Calcium carbonate rhinolithiasis associated with chronic lymphocytic rhinitis in a pet rabbit (Oryctolagus cuniculus).

A 6-year-old intact female domestic dwarf rabbit (Oryctolagus cuniculus) was referred because of a chronic obstructive rhinitis not resolving despite antibiotic treatments. Computed tomography examination revealed 2 sub-obstructive structures of mineral density in the right nasal cavity and nasopharynx. Neoplasia and rhinolithiasis were the main differential diagnoses. A dorsal rhinostomy was performed and 1 mineralized lesion was removed. Infrared spectrophotometric and histological examinations of the lesion and nasal mucosa were consistent with a 100% calcium carbonate rhinolith with bacterial colonization and chronic lymphocytic rhinitis. Clinical signs improved during the first 4 wk following surgery. However, despite inhaled anti-inflammatory treatment, the rabbit's condition deteriorated when the rhinostomy site closed, and she died 7 wk after surgery. Rhinolith and lymphocytic rhinitis should be considered as differential diagnoses for upper respiratory tract signs in rabbits resistant to antimicrobial treatment. Key clinical message: Rhinolithiasis and chronic lymphocytic rhinitis should be included in the differential diagnoses of rabbits presenting with chronic obstructive upper respiratory tract signs characterized by purulent nasal discharge and failure of treatment despite adequate antimicrobial therapy, especially with unilateral signs. Computed tomography and rhinoscopy with biopsies are suggested to explore those possibilities.

Rhinolithiase au carbonate de calcium associée à une rhinite lymphoïde chronique chez un lapin de compagnie (Oryctolagus cuniculus)Une lapine naine domestique (Oryctolagus cuniculus) intacte, âgée de 6 ans, a été référée en raison d'une rhinite obstructive chronique non résolue malgré des traitement antibiotiques. L'examen tomodensitométrique a révélé 2 structures sous-obstructives de densité minérale dans la cavité nasale droite et le nasopharynx. La néoplasie et la rhinolithiase étaient les principaux diagnostics différentiels. Une rhinostomie dorsale a été réalisée et 1 lésion minéralisée a été retirée. Les examens par spectrophotométrie infrarouge et histologiques de la lésion et de la muqueuse nasale étaient compatibles avec un rhinolithe à 100 % en carbonate de calcium avec colonisation bactérienne et rhinite lymphocytaire chronique. Les signes cliniques se sont améliorés au cours des 4 premières semaines suivant l'intervention chirurgicale. Cependant, malgré un traitement anti-inflammatoire inhalé, l'état de la lapine s'est détérioré lors de la fermeture du site de rhinostomie et elle est décédée 7 semaines après l'opération. Le rhinolithe et la rhinite lymphocytaire doivent être envisagés comme diagnostic différentiel des signes des voies respiratoires supérieures chez les lapins résistants au traitement antimicrobien.Message clinique clé :La rhinolithiase et la rhinite lymphocytaire chronique doivent être incluses dans les diagnostics différentiels des lapins présentant des signes obstructifs chroniques des voies respiratoires supérieures caractérisés par un écoulement nasal purulent et un échec du traitement malgré un traitement antimicrobien adéquat, en particulier avec des signes unilatéraux. La tomodensitométrie et la rhinoscopie avec biopsies sont suggérées pour explorer ces possibilités.(Traduit par Dr Serge Messier).

Application of machine learning models for property prediction to targeted protein degraders.

Machine learning (ML) systems can model quantitative structure-property relationships (QSPR) using existing experimental data and make property predictions for new molecules. With the advent of modalities such as targeted protein degraders (TPD), the applicability of QSPR models is questioned and ML usage in TPD-centric projects remains limited. Herein, ML models are developed and evaluated for TPDs' property predictions, including passive permeability, metabolic clearance, cytochrome P450 inhibition, plasma protein binding, and lipophilicity. Interestingly, performance on TPDs is comparable to that of other modalities. Predictions for glues and heterobifunctionals often yield lower and higher errors, respectively. For permeability, CYP3A4 inhibition, and human and rat microsomal clearance, misclassification errors into high and low risk categories are lower than 4% for glues and 15% for heterobifunctionals. For all modalities, misclassification errors range from 0.8% to 8.1%. Investigated transfer learning strategies improve predictions for heterobifunctionals. This is the first comprehensive evaluation of ML for the prediction of absorption, distribution, metabolism, and excretion (ADME) and physicochemical properties of TPD molecules, including heterobifunctional and molecular glue sub-modalities. Taken together, our investigations show that ML-based QSPR models are applicable to TPDs and support ML usage for TPDs' design, to potentially accelerate drug discovery.

