using Kidney Disease: Improving Global Outcomes criteria. DKA episodes with and without AKI were compared using univariable and multivariable methods, exploring associated factors. Results: Among 1359 DKA episodes (mean [SD] patient age, 11.6 [4.1] years; 727 [53.5%] girls; 651 patients [47.9%] with new-onset diabetes), AKI occurred in 584 episodes (43%; 95% CI, 40%-46%). A total of 252 AKI events (43%; 95% CI, 39%-47%) were stage 2 or 3. Multivariable analyses identified older age (adjusted odds ratio [AOR] per 1 year, 1.05; 95% CI, 1.00-1.09; P = .03), higher initial serum urea nitrogen (AOR per 1 mg/dL increase, 1.14; 95% CI, 1.11-1.18; P < .001), higher heart rate (AOR for 1-SD increase in z-score, 1.20; 95% CI, 1.09-1.32; P < .001), higher glucose-corrected sodium (AOR per 1 mEq/L increase, 1.03; 95% CI, 1.00-1.06; P = .001) and glucose concentrations (AOR per 100 mg/dL increase, 1.19; 95% CI, 1.07-1.32; P = .001), and lower pH (AOR per 0.1 increase, 0.63; 95% CI, 0.51-0.78; P < .001) as variables associated with AKI. Children with AKI, compared with those without, had lower scores on tests of short-term memory during DKA (mean [SD] digit span recall: 6.8 [2.4] vs 7.6 [2.2]; P = .02) and lower mean (SD) IQ scores 3 to 6 months after recovery from DKA (100.0 [12.2] vs 103.5 [13.2]; P = .005). Differences persisted after adjusting for DKA severity and demographic factors, including socioeconomic status. Conclusions and Relevance: These findings suggest that AKI may occur more frequently in children with greater acidosis and circulatory volume depletion during DKA and may be part of a pattern of multiple organ injury involving the kidneys and brain.
Document Type: Article
Publication Stage: Final
Source: Scopus
“Robot Assisted MRI-Guided LITT of the Anterior, Lateral, and Medial Temporal Lobe for Temporal Lobe Epilepsy” (2020) Frontiers in Neurology
Robot Assisted MRI-Guided LITT of the Anterior, Lateral, and Medial Temporal Lobe for Temporal Lobe Epilepsy
(2020) Frontiers in Neurology, 11, art. no. 572334, .
Gupta, K.a b , Dickey, A.S.c , Hu, R.d , Faught, E.c , Willie, J.T.a e
a Department of Neurosurgery, Emory University Hospital, Atlanta, GA, United States
b Department of Neurosurgery, Indiana University Health, Indianapolis, IN, United States
c Department of Neurology, Emory University Hospital, Atlanta, GA, United States
d Department of Radiology, Emory University Hospital, Atlanta, GA, United States
e Department of Neurological Surgery, Washington University School of Medicine, Washington, DC, United States
Abstract
Robotic systems have fundamentally altered the landscape of functional neurosurgery. These allow automated stereotaxy with high accuracy and reliability, and are rapidly becoming a mainstay in stereotactic surgeries such as deep brain stimulation (DBS), stereoelectroencephalography (SEEG), and stereotactic laser ablation/MRI guided laser interstitial thermal therapy (MRgLITT). Robotic systems have been effectively applied to create a minimally invasive approach for diagnostics and therapeutics in the treatment of epilepsy, utilizing robots for expeditious and accurate stereotaxy for SEEG and MRgLITT. MRgLITT has been shown to approach open surgical techniques in efficacy of seizure control while minimizing collateral injury. We describe the use of robot assisted MRgLITT for a minimally invasive laser anterior temporal lobotomy, describing the approach and potential pitfalls. Goals of MRgLITT are complete ablation of the epileptogenic zone and avoiding injury to uninvolved structures. In the middle fossa these include structures such as cranial nerves in the skull base and cavernous sinus and the thalamus. These can be mitigated with careful trajectory planning and control of laser ablation intensity. © Copyright © 2020 Gupta, Dickey, Hu, Faught and Willie.
Author Keywords
LITT (laser interstitial thermal therapy); ROSA (robotized stereotactic assistant); SEEG (stereoelectroencephalography); temporal lobe epilepsy; temporal lobectomy
Funding details
National Institute of Neurological Disorders and StrokeNINDS
Biogen
UCB
Centers for Disease Control and PreventionCDC
Document Type: Article
Publication Stage: Final
Source: Scopus
“A role for the microbiota in complex regional pain syndrome?” (2020) Neurobiology of Pain
A role for the microbiota in complex regional pain syndrome?
(2020) Neurobiology of Pain, 8, art. no. 100054, .
