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High post-menopausal levels of the pituitary gonadotropin follicle-stimulating hormone (FSH) are strongly associated with the onset of Alzheimer's disease (AD). We have shown recently that FSH directly activates the hippocampal FSH receptors (FSHRs) to drive AD-like pathology and memory loss in mice. To unequivocally establish a role for FSH in memory loss, we depleted the Fshr on a 3xTg background and utilized Morris Water Maze to study deficits in spatial memory. 3xTg;Fshr +/+ mice displayed impaired spatial memory at 5 months of age. The loss of memory acquisition and retrieval were both rescued in 3xTg;Fshr -/- mice and, to a lesser extent, in 3xTg;Fshr +/- mice-documenting clear gene-dose-dependent prevention of spatial memory loss. Furthermore, at 5 and 8 months, sham-operated 3xTg;Fshr -/- mice showed better memory performance during the learning and/or retrieval phases, further suggesting that Fshr deletion prevents age-related progression of memory deficits. This prevention was not seen when mice were ovariectomized, except in the 8-month-old 3xTg;Fshr -/- mice. There was also a gene-dose-dependent reduction mainly in the amyloid β40 isoform in whole brain extracts. Finally, serum FSH levels <8 ng/mL in 16-month-old APP/PS1 mice were associated with better retrieval of spatial memory. Collectively, the data provide compelling genetic evidence for a protective effect of inhibiting FSH signaling on the progression of spatial memory deficits in mice and lay a firm foundation for the use of an FSH-blocking agent for the early prevention of memory loss in post-menopausal women., Competing Interests: Competing interests MZ is inventor on issued and pending patients on the use of FSH as a target for osteoporosis, obesity and Alzheimer’s disease. MZ, SR and TY are inventors on a pending patent on an FSH antibody that is formulated at ultrahigh concentration. The patents will be held by the Icahn School of Medicine at Mount Sinai, and MZ, SR and TY would be recipient of royalties, per institutional policy. The other authors declare no competing financial interests. Ethics approval All methods were performed in accordance with the relevant guidelines and regulations. Animal handling and use were compliant with the National Institutes of Health’s Guide for the Care and Use of Laboratory Animals, and approved by the Icahn School of Medicine at Mount Sinai Institutional Animal Care and Use Committee (IACUC Approval # 2018-0047)., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

This report presents the first genomes from positive cases of cholera in Sudan. Genomic analysis of 10 Vibrio cholerae isolates, profiled as serogroup O1, reveals evidence of antimicrobial resistance genes and a 139-kb IncC plasmid with 99.74% identity to the multidrug-resistant plasmid pCNRVC190243 previously reported in Yemen and Lebanon., Competing Interests: The authors declare no conflict of interest.

Medical education has long relied upon the inherent rewards of teaching to secure necessary educators. In an era of increasing emphasis upon clinical productivity, the expectation of faculty engagement in medical education has been upended. In addition, the demands and stressors of modern medical education has contributed to the perceived cost of teaching by faculty. This article describes the factors that have coalesced to change the environment in which medical education has long succeeded and provides strategies that can be employed to help mitigate these forces, increase perceived value in teaching, and better support the academic faculty upon which medical education depends.

