Heterozygous UBR5 variants result in a neurodevelopmental syndrome with developmental delay, autism, and intellectual disability.

E3 ubiquitin ligases have been linked to developmental diseases including autism, Angelman syndrome (UBE3A), and Johanson-Blizzard syndrome (JBS) (UBR1). Here, we report variants in the E3 ligase UBR5 in 29 individuals presenting with a neurodevelopmental syndrome that includes developmental delay, autism, intellectual disability, epilepsy, movement disorders, and/or genital anomalies. Their phenotype is distinct from JBS due to the absence of exocrine pancreatic insufficiency and the presence of autism, epilepsy, and, in some probands, a movement disorder.

Septins regulate heart contractility through modulation of cardiomyocyte store-operated calcium entry.

Highly regulated cardiomyocyte Ca fluxes drive heart contractions. Recent findings from multiple organisms demonstrate that the specific Ca transport mechanism known as store-operated Ca entry (SOCE) is essential in cardiomyocytes for proper heart function, and SOCE dysregulation results in cardiomyopathy. Mechanisms that regulate SOCE in cardiomyocytes are poorly understood.

Quantitative Pupillometry Predicts Return to Play and Tracks the Clinical Evolution of Mild Traumatic Brain Injury in US Military Academy Cadets: A Military Traumatic Brain Injury Initiative Study.

Background And Objectives: The objective of this study was to determine the utility of the pupillary light reflex use as a biomarker of mild traumatic brain injury (mTBI).

Methods: This prospective cohort study was conducted at The US Military Academy at West Point. Cadets underwent a standard battery of tests including Balance Error Scoring System, Sports Concussion Assessment Tool Fifth Edition Symptom Survey, Standard Assessment of Concussion, and measure of pupillary responses.

The PreQuine Platform: A novel diagnostic tool for measuring glucose-6-phosphate dehydrogenase (G6PD) activity and hemoglobin concentration.

Quantitative diagnosis of glucose-6-phosphate dehydrogenase (G6PD) deficiency is essential for the safe administration of 8-aminoquinoline based radical cure for the treatment of Plasmodium vivax infections. Here, we present the PreQuine Platform (IVDS, USA), a quantitative biosensor that uses a dual-analyte assay for the simultaneous measurement of Hemoglobin (Hgb) levels and G6PD enzyme activity within the same sample. The platform relies on a downloadable mobile application.

Assessing mean corpuscular volume as a screening tool for gestational vitamin B12 deficiency based on NHANES.

Vitamin B12 can lead to neurological deficits. We assessed whether the mean corpuscular volume (MCV) could be a sufficiently sensitive measurement for abnormal serum methylmalonic Acid (MMA) and total plasma homocysteine (tHCY) (biomarkers of vitamin B12 or folate deficiency) and if so, at what cutoff value. A total of 26,397 participants (12,730 males and 13,667 females) were included in the analysis.

A Cross-Sectional Analysis of Military Physician Residency Websites.

Introduction: Medical physician residency program websites often serve as the first contact for any prospective applicant. No analysis of military residency program websites has yet been conducted, in contrast to their civilian counterparts. This study evaluated all military residency programs certified by the Accreditation Council for Graduate Medical Education (ACGME) 2021-2022 to determine program website comprehensiveness and accessibility and identify areas for improvement.

Online simulation-based education in graduate education: Initial implementation and content revision description.

Treating those with mental illness frequently requires collaboration among health care providers from different disciplines as well as easy access to care. Neither interprofessional collaboration (IPC) nor accessible care can be assumed to automatically occur or be available in the busy health care environment. Early and deliberate exposure of graduate students in health care disciplines to interprofessional educational activities is imperative to strengthen IPC.

A combinatorial approach increases SMN level in SMA model mice.

Spinal muscular atrophy (SMA) is a neurodegenerative disease caused by reduced expression of the survival motor neuron (SMN) protein. Current disease-modifying therapies increase SMN levels and dramatically improve survival and motor function of SMA patients. Nevertheless, current treatments are not cures and autopsy data suggest that SMN induction is variable.

Development of a Simulation Surgical Cricothyroidotomy Curriculum for Novice Providers: A Learning Curve Study.

Introduction: Airway obstruction is the third most common cause of preventable death on the battlefield, accounting for 1%-2% of total combat fatalities. No previous surgical cricothyroidotomy (SC) studies have analyzed the learning curve required to obtain proficiency despite being studied in numerous other surgical technique training experiments. The aims of this study were to establish expert SC performance criteria, develop a novel standardized SC curriculum, and determine the necessary number of practice iterations required by a novice to reach this pre-determined performance goal.

Exposure to Workplace Trauma and Posttraumatic Stress Disorder Among Intern Physicians.

Importance: Physicians are exposed to traumatic events during their work, but the impact and outcomes of these exposures are understudied.

Objective: To determine the prevalence and associations of work-related trauma exposure and posttraumatic stress disorder (PTSD) among a cohort of resident physicians in their internship year of training.

Design, Setting, And Participants: This cohort study involved physicians entering internship at US residency programs nationwide in 2018.

A Preligamentous Variant of the Thenar Motor Branch of the Median Nerve.

We report a rare variant of the thenar motor branch (TMB) of the median nerve. A preligamentous TMB was discovered during revision carpal tunnel release in a 49-year-old man. The prevalence and characteristics of TMB variations are discussed.

