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Abstract Background Tuberculosis medication nonadherence is a multi-dimensional public health problem with serious consequences worldwide. There is little information available for medication nonadherence in South Sudan. This study assessed the proportion, reasons, and associated factors for nonadherence among patients with TB in Wau Municipality, South Sudan. Methods A health facility based cross-sectional study was conducted among 234 tuberculosis (TB) patients receiving first line anti-TB regimen in Wau Municipality. Urine isoniazid metabolite testing (IsoScreen®) was used to determine nonadherence (visualized by negative test results) and a questionnaire was used to describe the reasons for nonadherence. Modified poisson regression with robust standard errors was performed since the proportion of nonadherence was

Bumble bees are essential pollinators that provide critical ecosystem services yet, studies are documenting global species declines while recognizing those declines may be understated due to insufficient baseline data. This study investigates bumble bee species richness and abundance across urban and natural sites in Prince Edward Island, Canada, focusing on Charlottetown (urban) and Prince Edward Island National Park (natural). We conducted fieldwork in August and September 2019 using a non-invasive photographic survey technique. We used published keys and sought feedback from citizen science platforms like iNaturalist and Bumble Bee Watch to verify species identification. Our results revealed nine bumble bee species, with Bombus impatiens being the most abundant and Bombus perplexus the rarest. Species richness was higher in natural sites, while urban sites demonstrated moderate levels of bumble bee diversity. Additionally, our findings suggest that sites containing a mix of natural and human-cultivated plant types, predominantly found in our urban study sites, may support higher diversity and evenness levels than those of homogenized plant types (natural or human-cultivated). This research illustrates the practicality of photographic surveys to document the species richness and diversity of bumble bees while avoiding disturbance to populations in urban and natural habitats of Prince Edward Island.

Objective We aimed to estimate the incidence of avoidant/restrictive food intake disorder (ARFID) in children and adolescents (CA) presenting to secondary care in the UK and Republic of Ireland (ROI).Design This observational surveillance study used the British Paediatric Surveillance Unit and the Child and Adolescent Psychiatry Surveillance System. Monthly electronic reports were submitted by consultant paediatricians and child and adolescent psychiatrists from 1 March 2021 to 31 March 2022, with outcomes assessed at a 1-year follow-up.Setting The UK and ROI.Participants Clinician-reported data on children and young people aged 5–17 (inclusive) in contact with paediatric services or CA mental health services for a new diagnosis of ARFID.Primary outcome measures Annual incidence rates (IRs) estimated as confirmed new cases per 100 000 population at risk.Results 319 newly diagnosed cases of ARFID were reported over the 13-month surveillance period and assessed as eligible for inclusion. The mean age of the sample was 11.2 years (SD=3.8). The sample consisted of 145 females (45.5%). Most cases were of white British ethnicity (71.2%). The observed IR (IR0) in the UK was 2.79 per 100 000 CA (95% CI 2.48 to 3.13), with a higher IRo in males (2.98 per 100 000 CA (95% CI 2.55 to 3.49)) than in females (2.58 per 100 000 CA (95% CI 2.18 to 3.07)). Comorbidity was common in this sample with anxiety and autism spectrum disorder. At follow-up, 54.8% of cases had improved according to clinicians’ clinical impression.Conclusions We conducted the first study reporting estimates of incidence of ARFID in CA in the UK and ROI presenting to secondary care. Our finding that ARFID is a disorder of relatively low incidence in CA should help inform service planning and resource allocation, as well as the development of evidence-based interventions.

The majority of bispecific costimulatory antibodies in cancer immunotherapy are capable of exerting tumor-specific T-cell activation by simultaneously engaging both tumor-associated targets and costimulatory receptors expressed by T cells. The amount of trimeric complex formed when the bispecific antibody is bound simultaneously to the T cell receptor and the tumor-associated target follows a bell-shaped curve with increasing bispecific antibody exposure/dose. The shape of the curve is determined by the binding affinities of the bispecific antibody to its two targets and target expression. Here, using the case example of FAP-4-1BBL, a fibroblast activation protein alpha (FAP)-directed 4-1BB (CD137) costimulator, the impact of FAP-binding affinity on trimeric complex formation and pharmacology was explored using mathematical modeling and simulation. We quantified (1) the minimum number of target receptors per cell required to achieve pharmacological effect, (2) the expected coverage of the patient population for 19 different solid tumor indications, and (3) the range of pharmacologically active exposures as a function of FAP-binding affinity. A 10-fold increase in FAP-binding affinity (from a dissociation constant [KD] of 0.7 nM–0.07 nM) was predicted to reduce the number of FAP receptors needed to achieve 90% of the maximum pharmacological effect from 13,400 to 4,000. Also, the number of patients with colon cancer that would achieve 90% of the maximum effect would increase from 6% to 39%. In this work, a workflow to select binding affinities for bispecific antibodies that integrates preclinical in vitro data, mathematical modeling and simulation, and knowledge on target expression in the patient population, is provided. The early implementation of this approach can increase the probability of success with cancer immunotherapy in clinical development.