Introduction: The shoulder is one of the most intricate articulation complexes in the human body. Any insult to its equilibrium can cause joint instability, pain, and dysfunction. The complex bony projections of the scapula, lengthy nature of the nerves, and extensive mobility of the joint places nerves at risk for impingement; this can, especially, be seen when examining the axillary and suprascapular nerves. Another rare cause of nerve impingement is a paralabral cyst secondary to labral tearing. If a paralabral cyst expands into the limited space occupied by the nerves, this can result in neuropraxia, muscle wasting, and loss of function. This phenomenon presents an interesting anatomic and clinical correlation., Case Report: A 41-year-old male with no past medical history presented with left shoulder pain for 3 months. Physical examination showed a great range of motion but diffusely decreased strength. Magnetic resonance imaging of the left shoulder demonstrated posterosuperior labral tearing with an associated paralabral cyst extending into the spinoglenoid notch. An additional anteroinferior labral tear with an associated paralabral cyst was also found. Extensive infraspinatus and teres minor muscle atrophy suggesting active denervation was present. The patient failed conservative management and underwent arthroscopic labral repair with posterosuperior and anteroinferior paralabral cysts excision. The patient had an unremarkable recovery and by 1 year had full motion and 5/5 strength in all planes., Conclusion: While paralabral cysts are well documented, there have been limited reports of cysts causing neural impingement of the axillary or the distal suprascapular nerve, let alone both occurring within the same individual. This case provides an interesting clinical scenario which very clearly depicts the neural innervation of the shoulder and pathologies that can impact function. This cystic impingement is a very interesting and rare finding that provides tremendous insight into both shoulder pathology and anatomy. This case is also useful to predict patient recovery after long-term nerve impingement and muscle denervation. This patient presented with significant loss of strength, motion, and shoulder dysfunction, but after surgical intervention, he regained complete motion and strength. This information can be used to help educate and guide patients in practice., Competing Interests: Conflict of Interest: Nil, (Copyright: © Indian Orthopaedic Research Group.)

Background: Older people living in care homes are at high risk of poor health outcomes and mortality if they contract coronavirus disease 2019. Protective measures include social distancing and isolation, although implementation is challenging., Objectives: To explore the real-life experiences of social distancing and isolation in care homes for older people, and to develop a toolkit of guidance and resources., Design: A mixed-methods, phased design., Setting: Six care homes in England caring for older adults., Participants: Care home staff ( n = 31), residents ( n = 17), family members ( n = 17), senior health and care leaders ( n = 13)., Methods: A rapid review to assess the social distancing and isolation measures used by care homes to control the transmission of coronavirus disease 2019 and other infectious diseases (phase 1), in-depth case studies of six care homes, involving remote individual interviews with staff, residents and families, collection of policies, protocols and routinely collected care home data, remote focus groups with senior health and care leaders (phase 2) and stakeholder workshops to co-design the toolkit (phase 3). Interview and focus group data and care home documents were analysed using thematic analysis and care home data using descriptive statistics., Results: The rapid review of 103 records demonstrated limited empirical evidence and the limited nature of policy documentation around social distancing and isolation measures in care homes. The case studies found that social distancing and isolation measures presented moral dilemmas for staff and often were difficult, and sometimes impossible to implement. Social distancing and isolation measures made care homes feel like an institution and denied residents, staff and families of physical touch and other forms of non-verbal communication. This was particularly important for residents with cognitive impairment. Care homes developed new visiting modalities to work around social distancing measures. Residents and families valued the work of care homes to keep residents safe and support remote communication. Social distancing, isolation and related restrictions negatively impacted on residents' physical, psychological, social and cognitive well-being. There were feelings of powerlessness for families whose loved ones had moved into the care home during the pandemic. It was challenging for care homes to capture frequent updates in policy and guidance. Senior health and care leaders shared that the care home sector felt isolated from the National Health Service, communication from government was described as chaotic, and trauma was inflicted on care home staff, residents, families and friends. These multiple data sources have informed the co-design of a toolkit to care for residents, families, friends and care home staff., Limitations: The review included papers published in English language only. The six care homes had a Care Quality Commission rating of either 'good' or 'outstanding'. There was a lack of ethnic diversity in resident and family participants., Conclusions: Care homes implemented innovative approaches to social distancing and isolation with varying degrees of success. A legacy of learning can help rebuild trust at multiple levels and address trauma-informed care for residents, families, friends and staff. Future work can include evaluation of the toolkit, research to develop a trauma-informed approach to caring for the care home sector and co-designing and evaluating an intervention to enable residents with different needs to transition to living well in a care home., Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme (NIHR award ref: NIHR132541) and is published in full in Health and Social Care Delivery Research ; Vol. 12, No. 45. See the NIHR Funding and Awards website for further award information.

