Aligning antimicrobial resistance surveillance with schistosomiasis research: an interlinked One Health approach.

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.

Dryland Performance Tests Are Not Good Predictors of World Aquatics Points in Elite Male and Female Swimmers.

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.

Scattering-Based Light-Sheet Microscopy Imaging of Human Papillomavirus-Associated Squamous Lesions of the Anal Canal: A Proof-of-Principle Study.

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.

Dyadic practice for the acquisition of laparoscopic skills (DALS)-A randomized controlled trial.

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.

Evaluation of multi-directional speed qualities throughout adolescence in youth soccer: The non-linear nature of transfer.

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.

The Musashi RNA binding proteins direct the translational activation of key pituitary mRNAs.

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.

The Use of Biofluid Markers to Evaluate the Consequences of Sport-Related Subconcussive Head Impact Exposure: A Scoping Review.

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.

Contrasting Characteristics and Outcomes of Sports-Related and Non-Sports-Related Traumatic Brain Injury.

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.

Secondary Public Safety Answering Points Delay the Response to out of Hospital Cardiac Arrest.

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.

When a dermatopathologist encounters the ultra-rare: A case series of superficial soft tissue/cutaneous myxopapillary ependymomas.

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.

Anterior Pituitary Transcriptomics Following a High-Fat Diet: Impact of Oxidative Stress on Cell Metabolism.

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.

Determinants and Temporal Trends of Dual Antiplatelet Therapy After Mild Noncardioembolic Stroke.

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.

Musashi Exerts Control of Gonadotrope Target mRNA Translation During the Mouse Estrous Cycle.

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.

Brain PET and SPECT imaging and quantification: a survey of the current status in the UK.

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.

Environmentally Resilient Microfluidic Point-of-Care Immunoassay Enables Rapid Diagnosis of Talaromycosis.

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.

Modelling the age-prevalence relationship in schistosomiasis: A secondary data analysis of school-aged-children in Mangochi District, Lake Malawi.

Schistosomiasis is an aquatic snail borne parasitic disease, with intestinal schistosomiasis (IS) and urogenital schistosomiasis (UGS) caused by Schistosoma mansoni and S. haematobium infections, respectively. School-aged-children (SAC) are a known vulnerable group and can also suffer from co-infections. Along the shoreline of Lake Malawi a newly emerging outbreak of IS is occurring with increasing UGS co-infection rates. Age-prevalence (co)infection profiles are not fully understood. To shed light on these (co)infection trends by Schistosoma species and by age of child, we conducted a secondary data analysis of primary epidemiological data collected from SAC in Mangochi District, Lake Malawi, as published previously. Available diagnostic data by child, were converted into binary response infection profiles for 520 children, aged 6-15, across 12 sampled schools. Generalised additive models were then fitted to mono- and dual-infections. These were used to identify consistent population trends, finding the prevalence of IS significantly increased [p = 8.45e-4] up to 11 years of age then decreasing thereafter. A similar age-prevalence association was observed for co-infection [p = 7.81e-3]. By contrast, no clear age-infection pattern for UGS was found [p = 0.114]. Peak prevalence of Schistosoma infection typically occurs around adolescence; however, in this newly established IS outbreak with rising prevalence of UGS co-infections, the peak appears to occur earlier, around the age of 11 years. As the outbreak of IS fulminates, further temporal analysis of the age-relationship with Schistosoma infection is justified. This should refer to age-prevalence models which could better reveal newly emerging transmission trends and Schistosoma species dynamics. Dynamical modelling of infections, alongside malacological niche mapping, should be considered to guide future primary data collection and intervention programmes.

Enhanced skeletal muscle contractile function and corticospinal excitability precede strength and architectural adaptations during lower-limb resistance training.

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.

Purification and characterization of human neural stem and progenitor cells.

The human brain undergoes rapid development at mid-gestation from a pool of neural stem and progenitor cells (NSPCs) that give rise to the neurons, oligodendrocytes, and astrocytes of the mature brain. Functional study of these cell types has been hampered by a lack of precise purification methods. We describe a method for prospectively isolating ten distinct NSPC types from the developing human brain using cell-surface markers. CD24-THY1-/lo cells were enriched for radial glia, which robustly engrafted and differentiated into all three neural lineages in the mouse brain. THY1hi cells marked unipotent oligodendrocyte precursors committed to an oligodendroglial fate, and CD24+THY1-/lo cells marked committed excitatory and inhibitory neuronal lineages. Notably, we identify and functionally characterize a transcriptomically distinct THY1hiEGFRhiPDGFRA- bipotent glial progenitor cell (GPC), which is lineage-restricted to astrocytes and oligodendrocytes, but not to neurons. Our study provides a framework for the functional study of distinct cell types in human neurodevelopment.

COVID-19 Diagnosis and SARS-CoV-2 Strain Identification by a Rapid, Multiplexed, Point-of-Care Antibody Microarray.

Antigen tests to detect SARS-CoV-2 have emerged as a promising rapid diagnostic method for COVID-19, but they are unable to differentiate between variants of concern (VOCs). Here, we report a rapid point-of-care test (POC-T), termed CoVariant-SPOT, that uses a set of antibodies that are either tolerant or intolerant to spike protein mutations to identify the likely SARS-CoV-2 strain concurrent with COVID-19 diagnosis using antibodies targeting the nucleocapsid protein. All reagents are incorporated into a portable, multiplexed, and sensitive diagnostic platform built upon a nonfouling polymer brush. To validate CoVariant-SPOT, we tested recombinant SARS-CoV-2 proteins, inactivated viruses, and nasopharyngeal swab samples from COVID-19 positive and negative individuals and showed that CoVariant-SPOT can readily distinguish between two VOCs: Delta and Omicron. We believe that CoVariant-SPOT can serve as a valuable adjunct to next-generation sequencing to rapidly identify variants using a scalable and deployable POC-T, thereby enhancing community surveillance efforts worldwide and informing treatment selection.