Investigating the effectiveness of web-based HIV self-test distribution and linkage to HIV treatment and PrEP among groups at elevated risk of HIV in Viet Nam provinces: a mixed-methods analysis of implementation from pilot to scale-up.

INTRODUCTION: In Viet Nam, key populations (KPs) face barriers accessing HIV services. Virtual platforms can be leveraged to increase access for KPs, including for HIV self-testing (HIVST). This study compares reach and effectiveness of a web-based HIVST intervention from pilot to scale-up in Viet Nam. METHODS: A mixed-methods explanatory sequential design used cross-sectional and thematic analysis. The pilot launched in Can Tho in November 2020, followed by Hanoi and Nghe An in April 2021. Scale-up included Can Tho and Nghe An, with 21 novel provinces from April to December 2022. After risk assessment, participants registered on the website, receiving HIVST (OraQuick®) by courier, peer educator or self-pick-up. Test result reporting and completing satisfaction surveys were encouraged. Intervention reach was measured through numbers accessing the testing, disaggregated by demographics, and proportion of individuals reporting self-testing post-registration. Effectiveness was measured through numbers reporting self-test results, testing positive and linking to care, and testing negative and using HIVST to manage pre-exposure prophylaxis (PrEP) use. Thematic content analysis of free-text responses from the satisfaction survey synthesized quantitative outcomes. RESULTS: In total, 17,589 participants registered on the HIVST website; 11,332 individuals ordered 13,334 tests. Participants were generally young, aged <25 years (4309/11,332, 38.0%), male (9418/11,332, 83.1%) and men who have sex with men (6437/11,332, 56.8%). Nearly half were first-time testers (5069/11,332, 44.9%). Scale-up participants were two times more likely to be assigned female at birth (scale-up; 1595/8436, 18.9% compared to pilot; 392/3727, 10.5%, p < 0.001). Fewer test results were reported in scale-up compared with pilot (pilot: 3129/4140, 75.6%, scale-up: 5811/9194, 63.2%, p < 0.001). 6.3% of all tests were reactive (pilot: 176/3129, 5.6% reactive compared to scale-up: 385/5811, 6.6% reactive, p = 0.063); of which most linked to care (509/522, 97.5%). One-fifth of participants with a negative test initiated or continued PrEP (pilot; 19.8%, scale-up; 18.5%, p = 0.124). Thematic analysis suggested that community delivery models increased programmatic reach. Live chat may also be a suitable proxy for staff support to increase result reporting. CONCLUSIONS: Web-based self-testing in Viet Nam reached people at elevated risk of HIV, facilitating uptake of anti-retroviral treatment and direct linkage to PrEP initiations. Further innovations such as the use of social-network testing services and incorporating features powered by artificial intelligence could increase the effectiveness and efficiency of the approach.

Pairwise Comparison of Heavy Dynamic Strength and Fast Dynamic Strength Interventions on Sprint Performance: A Systematic Review and Meta-Analysis.

ABSTRACT: Pairwise comparison of heavy dynamic strength and fast dynamic strength interventions on sprint performance: a systematic review and meta-analysis. J Strength Cond Res 38(8): 1509-1520, 2024-Previous studies have shown that both heavy dynamic strength (HDS) and fast dynamic strength (FDS) training can be used to improve sprint performance; however, a review and meta-analysis investigating pairwise studies that compare these two training interventions have not been performed. The aims of the study were to systematically review and analyze HDS and FDS training methodologies and evaluate their effect size difference, in pairwise comparison studies to determine and compare their effects on sprint performance. Databases were systematically searched using Boolean phrasing to identify eligible articles, and meta-analyses were performed on the extracted data. Seven studies met the inclusion criteria, which resulted in data from 138 subjects across 24 separate sprint assessments. Overall, there was a small effect in favor of FDS (standardized mean difference = 0.27, 95% confidence intervals [-0.07; 0.60], 95% prediction intervals [-1.01; 1.55]), but this was deemed not significant because of the wide-ranging prediction intervals. There is no distinguishable difference between HDS and FDS training on sprint performance. The wide-ranging prediction intervals suggest the variability is too great to determine whether one training type is more effective than the other. Practitioners should consider the individual needs of their athletes when deciding which training type to use for long-term sprint development.

Reliability and validity of the fulltrack AI application to determine cricket bowling line and length compared to 3D motion capture.

