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In this article we analyse the classic Hodgkin and Keynes 1955 paper describing investigations of the independence principle, with the expectation that there is much students and educators can learn from such exercises, most notably how the authors applied their diverse skill set to tackling the numerous obstacles that the study presented. The paper encompasses three of the physiology core concepts; cell membranes, flow down gradients and scientific reasoning, which were recently assigned to the classes The Biological World, The Physical World and Ways of Looking at the World, respectively. Thus, analysis of such a paper illuminates the relationships that exist between distinct concepts and encourages a holistic approach to understanding physiology. In depth analysis of the paper allows us to follow the authors' thought processes from their realisation that previous methods lacked the resolution to answer a fundamental question relating to ion movement across membranes, to the application of a more sensitive technique and ultimately the development a novel model describing ion flux. This paper was the culmination of work started in the mid 1930s, strongly supported the ionic theory of nervous conduction proposed by Hodgkin and Huxley, and predicted the presence of ion channels as narrow pores through which ions moved sequentially four decades before these characteristics were convincingly demonstrated.

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BACKGROUND: Male Genital Schistosomiasis (MGS) remains an often-overlooked chronic sequela of urogenital schistosomiasis in endemic areas of sub-Saharan Africa. As part of a 2-year longitudinal study on Hybridization of UroGenital Schistosomiasis (HUGS) in Malawi, a MGS sub-study was conducted to assess whether hybrid schistosomes were incriminated. METHODS: During recruitment, demographic, health and socio-economic data were collected through individual questionnaire interviews in Mthawira community from Nsanje District along Shire River and Samama community from Mangochi District along Lake Malawi shoreline. Urine and semen samples were collected and analysed to determine the identity of schistosome infection. Urine filtration and microscopy, direct microscopy of semen and its sediments (after centrifugation) were performed. Thereafter, the sediments were examined by molecular DNA analysis with a novel two-tube real-time PCR assay. The participants were also screened for Human papilloma virus (HPV) and other sexually transmitted infections (STIs). RESULTS: Twenty-two men were recruited for the sub-study, 8 in Nsanje District and 14 in Mangochi District, with a median age of 22.0 years. By microscopy, ten (45.7%) participants had Schistosoma ova in their urine, 11 (50.0%) in semen while 16 (72.7%) were positive by real-time PCR. One participant had both S. haematobium and S. mattheei ova in his semen, three showed symptoms, and one had a mixed infection of S. mansoni and possible S. haematobium-S. mattheei hybrid. Twelve men had detectable high-risk HPV serotypes 16, 18 and others while six had Trichomonas vaginalis and other STIs. CONCLUSION: Zoonotic and hybrid schistosomes can cause MGS similar to human schistosomes, which can be co-infected with HPV and STIs, thereby posing a new challenge in diagnosis, management and control measures in resource poor settings. Increased awareness of these infections among local communities and primary healthcare workers and improvement of disease management are needed and advocated.

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Introduction: There is a growing interest in characterizing the cognitive-motor processes that underlie superior performance in highly skilled athletes. The aim of this study was to explore neural markers of putting performance in highly skilled golfers by recording mobile EEG (electroencephalogram) during the pre-shot period. Methods: Twenty-eight right-handed participants (20 males) with a mean age of 24.2 years (± 6.4) and an average handicap of +1.7 (± 6.4) completed a testing session. Following the warm-up, participants completed 140 putts from a distance of 8ft (2.4m), with putts taken from 5 different positions. While putting, participants wore an eye tracker and a gel-based EEG system with 32 electrodes. Time and frequency domain features of the EEG signals were extracted to characterize Movement-Related Cortical Potentials (MRCP) and rhythmic modulations of neural activity in theta, alpha, sensorimotor and beta frequency bands associated with putting performance. Results: Eye-tracking data demonstrate that mean Quiet Eye durations are not a reliable marker of expertise as the same duration was found for both successful and unsuccessful putts. Following rigorous data processing data from 12 participants (8 males, mean age 21.6 years ± 5.4, average handicap +1.5 ± 4.4) were included in the EEG analysis. MRCP analysis revealed performance-based differences, with unsuccessful putts having a greater negative amplitude in comparison to successful putts. Time frequency analysis of the EEG data revealed that successful putts exhibit distinct neural activity profiles compared to unsuccessful ones. For successful putts, greater suppression of beta was present in the central region prior to the putt. By contrast, increased frontal theta power was present for unsuccessful putts immediately before the putt (consistent with hesitation and the need for motor plan adjustments prior to execution). Discussion: We propose that neural activity may provide plausible insights into the mechanisms behind why identical QE durations can lead to both success and failure. From an applied perspective, this study highlights the merits of a multi-measure approach to gain further insights into performance differences within highly skilled golfers. We discuss considerations for future research and solutions to address the challenges related to the complexities of collecting clean EEG signals within naturalistic sporting contexts.