Crock, L.W.a , Baldridge, M.T.b
a Department of Anesthesiology and Pain Medicine, Washington University in St. Louis, St. Louis, MO, United States
b Division of Infectious Diseases, Department of Medicine, Washington University in St. Louis, St. Louis, MO, United States
Abstract
Complex regional pain syndrome (CRPS) is a debilitating neuroinflammatory condition of unknown etiology. Symptoms include excruciating pain and trophic changes in the limbs as defined by the Budapest criteria. The severity and functional recovery of CRPS, unlike most pain conditions, is quantifiable using a variation of the Budapest criteria known as the CRPS severity score. Like many chronic pain conditions, CRPS is difficult to treat once pain has been present for more than 12 months. However, previous work has demonstrated that a subset of patients with new-onset CRPS (~50%) improve if treated within one year, while the rest have minimal to no symptom improvement. Unfortunately, this leads to permanent disability and often requires invasive and costly treatments such as spinal cord stimulation or long-term opioid therapy. Because the etiology is unknown, treatment is multimodal, and often supportive. Biomarkers that predict severity or resolution of symptoms would significantly change treatment but have not yet been identified. Interestingly, there are case reports of remission or resolution of CRPS symptoms with the use of antibiotics known to affect the gut flora. Mouse studies have demonstrated that modulation of the gut microbiome is anti-nociceptive in visceral, inflammatory and neuropathic pain models. We hypothesize that the variable clinical potential for recovery and response to therapy in CRPS may be secondary to or reflected in changes in the gut microbiota. We suggest that the microbiota may mediate or reflect clinical status via the metabolome, activation of the immune system and/or microglial activation. We hypothesize that the gut microbiome is a potential mediator in development and persistence of CRPS symptoms and propose that the clinical condition of CRPS could provide a unique opportunity to identify biomarkers of the microbiota and potential therapies to prevent pain chronification. © 2020
Author Keywords
Chronic pain; Complex regional pain syndrome; Gut microbiome; Gut microbiota; Metabolomics
Document Type: Review
Publication Stage: Final
Source: Scopus
“Association between Ambient Air Pollution and Amyloid Positron Emission Tomography Positivity in Older Adults with Cognitive Impairment” (2020) JAMA Neurology
Association between Ambient Air Pollution and Amyloid Positron Emission Tomography Positivity in Older Adults with Cognitive Impairment
(2020) JAMA Neurology, .
Iaccarino, L.a , La Joie, R.a , Lesman-Segev, O.H.a b , Lee, E.c , Hanna, L.d , Allen, I.E.e , Hillner, B.E.f , Siegel, B.A.g , Whitmer, R.A.h i , Carrillo, M.C.j , Gatsonis, C.d k , Rabinovici, G.D.a l
a Memory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, United States
b Department of Diagnostic Imaging, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel
c Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, United States
d Center for Statistical Sciences, Brown University School of Public Health, Providence, RI, United States
e Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, United States
f Department of Medicine, Virginia Commonwealth University, Richmond, United States
g Edward Mallinckrodt Institute of Radiology, Washington University School of Medicine in St Louis, St Louis, MO, United States
h Division of Research, Kaiser Permanente, Oakland, CA, United States
i Department of Public Health Sciences, University of California, Davis, Davis, United States
j Medical and Scientific Relations Division, Alzheimer’s Association, Chicago, IL, United States
k Department of Biostatistics, Brown University School of Public Health, Providence, RI, United States
l Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, United States
Abstract