Background: Cognitive deficits are the core component in persons with schizophrenia which impacts their socio-occupational functioning. Also, cognitive deficits cause significant impairment with the person's quality of life [3]. Hence, targeting such a pivotal aspect in persons with schizophrenia through suitable interventions is very important. Developed countries have designed various cognitive remediation programs using computers involving high-end software which cannot be generalized to low-resource settings, like India, due to various factors including sociocultural factors, educational standards, and living standards of the patient population. Compensatory cognitive training (CCT) was developed to be "brief, practical, low-tech" and found to be effective in the west [9]. As there are no structured cognitive intervention modules in India, we have adapted the English CCT manual to be used for an urban population in Chennai, India. CCT was found to be feasible in face-to-face group sessions in our setting [12] and is found to be feasible and acceptable as virtual one-one intervention (unpublished data). Therefore, this study aims to evaluate the effectiveness of V-CCT in enhancing cognition and socio-occupational functioning., Methods: The proposed study will be a multicenter assessor-blinded randomized controlled trial at two clinical sites in Chennai, India. The preparatory phase of the study would include translation of the manual to the local language, recruitment and training of research assistants, and pilot testing using the translated manual. The second phase will be the main randomized controlled trial (RCT), during which a total of 160 persons diagnosed with schizophrenia will be recruited from both sites. After obtaining informed consent, baseline assessments will be conducted on cognition, functioning, self-esteem, and quality of life. Participants will be randomly assigned to either the virtual CCT group or the control group using a computer-generated randomization table. End-line assessments will be conducted 6 weeks after the baseline by research assistants who are blinded to the randomization post-intervention., Discussion: If V-CCT is found to be effective, it will be available for use in Tamil for persons with schizophrenia, and it will have an effect on their functioning, quality of life, and self-esteem., Trial Registration: The study is registered under Clinical trial registry-India (CTRI), and the registration number is CTRI/2024/04/065267. Registered on April 2024., (© 2024. The Author(s).)