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One Health surveillance involves the analysis of human, animal and environmental samples, recognising their interconnectedness in health systems. Such considerations are crucial to investigate the transmission of many pathogens, including drug-resistant bacteria and parasites. The highest rates of antimicrobial resistance (AMR)-associated deaths are observed in sub-Saharan Africa, where concurrently the waterborne parasitic disease schistosomiasis can be highly endemic in both humans and animals. Although there is growing acknowledgment of significant interactions between bacteria and parasites, knowledge of relationships between schistosomes, microbes and AMR remains inadequate. In addition, newly emergent research has revealed the previously underappreciated roles of animals and the environment in both AMR and schistosomiasis transmission. We consider shared environmental drivers and colonisation linkage in this narrative review, with a focus on extended-spectrum beta-lactamase-mediated resistance among bacteria from the Enterobacteriaceae family, which is exceedingly prevalent and responsible for a high burden of AMR-associated deaths. Then we examine novel findings from Malawi, where the landscapes of AMR and schistosomiasis are rapidly evolving, and make comparisons to other geographic areas with similar co-infection epidemiology. We identify several knowledge gaps that could be addressed in future research, including the need to characterise the impact of intestinal schistosomiasis and freshwater contact on intestinal AMR colonisation, before proposing a rationale for connecting AMR surveillance and schistosomiasis research within a One Health framework.

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BACKGROUND: The rising prevalence of work-related musculoskeletal disorders has numerous physical, financial, and mental repercussions for surgeons. This study aims to establish whether the use of a wearable posture device can improve the operating time spent in suboptimal, high-risk postures. METHODS: Surgeons were recruited in Phase 1 of this prospective randomised study and baseline postural data was obtained. In Phase 2, participants were randomised to receive either a traditional educational workshop or intraoperative vibrations from the device to correct postural lapses. During minor elective day cases, intraoperative postural data was collected and stratified by forward flexion angle, into five risk categories (negligible to very high). Participants' experience with the sensor was also assessed. RESULTS: A total of 100 surgical procedures (Phase 1: n = 50; Phase 2: n = 50) were performed by eight surgeons of varying seniority. Exposure to the educational intervention increased time spent in suboptimal posture (Phase 1 vs. Phase 2); 47.5% vs. 67.8%, p = 0.05. However, the vibrational intervention significantly reduced this time; 50.0% vs. 20.7%, p = 0.005. Procedure type didn't influence posture although, laparoscopic interventions spent most time in negligible-risk postures; 47.7% vs. 49.3%, compared to open procedures. Surgical consultants spent less time in suboptimal posture compared to fellow/registrars; 30.3% vs. 72.6% (Phase 1) and 33.8% vs. 65.3% (Phase 2). CONCLUSION: Vibrational intervention from the device significantly decreased the time spent in suboptimal, high-risk postures. As procedure type wasn't correlated with postural changes, surgeon-specific factors in regulating posture are paramount. Finally, surgeon experience was positively correlated with improved surgical ergonomics.