This study examined reliability and validity of the Fulltrack AI application to identify cricket ball landing position (line, length). Nine hundred and thirty-two deliveries were compared to 3D motion capture, the criterion measure, with 836 included in analysis (516 bowled (pace = 420, spin = 96), 320 SidearmTM; 301 facing a batter). Agreement analysis indicated an intraclass correlation coefficient of >0.96 for raw and filter 3D line and length data, compared to Fulltrack AI. The coefficient of variation was acceptable for length (<10%) and larger for line (23.82%), albeit with a smaller standard error of measurement (SEM = 0.05 m), improving with outliers removed. Bland-Altman plots confirmed good statistical agreement between devices, with limits of agreement largely within maximal allowable difference values. There are potential practical application considerations, given SEM = 0.47 m for length (diameter of seven cricket balls); with greater variability detecting length closer to the batters-end, and line closer to the bowlers-end. Validity, using a generalised additive model, showed no significant differences between devices (p > 0.05), with no condition-based interaction effects. The Fulltrack AI application enables ecologically valid assessment of bowling performance. Considering the trade-off between this and the accuracy of information is warranted when deciding how best to apply it to coaching environments to support augmented feedback.

Targeted Muscle Reinnervation and Regenerative Peripheral Nerve Interfaces Versus Standard Management in the Treatment of Limb Amputation: A Systematic Review and Meta-Analysis.

Introduction: Painful neuromas are a common postoperative complication of limb amputation often treated with secondary reinnervation. Surgical reinnervation include Targeted Muscle Reinnervation (TMR) and Regenerative Peripheral Nerve Interface (RPNI), and can be primary and secondary. The aim of this review is to assess the effects of primary TMR/RPNI at the time of limb amputation on the incidence and intensity of post-operative neuroma and pain. Methods: This review was registered a priori on PROSPERO (CRD42021264360). A search of the following databases was performed in June 2021: Medline, EMBASE, and CENTRAL. Unpublished trials were searched using clinicaltrials.gov. All randomized and non-randomized studies assessing amputation with a reinnervation strategy (TMR, RPNI) were included. Outcomes evaluated included the incidences of painful neuroma, phantom limb pain (PLP), residual limb pain (RLP), as well as severity of pain, and Pain intensity, behavior, and interference (PROMIS). Results: Eleven studies were included in this systematic review, and five observational studies for quantitative synthesis. Observational study evidence suggests that TMR/RPNI results in a statistically significant reduction in incidence, pain scores and PROMIS scores of PLP and RLP. Decreased incidence of neuromas favored primary TMR/RPNI, but this did not achieve statistical significance (p = 0.07). Included studies had moderate to critical risk of bias. Conclusion: The observational data suggests that primary TMR/RPNI reduces incidence, pain scores and PROMIS scores of PLP and RLP. Going forward, randomized trials are warranted to evaluate this research question, particularly to improve the certainty of evidence.

Introduction: Les névromes douloureux sont une complication postopératoire courante de l'amputation d'un membre qui est souvent traitée par réinnervation secondaire. La réinnervation chirurgicale inclut la réinnervation musculaire ciblée (TMR) et l'interface nerveuse périphérique régénérative (RPNI) qui peuvent être primaires ou secondaires. Le but de cette revue était d'évaluer les effets de la TMR/RPNI primaires au moment de l'amputation du membre sur l'incidence et l'intensité du névrome et de la douleur postopératoire. Méthodes: Cette revue a été enregistrée a priori sur PROSPERO (CRD42021264360). Une recherche a été réalisée en juin 2021 dans les bases de données suivantes : MEDLINE, EMBASE et CENTRAL. Les essais non publiés ont été recherchés à l'aide du site clinicaltrials.gov. Toutes les études randomisées et non randomisées évaluant l'amputation avec stratégie de réinnervation (TMR, RPNI) ont été incluses. L'évaluation des résultats a inclus l'incidence des névromes douloureux, des douleurs du membre fantôme (PLP), de douleur résiduelle du membre (RLP) ainsi que la sévérité de la douleur, l'intensité de la douleur, le comportement et l'interférence (PROMIS). Résultats: Onze études ont été incluses dans cette revue systématique et cinq études observationnelles pour la synthèse quantitative. Les données probantes d'étude observationnelle suggèrent que la TMR/RPNI entraîne une réduction statistiquement significative de l'incidence, des scores de douleur et des scores PROMIS des PLP et RLP. La baisse de l'incidence des névromes favorisait les TMR/RPNI primaires, mais sans atteindre la signification statistique (P = 0,07). Les études incluses comportaient des risques de biais modérés à critiques. Conclusion: Les données observationnelles suggèrent que les TMR/RPNI réduisent l'incidence, les scores de douleur et les scores PROMIS de PLP et RLP. La réalisation d'essais randomisés est justifiée pour aller de l'avant et évaluer cette question de recherche, en particulier pour améliorer la certitude des données probantes.

Efficacy and safety of tixagevimab/cilgavimab as passive immunisation against COVID-19 infections in patients with hematological malignancies.

