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Introduction: CHARGE syndrome is a congenital collection of anomalies of various organs including various functional and structural anomalies of the ears. Surgical management of hearing loss in CHARGE syndrome is challenging due to various anatomical malformations of the middle and inner ear. Cochlear implantation surgery for profound sensorineural hearing loss is technically difficult due to these malformations whilst cochlea nerve hypoplasia or aplasia may compromise outcomes. Aberrant facial nerve position may increase perioperative morbidity whilst developmental delay often makes global assessment of patients with CHARGE difficult. We aim to provide surgical guidance on managment of patients with CHARGE Methods: We performed a systematic review of all trials involving cochlear implantation in CHARGE syndrome. We searched Cochrane Central Register of Controlled Trials, PubMed, EMBASE through Ovid SP and Web of Science. Primary outcome measures included Health-related quality of life, audiological outcomes as well as adverse events and complications. We also assessed the most commonly recorded ear anomalies including the findings of aberrant facial nerve positon. A retrospective series of patients with CHARGE syndrome assessed for cochlear implantation at Great Ormond Street Hospital was also performed. Results: 15 patients with CHARGE were assessed at our centre between 1993 and 2017 with ten cochlear implantations performed. Semicircular canal aplasia and vestibulocochlear dysplasia were seen in all patients. All patients had abnormal facial nerve anatomy. These findings were in keeping with the findings of our systematic review which consisted of case series/retrospective reviews. No randomised controlled trials were identified. Data from the systematic review is presented in an easy-to-interpret table. Conclusions: Cochlear implantation in CHARGE patients is surgically challenging with variable outcomes. We describe our experience and compare this to the literature through a systematic review of published outcome data. [ABSTRACT FROM AUTHOR]

Fecal microbiota transplantation (FMT) is the administration of fecal bacteria from a healthy donor into the intestinal tract of a recipient in order to directly change the recipient's gut microbial composition and confer a health benefit. The relationship between the gut microbiome and the central nervous system, termed the gut-brain axis, has been a frequent topic of gut microbiome studies. Commensal gut bacteria communicate with the central nervous system through various hormones, cytokines, and neural pathways. Therefore, influencing the gut microbiome via FMT may have the potential in treating symptoms of neurodegenerative conditions. This study aims to identify current uses of FMT in treating neurodegenerative diseases and highlight areas of future investigation. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) framework, a literature search was conducted of peer-reviewed sources on September 27, 2022, from Embase, MEDLINE, Web of Science, and Cochrane Central. Search terms were utilized that were related to the application of FMT and neurodegenerative disorders and limited those human studies, those that were published in English, and those that were published between 2017 and 2022. The initial search yielded 450 unique articles, and after the assessment of the title and abstract for inclusion and exclusion criteria, six articles were identified for full-text review. Studies that focused on either Parkinson's disease (PD) or multiple sclerosis (MS) demonstrated improvements in both motor symptoms and non-motor symptoms. FMT was also shown to provide significant relief of constipation and general gastrointestinal (GI) symptoms in all conditions studied. The studies related to MS showed the most mixed results with regard to symptomatic improvement. The data on the use of FMT as a treatment for neurodegenerative disorders is limited; however, studies have shown not only improvement in GI symptoms but also improvement in the cognitive symptoms of PD and dementia. The data on FMT as a treatment to improve the motor symptoms of PD is both more complete and more compelling than the data on the motor symptoms of MS. The studies that were reviewed showed no major adverse effects of FMT and generally promising results. There is a strong case to be made for larger, more well-controlled studies to be done on FMT and its potential use as a treatment not only for GI symptoms but for the motor and cognitive symptoms of neurodegenerative diseases., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Sanzone et al.)

As the sports medicine field has grown, the need for a more diverse workforce has become more evident. Given the growing athlete diversity that exists at all recreational and competitive levels of organized sports, it is important to better understand the current state of athletic health care diversity. This review assesses the current state of diversity in sports medicine from the perspective of the medical and athletic training professions. Men and women currently display nearly equivalent participation levels; however, the distribution of female team physicians and athletic trainers could better match the teams that they serve. Although progress has been made, much more needs to be done to bring more female athletic trainers and team physicians into athletic health care leadership roles. Early mentoring programs have shown efficacy for increasing the number of female candidates who might become the foundation of future athletic health care and academic program leaders., Level of Evidence: V, expert opinion., (© 2023 The Authors.)