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BACKGROUND: Laparoscopic simulation is integral to surgical education but requires significant resources. We aimed to compare the effectiveness of dyadic practice (DP), involving two individuals working together, to individual practice (IP) for novices acquiring laparoscopic skills and assess their learning experience. METHODS: We conducted a Randomized Controlled Trial comparing DP and IP for novice medical students who completed a laparoscopic simulation workshop. Participants were assessed individually pre-course (test 1), post-course (test 2), and 8-week retention (test 3) using a validated quantitative method. A post-course questionnaire and interview, analyzed with thematic analysis, assessed the learning experience. RESULTS: In total, 31 DP and 35 IP participants completed the study. There was no difference in mean scores between DP and IP groups in all three tests: test 1 (p = 0.55), test 2 (p = 0.26), test 3 (p = 0.35). In trend analysis, the DP group improved post-course (test 1 vs. 2: p = 0.02) and maintained this level at the retention test (2 vs. 3: p = 0.80, 1 vs. 3: p = 0.02). Whilst the IP group also improved post-course (test 1 vs. 2: p < 0.001), this improvement was not retained (2 vs. 3: p = 0.003, 1 vs. 3: p = 0.32). Thematic analysis revealed that DP participants valued peer support, peer feedback and observation time, but also acknowledged the limitations of reduced practical time and issues with teamwork. CONCLUSION: DP is non-inferior to IP for novices learning laparoscopic skills, is well received and may lead to superior long-term skill retention.

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Demand for anal cancer screening is expected to rise following the recent publication of the Anal Cancer-HSIL Outcomes Research trial, which showed that treatment of high-grade squamous intraepithelial lesions significantly reduces the rate of progression to anal cancer. While screening for human papillomavirus-associated squamous lesions in the cervix is well established and effective, this is less true for other sites in the lower anogenital tract. Current anal cancer screening and prevention rely on high-resolution anoscopy with biopsies. This procedure has a steep learning curve for providers and may cause patient discomfort. Scattering-based light-sheet microscopy (sLSM) is a novel imaging modality with the potential to mitigate these challenges through real-time, microscopic visualization of disease-susceptible tissue. Here, we report a proof-of-principle study that establishes feasibility of dysplasia detection using an sLSM device. We imaged 110 anal biopsy specimens collected prospectively at our institution's dysplasia clinic (including 30 nondysplastic, 40 low-grade squamous intraepithelial lesion, and 40 high-grade squamous intraepithelial lesion specimens) and found that these optical images are highly interpretable and accurately recapitulate histopathologic features traditionally used for the diagnosis of human papillomavirus-associated squamous dysplasia. A reader study to assess diagnostic accuracy suggests that sLSM images are noninferior to hematoxylin and eosin images for the detection of anal dysplasia (sLSM accuracy = 0.87; hematoxylin and eosin accuracy = 0.80; P = .066). Given these results, we believe that sLSM technology holds great potential to enhance the efficacy of anal cancer screening by allowing accurate sampling of diagnostic tissue at the time of anoscopy. While the current imaging study was performed on ex vivo biopsy specimens, we are currently developing a handheld device for in vivo imaging that will provide immediate microscopic guidance to high-resolution anoscopy providers.

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Background: Swim performance can be reliant on strength and power. Standardisation of swim performance in different events, distances, and sexes can be completed using World Aquatics points, allowing for ranking of swimmers. The aim of this retrospective cross-sectional study was to assess whether relationships between World Aquatics points and dryland markers of performance existed in male and female elite swimmers separately and combined. Methods: Dryland tests included Optojump® photoelectric cell countermovement jump, countermovement jump reach with a Vertec® system, standing broad jump using a tape measure, repetition maximum testing in the barbell back squat, barbell deadlift, and barbell bench press. Swim performance data and dryland test data on elite male (n = 38) and female (n = 20) Scottish swimmers from 2009-2017 were collected. Swim performance data were converted to World Aquatics federation points, and Bayesian linear regression analyses examined relationships between World Aquatics points and dryland performance tests: countermovement jump height (cm) using an Optojump® photoelectric cells system, countermovement jump height (cm) using a Vertec® device, standing broad jump distance (cm), relative strength (load lifted (kg) per kg of body mass) in the barbell bench press (kg/kg), barbell back squat (kg/kg), barbell deadlift (kg/kg). Results: The Bayesian estimates of change of World Aquatics points for a unit change in jump-based measures were: Optojump®-men = 0.6, women = 0.6, combined = 0.4; Vertec®-men = 4.3, women = -1.6, combined = 2.4; standing broad jump-men = 0, women = 0, combined = 0.4. Strength-based measures were: barbell back squat-men = 2.3, women = 22, combined = -2.5; barbell deadlift-men = -5; barbell bench press-men = 41.8. Conclusions: Dryland performance tests are not good predictors of World Aquatics points and should rather be used for assessing training quality and monitoring injury risks.