Monoclonal antibodies, as tixagevimab/cilgavimab, have been introduced as prophylaxis against COVID-19 infections in high-risk populations. However, data on efficacy are limited. This study investigates efficacy and tolerability of tixagevimab/cilgavimab in hematological patients under real-life conditions. Tixagevimab/cilgavimab was administered to 155 hematological patients (March-August 2022) at two Austrian centres. S/RBD-antibody assessments were performed before (T0), four weeks (T1), and six months (T2) after application. Side effects, the occurrence of COVID-19 infections, and the course of S/RBD-antibody titres were analysed retrospectively in relation to clinical variables. 155 hematological patients, who refused tixagevimab/cilgavimab, were included as a control group to compare the frequency of COVID-19 infections. Of all immunised patients (52.3% males; 91% triple vaccinated), 25.8% had a COVID-19 breakthrough infection (76% mild) compared to 43.9% in the control group. Patients with chronic lymphocytic leukaemia (CLL)/lymphoma were at highest risk of a COVID-19 infection (OR = 2.21; 95% CI 1.05-4.65; p = 0.037). After immunisation, a steep increase in median antibody levels (1193.4BAU/ml, IQR 0-2318.94) was observed in 67.8%, followed by a rapid decrease between T1 and T2 (465.95BAU/ml, IQR 0-1900.65.3) with the greatest declines in CLL/lymphoma (848.7BAU/ml, IQR 0-1949.6, p = 0.026). Side-effects occurred in 21.2% (CTCAE I/II). These real-world data indicate that S/RBD antibodies respond rapidly after passive immunisation in all hematological patients without safety concerns. Given the rapid decline in S/RBD antibodies, early booster immunisations should be considered for future scenarios in this vulnerable group.

The immediate and lasting balance outcomes of clinical falls-prevention programs: A non-randomised study.

PURPOSE: Exercise-based falls-prevention programs are cost-effective population-based approaches to reduce the risk of falling for older adults. The aim was to evaluate the short-term and long-term efficacy of three existing falls-prevention programs. METHODS: A non-randomized study design was used to compare the immediate-post and long-term physical outcome measures for three falls prevention programs; one high-level land-based program, one low-level land-based program and a water-based Ai Chi program. Timed-up-and-go (TUG), five-times sit-to-stand (5xSTS), six-minute walk test (6MWT) and six-meter walk test were assessed at baseline, post-program, and at six-months follow-up. Linear mixed models were used to analyze between- and within- group differences, with the high-level land-based program used as the comparator. RESULTS: Thirty-two participants completed post-program assessment and 26 returned for follow-up. There was a difference in the age (years) of participants between programs (p = 0.049). The intercept for TUG and six-meter walk test time was 47.70% (23.37, 76.83) and 32.31s (10.52, 58.41), slower for the low-level group and 40.49% (17.35, 69.89) and 36.34s (12.75, 64.87), slower for the Ai Chi group (p < 0.01), compared with the high-level group. Mean time taken to complete the TUG was less both immediately post-program and at 6-month follow-up (p = 0.05). Walking speed for the six-meter walk test was only faster at six-months (p < 0.05). The 5xSTS duration was significantly reduced only at post-intervention (p < 0.05). CONCLUSION: These results indicate land-based and water-based falls-prevention programs improve physical outcome measures associated with falls-risk and many improvements are maintained for six months after the completion of the program. (Retrospective trial registration: ACTRN1262300119069).

Reporting bias in breast reconstruction clinical trials: Which and when clinical trials get published.

BACKGROUND: Reporting bias refers to the phenomenon in which the reporting of research findings is influenced by the nature of the results. Without the totality of evidence, clinical practice may be misguided. The objective of this work was to examine the extent of reporting bias in clinical trials of breast reconstruction surgery. METHODS: We searched and extracted data from all completed breast reconstruction clinical trials published in ClinicalTrials.gov from database inception to August 2020. Investigators sought to identify published full manuscripts of the registered trials. The primary outcome was classified as positive or nonpositive and trials were classified as industry or nonindustry funded. Time to publication in a peer-reviewed journal was computed and compared using time-to-event analysis. Trial characteristics associated with publication were evaluated using logistic regression. RESULTS: A total of 156 clinical trials were identified, of which, 53 trials were published. The median time to publication was 22 months (IQR, 13-35 months). Industry-funded studies were associated with a longer time to publication (HR = 2.4, p = 0.023) and publication in lower-impact journals (OR = 3.7, p = 0.048). Randomized clinical trials were associated with faster times to publication than nonrandomized studies (aHR = 3.2, p = 0.030). Statistical significance and the effect size were not associated with time to publication. CONCLUSIONS: We found no evidence that industry-funded trials were more likely to report a positive primary outcome. However, industry-funded trials were associated with a longer time to publication and publication in lower-impact journals.