There are not enough board certified behavior analysts (BCBAs) with specialization in the treatment of individuals with autism to meet the growing patient demand for applied behavior analysis (ABA) treatment. In addition, there are no streamlined, organization-led fieldwork supervision systems to aid in the professional development of Trainees to meet this need. This article describes enhancements made to the Apprentice Model (Hartley et al., 2016), emphasizing the mutual benefit to the Apprentice, the Supervising BCBA, the organization for which they are both employed, and perhaps most important, the field of behavior analysis. Within the organization where the Apprentice Model has been adopted, 88% of Apprentices who took the exam, since the 2022 modifications were applied, passed on their first attempt despite attending universities with 2021 reported pass rates ranging from 34%-60% (Behavior Analysts Certification Board [BACB], 2023). In addition, through the 6-year history of the adoption of the Apprentice Model, 70% of the organization's BCBAs who supervise a caseload of patients were prior Apprentices. Structuring a wide-scale supervision model within an organization creates opportunities for the Trainee to experience high-quality tailored fieldwork, it allows the Supervising BCBA to provide supervision under a well-organized and structured framework, and it permits the organization to employ high-quality, newly certified BCBAs to begin meeting patient treatment needs., Supplementary Information: The online version contains supplementary material available at 10.1007/s40617-023-00799-9., Competing Interests: Conflicts with InterestWe have no conflict of interest to disclose., (© Association for Behavior Analysis International 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Background: Myocardial hypertrophy and dilation are key features of cardiomyopathies and involve several cellular and molecular events. ADAMs (a disintegrin and metalloproteinases) are membrane-bound proteinases with diverse functions whose role in heart disease remains underexplored. ADAM15 is expressed in the heart and is downregulated in the failing human heart. We investigated the role ADAM15 in pressure overload cardiomyopathy., Methods: We assessed ADAM15 levels in myocardial specimens from patients. Its direct role in pressure overload was investigated by subjecting wildtype and Adam15 -deficient mice to transverse aortic constriction (TAC)., Results: ADAM15 levels did not change in patients with concentric hypertrophy, but markedly decreased in eccentric hypertrophy and heart failure. Loss of ADAM15 alone did not cause cardiomyopathy in mice (1 year old). After TAC, Adam15 -/- mice exhibited worsened eccentric hypertrophy and dilation with greater increase in hypertrophy markers (pJNK, pERK1/2; Nppb, Nppa , Myh7 , Acta1 ) compared with wildtype-TAC. Expression of integrin-α7 (but not integrin β1) increased significantly more in Adam15 -/- -TAC hearts, while the interaction of these integrins with basement membrane (laminin), decreased consistent with worsened left ventricle dilation. In vitro, ADAM15 knockdown increased cardiomyocyte hypertrophy in response to mechanical stretch. Adam15 -/- -TAC hearts exhibited increased calcineurin activity and de-phosphorylation of nuclear factor of activated T cells. Calcineurin inhibition (cyclosporin-A) blocked the excess hypertrophy and dilation in Adam15 -/- -TAC mice. Proteome profiling demonstrated the increased abundance of the key proteins linked to worsened DCM in Adam15 -/- -TAC., Conclusion: This is the first report demonstrating that ADAM15 can suppress hypertrophy through regulating the integrin-laminin interaction and the calcineurin pathway.

Background The association between chronic obstructive pulmonary disease exacerbations and increased cardiovascular event risk has not been adequately studied in a heterogenous population with both low and high cardiovascular risk. Methods and Results This post hoc analysis of the IMPACT (Informing the Pathway of COPD Treatment) trial (N=10 355 symptomatic patients with chronic obstructive pulmonary disease at risk of exacerbations) evaluated time-dependent risk of cardiovascular adverse events of special interest (CVAESI) following exacerbations and impact of exacerbation history, cardiovascular risk factors, and study treatment on this association. Risk (time-to-first) of CVAESI or CVAESI resulting in hospitalization or death was assessed during and 1 to 30, 31 to 90, and 91 to 365 days after resolution of moderate or severe exacerbations. CVAESI risk was compared between the period before and during/after exacerbation. CVAESI risk increased significantly during a moderate (hazard ratio [HR], 2.63 [95% CI, 2.08-3.32]) or severe (HR, 21.84 [95% CI, 17.71-26.93]) exacerbation and remained elevated for 30 days following an exacerbation (moderate: HR, 1.63 [95% CI, 1.28-2.08]; severe: HR, 1.75 [95% CI, 0.99-3.11; nonsignificant]) and decreased over time, returning to baseline by 90 days. Risk of CVAESI resulting in hospitalization or death also increased during an exacerbation (moderate: HR, 2.46 [95% CI, 1.53-3.97]; severe: HR, 41.29 [95% CI, 30.43-56.03]) and decreased in a similar time-dependent pattern. Results were consistent regardless of exacerbation history, cardiovascular risk at screening, or study treatment. Conclusions Overall risk of cardiovascular events was higher during and in the 30 days following chronic obstructive pulmonary disease exacerbations, even among those with low cardiovascular risk, highlighting the need for exacerbation prevention and vigilance for cardiovascular events following exacerbations. Registration URL: https://clinicaltrials.gov/ct2/show/NCT02164513; Unique identifier: NCT02164513.

