Medicine and Health Sciences Commons^™

Risk Of Early Versus Later Rebleeding From Dural Arteriovenous Fistulas With Cortical Venous Drainage, Andrew J Durnford, Ridhima Guniganti, Akash P Kansagra, Gregory J Zipfel, Et Al

2020-Current year OA Pubs

BACKGROUND: Cranial dural arteriovenous fistulas with cortical venous drainage are rare lesions that can present with hemorrhage. A high rate of rebleeding in the early period following hemorrhage has been reported, but published long-term rates are much lower. No study has examined how risk of rebleeding changes over time. Our objective was to quantify the relative incidence of rebleeding in the early and later periods following hemorrhage.

METHODS: Patients with dural arteriovenous fistula and cortical venous drainage presenting with hemorrhage were identified from the multinational CONDOR (Consortium for Dural Fistula Outcomes Research) database. Natural history follow-up was defined as time …

Gan Training Acceleration Using Frechet Descriptor-Based Coreset, Yanzhe Xu, Teresa Wu, Jennifer R. Charlton, Kevin M. Bennett

2020-Current year OA Pubs

No abstract provided.

Association Between The Covid-19 Pandemic And Insurance-Based Disparities In Mortality After Major Surgery Among Us Adults, Laurent G Glance, Andrew W Dick, Ernie Shippey, Patrick J Mccormick, Richard Dutton, Patricia W Stone, Jingjing Shang, Stewart J Lustik, Heather L Lander, Igor Gosev, Karen E Joynt Maddox

2020-Current year OA Pubs

Importance: The COVID-19 pandemic caused significant disruptions in surgical care. Whether these disruptions disproportionately impacted economically disadvantaged individuals is unknown.

Objective: To evaluate the association between the COVID-19 pandemic and mortality after major surgery among patients with Medicaid insurance or without insurance compared with patients with commercial insurance.

Design, Setting, and Participants: This cross-sectional study used data from the Vizient Clinical Database for patients who underwent major surgery at hospitals in the US between January 1, 2018, and May 31, 2020.

Exposures: The hospital proportion of patients with COVID-19 during the first wave of COVID-19 cases between March 1 and …

Motor Network Reorganization Induced In Chronic Stroke Patients With The Use Of A Contralesionally-Controlled Brain Computer Interface, Joseph B. Humphries, Daniela J S Mattos, Jerrel Rutlin, Andy G S Daniel, Kathleen Rybczynski, Theresa Notestine, Joshua S. Shimony, Harold Burton, Alexandre Carter, Eric C. Leuthardt

2020-Current year OA Pubs

No abstract provided.

Comparative Effectiveness Of Diversion Of Cerebrospinal Fluid For Children With Severe Traumatic Brain Injury, Michael J Bell, Jose Pineda, Et Al.

2020-Current year OA Pubs

Importance: Diversion of cerebrospinal fluid (CSF) has been used for decades as a treatment for children with severe traumatic brain injury (TBI) and is recommended by evidenced-based guidelines. However, these recommendations are based on limited studies.

Objective: To determine whether CSF diversion is associated with improved Glasgow Outcome Score-Extended for Pediatrics (GOS-EP) and decreased intracranial pressure (ICP) in children with severe TBI.

Design, Setting, and Participants: This observational comparative effectiveness study was performed at 51 clinical centers that routinely care for children with severe TBI in 8 countries (US, United Kingdom, Spain, the Netherlands, Australia, New Zealand, South Africa, and …

Antibiotics For Preventing Recurrent Urinary Tract Infection: Systematic Review And Meta-Analysis, Philipp Jent, Julia Berger, Annette Kuhn, Barbara W Trautner, Andrew Atkinson, Jonas Marschall

2020-Current year OA Pubs

Recurrent urinary tract infections are a common health problem. The only comprehensive synthesis on antibiotic prophylaxis in the last 15 years has been a guideline-embedded meta-analysis. We conducted a systematic review and meta-analysis of randomized controlled trials published up to October 13, 2020, evaluating patients age ≥12 years with either ≥2 episodes of lower urinary tract infection (UTI) within 6 months or ≥3 in the past year. Placebo or antibiotics were allowed as comparators. Study quality was low. In the 11 placebo-controlled trials, the risk for developing UTI was 85% lower with prophylaxis in comparison with placebo (risk ratio [RR], …