Improving nitrogen content in soil and lemon balm (Melissa officinalis L.) yield by purple nonsulfur bacteria Rhodopseudomonas palustris in two consecutive seasons.

The study was conducted to assess the effects of nitrogen (N)-fixing purple nonsulfur bacteria (PNSB) Rhodopseudomonas palustris TLS06, VNW02, VNW64, and VNS89 on soil fertility, N uptake, essential oil (EO) content, growth, and yield of lemon balm. The experiment followed a completely randomized block design with 9 treatments and 3 replications. The treatments consisted of (i) applying 100% N as the recommended fertilizer rate (RFR), (ii) applying 85% N as RFR, (iii) applying 70% N as RFR, (iv) applying 55% N as RFR, (v) the treatment ii combined with N-PNSB, (vi) the treatment iii combined with N-PNSB, (vii) the treatment iv combined with N-PNSB, (viii) 0% as RFR combined with N-PNSB, and (ix) 0% N as RFR. The results showed that applying N-PNSB increased the plant height, and the number of primary branches in both seasons. In addition, the treatment without N fertilizer combined with N-PNSB increased stem leaf biomass by 41.2 and 50.3% in both seasons as compared with the treatment without neither N fertilizer nor N-PNSB. For soil properties, among treatments without N fertilizer, the treatment with N-PNSB increased concentrations of NH4+, soluble P, and exchangeable K+ by 41.3, 41.4, and 26.8%, respectively, as compared with the treatment without N-PNSB at the end of the second season. Applying 85% N as RFR combined with N-PNSB had a greater yield by 5.78-11.8% as compared with the treatment with 100% N as RFR, and a greater EO content by 23% as compared with the treatment with 85% N as RFR.

Examining Protein Translocation by ß-Barrel Membrane Proteins Using Reconstituted Proteoliposomes.

ß-barrel membrane proteins populate the outer membrane of Gram-negative bacteria, mitochondria, and chloroplasts, playing significant roles in multiple key cellular pathways. Characterizing the functions of these membrane proteins in vivo is often challenging due to the complex protein network in the periplasm of Gram-negative bacteria (or intermembrane space in mitochondria and chloroplasts) and the presence of other outer membrane proteins. In vitro reconstitution into lipid-bilayer-like environments such as nanodiscs or proteoliposomes provides an excellent method for examining the specific function and mechanism of these membrane proteins in an isolated system. Here, we describe the methodologies employed to investigate Slam, a 14-stranded ß-barrel membrane protein also known as the type XI secretion system that is responsible for translocating proteins across the outer membrane of many bacterial species.

Anxiety and its risk factors among non-Japanese residents living in Japan undergoing COVID-19 situation: A cross-sectional survey.

INTRODUCTION: In the context of collective efforts taken in Japan to control the spread of COVID-19, the state of emergency and social distancing have caused a negative impact on the mental health of all residents, including foreign communities in Japan. This study aimed to evaluate the level of anxiety and its associated factors among non-Japanese residents residing in Japan during the COVID-19 pandemic. METHODS: A web-based survey in 13 languages was conducted among non-Japanese residents living in Japan during the COVID-19 situation. The State-Trait Anxiety Inventory assessed the level of anxiety-State (STAI-S) scores prorated from its six-item version. The multivariable logistic regression using the Akaike Information Criterion (AIC) method was performed to identify the associated factors of anxiety among participants. RESULTS: From January to March 2021, we collected 392 responses. A total of 357 valid responses were analyzed. 54.6% of participants suffered from clinically significant anxiety (CSA). In multivariable logistic model analysis, the CSA status or the high level of anxiety was associated with three factors, including having troubles/difficulties in learning or working, decreased sleep duration, and decreased overall physical health (p<0.05). CONCLUSION: Our study suggests several possible risk factors of anxiety among non-Japanese residents living in Japan undergoing the COVID-19 pandemic, including the troubles or difficulties in learning or working, the decrease in sleep duration, and the decrease in overall physical health.

Estimating the Minimal Clinically Important Difference on the Visual Analogue Scale for Carpometacarpal Thumb Joint Osteoarthritis.