Abstract Background Maximal strength may contribute to soccer players’ performance. Several resistance training modalities offer the potential to improve maximal strength. During recent years, a large number of plyometric jump training (PJT) studies showed evidence for maximal strength improvements in soccer players. However, a comprehensive summary of the available data is lacking. Objective To examine the effects of PJT compared with active, passive or intervention controls on the maximal strength of soccer players, irrespective of age, sex or competitive level. Methods To perform a systematic review with meta-analysis following PRISMA 2020. Three electronic databases (PubMed, Web of Science, and SCOPUS) were systematically searched. Studies published from inception until March 2023 were included. A PICOS approach was used to rate studies for eligibility. The PEDro scale was used to assess risk of bias. Meta-analyses were performed using the DerSimonian and Laird random-effects model if ≥ 3 studies were available. Moderator and sensitivity analyses were performed, and meta-regression was conducted when ≥ 10 studies were available for a given comparison. We rated the certainty of evidence using GRADE. Results The search identified 13,029 documents, and from these 30 studies were eligible for the systematic review, and 27 for the meta-analyses. Overall, 1,274 soccer players aged 10.7–25.0 years participated in the included studies. Only one study recruited females. The PJT interventions lasted between 5 and 40 weeks (median = 8 weeks), with 1–3 weekly sessions. Compared to controls, PJT improved maximal dynamic strength (18 studies, 632 participants [7 females], aged 12.7–24.5 y; effect size [ES] = 0.43, 95% confidence interval [CI] = 0.08–0.78, p = 0.017, impact of statistical heterogeneity [I2] = 77.9%), isometric strength (7 studies; 245 participants, males, aged 11.1–22.5 y; ES = 0.58, 95% CI = 0.28–0.87, p

ABSTRACT: Salmonellosis is one of the leading causes of gastrointestinal infections in humans. In Canada, it is estimated that approximately 87,500 cases of salmonellosis occur every year in humans, resulting in 17 deaths. In the United States, it is estimated that 26,500 hospitalizations and 420 deaths occur every year. In dairy cattle, infections caused by nontyphoidal Salmonella enterica can cause mild to severe disease, including enteritis, pneumonia, and septicemia. Our study objectives were to determine the proportion of fecal samples positive for Salmonella in dairy cattle in Canada and determine the resistance pattern of these isolates. We used data collected through the Canadian Dairy Network for Antimicrobial Stewardship and Resistance (CaDNetASR). Pooled fecal samples from preweaning calves, postweaning heifers, lactating cows, and manure storage were cultured for Salmonella, and the isolates were identified using matrix-assisted laser desorption/ionization-time of flight mass spectrometry. Antimicrobial susceptibilities were determined using the minimum inhibitory concentration test, and resistance interpretation was made according to the Clinical and Laboratory Standards Institute. A 2-level, multivariable logistic regression model was built to determine the probability of recovering Salmonella from a sample, accounting for province, year, and sample source. The proportion of farms with at least one positive sample were 12% (17/140), 19% (28/144), and 17% (24/144) for the sampling years 2019, 2020, and 2021, respectively. Out of the 113 Salmonella isolates, 23 different serovars were identified. The occurrence of Salmonella appeared to be clustered by farms and provinces. The most common serovars identified were Infantis (14%) and Typhimurium (14%). Overall, 21% (24/113) of the Salmonella isolates were resistant to at least one antimicrobial. Resistance to tetracycline was commonly observed (17%); however, very limited resistance to category I antimicrobials (categorization according to Health Canada that includes third-generation cephalosporins, fluoroquinolones, polymyxins, and carbapenems) was observed, with one isolate resistant to amoxicillin and clavulanic acid. The proportion of Salmonella isolates resistant to 2 and 3 antimicrobial classes was 3.5% and 8.8%, respectively. Our study provided valuable information on the proportion of fecal samples positive for Salmonella, the serovars identified, and the associated resistance patterns across CaDNetASR herds, at regional and national levels.