Purpose: The use of a robotic arm has been well-described in the literature for the placement of pedicle screws in spine surgery as well as implants for sacroiliac joint fusion. There are no reports describing the use of a robotic arm to place screws in osseous fixation pathways (OFPs) employed in the treatment of pelvic ring and acetabular fractures outside of a single center in China. Using a Sawbones model, the authors describe a technique for using a robotic arm widely available in Europe and the Americas for placement of 6.5 mm cannulated screws into two OFPs commonly used in the treatment of pelvic and acetabular fractures., Methods: Using the Mazor X Stealth Edition (MSXE) robot from Medtronic, the authors were able to place a pin into the pelvis onto which the robot was docked. The authors were then able to designate the area of interest using navigated instruments, and in combination with the MSXE "scan and plan" marker, obtain cross-sectional imaging using the O-Arm and successfully register the MSXE robot. We then used the provided software to plan trajectories for the lateral compression type 2 (LC-II) screw pathway as well as a pathway for a trans-ilio-trans-sacral screw. We describe in detail the steps for setup, planning and placement of 6.5 mm cannulated screws using the MSXE robotic arm into these two OFPs., Results: Visual inspection and plain x-rays demonstrated successful placement of the screws into the two planned OFPs. No breach of cortical bone was seen on either visual inspection of the model or demonstrated on post-procedure x-rays., Conclusion: It is possible to use the Mazor X Stealth Edition robot to place screws into the LC-II and trans-ilio-transsacral screw pathways in a Sawbones model. This is only a feasibility study, and should in no way be taken to suggest that clinical application of this technique should be attempted., (© 2022. The Author(s).)

Introduction: In the IMPACT trial, single-inhaler triple therapy fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) reduced moderate/severe exacerbation rates versus FF/VI or UMEC/VI dual therapy in patients with chronic obstructive pulmonary disease (COPD); however, pneumonia incidence was higher in FF-containing arms. As COPD is a growing problem in Asia, we compared the efficacy and safety of FF/UMEC/VI in Asia versus non-Asia regions., Methods: IMPACT was a double-blind, 52-week trial in symptomatic COPD patients with ≥ 1 moderate/severe exacerbation in the prior year. This pre-specified analysis evaluated the annual rate of moderate/severe exacerbations, change from baseline in trough forced expiratory volume in 1 s, and St George's Respiratory Questionnaire total score, mortality, and safety (including pneumonia) in Asia versus non-Asia regions., Results: The intent-to-treat population comprised 10,355 patients (Asia n = 1644 [16%]). Rate ratios (95% confidence intervals) for moderate/severe exacerbations with FF/UMEC/VI were 0.89 (0.76-1.05) versus FF/VI and 0.86 (0.71-1.04) versus UMEC/VI in Asia, and 0.84 (0.79-0.90) and 0.74 (0.68-0.80) in non-Asia. Efficacy of FF/UMEC/VI on other endpoints was similar in both regions. There was an increased incidence of investigator-reported pneumonia in patients in Asia (FF/UMEC/VI: 13%; FF/VI: 14%; UMEC/VI: 6%) compared with non-Asia (FF/UMEC/VI: 6%; FF/VI: 5%; UMEC/VI: 4%). The increased risk of pneumonia in patients in Asia was most marked in patients with lower body mass index, lower lung function, and taking inhaled corticosteroids. In post hoc analysis of adjudicated on-treatment all-cause mortality, probabilities of death were numerically lower in both regions with FF/UMEC/VI (Asia: 1.16%; non-Asia: 1.35%) and FF/VI (Asia: 1.77%; non-Asia: 1.21%) versus UMEC/VI (Asia: 1.91%; non-Asia: 2.23%)., Conclusions: FF/UMEC/VI provides similar benefits in COPD patients in Asia and non-Asia regions. Clinical benefits of treatment, including reduction in mortality risk, should be weighed against risk of pneumonia, taking account of all known risk factors., Trial Registration: ClinicalTrials.gov identification, NCT02164513.