BACKGROUND: The minimal clinically important difference (MCID) is the smallest perceived treatment effect that patients deem clinically significant. There is currently no agreement on an appropriate MCID for the pain visual analogue scale (VAS) in the context of thumb osteoarthritis (OA). METHODS: We approximated MCIDs using a distribution-based approach that pooled standard deviations (SDs) associated with baseline mean values of the pain VAS (0-100 mm). We extracted the data from randomized controlled trials (RCTs) included in a systematic review of adults with long-term OA of the thumb. We excluded RCTs that did not report baseline SD values. The MCIDs were derived at 0.4 and 0.5 SDs of the pooled SD and compared with previously published MCIDs for the pain VAS in OA. RESULTS: A total of 403 patients were pooled from 7 RCTs for the analysis. The mean baseline VAS pain score was 5.6 cm. We derived an MCID of 0.72 cm at 0.4 SDs and 0.91 cm at 0.5 SDs using baseline SDs. We found that MCIDs derived from a distribution-based approach approximated published MCIDs for the VAS for pain for OA in the knee and hip. CONCLUSION: The authors propose that a change of 0.7 to 0.9 cm on the VAS is clinically meaningful in the context of long-term OA of the thumb.

The test-retest reliability of physiological and perceptual responses during treadmill load carriage.

PURPOSE: Understanding the test-retest reliability of physiological responses to load carriage influences the interpretation of those results. The aim of this study was to determine the test-retest reliability of physiological measures during loaded treadmill walking at 5.5 km h-1 using the MetaMax 3B. METHODS: Fifteen Australian Army soldiers (9 male, 6 female) repeated two 12-min bouts of treadmill walking at 5.5 km h-1 in both a 7.2 kg Control condition (MetaMax 3B, replica rifle) and a 23.2 kg Patrol condition (Control condition plus vest) across three sessions, separated by one week. Expired respiratory gases and heart rate were continuously collected, with the final 3 min of data analysed. Ratings of Perceived Exertion and Omnibus-Resistance Exercise Scale were taken following each trial. Reliability was quantified by coefficient of variation (CV), intra-class correlation coefficients (ICC), smallest worthwhile change (SWC), and standard error of the measurement. RESULTS: Metabolic and cardiovascular variables were highly reliable (≤ 5% CV; excellent-moderate ICC), while the respiratory variables demonstrated moderate reliability (< 8% CV; good-moderate ICC) across both conditions. Perceptual ratings had poorer reliability during the Control condition (12-45% CV; poor ICC) than the Patrol condition (7-16% CV; good ICC). CONCLUSIONS: The test-retest reliability of metabolic and cardiovascular variables was high and relatively consistent during load carriage. Respiratory responses demonstrated moderate test-retest reliability; however, as the SWC differed with load carriage tasks, such data should be interpreted independently across loads. Perceptual measures demonstrated poor to moderate reliability during load carriage, and it is recommended that they only be employed as secondary measures.

Preference and retention of daily and event-driven pre-exposure prophylaxis for HIV prevention: a prospective cohort in Can Tho city, Viet Nam.

OBJECTIVE: Pre-exposure prophylaxis (PrEP) was introduced in Viet Nam in 2017, but data on oral PrEP preference and effective use beyond 3 months are limited. We aimed to evaluate PrEP preferences for PrEP, factors influencing uptake, choice and effective use, as well as barriers to PrEP. METHODS: This is a prospective cohort study in Can Tho, Viet Nam. Participants who were eligible for PrEP and provided informed consent were interviewed at baseline on demographic information, willingness to pay, reasons for choosing their PrEP regimen and the anticipated difficulties in taking PrEP and followed up at 3 months, 6 months and 12 months after PrEP initiation. FINDINGS: Between May 2020 and April 2021, 926 individuals at substantial risk for HIV initiated PrEP. Of whom 673 (72.7%) choose daily PrEP and 253 (27.3%) choose event-driven (ED)-PrEP. The majority of participants were men (92.7%) and only 6.8% were women and 0.5% were transgender women. Median participant age was 24 years (IQR 20-28) and 84.7% reported as exclusively same-sex relationship. The three most common reasons for choosing daily PrEP were effectiveness (24.3%) and unplanning for sex (22.9%). Those opting for ED-PrEP also cited effectiveness (22.7%), as well as convenience (18.0%) and easier effective use (12.0%). Only 7.8% of PrEP users indicated they were unwilling to pay for PrEP and 76.4% would be willing to pay if PrEP were less than US$15 per month. The proportion of user effectively using PrEP at 12 months was 43.1% and 99.2% in daily PrEP and ED-PrEP users, respectively. CONCLUSIONS: ED-PrEP was preferred by more than a quarter of 23.5% of the participants and there was little concern about potential adverse events. High rates of effective use were reported by ED-PrEP users. Future research to inform implementation of PrEP in Viet Nam is needed to develop ways of measuring adherence to ED-PrEP more accurately and to understand and address difficulties in taking daily PrEP use.

Synthesis, crystal structure and Hirshfeld surface analysis of 2-({5-[(naphthalen-1-yl)meth-yl]-4-phenyl-4H-1,2,4-triazol-3-yl}sulfan-yl)-1-(4-nitro-phen-yl)ethanone.