Importance: Amyloid-β (Aβ) deposition is a feature of Alzheimer disease (AD) and may be promoted by exogenous factors, such as ambient air quality. Objective: To examine the association between the likelihood of amyloid positron emission tomography (PET) scan positivity and ambient air quality in individuals with cognitive impairment. Design, Setting, and Participants: This cross-sectional study used data from the Imaging Dementia – Evidence for Amyloid Scanning Study, which included more than 18 000 US participants with cognitive impairment who received an amyloid PET scan with 1 of 3 Aβ tracers (fluorine 18 [18F]-labeled florbetapir, 18F-labeled florbetaben, or 18F-labeled flutemetamol) between February 16, 2016, and January 10, 2018. A sample of older adults with mild cognitive impairment (MCI) or dementia was selected. Exposures: Air pollution was estimated at the patient residence using predicted fine particulate matter (PM2.5) and ground-level ozone (O3) concentrations from the Environmental Protection Agency Downscaler model. Air quality was estimated at 2002 to 2003 (early, or approximately 14 [range, 13-15] years before amyloid PET scan) and 2015 to 2016 (late, or approximately 1 [range, 0-2] years before amyloid PET scan). Main Outcomes and Measures: Primary outcome measure was the association between air pollution and the likelihood of amyloid PET scan positivity, which was measured as odds ratios (ORs) and marginal effects, adjusting for demographic, lifestyle, and socioeconomic factors and medical comorbidities, including respiratory, cardiovascular, cerebrovascular, psychiatric, and neurological conditions. Results: The data set included 18178 patients, of which 10991 (60.5%) had MCI and 7187 (39.5%) had dementia (mean [SD] age, 75.8 [6.3] years; 9333 women [51.3%]). Living in areas with higher estimated biennial PM2.5concentrations in 2002 to 2003 was associated with a higher likelihood of amyloid PET scan positivity (adjusted OR, 1.10; 95% CI, 1.05-1.15; z score = 3.93; false discovery rate [FDR]-corrected P <.001; per 4-μg/m3increments). Results were similar for 2015 to 2016 data (OR, 1.15; 95% CI, 1.05-1.26, z score = 3.14; FDR-corrected P =.003). An average marginal effect (AME) of +0.5% (SE = 0.1%; z score, 3.93; 95% CI, 0.3%-0.7%; FDR-corrected P <.001) probability of amyloid PET scan positivity for each 1-μg/m3increase in PM2.5was observed for 2002 to 2003, whereas an AME of +0.8% (SE = 0.2%; z score = 3.15; 95% CI, 0.3%-1.2%; FDR-corrected P =.002) probability was observed for 2015 to 2016. Post hoc analyses showed no effect modification by sex (2002-2003: interaction term β = 1.01 [95% CI, 0.99-1.04; z score = 1.13; FDR-corrected P =.56]; 2015-2016: β = 1.02 [95% CI, 0.98-1.07; z score = 0.91; FDR-corrected P =.56]) or clinical stage (2002-2003: interaction term β = 1.01 [95% CI, 0.99-1.03; z score = 0.77; FDR-corrected P =.58]; 2015-2016: β = 1.03; 95% CI, 0.99-1.08; z score = 1.46; FDR-corrected P =.47]). Exposure to higher O3concentrations was not associated with amyloid PET scan positivity in both time windows. Conclusions and Relevance: This study found that higher PM2.5concentrations appeared to be associated with brain Aβ plaques. These findings suggest the need to consider airborne toxic pollutants associated with Aβ pathology in public health policy decisions and to inform individual lifetime risk of developing AD and dementia.. © 2020 Georg Thieme Verlag. All rights reserved.
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Possible Consequences of the Approval of a Disease-Modifying Therapy for Alzheimer Disease” (2020) JAMA Neurology
Possible Consequences of the Approval of a Disease-Modifying Therapy for Alzheimer Disease
(2020) JAMA Neurology, .
Musiek, E.S., Morris, J.C.
Knight Alzheimer’s Disease Research Center, Department of Neurology, Washington University School of Medicine in St Louis, St Louis, MO, United States
Document Type: Note
Publication Stage: Article in Press
Source: Scopus
“Integrated Proteogenomic Characterization across Major Histological Types of Pediatric Brain Cancer” (2020) Cell
Integrated Proteogenomic Characterization across Major Histological Types of Pediatric Brain Cancer
(2020) Cell, .
Petralia, F.a , Tignor, N.a , Reva, B.a , Koptyra, M.b ag , Chowdhury, S.a , Rykunov, D.a , Krek, A.a , Ma, W.a , Zhu, Y.b ag , Ji, J.c d , Calinawan, A.a , Whiteaker, J.R.e , Colaprico, A.f , Stathias, V.h , Omelchenko, T.i , Song, X.c d , Raman, P.b j ag , Guo, Y.b ag , Brown, M.A.b ag , Ivey, R.G.e , Szpyt, J.k , Guha Thakurta, S.k , Gritsenko, M.A.l , Weitz, K.K.l , Lopez, G.a , Kalayci, S.a , Gümüş, Z.H.a , Yoo, S.a , da Veiga Leprevost, F.m , Chang, H.-Y.m , Krug, K.n , Katsnelson, L.o , Wang, Y.o , Kennedy, J.J.e , Voytovich, U.J.e , Zhao, L.e , Gaonkar, K.S.b j ag , Ennis, B.M.b ag , Zhang, B.b ag , Baubet, V.b ag , Tauhid, L.b ag , Lilly, J.V.b ag , Mason, J.L.b ag , Farrow, B.b ag , Young, N.b ag , Leary, S.e p q , Moon, J.l , Petyuk, V.A.l , Nazarian, J.r s , Adappa, N.D.t , Palmer, J.N.t , Lober, R.M.u , Rivero-Hinojosa, S.r , Wang, L.