ABSTRACT Glycogen plays a vital role as an energy reserve in various bacterial and fungal species. Clostridioides difficile possesses a glycogen metabolism operon that contains genes for both glycogen synthesis and utilization. In our investigation, we focused on understanding the significance of glycogen metabolism in the physiology and pathogenesis of C. difficile. To explore this, we engineered a C. difficile JIR8094 strain lacking glycogen synthesis capability by introducing a group II intron into the glgC gene, the operon’s first component. Quantification of intracellular glycogen levels validated the impact of this modification. Interestingly, the mutant strain exhibited a 1.5-fold increase in toxin production compared with the parental strain, without significant changes in the sporulation rate. Our analysis also revealed that wild-type C. difficile spores contained glycogen, whereas spores from the mutant strain lacking stored glycogen showed increased sensitivity to physical and chemical treatments and had a shorter storage life. By suppressing glgP expression, the gene coding for glycogen-phosphorylase, via CRISPRi, we demonstrated that glycogen accumulation but not the utilization is needed for spore resilience in C. difficile. Transmission electron microscopy analysis revealed a significantly lower core/cortex ratio in glgC mutant strain spores. In hamster challenge experiments, both the parental and glgC mutant strains colonized hosts similarly; however, the mutant strain failed to induce infection relapse after antibiotic treatment cessation. These findings highlight the importance of glycogen metabolism in C. difficile spore resilience and suggest its role in disease relapse.IMPORTANCEThis study on the role of glycogen metabolism in Clostridioides difficile highlights its critical involvement in the pathogen’s energy management, its pathogenicity, and its resilience. Our results also revealed that glycogen presence in spores is pivotal for their structural integrity and resistance to adverse conditions, which is essential for their longevity and infectivity. Importantly, the inability of the mutant strain to cause infection relapse in hamsters post-antibiotic treatment pinpoints a potential target for therapeutic interventions, highlighting the importance of glycogen in disease dynamics. This research thus significantly advances our understanding of C. difficile physiology and pathogenesis, offering new avenues for combating its persistence and recurrence.

Papanicolaou (Pap) smear on cervical cells heralded the revolution of modern cytopathology in the middle of the 19th century, and cervical screening is now considered one of medicine’s greatest success stories. While routine cervical cytology has significantly reduced the incidence of cervical cancer worldwide, it is not without limitations. Although the specificity of Pap smear to detect high-grade intraepithelial lesion (HSIL)/cervical intraepithelial neoplasia (CIN) 2–3 is consistently high, the sensitivity ranges broadly from 34 % to 94 % [1]. Given the rapid evolution in understanding the etiologic role of high-risk human papillomavirus (hrHPV) in cervical cancer development, the clinical guidelines have transitioned from “evidence-based” to “risk-stratified” algorithms. Primary hrHPV testing as a more sensitive test for high-risk cervical lesion (CIN2+) detection is considered the preferred screening test in some guidelines, but due to its low specificity, a follow-up triage test is needed to reduce unnecessary colposcopy referrals. Candidates for the triage test include cytology, biomarkers such as P16/Ki67 dual stain (DS), and hrHPV genotyping. This review discusses the advantages and potential issues with primary hrHPV testing and dual stain, the current American Society of Colposcopy and Cervical Pathology (ASCCP) guideline with a focus on new endocervical curettage (ECC) guidelines, as well as the new World Health Organization (WHO) classification of endocervical adenocarcinoma and the impact on cervical cytopathology.

Irrigation systems significantly enhance agricultural productivity but are also substantial consumers of water, energy, and natural resources. The need to optimize their design encouraged agronomic engineering to develop various methods for improving the design and management of these irrigation networks. This development focuses on creating a tool to define the optimal flow distribution according to the system's irrigation or consumption needs, thereby determining the design flows. The aim is to optimize the design of pipe diameters to improve sustainability (i.e., reducing CO2 emissions, minimizing service pressure, and maximizing recoverable energy within the system). These principles ensure a better evaluation of sustainable development goals within agricultural production. The proposed procedure develops a strategy to define the best-fitting distribution using a multicriteria solution. As novel, the research develops a tool, which characterizes flow distributions deviating from the classic Clement's formulation used in irrigation systems. The proposed method was applied in a Mediterranean irrigation system in Spain, achieving a correlation coefficient above 0.9 in the model. This methodology addresses design criteria in terms of sustainability and reduces energy consumption in networks. It achieved material savings of 6.01 % compared to the observed network, reducing CO2 emissions between 5.61 and 5.72 TnCO2/ha over its lifecycle.