The title compound, C27H20N4O3S, crystallizes in the monoclinic system, space group P21/n, with Z = 4. The global shape of the mol-ecule is determined by the orientation of the substituents on the central 4H-1,2,4-triazole ring. The nitro-phenyl ring, phenyl ring, and naphthalene ring system are oriented at dihedral angles of 82.95 (17), 77.14 (18) and 89.46 (15)°, respectively, with respect to the triazole ring. The crystal packing features chain formation in the b-axis direction by S⋯O inter-actions. A Hirshfeld surface analysis indicates that the highest contributions to surface contacts arise from contacts in which H atoms are involved.

The Relationship Between Isometric and Dynamic Strength Following Resistance Training: A Systematic Review, Meta-Analysis, and Level of Agreement.

BACKGROUND: Maximal lower-body strength can be assessed both dynamically and isometrically; however, the relationship between the changes in these 2 forms of strength following resistance training is not well understood. PURPOSE: To systematically review and analyze the effects of resistance training on changes in maximal dynamic (1-repetition-maximum back squat, deadlift, and power clean) and position-matched isometric strength (isometric midthigh pull and the isometric squat). In addition, individual-level data were used to quantify the agreement and relationship between changes in dynamic and isometric strength. METHODS: Databases were systematically searched to identify eligible articles, and meta-analysis procedures were performed on the extracted data. The raw results from 4 studies were acquired, enabling bias and absolute reliability measures to be calculated using Bland-Altman test of agreement. RESULTS: Eleven studies met the inclusion criteria, which resulted in 29 isometric-dynamic change comparisons. The overall pooled effect was 0.13 in favor of dynamic testing; however, the prediction interval ranged from g = -0.49 to 0.75. There was no evidence of bias (P = .825) between isometric and dynamic tests; however, the reliability coefficient was estimated to be 16%, and the coefficient of variation (%) was 109.27. CONCLUSIONS: As a range of future effects can be expected when comparing isometric to dynamic strength changes following resistance training, and limited proportionality exists between changes in these 2 strength qualities, there is strong evidence that isometric and dynamic strength represent separate neuromuscular domains. These findings can be used to inform strength-assessment models in athlete populations.

Under the Gun: Percussive Massage Therapy and Physical and Perceptual Recovery in Active Adults.

CONTEXT: Handheld percussive massage devices (ie, massage guns) are a relatively new and under-researched recovery tool. These tools are intended to increase range of motion and reduce muscle soreness by delivering targeted vibration to soft tissues. Empirical knowledge about the potential influence of these devices on perceptual recovery and the recovery of performance characteristics after exercise is scarce. OBJECTIVE: To investigate the effect of a 5-minute massage gun application, using a commercially available device, on physical and perceptual recovery after a strenuous bout of lower body exercise. DESIGN: Controlled laboratory study. SETTING: Physiology laboratory. PATIENTS OR OTHER PARTICIPANTS: A total of 65 active young adults (age = 21.3 ± 1.4 years; age range = 18-30 years; 34 women: height = 165.8 ± 6.1 cm, mass = 66.0 ± 7.4 kg; 31 men: height = 181.1 ± 6.0 cm, mass = 81.5 ± 11.8 kg). INTERVENTION(S): Participants applied a massage gun on the calf muscles of 1 leg after strenuous exercise (massage gun recovery group) for 5 minutes and used no recovery intervention on the other leg (control group). MAIN OUTCOME MEASURE(S): Ankle range of motion, calf circumference, isometric strength, calf endurance, and perceived muscle soreness measures were collected at baseline and at various points after lower body exercise. RESULTS: No significant group × time interactions were recorded for any of the performance or perceptual measures (P values > .05). Effect sizes were mostly unclear, except for a small increase in perceived muscle soreness in the massage gun recovery group compared with the control group immediately (d = -0.35) and 4 hours (d = -0.48) postrecovery. CONCLUSIONS: Massage guns appeared to have little effect on physical measures when applied for 5 minutes immediately after strenuous calf exercise. Given the small increase in muscle soreness up to 4 hours after their use, caution is recommended when using massage guns immediately after strenuous lower body exercise.

The Effects of Repeated-Sprint Training on Physical Fitness and Physiological Adaptation in Athletes: A Systematic Review and Meta-Analysis.