-B.v w , Wang, J.M.o , Broberg, M.o , Chu, R.K.l , Moore, R.J.l , Monroe, M.E.l , Zhao, R.l , Smith, R.D.l , Zhu, J.a , Robles, A.I.y , Mesri, M.y , Boja, E.y , Hiltke, T.y , Rodriguez, H.y , Zhang, B.z aa ab , Schadt, E.E.a , Mani, D.R.n , Ding, L.v w x , Iavarone, A.ac , Wiznerowicz, M.ad ae , Schürer, S.h , Chen, X.S.f g , Heath, A.P.b ag , Rokita, J.L.b j ag , Nesvizhskii, A.I.m af , Fenyö, D.o , Rodland, K.D.l ah , Liu, T.l , Gygi, S.P.k , Paulovich, A.G.e , Resnick, A.C.b ag , Storm, P.B.b ag , Rood, B.R.r , Wang, P.a , Francis, A.ai , Morgan, A.M.ai , Waanders, A.J.ai , Viaene, A.N.ai , Buccoliero, A.M.ai , Chinnaiyan, A.M.ai , Leonard, C.A.ai , Kline, C.N.ai , Caporalini, C.ai , Kinsinger, C.R.ai , Li, C.ai , Kram, D.E.ai , Hanson, D.ai , Appert, E.ai , Kawaler, E.A.ai , Raabe, E.H.ai , Jackson, E.M.ai , Greenfield, J.P.ai , Stone, G.S.ai , Getz, G.ai , Grant, G.ai , Teo, G.C.ai , Pollack, I.F.ai , Cain, J.E.ai , Foster, J.B.ai , Phillips, J.J.ai , Palma, J.E.ai , Ketchum, K.A.ai , Ruggles, K.V.ai , Blumenberg, L.ai , Cornwell, M.ai , Sarmady, M.ai , Domagalski, M.J.ai , Cieślik, M.P.ai , Santi, M.ai , Li, M.M.ai , Ellis, M.J.ai , Wyczalkowski, M.A.ai , Connors, M.ai , Scagnet, M.ai , Gupta, N.ai , Edwards, N.J.ai , Vitanza, N.A.ai , Vaske, O.M.ai , Becher, O.ai , McGarvey, P.B.ai , Firestein, R.ai , Mueller, S.ai , Winebrake, S.G.ai , Dhanasekaran, S.M.ai , Cai, S.ai , Partap, S.ai , Patton, T.ai , Le, T.ai , Lorentzen, T.D.ai , Liu, W.ai , Bocik, W.E.ai , Children’s Brain Tumor Networkaj , Clinical Proteomic Tumor Analysis Consortiumaj
a Department of Genetics and Genomic Sciences and Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States
b Center for Data-Driven Discovery in Biomedicine, Division of Neurosurgery, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, United States
c Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States
d Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States
e Fred Hutchinson Cancer Research Center, Seattle, WA 98109, United States
f Department of Public Health Science, University of Miami Miller School of Medicine, Miami, FL 33136, United States
g Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL 33136, United States
h Department of Pharmacology, Institute for Data Science and Computing, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL 33146, United States
i Cell Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, United States
j Department of Bioinformatics and Health Informatics, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, United States
k Thermo Fisher Scientific Center for Multiplexed Proteomics, Department of Cell Biology, Harvard Medical School, Boston, MA 02115, United States
l Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99354, United States
m Department of Pathology, University of Michigan, Ann Arbor, MI 48109, United States
n Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02412, United States
o Institute for Systems Genetics; Department of Biochemistry and Molecular Pharmacology, NYU Grossman School of Medicine, New York, NY 10016, United States
p Cancer and Blood Disorders Center, Seattle Children’s Hospital, Seattle, WA 98105, United States
q Department of Pediatrics, University of Washington, Seattle, WA 98195, United States
r Children’s National Research Institute, George Washington University School of Medicine, Washington, DC, 20010, United States
s Department of Oncology, Children’s Research Center, University Children’s Hospital Zürich, Zürich, Switzerland 8032, Switzerland
t Department of Otorhinolaryngology, University of Pennsylvania, Philadelphia, PA 19104, United States
u Department of Neurosurgery, Dayton Children’s Hospital, Dayton, OH 45404, United States
v Department of Medicine, Washington University in St. Louis, St. Louis, MO 631110, United States
w McDonnell Genome Institute, Washington University in St. Louis, St. Louis, MO 63108, United States
x Siteman Cancer Center, Washington University in St. Louis, St. Louis, MO 63110, United States
y Office of Cancer Clinical Proteomics Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, United States
z Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, United States
aa Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, United States
ab Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, United States
ac Institute for Cancer Genetics, Department of Neurology, Department of Pathology and Cell Biology, Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY 10032, United States
ad Poznan University of Medical Sciences, Poznań, 61-701, Poland
ae International Institute for Molecular Oncology, Poznań, 61-203, Poland
af Department of Computational Medicine & Bioinformatics, University of Michigan, Ann Arbor, MI 48109, United States
ag Division of Neurosurgery, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, United States