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The pituitary functions as a master endocrine gland that secretes hormones critical for regulation of a wide variety of physiological processes including reproduction, growth, metabolism and stress responses. The distinct hormone-producing cell lineages within the pituitary display remarkable levels of cell plasticity that allow remodeling of the relative proportions of each hormone-producing cell population to meet organismal demands. The molecular mechanisms governing pituitary cell plasticity have not been fully elucidated. Our recent studies have implicated a role for the Musashi family of sequence-specific mRNA binding proteins in the control of pituitary hormone production, pituitary responses to hypothalamic stimulation and modulation of pituitary transcription factor expression in response to leptin signaling. To date, these actions of Musashi in the pituitary appear to be mediated through translational repression of the target mRNAs. Here, we report Musashi1 directs the translational activation, rather than repression, of the Prop1, Gata2 and Nr5a1 mRNAs which encode key pituitary lineage specification factors. We observe that Musashi1 further directs the translational activation of the mRNA encoding the glycolipid Neuronatin (Nnat) as determined both in mRNA reporter assays as well as in vivo. Our findings suggest a complex bifunctional role for Musashi1 in the control of pituitary cell function.

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Training and assessment of agility is often prioritised by soccer coaches and practitioners aiming to develop multi-directional speed. Although the importance of agility is advocated throughout childhood and adolescence, limited data evidence agility performance at different stages of adolescence. The purpose of this study was to examine differences in multi-directional speed performance in youth soccer players spanning an entire soccer academy. A total of 86 male junior-elite soccer players volunteered to participate. Anthropometric data were collected, alongside performance data from a battery of physical tests including sprinting, jumping, change of direction, reaction time, and agility. Bayesian models using log-likelihoods from posterior simulations of parameter values displayed linear or curvilinear relationships between both chronological and biological age and performance in all tests other than agility and reaction time. For agility and reaction time tests, performance improved until ~14 years of age or the estimated age of peak height velocity whereby arrested development in performance was observed. Our results demonstrate that while most performance skills improve as chronological or biological age increases, measures of agility and reaction time may not. These findings support the notion that agility performance is complex and multifaceted, eliciting unique, challenging physical demands and non-linear development.