IntroductionPatients with coronary artery disease (CAD) have a higher risk of developing cognitive impairment and mental health disorders compared to the general population. Physical exercise might improve their brain health. The overall goal of the HEART-BRAIN randomized controlled trial (RCT) is to investigate the effects of different types of exercise on brain health outcomes in patients with CAD, and the underlying mechanisms.MethodsThis three-arm, single-blinded RCT will include 90 patients with CAD (50–75 years). Participants will be randomized into: (1) control group—usual care (n = 30), (2) aerobic high-intensity interval training (HIIT) (n = 30), or (3) HIIT combined with resistance exercise training (n = 30). The 12-week intervention includes 3 supervised sessions (45-min each) per week for the exercise groups. Outcomes will be assessed at baseline and post-intervention. The primary outcome is to determine changes in cerebral blood flow assessed by magnetic resonance imaging. Secondary outcomes include changes in brain vascularization, cognitive measures (i.e., general cognition, executive function and episodic memory), and cardiorespiratory fitness. Additional health-related outcomes, and several potential mediators and moderators will be investigated (i.e., brain structure and function, cardiovascular and brain-based biomarkers, hemodynamics, physical function, body composition, mental health, and lifestyle behavior).ConclusionThe HEART-BRAIN RCT will provide novel insights on how exercise can impact brain health in patients with CAD and the potential mechanisms explaining the heart-brain connection, such as changes in cerebral blood flow. The results may have important clinical implications by increasing the evidence on the effectiveness of exercise-based strategies to delay cognitive decline in this high-risk population.Clinical trial registrationClinicalTrials.gov, identifier [NCT06214624].

ABSTRACT: As clinical mastitis (CM) treatments are responsible for a large portion of antimicrobial use on dairy farms, many selective CM treatment protocols have been developed and evaluated against a blanket treatment approach of CM cases. Selective treatment protocols use outcomes of diagnostic tests to exclude CM cases from antimicrobial treatment when they are unlikely to benefit. To tailor interventions to increase uptake of selective treatment strategies, a comprehension of current on-farm treatment practices and factors affecting treatment decisions is vital. Two questionnaires were conducted among 142 farms across 5 provinces participating in the Canadian Dairy Network for Antimicrobial Stewardship and Resistance in this cross-sectional study. Self-reported adoption of selective CM treatments by dairy farmers was 64%, with median of 82% of cows treated in those herds using selective treatment. Using logistic regression models, the odds to implement a selective CM treatment protocol increased with a decreasing average cow somatic cell count. No other associations were identified between use of a selective CM treatment protocol and farm characteristics (herd size, CM incidence, province, milking system, and housing system). Three subsets of farmers making cow-level CM treatment decisions were identified using a cluster analysis approach: those who based decisions almost exclusively on severity of clinical signs, those who used various udder health indicators, and farmers who also incorporated more general cow information such as production, age, and genetics. When somatic cell count was considered, the median threshold used for treating was >300,000 cells/mL at the last Dairy Herd Improvement test. Various thresholds were present among those considering CM case history. Veterinary laboratories were most frequently used for bacteriological testing. Test results were used to start, change, and stop treatments. Regardless of protocol, reasons for antimicrobial treatment withheld included cow being on a cull list, having a chronic intramammary infection, or being at end of lactation (i.e., close to dry off). If clinical signs persisted after treatment, farmers indicated that they would ask veterinarians for advice, stop treatment, or continue with the same or different antibiotics. Results of this study can be used to design interventions targeting judicious mastitis-related antimicrobial use, and aid discussions between veterinarians and dairy producers regarding CM-related antimicrobial use.

The aim was to analyse the consequences of a congested schedule (due to the COVID-19 lockdown) on creatine kinase (CK) in elite football players using GPS tracking technology. A total of 17 elite football players were monitored in training and competition with a global positioning system. Variables including total distance, high-intensity distance, and distance acceleration and deceleration were analysed. Different measurements of serum creatine kinase (CK) concentration were performed on match day (MD) and at 24 h (MD+1), 48 h (MD+2), and 72 h (MD+3) after each match to study the muscle damage of each individual player caused during the match. The results showed a significant increase in physical demands in training (in relative terms regarding the match) at MD+3 compared to MD+1 and MD+2. Furthermore, at +72 h, CK decreases to a value almost the same as that before MD. On the other hand, the players with lower demands for high-intensity actions in the match showed a higher reduction in the concentration of CK at MD+3 compared to MD+1 and MD+2 (p < 0.05). It became evident that players with high-intensity demand and a high number of accelerations and decelerations need more time to assimilate the match load and can remain in a state of muscle fatigue for up to 3 days. In addition, a congested schedule can lead to a state of chronic fatigue in elite football players, limiting physical performance and possibly increasing the potential risk of injury for football players.