ah Department of Cell, Developmental, and Cancer Biology, Oregon Health & Science University, Portland, OR 97221, United States
Abstract
We report a comprehensive proteogenomics analysis, including whole-genome sequencing, RNA sequencing, and proteomics and phosphoproteomics profiling, of 218 tumors across 7 histological types of childhood brain cancer: low-grade glioma (n = 93), ependymoma (32), high-grade glioma (25), medulloblastoma (22), ganglioglioma (18), craniopharyngioma (16), and atypical teratoid rhabdoid tumor (12). Proteomics data identify common biological themes that span histological boundaries, suggesting that treatments used for one histological type may be applied effectively to other tumors sharing similar proteomics features. Immune landscape characterization reveals diverse tumor microenvironments across and within diagnoses. Proteomics data further reveal functional effects of somatic mutations and copy number variations (CNVs) not evident in transcriptomics data. Kinase-substrate association and co-expression network analysis identify important biological mechanisms of tumorigenesis. This is the first large-scale proteogenomics analysis across traditional histological boundaries to uncover foundational pediatric brain tumor biology and inform rational treatment selection. © 2020 Elsevier Inc.
Integrative proteogenomics analysis of pediatric tumors identifies common underlying biological processes and potential treatments as well as the functional effects of somatic mutations and CNVs driving tumorigenesis. © 2020 Elsevier Inc.
Author Keywords
BRAF alteration; CPTAC; CTNNB1 mutation; kinase activity score; kinase substrate regulation; pediatric brain tumor; post-translational modification; proteomic cluster; recurrent versus primary tumors; tumor microenvironment
Funding details
U01 CA214114, U24CA210972, U24CA210954, U24CA210993, U24CA210955, U24CA210967, U24CA210979, R50 CA211499
National Cancer InstituteNCI
U.S. Department of EnergyUSDOEDE-AC05-76RL01830
Battelle
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“A Paradoxical Kind of Sleep in Drosophila melanogaster” (2020) Current Biology
A Paradoxical Kind of Sleep in Drosophila melanogaster
(2020) Current Biology, .
Tainton-Heap, L.A.L.a , Kirszenblat, L.C.a b , Notaras, E.T.a , Grabowska, M.J.a , Jeans, R.a , Feng, K.a , Shaw, P.J.c , van Swinderen, B.a
a Queensland Brain Institute, The University of Queensland, Brisbane, QLD 4072, Australia
b RIKEN Center for Brain Science, 2-1 Hirosawa, Wako, Saitama, 351-0198, Japan
c Department of Neuroscience, Washington University School of Medicine, St. Louis, MO 63110, United States
Abstract
Tainton-Heap et al. track calcium activity in neurons across the fly brain to compare spontaneous and optogenetically induced sleep. They uncover an active, wake-like sleep stage as well as a less active deep sleep stage. Induced sleep appears to promote wake-like levels of brain activity while suppressing responsiveness to external stimuli. © 2020 Elsevier Inc.
The dynamic nature of sleep in many animals suggests distinct stages that serve different functions. Genetic sleep induction methods in animal models provide a powerful way to disambiguate these stages and functions, although behavioral methods alone are insufficient to accurately identify what kind of sleep is being engaged. In Drosophila, activation of the dorsal fan-shaped body (dFB) promotes sleep, but it remains unclear what kind of sleep this is, how the rest of the fly brain is behaving, or if any specific sleep functions are being achieved. Here, we developed a method to record calcium activity from thousands of neurons across a volume of the fly brain during spontaneous sleep and compared this to dFB-induced sleep. We found that spontaneous sleep typically transitions from an active “wake-like” stage to a less active stage. In contrast, optogenetic activation of the dFB promotes sustained wake-like levels of neural activity even though flies become unresponsive to mechanical stimuli. When we probed flies with salient visual stimuli, we found that the activity of visually responsive neurons in the central brain was blocked by transient dFB activation, confirming an acute disconnect from the external environment. Prolonged optogenetic dFB activation nevertheless achieved a key sleep function by correcting visual attention defects brought on by sleep deprivation. These results suggest that dFB activation promotes a distinct form of sleep in Drosophila, where brain activity appears similar to wakefulness, but responsiveness to external sensory stimuli is profoundly suppressed. © 2020 Elsevier Inc.