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Importance: Exposure to traumatic brain injury (TBI) has raised widespread concern over participation in sports, particularly over possible long-term consequences. However, little is known about the outcomes of individuals presenting to hospitals with sports-related TBI. Objective: To compare the characteristics and outcomes of individuals presenting to hospitals with sports-related and non-sports-related TBI. Design, Setting, and Participants: The CENTER-TBI (Collaborative European NeuroTrauma Effectiveness Research in TBI) observational cohort study was conducted at hospitals in 18 countries. The study enrolled 4509 patients who had TBI and had an indication for computed tomography (CT), of whom 4360 were 16 years or older. Outcomes were assessed at 3 and 6 months, and groups were compared using regression analyses adjusting for clinical and demographic differences. Data were collected between December 9, 2014, and December 17, 2017, and analyzed from August 2022 to March 2023. Exposure: Sports-related and non-sports-related TBI with subgroups selected by severity of injury. Main Outcomes and Measures: The main outcome was the Glasgow Outcome Scale-Extended (GOSE) at 6 months, with secondary outcomes covering postconcussion symptoms, health-related quality of life, and mental health. Results: A total of 4360 patients were studied, including 256 (6%) with sports-related TBI (mean [SD] age, 38.9 [18.1] years; 161 [63%] male) and 4104 with non-sports-related TBI (mean [SD] age, 51.0 [20.2] years; 2773 [68%] male). Compared with patients with non-sports-related TBI, patients with sports-related TBI were younger, more likely to have tertiary education, more likely to be previously healthy, and less likely to have a major extracranial injury. After adjustment, the groups did not differ in incomplete recovery (GOSE scores <8) at 6 months (odds ratio [OR], 1.27; 95% CI, 0.90-1.78; P = .22 for all patients; OR, 1.20; 95% CI, 0.83-1.73; P = .34 for those with mild TBI; and OR, 1.19; 95% CI, 0.74-1.92; P = .65 for those with mild TBI and negative CT findings). At 6 months, there was incomplete recovery in 103 of 223 patients (46%) with outcomes in the sports-related TBI group, 65 of 168 (39%) in those with mild sports-related TBI, and 30 of 98 (31%) in those with mild sports-related TBI and negative CT findings. In contrast, at 6 months, the sports-related TBI group had lower prevalence of anxiety, depression, posttraumatic stress disorder, and postconcussion symptoms than the non-sports-related group. Conclusions and Relevance: In this cohort study of 4360 patients with TBI, functional limitations 6 months after injury were common after sports-related TBI, even mild sports-related TBI. Persisting impairment was evident in the sports-related TBI group despite better recovery compared with non-sports-related TBI on measures of mental health and postconcussion symptoms. These findings caution against taking an overoptimistic view of outcomes after sports-related TBI, even if the initial injury appears mild.

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BACKGROUND: Amidst growing concern about the safety of sport-related repetitive subconcussive head impacts (RSHI), biofluid markers may provide sensitive, informative, and practical assessment of the effects of RSHI exposure. OBJECTIVE: This scoping review aimed to systematically examine the extent, nature, and quality of available evidence from studies investigating the effects of RSHI on biofluid markers, to identify gaps and to formulate guidelines to inform future research. METHODS: PRISMA extension for Scoping Reviews guidelines were adhered to. The protocol was pre-registered through publication. MEDLINE, Scopus, SPORTDiscus, CINAHL, PsycINFO, Cochrane Library, OpenGrey, and two clinical trial registries were searched (until March 30, 2022) using descriptors for subconcussive head impacts, biomarkers, and contact sports. Included studies were assessed for risk of bias and quality. RESULTS: Seventy-nine research publications were included in the review. Forty-nine studies assessed the acute effects, 23 semi-acute and 26 long-term effects of RSHI exposure. The most studied sports were American football, boxing, and soccer, and the most investigated markers were (in descending order): S100 calcium-binding protein beta (S100B), tau, neurofilament light (NfL), glial fibrillary acidic protein (GFAP), neuron-specific enolase (NSE), brain-derived neurotrophic factor (BDNF), phosphorylated tau (p-tau), ubiquitin C-terminal hydrolase L1 (UCH-L1), and hormones. High or moderate bias was found in most studies, and marker-specific conclusions were subject to heterogeneous and limited evidence. Although the evidence is weak, some biofluid markers-such as NfL-appeared to show promise. More markedly, S100B was found to be problematic when evaluating the effects of RSHI in sport. CONCLUSION: Considering the limitations of the evidence base revealed by this first review dedicated to systematically scoping the evidence of biofluid marker levels following RSHI exposure, the field is evidently still in its infancy. As a result, any recommendation and application is premature. Although some markers show promise for the assessment of brain health following RSHI exposure, future large standardized and better-controlled studies are needed to determine biofluid markers' utility.