Background: Systemic lupus erythematosus (SLE) exhibits a mortality rate four times higher in historically marginalized populations compared to the general population. It is essential for clinical trials to accurately represent the disease population to effectively evaluate treatment modalities. However, the current trial design lacks appropriate diversity, limiting the generalizability of results. We aim to assess the recruitment and retention strategies of historically marginalized populations in SLE clinical trials., Methods: In this cross-sectional analysis, relevant clinical trials were obtained in a comprehensive search of MEDLINE (PubMed) and Embase (Elsevier) in May of 2024. Included trials were published between January 1, 2018, and December 31, 2023, with a focus on SLE interventions. Reviewers KR and SS independently performed screening and data extraction via a standardized Google Form. The main outcome measured was the usage of recruitment and retention strategies, concerning under-resourced populations. All statistical analyses were performed via Stata 18 SE., Findings: Our initial database search returned 747 trials, but only 86 were included in this sample. Of these, 4/86 (4.7 %) implemented recruitment strategies while 6/86 (7.0 %) reported the use of specific retention strategies. Nineteen of the 86 studies (22.1 %) reported challenges to the recruitment of inequitable populations, primarily identifying the disproportionate representation of female participants and socioeconomic obstacles as a limitation., Interpretation: Key strengths include a thorough methodology from adherence to PRISMA guidelines and generalizable findings with the inclusion of international trials. Limitations include publication bias and exclusion of trials in non-English languages. Our study highlights the need for practical initiation of effective recruitment and retention strategies that aim to engage historically marginalized populations in SLE clinical trials. Addressing these gaps is necessary to prioritize the participation of inequitable populations, increase standardization of SLE treatments, and improve the relevance of SLE research., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: No financial or other sources of support were provide during the development of this manuscript. Dr. Matt Vassar reports receipt of funding from the National Institute on Drug Abuse, the National Institute on Alcohol Abuse and Alcoholism, the US Office of Research Integrity, Oklahoma Center for Advancement of Science and Technology, and internal grants from Oklahoma State University Center for Health Sciences — all outside of the present work. Dr. Alicia Ford reports receipt of funding from the Center for Integrative Research on Childhood Adversity, the Oklahoma Shared Clinical and Translational Resources, and internal grants from Oklahoma State University and Oklahoma State University Center for Health Sciences — all outside of the present work. All other authors have nothing to report., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: To identify risk factors for developing a fracture-related infection in operatively treated ballistic tibia fractures and to report the microbiologic results of intraoperative cultures., Design: Retrospective review., Setting: Level 1 trauma center., Patients/participants: One hundred thirty-three adults with operatively treated low-velocity ballistic tibia fractures, from 2011 to 2021., Intervention: One dose of prophylactic cefazolin or equivalent as well as perioperative prophylaxis., Main Outcome Measurements: Deep infection rate., Results: The deep infection rate was 12% (16/134) with no significant difference in injury characteristics, index surgical characteristics, or time to antibiotics between the groups ( P > 0.05). Patients who were slightly older (35.5 vs. 27 median years, P = 0.005) and with higher median body mass indexes (BMIs) (30.09 vs. 24.51, P = 0.021) developed a deep infection. 56.3% of patients presented with signs of infection within the first 100 days after injury. Nine patients had polymicrobial infections. There were 29 isolated organisms, 69% were uncovered by first-generation cephalosporin prophylaxis (anaerobes, gram-negative rods, Enterococcus, methicillin resistant Staphylococcus Aureus [MRSA] ), and 50% of patients developed recalcitrant infection and required a second reoperation where 6 organisms were isolated, half of which were not covered by first-generation prophylaxis ( Enterococcus, Staphylococcus Aureus MRSA )., Conclusions: We found a deep infection rate of 12% among ballistic tibia fractures receiving standard-of-care antibiotic prophylaxis. Increased age and body mass index were associated with deep infections. Half became recalcitrant requiring a second reoperation. 66.7% of isolated organisms were not covered by first-generation cephalosporin prophylaxis. Consideration should be given to treatment options such as broader prophylaxis or local antibiotic treatment., Level of Evidence: IV., Competing Interests: Dr. Brianna R. Fram reports paid consulting for Synthes. Dr. Joseph R. Hsu reports consultancy and speaker fees for Stryker, consultancy for Globus Medical, speaker fees from Smith & Nephew speakers' bureau, speaker fees from Integra Lifesciences, and speaker fees from Depuy/Synthes. The remaining authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Orthopaedic Trauma Association.)

Objective: The purpose of this study was to determine quality improvement outcomes following the pilot implementation of an in-situ simulation designed to enhance surgical safety checklist performance., Background: OR Black Box (ORBB) technology allows near real-time assessment for surgical safety checklist performance. Before our study, timeout quality was 73.3%, compliance was 99.9%, and engagement was 89.7% (n=1993 cases); Debrief Quality was 76.0%, compliance was 66.9%, and engagement was 66.7% (n=1842 cases)., Methods: This IRB-approved study used prospective convergent multi-methods. During 2 months, a 15-minute in-situ simulation, incorporating rapid cycle deliberate practice, was implemented for OR teams. ORBB analytics generated Timeout and Debrief scores for actual operations performed by surgeons who participated in simulation (Sim-group) versus those who did not (No-sim group) over 6 months, including 2 months pre-intervention, during-intervention, and post-intervention. Inductive content analysis was performed based on simulation discussions to determine team member perspectives., Results: Thirty simulations with 163 interprofessional participants were conducted. ORBB data from 1570 cases were analyzed. Scores were significantly better for the Sim-group compared with the No-sim group for debrief quality (84% vs. 79% P<0.001, during-intervention), compliance (73% vs. 66%, P<0.001, post-intervention), and engagement (80% vs. 73%, P=0.012, during-intervention). There were no between-group differences for Timeout scores. Thematic analysis identified 2 primary categories: "culture of safety" and "policy.", Conclusions: This simulation-based QI intervention created a psychologically safe training environment for OR teams. The novel use of ORBB technology facilitated outcome analysis and showed significantly better Debrief scores for simulation-trained surgeons compared with nontrained surgeons., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Fibromuscular dysplasia (FMD) is a non-atherosclerotic, non-inflammatory vascular disease that was once underrecognized and is significantly more prevalent in women than men. Although it most commonly affects the renal and extracranial carotid arteries, FMD can affect any vascular bed. Complications of FMD can include hypertension, dissection, and stroke. Presentation may vary between the sexes, with male patients having an increased frequency of arterial dissection and aneurysms compared with female patients. Diagnosis requires a high index of suspicion by the treating physician. Several imaging studies can assist with diagnosis, and treatment focuses on the monitoring of affected vessels and intervention only as needed. Antiplatelet therapy for prevention of thrombotic complications is recommended. Studies are still underway to examine the genetic underpinnings of FMD pathophysiology and to evaluate the underlying mechanism of this disease that affects more female than male patients., Competing Interests: Disclosure: The authors have no conflicts of interest to declare., (Copyright © The Author(s), 2024. Published by Radcliffe Group Ltd.)