Author Keywords
brain; calcium imaging; dorsal fan-shaped body; optogenetics; REM sleep; sleep stages; two-photon microscopy; visual attention
Funding details
National Institutes of HealthNIHNS076980-01
National Health and Medical Research CouncilNHMRCGNT1065713
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Adherence to a healthy lifestyle and multiple sclerosis: a case–control study from the UK Biobank” (2020) Nutritional Neuroscience
Adherence to a healthy lifestyle and multiple sclerosis: a case–control study from the UK Biobank
(2020) Nutritional Neuroscience, .
Veronese, N.a b , Yang, L.c d , Piccio, L.e f , Smith, L.g , Firth, J.h i , Marx, W.j k , Giannelli, G.l , Caruso, M.G.l , Cisternino, A.M.l , Notarnicola, M.l , Donghia, R.l , Barbagallo, M.a , Fontana, L.m n o
a Geriatric Unit, Department of Internal Medicine and Geriatrics, University of Palermo, Palermo, Italy
b Primary Care Department, Azienda ULSS, Unità Locale Socio Sanitaria) “Serenissima”, Venice, Italy
c Department of Cancer Epidemiology and Prevention Research, Cancer Control Alberta, Alberta Health Services, Calgary, Canada
d Departments of Oncology and Community Health Sciences, University of Calgary, Calgary, Canada
e Department of Neurology, Washington University in St. Louis, United States
f Brain and Mind Centre, University of Sydney, Sydney, NSW, Australia
g The Cambridge Centre for Sport and Exercise Sciences, Anglia Ruskin University, Cambridge, United Kingdom
h Division of Psychology and Mental Health, Faculty of Biology, Medicine and Health, University of Manchester, United Kingdom
i NICM Health Research Institute, School of Science and Health, University of Western Sydney, Australia
j Food Mood Centre, iMPACT, School of Medicine, Deakin University, Geelong, Australia
k Department of Rehabilitation, Nutrition and Sport, School of Allied Health, College of Science, Health and Engineering, La Trobe University, Bundoora, VIC, Australia
l National Institute of Gastroenterology “S. de Bellis”, Research Hospital, Castellana Grotte, Italy
m Charles Perkins Center, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia
n Department of Endocrinology, Royal Prince Alfred Hospital, Sydney, Australia
o Department of Clinical and Experimental Sciences, Brescia University, Brescia, Italy
Abstract
Background: Multiple sclerosis (MS) is a common and disabling condition. The importance of healthy lifestyle for this disease is poorly explored. Objective: To test whether adherence to healthier lifestyle patterns is associated with a lower presence of multiple sclerosis (MS). Methods: By using a case–control design, we investigated the combined association of four healthy lifestyle-related factors (no current smoking, healthy diet, exercising regularly, body mass index <30 kg/m2) and the prevalence of MS. A logistic regression analysis, adjusted for potential confounders, was used and data reported as odds ratios (ORs) with their 95% confidence intervals (CIs). Results: 728 participants with MS were matched with healthy controls (n = 2,912) using a propensity score approach. In a multivariable analysis, compared to those who scored low in the composite lifestyle score (0–1 healthy lifestyle factors), people who adopted all four low risk lifestyle factors showed a 71% lower odds of having MS (OR = 0.29; 95% CI: 0.15–0.56). Moreover, there was a strong linear trend, suggesting that the higher number of healthy lifestyle behaviors was associated with lower odds of having MS. Conclusion: Following a healthy lifestyle is associated with a lower prevalence of MS. This association should be explored further in cohort studies. © 2020 Informa UK Limited, trading as Taylor & Francis Group.
Author Keywords
exercise; healthy diet; healthy lifestyle; Multiple sclerosis; obesity; smoking; UK biobank
Funding details
Canadian Cancer SocietyCBCF
Canadian Institutes of Health ResearchCIHR
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“De novo variants in SNAP25 cause an early-onset developmental and epileptic encephalopathy” (2020) Genetics in Medicine
De novo variants in SNAP25 cause an early-onset developmental and epileptic encephalopathy
(2020) Genetics in Medicine, .