BACKGROUND: Repeated-sprint training (RST) is a common training method for enhancing physical fitness in athletes. To advance RST prescription, it is important to understand the effects of programming variables on physical fitness and physiological adaptation. OBJECTIVES: This study (1) quantifies the pooled effects of running RST on changes in 10 and 20 m sprint time, maximal oxygen consumption (VO2max), Yo-Yo Intermittent Recovery Test Level 1 (YYIR1) distance, repeated-sprint ability (RSA), countermovement jump (CMJ) height and change of direction (COD) ability in athletes, and (2) examines the moderating effects of program duration, training frequency, weekly volume, sprint modality, repetition distance, number of repetitions per set and number of sets per session on changes in these outcome measures. METHODS: Pubmed, SPORTDiscus and Scopus databases were searched for original research articles up to 04 July 2023, investigating RST in healthy, able-bodied athletes, between 14 and 35 years of age, and a performance calibre of trained or above. RST interventions were limited to repeated, maximal running (land-based) sprints of ≤ 10 s duration, with ≤ 60 s recovery, performed for 2-12 weeks. A Downs and Black checklist was used to assess the methodological quality of the included studies. Eligible data were analysed using multi-level mixed-effects meta-analysis, with standardised mean changes determined for all outcomes. Standardised effects [Hedges G (G)] were evaluated based on coverage of their confidence (compatibility) intervals (CI) using a strength and conditioning specific reference value of G = 0.25 to declare an improvement (i.e. G > 0.25) or impairment (i.e. G < - 0.25) in outcome measures. Applying the same analysis, the effects of programming variables were then evaluated against a reference RST program, consisting of three sets of 6 × 30 m straight-line sprints performed twice per week for 6 weeks (1200 m weekly volume). RESULTS: 40 publications were included in our investigation, with data from 48 RST groups (541 athletes) and 19 active control groups (213 athletes). Across all studies, the effects of RST were compatible with improvements in VO2max (G 0.56, 90% CI 0.32-0.80), YYIR1 distance (G 0.61, 90% CI 0.43-0.79), RSA decrement (G - 0.61, 90% CI - 0.85 to - 0.37), linear sprint times (10 m: G - 0.35, 90% CI - 0.48 to - 0.22; 20 m: G - 0.48, 90% CI - 0.69 to - 0.27), RSA average time (G - 0.34, 90% CI - 0.49 to - 0.18), CMJ height (G 0.26, 90% CI 0.13-0.39) and COD ability (G - 0.32, 90% CI - 0.52 to - 0.12). Compared with the reference RST program, the effects of manipulating training frequency (+ 1 session per week), program duration (+ 1 extra training week), RST volume (+ 200 m per week), number of reps (+ 2 per set), number of sets per session (+ 1 set) or rep distance (+ 10 m per rep) were either non-substantial or comparable with an impairment in at least one outcome measure per programming variable. CONCLUSIONS: Running-based RST improves speed, intermittent running performance, VO2max, RSA, COD ability and CMJ height in trained athletes. Performing three sets of 6 × 30 m sprints, twice per week for 6 weeks is effective for enhancing physical fitness and physiological adaptation. Additionally, since our findings do not provide conclusive support for the manipulation of RST variables, further work is needed to better understand how programming factors can be manipulated to augment training-induced adaptations. STUDY REGISTRATION: Open Science Framework registration https://doi.org/10.17605/OSF.IO/RVNDW .

RHOAL57V drives the development of diffuse gastric cancer through IGF1R-PAK1-YAP1 signaling.

Cancer-associated mutations in the guanosine triphosphatase (GTPase) RHOA are found at different locations from the mutational hotspots in the structurally and biochemically related RAS. Tyr42-to-Cys (Y42C) and Leu57-to-Val (L57V) substitutions are the two most prevalent RHOA mutations in diffuse gastric cancer (DGC). RHOAY42C exhibits a gain-of-function phenotype and is an oncogenic driver in DGC. Here, we determined how RHOAL57V promotes DGC growth. In mouse gastric organoids with deletion of Cdh1, which encodes the cell adhesion protein E-cadherin, the expression of RHOAL57V, but not of wild-type RHOA, induced an abnormal morphology similar to that of patient-derived DGC organoids. RHOAL57V also exhibited a gain-of-function phenotype and promoted F-actin stress fiber formation and cell migration. RHOAL57V retained interaction with effectors but exhibited impaired RHOA-intrinsic and GAP-catalyzed GTP hydrolysis, which favored formation of the active GTP-bound state. Introduction of missense mutations at KRAS residues analogous to Tyr42 and Leu57 in RHOA did not activate KRAS oncogenic potential, indicating distinct functional effects in otherwise highly related GTPases. Both RHOA mutants stimulated the transcriptional co-activator YAP1 through actin dynamics to promote DGC progression; however, RHOAL57V additionally did so by activating the kinases IGF1R and PAK1, distinct from the FAK-mediated mechanism induced by RHOAY42C. Our results reveal that RHOAL57V and RHOAY42C drive the development of DGC through distinct biochemical and signaling mechanisms.