Guideline Adherence and Hearing Outcomes of Sudden Sensorineural Hearing Loss in the Military Health System.

Introduction: The American Academy of Otolaryngology-Head and Neck Surgery Foundation clinical practice guideline (CPG) proposes several treatment recommendations regarding sudden sensorineural hearing loss (SSNHL). The treatments for this disorder have been controversial and remain varied. We sought to determine CPG adherence and hearing outcomes of SSNHL within the Military Health System (MHS).

Progress Toward a Gonococcal Vaccine: The Way Forward.

The concept of immunizing against gonorrhea has received renewed interest because of the recent emergence of strains of that are resistant to most currently available antibiotics, an occurrence that threatens to render gonorrhea untreatable. However, despite efforts over many decades, no vaccine has yet been successfully developed for human use, leading to pessimism over whether this goal was actually attainable. Several factors have contributed to this situation, including extensive variation of the expression and specificity of many of the gonococcal surface antigens, and the ability of to resist destruction by complement and other innate immune defense mechanisms.

Diagnosis and Management of Rhabdomyolysis in the Absence of Creatine Phosphokinase: A Medical Record Review.

Introduction: Rhabdomyolysis is often encountered in austere environments where the diagnosis can be challenging due to the expense or unavailability of creatine phosphokinase (CPK) testing. CPK concentration ≥5,000 U/L has previously been found to be a sensitive marker for progression to renal failure. This study sought to propose a model utilizing an alternate biomarker to allow for the diagnosis and monitoring of clinically significant rhabdomyolysis in the absence of CPK.

Ranolazine in High-Risk Patients With Implanted Cardioverter-Defibrillators: The RAID Trial.

Background: Ventricular tachycardia (VT) and ventricular fibrillation (VF) remain a challenging problem in patients with implantable cardioverter-defibrillators (ICDs).

Objectives: This study aimed to determine whether ranolazine administration decreases the likelihood of VT, VF, or death in patients with an ICD.

Methods: This was double-blind, placebo-controlled clinical trial in which high-risk ICD patients with ischemic or nonischemic cardiomyopathy were randomized to 1,000 mg ranolazine twice a day or placebo.

Biological feasibility and importance of a gonorrhea vaccine for global public health.

There is a growing public health interest in controlling sexually transmitted infections (STIs) through vaccination due to increasing recognition of the global disease burden of STIs and the role of STIs in women's reproductive health, adverse pregnancy outcomes, and the health and well-being of neonates. Neisseria gonorrhoeae has historically challenged vaccine development through the expression of phase and antigenically variable surface molecules and its capacity to cause repeated infections without inducing protective immunity. An estimated 78 million new N.

Both MisR (CpxR) and MisS (CpxA) Are Required for Neisseria gonorrhoeae Infection in a Murine Model of Lower Genital Tract Infection.

During infection, senses and responds to stress; such responses may be modulated by MisRS (NGO0177 and NGO0176), a two-component system that is a homolog of CpxRA. In , CpxRA senses and responds to envelope stress; CpxA is a sensor kinase/phosphatase for CpxR, a response regulator. When a mutant is grown in medium containing glucose, CpxR is phosphorylated by acetyl phosphate but cannot be dephosphorylated, resulting in constitutive activation.

One Hundred Case Series of Vocal Cord Dysfunction in a Military Treatment Facility.

The authors' evaluation of vocal cord dysfunction cases reveals that prevalence may be higher than previously reported in the literature.

Proteomics-driven Antigen Discovery for Development of Vaccines Against Gonorrhea.

Expanding efforts to develop preventive gonorrhea vaccines is critical because of the dire possibility of untreatable gonococcal infections. Reverse vaccinology, which includes genome and proteome mining, has proven very successful in the discovery of vaccine candidates against many pathogenic bacteria. However, progress with this approach for a gonorrhea vaccine remains in its infancy.

Hip arthroscopy in the warrior athlete: 2 to 10 year outcomes.

Hip disorders are increasingly recognized among athletic populations. The rigors of military service expose individuals to the same risks as those participating in competitive sports, compounded by potential exposure to violent macrotrauma. This is a retrospective review of prospectively collected data among 62 active duty military personnel (64 hips) with 2-10-year follow-up.

Overproduction of the MtrCDE efflux pump in Neisseria gonorrhoeae produces unexpected changes in cellular transcription patterns.

The global consequence of drug efflux gene overexpression in bacteria has not been specifically analyzed because strains showing high-level expression typically have mutations in genes encoding regulatory proteins that control other genes. Results from a transcriptional profiling study performed with a strain of Neisseria gonorrhoeae that is capable of high-level transcription of the mtrCDE efflux pump operon independently of control by cognate regulatory proteins revealed that its overexpression has ramifications for systems other than drug efflux.

Phase-variable expression of lptA modulates the resistance of Neisseria gonorrhoeae to cationic antimicrobial peptides.

Phosphoethanolamine (PEA) decoration of lipid A produced by Neisseria gonorrhoeae has been linked to bacterial resistance to cationic antimicrobial peptides/proteins (CAMPs) and in vivo fitness during experimental infection. We now report that the lptA gene, which encodes the PEA transferase responsible for this decoration, is in an operon and that high-frequency mutation in a polynucleotide repeat within lptA can influence gonococcal resistance to CAMPs.