Onasemnogene Abeparvovec For Presymptomatic Infants With Two Copies Of Smn2 At Risk For Spinal Muscular Atrophy Type 1: The Phase Iii Spr1nt Trial, Kevin A Strauss, Craig M Zaidman, Et Al

2020-Current year OA Pubs

SPR1NT ( NCT03505099 ) was a Phase III, multicenter, single-arm study to investigate the efficacy and safety of onasemnogene abeparvovec for presymptomatic children with biallelic SMN1 mutations treated at ≤6 weeks of life. Here, we report final results for 14 children with two copies of SMN2, expected to develop spinal muscular atrophy (SMA) type 1. Efficacy was compared with a matched Pediatric Neuromuscular Clinical Research natural-history cohort (n = 23). All 14 enrolled infants sat independently for ≥30 seconds at any visit ≤18 months (Bayley-III item #26; P < 0.001; 11 within the normal developmental window). All survived without permanent ventilation at 14 months as per protocol; 13 maintained body weight (≥3rd WHO percentile) through 18 months. No child used nutritional or respiratory support. No serious adverse events were considered related to treatment by the investigator. Onasemnogene abeparvovec was effective and well-tolerated for children expected to develop SMA type 1, highlighting the urgency for universal newborn screening.

Accuracy And Reliability Of Diffusion Imaging Models, Nicole A. Seider, Babatunde Adeyemo, Ryland Miller, Dillan J. Newbold, Jacqueline M. Hampton, Kristen M. Scheidter, Jerrel Rutlin, Timothy O. Laumann, Jarod L. Roland, David F. Montez, Andrew N. Van, Annie Zheng, Scott Marek, Benjamin P. Kay, G. Larry Bretthorst, Yong Wang, Steven E. Petersen, Deanna M. Barch, Evan M. Gordon, Abraham Z. Snyder, Joshua S. Shimony, Nico U. F. Dosenbach

2020-Current year OA Pubs

Diffusion imaging aims to non-invasively characterize the anatomy and integrity of the brain's white matter fibers. We evaluated the accuracy and reliability of commonly used diffusion imaging methods as a function of data quantity and analysis method, using both simulations and highly sampled individual-specific data (927-1442 diffusion weighted images [DWIs] per individual). Diffusion imaging methods that allow for crossing fibers (FSL's BedpostX [BPX], DSI Studio's Constant Solid Angle Q-Ball Imaging [CSA-QBI], MRtrix3's Constrained Spherical Deconvolution [CSD]) estimated excess fibers when insufficient data were present and/or when the data did not match the model priors. To reduce such overfitting, we developed …

A Staged Reconstruction Technique Utilizing Bioprosthetic Mesh Reinforcement In The Repair Of Giant Omphalocele, Annahita R. Fotouhi, Justin M. Sacks, Martin S. Keller, Kamlesh B. Patel

2020-Current year OA Pubs

No abstract provided.

Prediction Of Patient Outcomes Through Social Determinants Of Health: The Pulmonary Hypertension Association Registry (Phar) Evaluation, Dan Grinnan, Murali Chakinala, Et Al.

2020-Current year OA Pubs

Outcomes of patients with pulmonary arterial hypertension (PAH) may be associated with social determinants of health (SDOH) and other baseline patient characteristics. At present, there is no prognostic model to predict important patient outcomes in PAH based on SDOH. Utilizing information from the Pulmonary Hypertension Association Registry (PHAR), we derive a model (PHAR Evaluation or PHARE) to predict an important composite patient outcomes based on SDOH and other patient characteristics. Baseline data regarding SDOH from adult patients with PAH enrolled in the PHAR between 2015 and March 23, 2020, were included for analysis. We performed repeated measures logistic regression modeling …

Management Of Histoplasmosis By Infectious Disease Physicians, Patrick B Mazi, Sandra R Arnold, John W Baddley, Nathan C Bahr, Susan E Beekmann, Todd P Mccarty, Philip M Polgreen, Adriana M Rauseo, Andrej Spec

2020-Current year OA Pubs

BACKGROUND: The Infectious Diseases Society of America (IDSA) guidelines for the management of histoplasmosis were last revised 15 years ago. Since those guidelines were compiled, new antifungal treatment options have been developed. Furthermore, the ongoing development of immunomodulatory therapies has increased the population at increased risk to develop histoplasmosis.

METHODS: An electronic survey about the management practices of histoplasmosis was distributed to the adult infectious disease (ID) physician members of the IDSA's Emerging Infections Network.