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Background: National guidelines recommend that high-performing systems process 9-1-1 calls within 60 s and deliver the first telecommunicator cardiopulmonary resuscitation compression within 90 s. The inability of systems employing secondary public safety answering points (PSAPs) to capture the call arrival timestamp at the primary PSAP is a challenge in out-of-hospital cardiac arrest response time research.Objective: We sought to measure the interval from call receipt at primary PSAPs to call answer at secondary PSAPs in metropolitan areas.Methods: This was a retrospective observational study evaluating 9-1-1 call transfers between PSAPs serving large urban populations. Call transfer records were extracted from the 9-1-1 telephony systems at the primary and secondary PSAPs covering seven metropolitan EMS systems. For each transferred call, we obtained the call arrival timestamp at both the primary and secondary PSAPs. The primary outcome was the interval between these two times. Results were compared to a national standard of 90% of calls forwarded within 30 s of receipt.Results: Data collected at seven metropolitan EMS agencies from January 1, 2021, through June 30, 2021, yielded 299,679 records for evaluation. The median interval required to transfer a 9-1-1 caller from primary to secondary PSAPs was 41 s (IQR 31, 59), and 86 s at the 90th percentile. The 90th percentile performance level at individual agencies ranged from 63 s to 117 s.Conclusions: The primary to secondary PSAP transfer interval lengths observed in this study preclude these EMS agencies from meeting out-of-hospital cardiac arrest performance recommendations at the 90% percentile performance level.

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Myxopapillary ependymoma (MPE) is an uncommon variant of ependymoma, almost exclusively seen in conus medullaris or filum terminale. MPE can be diagnostically challenging, especially when arising extra-axially. Here we report 5 cases of superficial soft tissue/cutaneous MPE, identified across three tertiary institutions. All patients were female and three of them (3/5, 60%) were children (median age 11 years, range 6-58 years). The tumors presented as slow-growing masses of the sacrococcygeal subcutaneous soft tissues, occasionally identified after minor trauma and clinically favored to be pilonidal sinuses. Imaging showed no neuraxis connection. Macroscopically, tumors were well-circumscribed, lobulated, and solid and microscopically they exhibited typical histopathology of MPE, at least focally. Two of the tumors (2/5, 40%) showed predominantly solid or trabecular architecture with greater cellular pleomorphism, scattered giant cells, and increased mitotic activity. All tumors (5/5, 100%) showed strong diffuse immunohistochemical expression of GFAP. One tumor clustered at the category "ependymoma, myxopapillary" by methylome analysis. Two patients (2/5, 40%) had local recurrence at 8 and 30 months after the initial surgery. No patients developed metastases during the follow-up period (median 60 months, range 6-116 months). Since a subset of extra-axial MPEs behaves more aggressively, timely and accurate diagnosis is of paramount importance.

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Anterior pituitary cell function requires a high level of protein synthesis and secretion which depend heavily on mitochondrial adenosine triphosphate production and functional endoplasmic reticula. Obesity adds stress to tissues, requiring them to adapt to inflammation and oxidative stress, and adding to their allostatic load. We hypothesized that pituitary function is vulnerable to the stress of obesity. Here, we utilized a 10- to 15-week high-fat diet (HFD, 60%) in a thermoneutral environment to promote obesity, testing both male and female FVB.129P mice. We quantified serum hormones and cytokines, characterized the metabolic phenotype, and defined changes in the pituitary transcriptome using single-cell RNA-sequencing analysis. Weight gain was significant by 3 weeks in HFD mice, and by 10 weeks all HFD groups had gained 20 g. HFD females (15 weeks) had increased energy expenditure and decreased activity. All HFD groups showed increases in serum leptin and decreases in adiponectin. HFD caused increased inflammatory markers: interleukin-6, resistin, monocyte chemoattractant protein-1, and tumor necrosis factorα. HFD males and females also had increased insulin and increased TSH, and HFD females had decreased serum prolactin and growth hormone pulse amplitude. Pituitary single-cell transcriptomics revealed modest or no changes in pituitary cell gene expression from HFD males after 10 or 15 weeks or from HFD females after 10 weeks. However, HFD females (15 weeks) showed significant numbers of differentially expressed genes in lactotropes and pituitary stem cells. Collectively, these studies reveal that pituitary cells from males appear to be more resilient to the oxidative stress of obesity than females and identify the most vulnerable pituitary cell populations in females.