Subglottic haemangioma presents as progressive obstruction in the neonatal and infantile airway, with a soft lesion seen during endoscopy. Diagnosis is based on macroscopic findings, biopsy is not usually performed and propranolol is first-line treatment. In contrast, ectopic thymus is a rare differential diagnosis for subglottic mass made by histopathological examination after excision or autopsy. In this article, we present a case of an infant with a subglottic lesion with endoscopic features consistent with haemangioma. After initial clinical response to propranolol, the patient represented with progressive stridor no longer responding to therapy. Open excision of the lesion was performed, and histopathology revealed ectopic thymus tissue. In this case, ectopic thymus tissue mimicked the presentation of subglottic haemangioma, and confirmation bias persisted due to an apparent initial clinical response to treatment with propranolol. In cases of subglottic mass refractory to medical treatment, excision of the lesion should be considered., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: Competing interests: None declared.

A 1-week-old female infant presented with a transilluminating neck lump that increased in size with crying. The presumptive diagnosis was lymphatic malformation, but imaging raised the possibility of an abscess or necrotic tumour. A biopsy revealed a likely developmental cyst with local inflammatory change. Microlaryngoscopy revealed a fourth branchial pouch sinus, which was cauterised. The sinus and neck lump resolved without need for further treatment., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Despite near-equal enrollment of males and females in medical schools, orthopaedic surgery continues to have one of the lowest percentage of female orthopaedic residents. This suggests there may be factors that specifically influence females to select other specialties. Some of these possible reasons have been explored in other studies; however, in this study, we sought to identify latent or unobserved variables that may be influencing this difference by conducting an explanatory factor analysis of male and female residency preferences., Purposes/questions: In this study, by surveying a cohort of medical students at a single institution, we asked, is there a difference between males and females (1) in their perception of orthopaedic surgery and (2) in their preferences for residency and practice? We further asked, if there are differences, (3) is there a correlation between perception and preferences for residency and practice?, Methods: A 46-question survey was sent to all current medical students (n = 628) at a major urban university with near-equal enrollment of males (55%, 345 of 628) and females (45%, 283 of 628) from September 2017 to November 2017. The survey consisted of two main parts: (1) desired attributes of a residency program and (2) perceptions of orthopaedic residency and practice. The design of the survey instruments closely followed The Checklist for Reporting Results of Internet E-Surveys (CHERRIES) checklist and went through several variations and pilot studies before release. In all, 33% (205 of 628) total medical students responded to the email survey, 55% (112 of 205) were male and 45% (93 of 205) were female. The proportion of male and female respondents matched the gender distribution of the total population surveyed, which at the time of the survey was 55% male and 45% female.The data analysis was performed using a Mann-Whitney U test and an explanatory factor analysis. The explanatory factor analysis was used to identify the correlation between survey variables among male and female students. An alpha less than 0.05 was considered significant for the Mann-Whitney U test and a factor greater than 0.5 was considered significant for the factor analysis., Results: Both male and female students ranked "work-life balance" and "variety in specialty" among the top three most important preferences. Females ranked "range of practice options," higher than males (72% females versus 60% males, r = 0.18; p = 0.009), and males ranked "previous exposure to the specialty" higher than females (65% females versus 71% males, r = 0.03; p = 0.70). Both male and female students had similar overall perceptions of orthopaedic surgery. Both males and females indicated that orthopedics is "male dominated," has "competitive entrance requirements," and requires "long residency work hours." They differed in their perception of "requires physical strength" (60% females versus 38% males, r = 0.28; p < 0.0005), and by how much orthopaedics is "male dominated" (95% females versus 77% males, r = 0.26; p < 0.0005). The factor analysis recognized that, although male and female students do have some similar residency preferences, the influence or weighing of those preferences is different for male and female students. In a manner similar to a personality assessment, the factor analysis produced four latent factors that can help explain variation seen in responses and helped identify influential factors that were not directly tested by the survey. The first such latent factor for females consisted of "work-life balance," "residency length," 'residency work hours," and "family-friendly specialty." Although the first latent factor for males consisted of "prestige," "income potential," "grade or step scores," and "competitiveness of residency program." The three subsequent latent factors also displayed variation in the make-up of the latent factors between males and female students., Conclusions: This study of medical students at an urban medical school found that male and female students shared many preferences for residency specialties and held many of the same perceptions regarding orthopaedic surgery. The explanatory factor analysis indicated that male and female students weight preferences differently when selecting a specialty; this difference may account for the large differences in proportion between males and females in orthopaedic residency., Clinical Relevance: Attracting talented residents and attending physicians is important for the success of any medical department. Although orthopaedics attracts some of the most talented students, these students are predominantly male. By identifying the multifactorial areas that may be inadvertently discouraging females from applying, orthopaedic residency programs may be able to better address those issues and attract the best talent of both genders.