RESULTS: The survey response rate was 37% (551/1477). Only 46% (253/551) of respondents reported seeing patients with histoplasmosis. Regions considered endemic had 82% (158/193) of …

Online Learning For Infectious Disease Fellows-A Needs Assessment, Miguel A Chavez, Nathanial S Nolan, Emily Gleason, Saman Nematollahi, Emily Abdoler, Gerome Escota

2020-Current year OA Pubs

BACKGROUND: Online resources and social media have become increasingly ubiquitous in medical education. Little is known about the need for educational resources aimed at infectious disease (ID) fellows.

METHODS: We conducted an educational needs assessment through a survey that aimed to describe ID fellows' current use of online and social media tools, assess the value of online learning, and identify the educational content preferred by ID fellows. We subsequently convened focus groups with ID fellows to explore how digital tools contribute to fellow learning.

RESULTS: A total of 110 ID fellows responded to the survey. Over half were second-year fellows …

Environmental Conditions To Promote Healthy Childhood Brain/Behavioral Development: Informing Early Preventive Interventions For Delivery In Routine Care, Joan L Luby, Cynthia Rogers, Katie A Mclaughlin

2020-Current year OA Pubs

Environmental experiences early in life have strong and enduring consequences for cognitive, emotional, and neurobiological development and related physical and mental health trajectories. The powerful influence of early caregiver nurturance and stimulation on promoting positive neurodevelopmental outcomes has been demonstrated across species. These findings elucidate the environmental conditions known to facilitate healthy neurodevelopment and underscore the potential for modifiable psychosocial factors in the environment to be harnessed to inform early preventive interventions to promote health and adaptive development. A framework for early preventive interventions to enhance nurturing and responsive caregiving for implementation during early sensitive periods of brain development delivered …

Is Combined Surgical Dislocation And Proximal Femoral Osteotomy A Safe Procedure For Correction Of Complex Hip Deformities?, Frank W Parilla, Jeffrey J Nepple, Gail E Pashos, Perry L Schoenecker, John C Clohisy

2020-Current year OA Pubs

Complex deformities of the hip requiring intra-articular and proximal femoral correction are challenging with regard to surgical access and complication risk. Combined surgical dislocation and proximal femoral osteotomy (SD/PFO) is a surgical strategy that provides unrestricted access to the joint with the capability for adjunctive PFO. Although providing excellent surgical access, concerns over a potentially high risk of postoperative complications remain, and published information on the safety of this technique remain scarce. In this study, we defined the early complication profile of combined surgery across 48 hips with a variety of complex deformities using a standardized, validated complication grading scheme …

Treatment Patterns And Standardized Outcome Assessments Among Patients With Inflammatory Conditions Of The Pouch In A Prospective Multicenter Registry, Edward L Barnes, Parakkal Deepak, Poonam Beniwal-Patel, Laura Raffals, Maia Kayal, Marla Dubinsky, Shannon Chang, Peter D R Higgins, Jennifer I Barr, Joseph Galanko, Yue Jiang, Raymond K Cross, Millie D Long, Hans H Herfarth

2020-Current year OA Pubs

BACKGROUND: Much of our understanding about the natural history of pouch-related disorders has been generated from selected populations. We designed a geographically diverse, prospective registry to study the disease course among patients with 1 of 4 inflammatory conditions of the pouch. The primary objectives in this study were to demonstrate the feasibility of a prospective pouch registry and to evaluate the predominant treatment patterns for pouch-related disorders.

METHODS: We used standardized diagnostic criteria to prospectively enroll patients with acute pouchitis, chronic antibiotic-dependent pouchitis (CADP), chronic antibiotic refractory pouchitis (CARP), or Crohn's disease (CD) of the pouch. We obtained detailed clinical …

Prophetic Eu: Prospective Identification Of Pneumonia In Hospitalized Patients In The Intensive Care Unit In European And United States Cohorts, Stephen P Bergin, Marin H Kollef, Et Al.

2020-Current year OA Pubs

BACKGROUND: The prospective identification of patients at high risk for hospital-acquired/ventilator-associated bacterial pneumonia may improve clinical trial feasibility and foster antibacterial development. In a prior study conducted in the United States, clinical criteria were used to prospectively identify these patients; however, these criteria have not been applied in a European population.