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BACKGROUND: Short-term dual antiplatelet therapy (DAPT) reduces early stroke recurrence after mild noncardioembolic ischemic stroke (NCIS). We aim to evaluate temporal trends and determinants of DAPT prescription after mild NCIS in the Florida Stroke Registry, a statewide registry across Get With The Guidelines-Stroke participating hospitals. METHODS: In this cross-sectional analysis of a cohort study, we included patients with mild NCIS (National Institutes of Health Stroke Scale score ≤3) who were potentially eligible for DAPT across 168 Florida Stroke Registry participating hospitals between January 2010 and September 2022. Using antiplatelet prescription as the dependent variable (DAPT versus single antiplatelet therapy), we fit logistic regression models adjusted for patient-related factors, hospital-related factors, clinical presentation, vascular risk factors, and ischemic stroke subtype, to obtain adjusted odds ratios (aORs) with 95% CIs. RESULTS: From 283 264 Florida Stroke Registry ischemic stroke patients during the study period, 109 655 NCIS were considered eligible. Among these, 37 058 patients with National Institutes of Health Stroke Scale score >3 were excluded, resulting in a sample of 72 597 mild NCIS (mean age 68±14 years; female 47.3%). Overall, 24 693 (34.0%) patients with mild NCIS were discharged on DAPT and 47 904 (66.0%) on single antiplatelet therapy. DAPT prescription increased from 25.7% in 2010 to 52.8% in 2022 (ß/year 2.5% [95% CI, 1.5%-3.4%]). Factors associated with DAPT prescription were premorbid antiplatelet therapy (aOR, 4.66 [95% CI, 2.20-9.88]), large-artery atherosclerosis (aOR, 1.68 [95% CI, 1.43-1.97]), diabetes (aOR, 1.29 [95% CI, 1.13-1.47]), and hyperlipidemia (aOR, 1.24 [95% CI, 1.10-1.39]), whereas female sex (aOR, 0.83 [95% CI, 0.75-0.93]), being non-Hispanic Black patients (compared with non-Hispanic White patients; aOR, 0.78 [95% CI, 0.68-0.90]), admission to a Thrombectomy-capable Stroke Center (compared with Comprehensive Stroke Center; aOR, 0.78 [95% CI, 0.66-0.92]), time-to-presentation 1 to 7 days from last seen well (compared with <24 h; aOR, 0.86 [95% CI, 0.76-0.96]), and small-vessel disease stroke (aOR, 0.81 [95% CI, 0.72-0.94]) were associated with not receiving DAPT at discharge. CONCLUSIONS: Despite a temporal trend increase in DAPT prescription after mild NCIS, we found substantial underutilization of evidence-based DAPT associated with significant disparities in stroke care.

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The anterior pituitary controls key biological processes, including growth, metabolism, reproduction, and stress responses through distinct cell types that each secrete specific hormones. The anterior pituitary cells show a remarkable level of cell type plasticity that mediates the shifts in hormone-producing cell populations that are required to meet organismal needs. The molecular mechanisms underlying pituitary cell plasticity are not well understood. Recent work has implicated the pituitary stem cell populations and specifically, the mRNA binding proteins of the Musashi family in control of pituitary cell type identity. In this study we have identified the target mRNAs that mediate Musashi function in the adult mouse pituitary and demonstrate the requirement for Musashi function in vivo. Using Musashi RNA immunoprecipitation, we identify a cohort of 1184 mRNAs that show specific Musashi binding. Identified Musashi targets include the Gnrhr mRNA, which encodes the gonadotropin-releasing hormone receptor (GnRHR), and the Fshb mRNA, encoding follicle-stimulating hormone (FSH). Reporter assays reveal that Musashi functions to exert repression of translation of the Fshb mRNA, in addition to the previously observed repression of the Gnrhr mRNA. Importantly, mice engineered to lack Musashi in gonadotropes demonstrate a failure to repress translation of the endogenous Gnrhr and Fshb mRNAs during the estrous cycle and display a significant heterogeneity in litter sizes. The range of identified target mRNAs suggests that, in addition to these key gonadotrope proteins, Musashi may exert broad regulatory control over the pituitary proteome in a cell type-specific manner.