KCNQ2 variants in children with neurodevelopmental impairment are difficult to assess due to their heterogeneity and unclear pathogenic mechanisms. We describe a child with neonatal-onset epilepsy, developmental impairment of intermediate severity, and KCNQ2 G256W heterozygosity. Analyzing prior KCNQ2 channel cryoelectron microscopy models revealed G256 as a node of an arch-shaped non-covalent bond network linking S5, the pore turret, and the ion path. Co-expression with G256W dominantly suppressed conduction by wild-type subunits in heterologous cells. Ezogabine partly reversed this suppression. G256W/+ mice have epilepsy leading to premature deaths. Hippocampal CA1 pyramidal cells from G256W/+ brain slices showed hyperexcitability. G256W/+ pyramidal cell KCNQ2 and KCNQ3 immunolabeling was significantly shifted from axon initial segments to neuronal somata. Despite normal mRNA levels, G256W/+ mouse KCNQ2 protein levels were reduced by about 50%. Our findings indicate that G256W pathogenicity results from multiplicative effects, including reductions in intrinsic conduction, subcellular targeting, and protein stability. These studies provide evidence for an unexpected and novel role for the KCNQ2 pore turret and introduce a valid animal model of KCNQ2 encephalopathy. Our results, spanning structure to behavior, may be broadly applicable because the majority of KCNQ2 encephalopathy patients share variants near the selectivity filter.

The pituitary gland orchestrates multiple endocrine organs by secreting tropic hormones, and therefore plays a significant role in a myriad of physiological processes, including skeletal modeling and remodeling, fat and glucose metabolism, and cognition. Expression of receptors for each pituitary hormone and the hormone itself in the skeleton, fat, immune cells, and the brain suggest that their role is much broader than the traditionally attributed functions. FSH, believed solely to regulate gonadal function is also involved in fat and bone metabolism, as well as in cognition. Our emerging understanding of nonreproductive functions of FSH, thus, opens potential therapeutic opportunities to address detrimental health consequences during and after menopause, namely, osteoporosis, obesity, and dementia. In this review, we outline current understanding of the cross-talk between the pituitary, bone, adipose tissue, and brain through FSH. Preclinical evidence from genetic and pharmacologic interventions in rodent models, and human data from population-based observations, genetic studies, and a small number of interventional studies provide compelling evidence for independent functions of FSH in bone loss, fat gain, and congnitive impairment.