Abstract Background Data extraction (DE) is a challenging step in systematic reviews (SRs). Complex SRs can involve multiple interventions and/or outcomes and encompass multiple research questions. Attempts have been made to clarify DE aspects focusing on the subsequent meta-analysis; there are, however, no guidelines for DE in complex SRs. Comparing datasets extracted independently by pairs of reviewers to detect discrepancies is also cumbersome, especially when the number of extracted variables and/or studies is colossal. This work aims to provide a set of practical steps to help SR teams design and build DE tools and compare extracted data for complex SRs. Methods We provided a 10-step guideline, from determining data items and structure to data comparison, to help identify discrepancies and solve data disagreements between reviewers. The steps were organised into three phases: planning and building the database and data manipulation. Each step was described and illustrated with examples, and relevant references were provided for further guidance. A demonstration example was presented to illustrate the application of Epi Info and R in the database building and data manipulation phases. The proposed guideline was also summarised and compared with previous DE guidelines. Results The steps of this guideline are described generally without focusing on a particular software application or meta-analysis technique. We emphasised determining the organisational data structure and highlighted its role in the subsequent steps of database building. In addition to the minimal programming skills needed, creating relational databases and data validation features of Epi info can be utilised to build DE tools for complex SRs. However, two R libraries are needed to facilitate data comparison and solve discrepancies. Conclusions We hope adopting this guideline can help review teams construct DE tools that suit their complex review projects. Although Epi Info depends on proprietary software for data storage, it can still be a potential alternative to other commercial DE software for completing complex reviews.

Abstract Introduction Patients with follicular lymphoma (FL) receiving third-line or later (3L +) therapy have long survival, which can make estimating long-term overall survival (OS) from trial data challenging. The objective of this study was to estimate long-term OS for mosunetuzumab from the GO29781 trial (NCT02500407) using multiple real-world databases (RWDs) in a Bayesian framework. Methods Seven RWD sources for patients with FL receiving 3L + therapy and the expansion cohort in the GO29781 trial for mosunetuzumab were used. Hazard trends from the RWD sources were analyzed, and disease-wide pointwise OS and its corresponding uncertainty were estimated using Bayesian random-effects meta-analysis from the RWD sources. Pointwise OS obtained was used as an informative prior in Bayesian survival extrapolations to data from patients receiving mosunetuzumab. Results after adjusting for background mortality were compared to equivalent frequentist extrapolations using trial data only. Results Hazard patterns from RWD sources supported a constant or linearly decreasing hazard. Mean pointwise OS for patients with FL receiving 3L + therapy was estimated at 0.52 (95% credible interval, 0.29–0.85) at 8 years. Bayesian extrapolations for mosunetuzumab produced median survival estimates of 11.6 (6.7–20.7) years to 17.0 (6.4–22.7) years depending on the distribution used, reducing uncertainty by 20% to 46% relative to the frequentist estimation. Conclusion Multiple RWD sources can be synthesized to augment the credibility of data with short follow-up, long patient survival, and few events to effectively estimate long-term survival and reduce estimated uncertainty. This method can be applied to other indications with similar characteristics. Clinical Trial Registration Number and Date of Registration NCT02500407, July 16, 2015.

Abstract Inherent to any stenting procedure is the prescription of dual antiplatelet therapy (DAPT) to reduce the platelet response. Clinical guidelines recommend 6–12 months of DAPT, depending on stent type, clinical picture and patient factors. Our hypothesis is that a nanostructured noble metal coating has the potential to reduce protein deposition and platelet activation. These effects would reduce subsequent thrombo-inflammatory reactions, potentially mitigating the need for an extensive DAPT in the acute phase. Here, a noble metal nanostructure coating on stents is investigated. Twelve pigs underwent endovascular implantation of coated and non-coated stents for paired comparisons in a blinded study design. The non-coated control stent was placed at the contralateral corresponding artery. Volumetric analysis of angiographic data, performed by a treatment blinded assessor, demonstrated a significant thrombus reduction for one of the coatings compared to control. This effect was already seen one hour after implantation. This finding was supported by in vitro data showing a significant reduction of coagulation activation in the coated group. This novel coating shows promise as an implant material addition and could potentially decrease the need for DAPT in the early phases of stent implementation.

ABSTRACT: Infections with antimicrobial resistant pathogens are a major threat to human and animal health worldwide. Further, reduction of livestock-associated antimicrobial use (AMU) is often identified as an area of focus. Selective dry cow therapy (DCT) warrants consideration as an important way to decrease AMU on Canadian dairy farms. In addition, teat sealants (TS) are a nonantimicrobial alternative for prevention of intramammary infection during the dry period. Therefore, objectives of this study were to determine how antimicrobials and TS are used at dry-off on Canadian dairy farms to determine selective DCT uptake and enacted selection protocols. It was expected that these data will provide a baseline understanding of DCT practices and highlight areas for future intervention to further reduce AMU. An observational study was conducted utilizing 2 in-person questionnaires conducted between July 2019 and September 2021 on 144 participating dairy farms in 5 Canadian provinces (British Columbia = 30, Alberta = 30, Ontario = 31, Québec = 29, and Nova Scotia = 24). Overall, 45 farms (31%) reported adopting selective DCT, 95 (66%) enacted blanket DCT, and 4 (3%) did not provide antimicrobial DCT. Farms enacting selective DCT had approximately 50% less intramammary antimicrobials used at dry-off compared with blanket DCT farms. Cow somatic cell count history was the most common criterion for selective DCT decision-making, followed by previous clinical mastitis history, bacteriological culture, and milk production. A slight majority of farms (56%) applied TS to all cows at dry-off, whereas 17 farms (12%) used TS selectively, and 46 farms (32%) did not use TS. Larger herds more often used TS, and farms with an automatic milking system more often used TS selectively than applied to all cows. Results highlighted the variability in antimicrobial treatment and TS use protocols at dry-off on Canadian dairy farms, and the potential for further antimicrobial reduction with increased adoption of selective DCT.