Klöckner, C.a , Sticht, H.b , Zacher, P.c , Popp, B.a , Babcock, H.E.d , Bakker, D.P.e , Barwick, K.f , Bonfert, M.V.g , Bönnemann, C.G.h , Brilstra, E.H.i , Chung, W.K.j , Clarke, A.J.k , Devine, P.l , Donkervoort, S.h , Fraser, J.L.m , Friedman, J.n o , Gates, A.p , Ghoumid, J.q , Hobson, E.r , Horvath, G.s , Keller-Ramey, J.t , Keren, B.u , Kurian, M.A.f , Lee, V.v , Leppig, K.A.p , Lundgren, J.w , McDonald, M.T.x , McTague, A.f , Mefford, H.C.y , Mignot, C.z , Mikati, M.A.aa , Nava, C.ab , Raymond, F.L.ac ad , Sampson, J.R.k , Sanchis-Juan, A.ac ae , Shashi, V.x , Shieh, J.T.C.af ag , Shinawi, M.ah , Slavotinek, A.af , Stödberg, T.ai , Stong, N.aj , Sullivan, J.A.x , Taylor, A.C.ak , Toler, T.L.ah , van den Boogaard, M.-J.i , van der Crabben, S.N.al , van Gassen, K.L.I.i , van Jaarsveld, R.H.i , Van Ziffle, J.l , Wadley, A.F.am , Wagner, M.an , Wigby, K.ao , Wortmann, S.B.ap aq , Zarate, Y.A.ar , Møller, R.S.as at , Lemke, J.R.a , Platzer, K.a , Care4Rare Canada Consortiumau
a Institute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany
b Institute of Biochemistry, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
c The Saxon Epilepsy Center Kleinwachau, Radeberg, Germany
d Rare Disease Institute, Children’s National Hospital, Washington, DC, United States
e Department of Child Neurology, Amsterdam University Medical Centers, Amsterdam, Netherlands
f Institute of Child Health, University Collge London, London, United Kingdom
g Department of Pediatric Neurology and Developmental Medicine and LMU Center for Children with Medical Complexity, Dr. von Hauner Children’s Hospital, LMU – University Hospital, Ludwig-Maximilians-Universität, Munich, Germany
h Neuromuscular and Neurogenetic Disorders of Childhood Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States
i Department of Genetics, University Medical Center Utrecht, Utrecht, Netherlands
j Departments of Pediatrics and Medicine, Columbia University Medical Center, New York, NY, United States
k Division of Cancer & Genetics, School of Medicine, Cardiff University, Wales, United Kingdom
l Department of Pathology, University of California San Francisco, San Francisco, CA, United States
m Rare Disease Institute, Division of Genetics and Metabolism, Children’s National Hospital, Washington, DC, United States
n Departments of Neurosciences and Pediatrics, University of California San Diego and Division of Neurology, Rady Children’s Hospital, San Diego, CA, United States
o Rady Children’s Institute for Genomic Medicine, San Diego, CA, United States
p Department of Genetic Services, Kaiser Permanente Washington, Seattle, WA, United States
q Service de Génétique Clinique, Hôpital Jeanne de Flandre, CHU Lille, Lille, France
r Yorkshire Clinical Genetics Service, Chapel Allerton Hospital, Leeds, United Kingdom
s Department of Pediatrics, Division of Biochemical Diseases, University of British Columbia, Vancouver, Canada
t GeneDx, Gaithersburg, MD, United States
u APHP, Département de Génétique, Groupe Hospitalier Pitié Salpêtrière, Paris, France
v Department of Neurology, University of California San Francisco, San Francisco, CA, United States
w Institute of Clinical Sciences, Skane University Hospital, Lund, Sweden
x Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC, United States
y Division of Genetic Medicine, Department of Pediatrics, University of Washington, Seattle, WA, United States
z Département de Génétique, Centre de Référence Déficiences Intellectuelles de Causes Rares, Groupe Hospitalier Pitié Salpêtrière et Hôpital Trousseau, APHP, Sorbonne Université, Paris, France
aa Division of Pediatric Neurology, Department of Pediatrics, Duke University Medical Center, Durham, NC, United States
ab Sorbonne University, Paris Brain Institute, Inserm U1127, CNRS UMR 7225, AP-HP, Pitié Salpêtrière Hospital, Department of Genetics, Paris, France
ac NIHR BioResource, Cambridge University Hospitals NHS Foundation Trust, Cambridge Biomedical Campus, Cambridge, United Kingdom
ad Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom
ae Department of Haematology, University of Cambridge, NHS Blood and Transplant Centre, Cambridge, United Kingdom
af Division of Medical Genetics, University of California, San Francisco, San Francisco, CA, United States
ag Institute for Human Genetics, University of California, San Francisco, San Francisco, CA, United States
ah Department of Pediatrics, Division of Genetics and Genomic Medicine, Washington University School of Medicine, St. Louis, MO, United States
ai Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden
aj Institute for Genomic Medicine, Columbia University, New York, NY, United States
ak Section of Genetics, Department of Pediatrics, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States
al Department of Clinical Genetics, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands
am University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States
an Institute of Neurogenomics, Helmholtz Zentrum Munich, Neuherberg, Germany