METHODS: Adults considered high risk for pneumonia (treatment with ventilation or high levels of supplemental oxygen) in the intensive care units of 7 European hospitals were prospectively enrolled from June 12 to December 27, 2017. We estimated the proportion of high-risk patients developing pneumonia according to US Food and …

Caspase-1-Driven Neutrophil Pyroptosis And Its Role In Host Susceptibility To Pseudomonas Aeruginosa, Karin Santoni, Christine T. N. Pham, Et Al

2020-Current year OA Pubs

Multiple regulated neutrophil cell death programs contribute to host defense against infections. However, despite expressing all necessary inflammasome components, neutrophils are thought to be generally defective in Caspase-1-dependent pyroptosis. By screening different bacterial species, we found that several Pseudomonas aeruginosa (P. aeruginosa) strains trigger Caspase-1-dependent pyroptosis in human and murine neutrophils. Notably, deletion of Exotoxins U or S in P. aeruginosa enhanced neutrophil death to Caspase-1-dependent pyroptosis, suggesting that these exotoxins interfere with this pathway. Mechanistically, P. aeruginosa Flagellin activates the NLRC4 inflammasome, which supports Caspase-1-driven interleukin (IL)-1β secretion and Gasdermin D (GSDMD)-dependent neutrophil pyroptosis. Furthermore, P. aeruginosa-induced GSDMD activation …

The Novel Data Collection And Analytics Tools For Remote Patient Monitoring In Heart Failure (Nov-Rpm-Hf) Trial: Protocol For A Single-Center Prospective Trial, Ankit Bhatia, Gregory Ewald, Thomas Maddox

2020-Current year OA Pubs

BACKGROUND: Heart failure remains a leading cause of mortality and a major driver of health care utilization. Despite numerous medical advances in heart failure, associated hospitalizations continue to increase, owing largely to suboptimal outpatient management. Remote patient monitoring (RPM) aims to further address this current need in heart failure care by providing data to clinical teams to act pre-emptively to address clinical decompensation. However, to date, RPM approaches using noninvasive home-based patient sensors have failed to demonstrate clinical efficacy.

OBJECTIVE: The Novel Data Collection and Analytics Tools for Remote Patient Monitoring in Heart Failure (Nov-RPM-HF) Trial aims to address current …

Enabling Hotspot Detection And Public Health Response To The Covid-19 Pandemic, Randi Foraker, Joshua Landman, Ian Lackey, Matthew D Haslam, Alison L Antes, Dennis Goldfarb

2020-Current year OA Pubs

INTRODUCTION: Public-facing maps of COVID-19 cases, hospital admissions, and deaths are commonly displayed at the state, county, and zip code levels, and low case counts are suppressed to protect confidentiality. Public health authorities are tasked with case identification, contact tracing, and canvasing for educational purposes during a pandemic. Given limited resources, authorities would benefit from the ability to tailor their efforts to a particular neighborhood or congregate living facility.

METHODS: We describe the methods of building a real-time visualization of patients with COVID-19-positive tests, which facilitates timely public health response to the pandemic. We developed an interactive street-level visualization that …

All-In-Focus Fine Needle Aspiration Biopsy Imaging Based On Fourier Ptychographic Microscopy, Mingshu Liang, Cory Bernadt, Soon Boon Justin Wong, Changsoon Choi, Richard Cote, Changhuei Yang

2020-Current year OA Pubs

Context: Cytology is the study of whole cells in diagnostic pathology. Unlike standard histologic thinly sliced specimens, cytologic preparations consist of preparations of whole cells where cells commonly cluster and aggregate. As such, cytology preparations are generally much thicker than histologic slides, resulting in large patches of defocus when examined under the microscope. A diagnostic aggregate of cells often cannot be viewed in focus together, requiring pathologists to continually manipulate the focal plane, complicating the task of accurately assessing the entire cellular aggregate and thus in making a diagnosis. Further, it is extremely difficult to acquire useful uniformly in-focus digital …

Whole Exome Sequencing Enhanced Imputation Identifies 85 Metabolite Associations In The Alpine Chris Cohort, Eva König, Johannes Rainer, Vinicius Verri Hernandes, Giuseppe Paglia, Fabiola Del Greco M, Daniele Bottigliengo, Xianyong Yin, Lap Sum Chan, Alexander Teumer, Peter P Pramstaller, Adam E Locke, Christian Fuchsberger