Background: Clinical trials for brain tumors represent a significant opportunity for both patients and providers to understand and combat a disease with substantial morbidity. The aim of this study was to quantify and map ethnic and racial representation in brain tumor trials and examine the potential gaps in trial recruitment. We also show that these representation gaps persist even in large multicultural cities like New York City., Methods: We analyzed brain tumor clinical trials registered on www.clinicaltrials.gov between July 1, 2005 and completed on or before November 11, 2017. We used a combination of PubMed/MEDLINE and Google Scholar to find associated publications and obtained trial information as well as patient demographic information (when available) including race or ancestry., Results: Out of 471 trials, 27% had no published results. Only 28.4% of trials with results reported race or ethnicity of trial participants, with no observed upward trend by year. Whites were significantly overrepresented in trials for metastatic brain tumors ( P < .001) and high-grade trials ( P < .001). Blacks/African Americans (AAs), Hispanics, and Asians were significantly underrepresented ( P < .001) in high-grade trials, while only Blacks/AAs were underrepresented in trials for metastatic brain tumors ( P < .001). Representation gaps were not observed in pediatric trials. Despite being a multicultural hub, New York City displayed similar gaps in trial representation., Conclusions: Despite increasing representation in the American population, minorities are underrepresented in brain tumor trials. In addition, despite numerous legal requirements and ethical mandates, published results including race-based information are remarkably absent from 70% of brain tumor trials., (© The Author(s) 2020. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

Aims: Matrix metalloproteinase-2 (MMP-2) is a zinc-dependent protease which contributes to cardiac contractile dysfunction when activated during myocardial ischaemia-reperfusion (IR) injury. MMP-2 is localized to several subcellular sites inside cardiac myocytes; however, its role in the sarcoplasmic reticulum (SR) is unknown. The Ca2+ ATPase SERCA2a, which pumps cytosolic Ca2+ into the SR to facilitate muscle relaxation, is degraded in cardiac IR injury; however, the protease responsible for this is unclear. We hypothesized that MMP-2 contributes to cardiac contractile dysfunction by proteolyzing SERCA2a, thereby impairing its activity in IR injury., Methods and Results: Isolated rat hearts were subjected to IR injury in the presence or absence of the selective MMP inhibitor ARP-100, or perfused aerobically as a control. Inhibition of MMP activity with ARP-100 significantly improved the recovery of cardiac mechanical function and prevented the increase of a 70 kDa SERCA2a degradation fragment following IR injury, although 110 kDa SERCA2a and phospholamban levels appeared unchanged. Electrophoresis of IR heart samples followed by LC-MS/MS confirmed the presence of a SERCA2a fragment of ∼70 kDa. MMP-2 activity co-purified with SR-enriched microsomes prepared from the isolated rat hearts. Endogenous SERCA2a in SR-enriched microsomes was proteolyzed to ∼70 kDa products when incubated in vitro with exogenous MMP-2. MMP-2 also cleaved purified porcine SERCA2a in vitro. SERCA activity in SR-enriched microsomes was decreased by IR injury; however, this was not prevented with ARP-100., Conclusion: This study shows that MMP-2 activity is found in SR-enriched microsomes from heart muscle and that SERCA2a is proteolyzed by MMP-2. The cardioprotective actions of MMP inhibition in myocardial IR injury may include the prevention of SERCA2a degradation., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

The brain-specific tyrosine phosphatase, STEP (STriatal-Enriched protein tyrosine Phosphatase) is an important regulator of synaptic function. STEP normally opposes synaptic strengthening by increasing N-methyl D-aspartate glutamate receptor (NMDAR) internalization through dephosphorylation of GluN2B and inactivation of the kinases extracellular signal-regulated kinase 1/2 and Fyn. Here we show that STEP 61 is elevated in the cortex in the Nrg1 +/- knockout mouse model of schizophrenia (SZ). Genetic reduction or pharmacological inhibition of STEP prevents the loss of NMDARs from synaptic membranes and reverses behavioral deficits in Nrg1 +/- mice. STEP 61 protein is also increased in cortical lysates from the central nervous system-specific ErbB2/4 mouse model of SZ, as well as in human induced pluripotent stem cell (hiPSC)-derived forebrain neurons and Ngn2-induced excitatory neurons, from two independent SZ patient cohorts. In these selected SZ models, increased STEP 61 protein levels likely reflect reduced ubiquitination and degradation. These convergent findings from mouse and hiPSC SZ models provide evidence for STEP 61 dysfunction in SZ.