ao Department of Pediatrics, Division of Genetics, University of California, San Diego and Rady Children’s Hospital-San Diego, San Diego, CA, United States
ap Amalia Children’s Hospital, Radboud University Nijmegen, Nijmegen, Netherlands
aq University Childrens Hospital, Paracelsus Medical University, Salzburg, Austria
ar Section of Genetics and Metabolism, Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, United States
as Institute for Regional Health Services, University of Southern Denmark, Odense, Denmark
at Department of Epilepsy Genetics and Personalized Medicine, Danish Epilepsy Centre Filadelfia, Dianalund, Denmark
Abstract
Purpose: This study aimsed to provide a comprehensive description of the phenotypic and genotypic spectrum of SNAP25 developmental and epileptic encephalopathy (SNAP25-DEE) by reviewing newly identified and previously reported individuals. Methods: Individuals harboring heterozygous missense or loss-of-function variants in SNAP25 were assembled through collaboration with international colleagues, matchmaking platforms, and literature review. For each individual, detailed phenotyping, classification, and structural modeling of the identified variant were performed. Results: The cohort comprises 23 individuals with pathogenic or likely pathogenic de novo variants in SNAP25. Intellectual disability and early-onset epilepsy were identified as the core symptoms of SNAP25-DEE, with recurrent findings of movement disorders, cerebral visual impairment, and brain atrophy. Structural modeling for all variants predicted possible functional defects concerning SNAP25 or impaired interaction with other components of the SNARE complex. Conclusion: We provide a comprehensive description of SNAP25-DEE with intellectual disability and early-onset epilepsy mostly occurring before the age of two years. These core symptoms and additional recurrent phenotypes show an overlap to genes encoding other components or associated proteins of the SNARE complex such as STX1B, STXBP1, or VAMP2. Thus, these findings advance the concept of a group of neurodevelopmental disorders that may be termed “SNAREopathies.”. © 2020, American College of Medical Genetics and Genomics.
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Association between paediatric intraoperative anaesthesia handover and adverse postoperative outcomes” (2020) BMJ Quality and Safety
Association between paediatric intraoperative anaesthesia handover and adverse postoperative outcomes
(2020) BMJ Quality and Safety, art. no. 12298, .
Kannampallil, T.a , Lew, D.b , Pfeifer, E.E.a , Sharma, A.a , Abraham, J.a
a Department of Anesthesiology, Washington University School of Medicine in Saint Louis, Saint Louis, MO, United States
b Division of Biostatistics, Washington University in St Louis School of Medicine, Saint Louis, MO, United States
Abstract
Objective: To determine whether intraoperative handover of patient care from one anaesthesia clinician to another was associated with an increased risk of adverse postoperative outcomes during paediatric surgeries. Design, setting and participants: A retrospective, population-based cohort study (1 April 2013-1 June 2018) at an academic medical centre. Exposure: Intraoperative handover of care between pairs of anaesthesia clinicians from one care provider to another compared with no handover of anaesthesia care. Main outcomes and measures: The primary outcome was a composite of all-cause mortality and major postoperative morbidity within 30 days after surgery. Secondary outcomes included individual components of the primary outcome and 30-day hospital readmission. Inverse probability of exposure weighting using propensity scores for intraoperative handovers was calculated. Weighted logistic regression was used to determine the association between intraoperative anaesthesia handovers and outcomes. Results: 78 321 paediatric surgical cases (n=5411 with handovers) were included for analysis. Patients were predominantly male (56.5%) with a median age of 6.56 (IQR: 2.65-12.53) years and a median anaesthesia duration of 76 (IQR: 55-126) min. In the weighted sample, the odds of the primary outcome (OR: 0.92; 95% CI 0.75 to 1.13; p=0.43), any morbidity (OR: 0.93; 95% CI 0.75 to 1.16; p=0.515), all-cause mortality (OR: 0.8; 95% CI 0.37 to 1.73; p=0.565) or 30-day readmission following surgery (OR: 0.99; 95% CI 0.84 to 1.18; p=0.95) did not significantly differ among surgeries with and without handovers. Conclusions: Among paediatric patients undergoing surgery, intraoperative anaesthesia handovers were not associated with adverse postoperative outcomes, after accounting for relevant covariates. These findings provide a preliminary perspective on the role of intraoperative handovers as a care-neutral event, with implications for improving safety. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.
Author Keywords
handoffs; Intraoperative handovers; paediatric; postoperative outcomes; safety; surgery; transition of care
Document Type: Article
Publication Stage: Article in Press
Source: Scopus