The COVID-19 pandemic starting in 2020 has had massive mental health consequences worldwide. It has caused generalised fear and anxiety about catching, spreading and suffering from the virus. This article describes a fictionalised patient's presentation of life-threatening obsessive–compulsive disorder (OCD) associated with fears of catching COVID-19. The fears resulted in refusal to eat and drink, with subsequent weight loss that required paediatric admission. The scenario portrays the association between COVID-19 and life-threatening OCD symptoms and goes on to illustrate the patient's good response to standard OCD treatments.

Background: Alzheimer’s disease is a progressive neurodegenerative disease characterized by structural changes in the brain, including hippocampal atrophy, cortical thinning, amyloid plaques, and tau tangles. Due to the aging of the global population, the burden of Alzheimer’s disease is expected to increase, making the exploration of non-pharmacological interventions, such as physical exercise, an urgent priority. Results: There is emerging evidence that regular physical exercise may mitigate the structural and functional declines associated with Alzheimer’s disease. The underlying mechanisms, however, remain poorly understood. Gut–brain axis research is a promising area for further investigation. This system involves bidirectional communication between the gut microbiome and the brain. According to recent studies, the gut microbiome may influence brain health through modulating neuroinflammation, producing neuroactive compounds, and altering metabolic processes. Exercise has been shown to alter the composition of the gut microbiome, potentially impacting brain structure and function. In this review, we aim to synthesize current research on the relationship between physical exercise, structural brain changes in Alzheimer’s disease, and the gut–brain axis. Conclusions: In this study, we will investigate whether changes in the gut microbiome induced by physical exercise can mediate its neuroprotective effects, offering new insights into the prevention and treatment of Alzheimer’s disease. By integrating findings from neuroimaging studies, clinical trials, and microbiome research, this review will highlight potential mechanisms. It will also identify key gaps in the literature. This will pave the way for future research directions.

We aimed to (1) compare external training loads obtained in futsal players during pre-season and in-season training weeks to explore how these loads are periodized by the coaching staff; and (2) compare the external training loads using the match day minus approach during the pre-season and in-season periods to determine how the within-microcycle training load varies between these periods. A total of 432 recordings were obtained of twelve national-level male amateur players using IPS devices. These data were collected over four consecutive microcycles from the beginning to the end of the pre-season, as well as during four additional consecutive microcycles at the start of the in-season. The external load variables evaluated were: total distance covered (TD; m), relative distance covered (Drel; m/min), high-speed running (HSR; m > 18.8 km/h), sprint distance (SPR; m > 25.2 km/h), number of intense accelerations (ACC; >2.5 m/s2) and decelerations (DEC; >−2.5 m/s2). Results indicated significant week-by-week variation (p < 0.05) in all external load variables during the pre-season. During the in-season, significant variations (p < 0.05) were observed only in Drel, HSR, and ACC. In both phases, all variables were higher (p < 0.05) two days before the match. In conclusion, it is important to consistently quantify the external loads of futsal players to ensure appropriate variation in loading and tapering within the microcycle, as well as during the pre-season and in-season periods.

Basketball demands a sophisticated blend of tactical, technical, physical, and psychological skills, and various methods have been proposed to prepare players for these demands, including resistance training to enhance strength, power, speed, agility, and endurance. Complex training (CT) integrates diverse strength training methodologies by combining heavy-resistance exercises (e.g., squat at 90% of one repetition maximum) with high-velocity movements or plyometrics, both sharing the same biomechanical pattern. However, the optimal application of CT in basketball remains uncertain due to diverse protocols and a lack of consensus in the literature. The aim of this systematic review was to evaluate the acute and chronic effects of CT interventions on physical fitness performance in basketball players and identify the most effective characteristics of moderators. Methods: A bibliographic search was conducted using PubMed, SCOPUS, and Web of Science databases following the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines using the PICOS strategy. Results: Fourteen studies met the inclusion criteria, three articles analyzed acute effects, and thirteen analyzed chronic effects. The total number of participants in the studies analyzing acute effects was 50, while for studies examining chronic effects, it was 362. Conclusions: Acutely, CT triggers post-activation potentiation and enhances sprint performance when coupled with brief rest intervals. Over time, these acute improvements contribute to more substantial, long-lasting benefits. Chronic effects of CT improve strength, as evidenced by enhanced 1 RM performance, jumps, sprints, and core muscle strength.