2020-Current year OA Pubs

Metabolites are intermediates or end products of biochemical processes involved in both health and disease. Here, we take advantage of the well-characterized Cooperative Health Research in South Tyrol (CHRIS) study to perform an exome-wide association study (ExWAS) on absolute concentrations of 175 metabolites in 3294 individuals. To increase power, we imputed the identified variants into an additional 2211 genotyped individuals of CHRIS. In the resulting dataset of 5505 individuals, we identified 85 single-variant genetic associations, of which 39 have not been reported previously. Fifteen associations emerged at ten variants with >5-fold enrichment in CHRIS compared to non-Finnish Europeans reported in …

Selective Whole-Genome Amplification As A Tool To Enrich Specimens With Low Treponema Pallidum Genomic Dna Copies For Whole-Genome Sequencing, Charles M Thurlow, Sandeep J Joseph, Lilia Ganova-Raeva, Samantha S Katz, Lara Pereira, Cheng Chen, Alyssa Debra, Kendra Vilfort, Kimberly Workowski, Stephanie E Cohen, Hilary Reno, Yongcheng Sun, Mark Burroughs, Mili Sheth, Kai-Hua Chi, Damien Danavall, Susan S Philip, Weiping Cao, Ellen N Kersh, Allan Pillay

2020-Current year OA Pubs

Downstream next-generation sequencing (NGS) of the syphilis spirochete Treponema pallidum subspecies

The Translational Landscape Of Sars-Cov-2-Infected Cells Reveals Suppression Of Innate Immune Genes, Maritza Puray-Chavez, Nakyung Lee, Kasyap Tenneti, Yiqing Wang, Hung R Vuong, Yating Liu, Amjad Horani, Tao Huang, Sean P Gunsten, James B Case, Wei Yang, Michael S Diamond, Steven L Brody, Joseph Dougherty, Sebla B Kutluay

2020-Current year OA Pubs

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) utilizes a number of strategies to modulate viral and host mRNA translation. Here, we used ribosome profiling in SARS-CoV-2-infected model cell lines and primary airway cells grown at an air-liquid interface to gain a deeper understanding of the translationally regulated events in response to virus replication. We found that SARS-CoV-2 mRNAs dominate the cellular mRNA pool but are not more efficiently translated than cellular mRNAs. SARS-CoV-2 utilized a highly efficient ribosomal frameshifting strategy despite notable accumulation of ribosomes within the slippery sequence on the frameshifting element. In a highly permissive cell line model, …

Loss Of Stathmin-2, A Hallmark Of Tdp-43-Associated Als, Causes Motor Neuropathy, Kelsey L Krus, Amy Strickland, Yurie Yamada, Laura Devault, Robert E Schmidt, A Joseph Bloom, Jeffrey Milbrandt, Aaron Diantonio

2020-Current year OA Pubs

TDP-43 mediates proper Stathmin-2 (STMN2) mRNA splicing, and STMN2 protein is reduced in the spinal cord of most patients with amyotrophic lateral sclerosis (ALS). To test the hypothesis that STMN2 loss contributes to ALS pathogenesis, we generated constitutive and conditional STMN2 knockout mice. Constitutive STMN2 loss results in early-onset sensory and motor neuropathy featuring impaired motor behavior and dramatic distal neuromuscular junction (NMJ) denervation of fast-fatigable motor units, which are selectively vulnerable in ALS, without axon or motoneuron degeneration. Selective excision of STMN2 in motoneurons leads to similar NMJ pathology. STMN2 knockout heterozygous mice, which better model the partial loss …

Infants Later Diagnosed With Autism Have Lower Canonical Babbling Ratios In The First Year Of Life, L D Yankowitz, J R Pruett Jr, N Marrus, K Botteron, J N Constantino, Et Al.

2020-Current year OA Pubs

BACKGROUND: Canonical babbling-producing syllables with a mature consonant, full vowel, and smooth transition-is an important developmental milestone that typically occurs in the first year of life. Some studies indicate delayed or reduced canonical babbling in infants at high familial likelihood for autism spectrum disorder (ASD) or who later receive an ASD diagnosis, but evidence is mixed. More refined characterization of babbling in the first year of life in infants with high likelihood for ASD is needed.