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OBJECTIVES: With disease-modifying therapies in development for neurological disorders, quantitative brain imaging techniques become increasingly relevant for objective early diagnosis and assessment of response to treatment. The aim of this study was to evaluate the use of Brain SPECT and PET scans in the UK and explore drivers and barriers to using quantitative analysis through an online survey. METHODS: A web-based survey with 27 questions was used to capture a snapshot of brain imaging in the UK. The survey included multiple-choice questions assessing the availability and use of quantification for DaTscan, Perfusion SPECT, FDG PET and Amyloid PET. The survey results were reviewed and interpreted by a panel of imaging experts. RESULTS: Forty-six unique responses were collected and analysed, with 84% of responses from brain imaging sites. Within these sites, 88% perform DaTscan, 50% Perfusion SPECT, 48% FDG PET, and 33% Amyloid PET, while a few sites use other PET tracers. Quantitative Brain analysis is used in 86% of sites performing DaTscans, 40% for Perfusion SPECT, 63% for FDG PET and 42% for Amyloid PET. Commercial tools are used more frequently than in-house software. CONCLUSION: The survey showed variations across the UK, with high availability of DaTscan imaging and quantification and lower availability of other SPECT and PET scans. The main drivers for quantification were improved reporting confidence and diagnostic accuracy, while the main barriers were a perception of a need for an appropriate database of healthy controls and a lack of training, time, and software availability.

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Point-of-care tests (POCTs) are increasingly being used in field settings, particularly outdoors. The performance of current POCTs─most commonly the lateral flow immunoassay─can be adversely affected by ambient temperature and humidity. We developed a self-contained immunoassay platform─the D4 POCT─that can be conducted at the POC by integrating all reagents in a capillary-driven passive microfluidic cassette that minimizes user intervention. The assay can be imaged and analyzed on a portable fluorescence reader─the D4Scope─and provide quantitative outputs. Here, we systematically investigated the resilience of our D4 POCT to varied temperature and humidity and to physiologically diverse human whole blood samples that span a wide range of physiological hematocrit (30-65%). For all conditions, we showed that the platform maintained high sensitivity (0.05-0.41 ng/mL limits of detection). The platform also demonstrated good accuracy in reporting true analyte concentration across environmental extremes when compared to the manually operated format of the same test to detect a model analyte─ovalbumin. Additionally, we engineered an improved version of the microfluidic cassette that improved the ease-of-use of the device and shortened the time-to-result. We implemented this new cassette to create a rapid diagnostic test to detect talaromycosis infection in patients with advanced HIV disease at the POC, demonstrating comparable sensitivity and specificity to the laboratory test for the disease.

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PURPOSE: Evolving investigative techniques are providing greater understanding about the early neuromuscular responses to resistance training among novice exercisers. The aim of this study was to investigate the time-course of changes in muscle contractile mechanics, architecture, neuromuscular, and strength adaptation during the first 6-weeks of lower-limb resistance training. METHODS: Forty participants: 22 intervention (10 males/12 females; 173.48 ± 5.20 cm; 74.01 ± 13.13 kg) completed 6-week resistance training, and 18 control (10 males/8 females; 175.52 ± 7.64 cm; 70.92 ± 12.73 kg) performed no resistance training and maintained their habitual activity. Radial muscle displacement (Dm) assessed via tensiomyography, knee extension maximal voluntary contraction (MVC), voluntary activation (VA), corticospinal excitability and inhibition via transcranial magnetic stimulation, motor unit (MU) firing rate, and muscle thickness and pennation angle via ultrasonography were assessed before and after 2, 4, and 6-weeks of dynamic lower-limb resistance training or control. RESULTS: After 2-weeks training, Dm reduced by 19-25% in the intervention group; this was before any changes in neural or morphological measures. After 4-weeks training, MVC increased by 15% along with corticospinal excitability by 16%; however, there was no change in VA, corticospinal inhibition, or MU firing rate. After 6-weeks training there was further MVC increase by 6% along with muscle thickness by 13-16% and pennation angle by 13-14%. CONCLUSION: Enhanced contractile properties and corticospinal excitability occurred before any muscle architecture, neural, and strength adaptation. Later increases in muscular strength can be accounted for by architectural adaptation.

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