Abstract The demanding nature of elite football requires players to be closely monitored to ensure optimal performance and minimize injury risk. This study aimed to evaluate the relationship between physical demands, skin temperature, and well-being status in 30 elite football players over a 12-week competitive period. Thermography assessments, weekly Well-being questionnaires, and daily training and match load recordings were used to gather data. Results indicated that along the microcycles there was a decrease in high-intensity accelerations and decelerations distance completed, while maintaining other high-intensity actions. Furthermore, it was found that high-intensity movements contribute to the generation of thermal asymmetries in the thighs; the adductor thermal asymmetry showed a positive relationship with stress and muscle soreness, the knee thermal asymmetry had a positive relationship with fatigue and a negative relationship with rest and quality of rest, and finally the hamstrings muscles exhibited significant differences between the thermal asymmetry groups, with the high asymmetry completing less high intensity actions than the low asymmetry group. In conclusion, this study highlights the interconnections between physical demands, skin temperature, and well-being in elite football players and provides valuable insights for coaches and trainers in their efforts to optimize performance and health.

IntroductionLow frequency (1 Hz) repetitive transcranial stimulation (rTMS) applied over right posterior parietal cortex (rPPC) has been shown to reduce cortical excitability both of the stimulated area and of the interconnected contralateral homologous areas. In the present study, we investigated the whole pattern of intra- and inter-hemispheric cortico-cortical connectivity changes induced by rTMS over rPPC.MethodsTo do so, 14 healthy participants underwent resting state EEG recording before and after 30 min of rTMS at 1 Hz or sham stimulation over the rPPC (electrode position P6). Real stimulation was applied at 90% of motor threshold. Coherence values were computed on the electrodes nearby the stimulated site (i.e., P4, P8, and CP6) considering all possible inter- and intra-hemispheric combinations for the following frequency bands: delta (0.5–4 Hz), theta (4–8 Hz), alpha (8–12Hz), low beta (12–20 Hz), high beta (20–30 Hz), and gamma (30–50 Hz).Results and discussionResults revealed a significant increase in coherence in delta, theta, alpha and beta frequency bands between rPPC and the contralateral homologous sites. Moreover, an increase in coherence in theta, alpha, beta and gamma frequency bands was found between rPPC and right frontal sites, reflecting the activation of the fronto-parietal network within the right hemisphere. Summarizing, subthreshold rTMS over rPPC revealed cortico-cortical inter- and intra-hemispheric connectivity as measured by the increase in coherence among these areas. Moreover, the present results further confirm previous evidence indicating that the increase of coherence values is related to intra- and inter-hemispheric inhibitory effects of rTMS. These results can have implications for devising evidence-based rehabilitation protocols after stroke.

Summary: Background: The Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) describes three primary avoidant/restrictive food intake disorder (ARFID) subtypes including sensory sensitivity, lack of interest in food or eating, and fear of aversive consequences. Studies exploring these subtypes have yielded varying results. We used latent class analysis (LCA) based on the psychopathology of ARFID in a sample of children and adolescents to empirically identify classes. Methods: We carried out a surveillance study of ARFID in collaboration with the British Paediatric Surveillance Unit (BPSU) and the Child and Adolescent Psychiatry Surveillance System (CAPSS) in the United Kingdom and the Republic of Ireland from 1st of March 2021 to 31st of March 2022. Paediatricians and child and adolescent psychiatrists were contacted monthly to report newly diagnosed cases of ARFID electronically and complete a detailed clinical questionnaire. Cases aged 5–18 years were included. LCA was performed specifying 1–6 classes and likelihood-based tests for model selection. The Bayesian Information Criterion (BIC), the Akaike Information Criterion (AIC) and the Sample-Size Adjusted BIC were used to determine the most parsimonious model. Analysis of variance (ANOVA) and χ2 tests were used to compare the characteristics of the identified classes. A multinomial logistic regression (MLR) was performed to investigate predicting factors for the latent classes. Findings: We identified 319 children and adolescents with ARFID. LCA revealed four distinct classes which were labelled as Fear subtype, Lack of Interest subtype, Sensory subtype, and Combined subtype. The probability of being classified as these were 7.2% (n = 23), 25.1% (n = 80), 29.5% (n = 94) and 38.2% (n = 122), respectively. Age at diagnosis, sex, weight loss, distress associated with eating, and autism spectrum disorder diagnosis were identified as predictors of class membership. Interpretation: LCA identified four different classes in a sample of children and adolescents with ARFID. The Combined Subtype, a mixed presentation was the most common. The other three classes resembled the subtypes described in the literature. Clinicians should be aware of these different presentations of ARFID as they may benefit from different clinical interventions. Funding: This study was funded by the Former EMS Ltd (charity number 1098725, registered October 9th 2017).