METHODS: Vocalizations produced at 6 and 12 months by infants (n = 267) taking part in a longitudinal study were coded for canonical and …

A Human Single-Neuron Dataset For Face Perception, Runnan Cao, Chujun Lin, Nicholas J Brandmeir, Shuo Wang

2020-Current year OA Pubs

The human amygdala and hippocampus have long been associated with face perception. Here, we present a dataset of single-neuron activity in the human amygdala and hippocampus during face perception. We recorded 2082 neurons from the human amygdala and hippocampus when neurosurgical patients with intractable epilepsy performed a one-back task using natural face stimuli, which mimics natural face perception. Specifically, our data include (1) single-neuron activity from the amygdala (996 neurons) and hippocampus (1086 neurons), (2) eye movements (gaze position and pupil), (3) psychological assessment of the patients, and (4) social trait judgment ratings from a subset of patients and a …

Dialysis Service In The Embattled Tigray Region Of Ethiopia: A Call To Action, Ephrem Berhe, Will Ross, Hale Teka, Hiluf Ebuy Abraha, Lewis Wall

2020-Current year OA Pubs

Haemodialysis is extremely limited in low-income countries. Access to haemodialysis is further curtailed in areas of active conflict and political instability. Haemodialysis in the Tigray region of Ethiopia has been dramatically affected by the ongoing civil war. Rapid assessment from the data available at Ayder Hospital's haemodialysis unit registry, 2015-2021, shows that enrollment of patients in the haemodialysis service has plummeted since the war broke out. Patient flow has decreased by 37.3% from the previous yearly average. This is in contrary to the assumption that enrollment would increase because patients could not travel to haemodialysis services in the rest of …

The Gut Microbiome-Brain Crosstalk In Neurodegenerative Diseases, Laura Ghezzi, Claudia Cantoni, Emanuela Rotondo, Daniela Galimberti

2020-Current year OA Pubs

The gut-brain axis (GBA) is a complex interactive network linking the gut to the brain. It involves the bidirectional communication between the gastrointestinal and the central nervous system, mediated by endocrinological, immunological, and neural signals. Perturbations of the GBA have been reported in many neurodegenerative diseases, suggesting a possible role in disease pathogenesis, making it a potential therapeutic target. The gut microbiome is a pivotal component of the GBA, and alterations in its composition have been linked to GBA dysfunction and CNS inflammation and degeneration. The gut microbiome might influence the homeostasis of the central nervous system homeostasis through the …

Blocking Cell Cycle Progression Through Cdk4/6 Protects Against Chronic Kidney Disease, Yosuke Osaki, Marika Manolopoulou, Alla V Ivanova, Nicholas Vartanian, Melanie Phillips Mignemi, Justin Kern, Jianchun Chen, Haichun Yang, Agnes B Fogo, Mingzhi Zhang, Cassianne Robinson-Cohen, Leslie S. Gewin

2020-Current year OA Pubs

Acute and chronic kidney injuries induce increased cell cycle progression in renal tubules. While increased cell cycle progression promotes repair after acute injury, the role of ongoing tubular cell cycle progression in chronic kidney disease is unknown. Two weeks after initiation of chronic kidney disease, we blocked cell cycle progression at G1/S phase by using an FDA-approved, selective inhibitor of CDK4/6. Blocking CDK4/6 improved renal function and reduced tubular injury and fibrosis in 2 murine models of chronic kidney disease. However, selective deletion of cyclin D1, which complexes with CDK4/6 to promote cell cycle progression, paradoxically increased tubular injury. Expression …

A Pathogenic Mechanism Associated With Myopathies And Structural Birth Defects Involves Tpm2-Directed Myogenesis, Jennifer Mcadow, Shuo Yang, Tiffany Ou, Gary Huang, Matthew B. Dobbs, Christina A. Gurnett, Michael J. Greenberg, Aaron N. Johnson

2020-Current year OA Pubs

Nemaline myopathy (NM) is the most common congenital myopathy, characterized by extreme weakness of the respiratory, limb, and facial muscles. Pathogenic variants in Tropomyosin 2 (TPM2), which encodes a skeletal muscle-specific actin binding protein essential for sarcomere function, cause a spectrum of musculoskeletal disorders that include NM as well as cap myopathy, congenital fiber type disproportion, and distal arthrogryposis (DA). The in vivo pathomechanisms underlying TPM2-related disorders are unknown, so we expressed a series of dominant, pathogenic TPM2 variants in Drosophila embryos and found 4 variants significantly affected muscle development and muscle function. Transient overexpression of the 4 variants also …