Background: Females of reproductive age with concussion report a greater number of symptoms that can be more severe and continue for longer than age matched males. Underlying mechanisms for sex differences are not well understood. Short non-coding Ribonucleic Acids (sncRNAs) are candidate salivary biomarkers for concussion and have been studied primarily in male athletes. Female sex hormones influence expression of these biomarkers, and it remains unclear whether a similar pattern of sncRNA expression would be observed in females following concussion. This study aims to evaluate recovery time, the ratio of salivary sncRNAs and symptom severity across different hormone profiles in females presenting to emergency departments (ED) with concussion and, to investigate the presence of low energy availability (LEA) as a potential modifier of concussion symptoms., Methods: This prospective cohort study recruits participants from New Zealand EDs who are biologically female, of reproductive age (16-50 years) and with a confirmed diagnosis of concussion from an ED healthcare professional. Participants are excluded by ED healthcare professionals from study recruitment as part of initial routine assessment if they have a pre-diagnosed psychiatric condition, neurological condition (i.e., epilepsy, cerebral palsy) or more than three previously diagnosed concussions. Participants provide a saliva sample for measurement of sncRNA's, and online survey responses relating to hormone profile and symptom recovery at 7-day intervals after injury until they report a full return to work/study. The study is being performed in accordance with ethical standards of the Declaration of Helsinki with ethics approval obtained from the Health and Disability Ethics Committee (HDEC #2021 EXP 11655), Auckland University of Technology Ethics Committee (AUTEC #22/110) and locality consent through Wellington hospital research office., Discussion: If saliva samples confirm presence of sncRNAs in females with concussion, it will provide evidence of the potential of saliva sampling as an objective tool to aid in diagnosis of, and confirmation of recovery from, concussion. Findings will determine whether expression of sncRNAs is influenced by steroid hormones in females and may outline the need for sex specific application and interpretation of sncRNAs as a clinical and/or research tool., Trial Registration: Australian New Zealand Clinical Trials Registry (ANZCTR) registration number ACTRN12623001129673., (© 2024. The Author(s).)

Purpose: This article is prepared by the Association of Professors of Gynecology and Obstetrics Undergraduate Medical Education Committee and provides educators recommendations for optimizing inclusive education for our students with disabilities. Medical educators are increasingly encountering students with disabilities and have the responsibility of ensuring requirements are met., Method: Medical education committee members from the US and Canada reviewed the literature on disabilities in medical student education to identify best practices and key discussion points. An iterative review process was used to determine the contents of an informative paper., Results: Medical schools are required to develop technical standards for admission, retention, and graduation of their students to practice medicine safely and effectively with reasonable accommodation. A review of the literature and obstetrics and gynecology expert opinion formed a practical list of accommodation strategies and administrative steps to assist educators and students., Conclusion: Medical schools must support the inclusion of students with disabilities. We recommend a collaborative approach to the interactive process of determining reasonable and effective accommodations that includes the students, a disability resource professional and faculty as needed. Recruiting and supporting medical students with a disability strengthens the diversity commitment and creates a more inclusive workforce.

Objectives: To evaluate the work relative value units (RVUs) attributed per minute of operative time (wRVU/min) in fixation of acetabular fractures, evaluate surgical factors that influence wRVU/min, and compare wRVU/min with other procedures., Design: Retrospective., Setting: Level 1 academic center., Patient Selection Criteria: Two hundred fifty-one operative acetabular fractures (62 A, B, C) from 2015 to 2021., Outcome Measures and Comparisons: Work relative value unit per minute of operative time for each acetabular current procedural terminology (CPT) code. Surgical approach, patient positioning, total room time, and surgeon experience were collected. Comparison wRVU/min were collected from the literature., Results: The mean wRVU per surgical minute for each CPT code was (1) CPT 27226 (isolated wall fracture): 0.091 wRVU/min, (2) CPT 27227 (isolated column or transverse fracture): 0.120 wRVU/min, and (3) CPT 27228 (associated fracture types): 0.120 wRVU/min. Of fractures with single approaches, anterior approaches generated the least wRVU/min (0.091 wRVU/min, P = 0.0001). Average nonsurgical room time was 82.1 minutes. Surgeon experience ranged from 3 to 26 years with operative time decreasing as surgeon experience increased ( P = 0.03). As a comparison, the wRVU/min for primary and revision hip arthroplasty have been reported as 0.26 and 0.249 wRVU/min, respectively., Conclusions: The wRVUs allocated per minute of operative time for acetabular fractures is less than half of other reported hip procedures and lowest for isolated wall fractures. There was a significant amount of nonsurgical room time that should be accounted for in compensation models. This information should be used to ensure that orthopaedic trauma surgeons are being appropriately supported for managing these fractures., Level of Evidence: Economic Level IV. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: The authors report no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)