Microbiota analyses are key to understanding the bacterial communities within dairy cattle, but the impact of different storage conditions on these analyses remains unclear. This study sought to examine the effects of freezing at -80°C immediately after collection, refrigeration at 4°C for three days and seven days and absolute ethanol preservation on the microbiota diversity of pooled fecal samples from dairy cattle. Examining 16S rRNA gene sequences, alpha (Shannon, Pielou evenness, observed features and Faith PD indices) and beta (Bray-Curtis, βw and Weighted UniFrac) diversity were assessed. The effects of storage conditions on these metrics were evaluated using linear mixed models and PERMANOVA, incorporating the farm as a random effect. Our findings reveal that 7d and E significantly altered the Shannon index, suggesting a change in community composition. Changes in Pielou evenness for 3d and 7d storage when compared to 0d were found, indicating a shift in species evenness. Ethanol preservation impacted both observed features and Faith PD indices. Storage conditions significantly influenced Bray-Curtis, βw, and Weighted UniFrac metrics, indicating changes in community structure. PERMANOVA analysis showed that these storage conditions significantly contributed to microbiota differences compared to immediate freezing. In conclusion, our results demonstrate that while refrigeration for three days had minimal impact, seven days of refrigeration and ethanol preservation significantly altered microbiota analyses. These findings highlight the importance of sample storage considerations in microbiota research.

Abstract Mechanisms underlying the negative effects of obesity on the brain are still unknown. Obesity is associated with oxidative stress in the brain and neuroinflammation that promotes neurodegenerative diseases. Chronic low‐grade neuroinflammation in obesity could be associated with lower volumes of gray matter and lower neuronal density. If neuroinflammation mediated by the expression of cytokines and chemokines leads to apoptosis, this can be assessed by examining caspase expression. The aim of this study was to compare the expression of caspases in the 16 brains of donors with obesity/overweight (n = 8; Body Mass Index [BMI] = 31.6 ± 4.35 kg/m2; 2 females; Age = 52.9 ± 4.76 years) and normal weight (n = 8; BMI = 21.8 ± 1.5 kg/m2; 3 females; Age = 37.8 ± 19.2 years). Sixteen human brain samples were processed. Serial paraffin sections were examined by anti‐caspase immunochemistry (caspase‐3, caspase‐4, caspase‐6, caspase‐1, caspase‐8, and caspase‐9 antibodies). Postmortem samples of cerebral cortex tissue were captured as photomicrographs and the images obtained were analyzed using ImageJ software to obtain the percentage of positive caspase expression. Nonparametric Mann–Whitney U tests were performed to compare caspase expression between samples from donors with obesity/overweight and normal weight. Taking into consideration the immunohistochemistry results, the Search Tool for the Retrieval of Interacting Genes was used to model molecular interactions. Results showed that brain samples from individuals with obesity/overweight exhibited significantly greater values of positive expression for Caspase‐1 (U = 16.5, p = 0.05, Cohen d = 0.89) and −8 (U = 15, p = 0.03, Cohen d = 0.99) than those from donors with normal weight. This study contributes to the knowledge about the inflammatory effects of obesity/overweight on brain, suggesting the activation of the alternative inflammasome pathway in which interact caspase‐1 and ‐8.

Summary Wind turbine (WT) reliability has come to the forefront of research due to the rapid growth of wind energy in recent years. Reliability information can help understand failure causes and focus maintenance and prevention efforts on the most critical components, reducing costs and increasing profits. This paper offers new insights into WT reliability after analysing the data provided by the Supervisory Control And Data Acquisition (SCADA) system collected from seven onshore WTs located in central Spain from January 2014 to September 2021. To this end, we propose a method to link SCADA data to failure and maintenance records based on checking whether each 10‐min average time sample was collected when any failure or maintenance action had been reported. These records have been manually mapped to the WT taxonomy based on the standard Reference Designation System for Power Plants (RDS‐PP®) with minor changes. We present three different results: (i) The capacity factor and time‐based availability of each WT; (ii) the subsystem failure rate and downtime to identify the most critical ones; and (iii) each WT power curve with the 10‐min time samples labelled as healthy, under maintenance, or failure states, along with a ranking of the subsystems causing the most failures in each part of the power curves. It is the first time that time samples are linked to failure and maintenance records to visualise their distribution on the power curves. These results can help research point in the right direction to improve reliability and increase electricity production worldwide.