Extending MeCP2 interactome: canonical nucleosomal histones interact with MeCP2.

MeCP2 is a general regulator of transcription involved in the repression/activation of genes depending on the local epigenetic context. It acts as a chromatin regulator and binds with exquisite specificity to gene promoters. The set of epigenetic marks recognized by MeCP2 has been already established (mainly, cytosine modifications in CpG and CpA), as well as many of the constituents of its interactome. We unveil a new set of interactions for MeCP2 with the four canonical nucleosomal histones. MeCP2 interacts with high affinity with H2A, H2B, H3 and H4. In addition, Rett syndrome associated mutations in MeCP2 and histone epigenetic marks modulate these interactions. Given the abundance and the structural/functional relevance of histones and their involvement in epigenetic regulation, this new set of interactions and its modulating elements provide a new addition to the 'alphabet' for this epigenetic reader.

Should patients with exceptional longevity be treated for osteoporosis after a hip fracture?

BACKGROUND: There are no studies focusing on treatment for osteoporosis in patients with exceptional longevity after suffering a hip fracture. OBJECTIVE: To assess the advisability of initiating treatment for osteoporosis after a hip fracture according to the incidence of new fragility fractures after discharge, risk factors for mortality and long-term survival. DESIGN: Retrospective review. SETTING: A tertiary university hospital serving a population of ~425 000 inhabitants in Barcelona. SUBJECTS: All patients >95 years old admitted with a fragility hip fracture between December 2009 and September 2015 who survived admission were analysed until the present time. METHODS: Pre-fracture ambulation ability and new fragility fractures after discharge were recorded. Risk factors for 1-year and all post-discharge mortality were calculated with multivariate Cox regression. Kaplan-Meier survival curve analyses were performed. RESULTS: One hundred and seventy-five patients were included. Median survival time was 1.32 years [95% confidence interval (CI) 1.065-1.834], with a maximum of 9.2 years. Male sex [hazard ratio (HR) 2.488, 95% CI 1.420-4.358] and worse previous ability to ambulate (HR 2.291, 95% CI 1.417-3.703) were predictors of mortality. After discharge and up to death or the present time, 10 (5.7%) patients had a new fragility fracture, half of them during the first 6 months. CONCLUSIONS: Few new fragility fractures occurred after discharge and half of these took place in the first 6 months. The decision to start treatment of osteoporosis should be individualised, bearing in mind that women and patients with better previous ambulation ability will have a better chance of survival.

Indoor falls and number of previous falls are independent risk factors for long-term mortality after a hip fracture.

BACKGROUND: Hip fractures are almost always the result of a fall. Causes and circumstances of falls may differ between frail and vigorous patients. AIM: To describe the circumstances of falls causing hip fractures, number of falls during the previous year, and their association with long-term mortality. PATIENTS AND METHODS: The study is a retrospective review conducted in a tertiary university hospital serving a population of 425,000 inhabitants in Barcelona. All patients admitted with hip fractures with medical records describing the circumstances and number of previous falls were included. The number of falls in the previous 12 months was recorded, including the one causing the fracture. The circumstances of the index fall were dichotomized according to whether it was from the patient's own height or above; day or night; indoors or outdoors, due to intrinsic or extrinsic causes. Cumulative mortality was recorded for almost 5 years after hip fracture. RESULTS: Indoor falls were strongly associated with shorter survival. Falling more than once in the previous year was also a risk factor for long-term mortality (hazard ratio 1.461, p < 0.001 and hazard ratio 1.035, p = 0.008 respectively). CONCLUSION: Indoor falls and falling more than once in the previous year are long-term risk factors for mortality after hip fractures. It is always essential to take a careful patient history on admission to determine the number of falls and their circumstances, and special care should be taken to reduce mortality in patients at high risk.

Heterophil/lymphocyte response of local Spanish breeds of laying hens to cold stress, heat stress, and water restriction.

Environmental challenges may adversely affect poultry production. Autochthonous breeds are particularly valuable in a climate change context because of adaptation to the local environment. The objective of the present study was to determine the impact of cold stress, water restriction, and heat stress on the stress response quantified by the heterophil to lymphocyte ratio (H/L) of ten local Spanish breeds of laying hens. Hens of these local breeds were consecutively subjected to three treatments: natural cold stress (2, 4, 6, 7, 9, and 13 °C), water restriction (with a duration of 2.5, 4.5, 7, 10, and 12 h, respectively), and natural heat stress (23, 26, 28, 30, 34, 38, 40, and 42 °C). During cold stress, H/L was higher at 9 and 13 °C than at 2, 4, and 6 °C, and higher at 9 °C than at 7 °C (P < 0.05). H/L values were similar during all water restriction levels. During heat stress, H/L was particularly elevated at temperatures higher than 40 °C (P < 0.05). Overall, Andaluza Azul, Andaluza Perdiz and Prat Codorniz showed lowest resilience to stress based on their H/L response, whereas Pardo de Leon, Villafranquina Roja, and Prat Leonada showed highest resilience.

Global Impairment of Immediate-Early Genes Expression in Rett Syndrome Models and Patients Linked to Myelination Defects.

Rett syndrome (RTT) is a severe neurodevelopmental disease caused almost exclusively by mutations to the MeCP2 gene. This disease may be regarded as a synaptopathy, with impairments affecting synaptic plasticity, inhibitory and excitatory transmission and network excitability. The complete understanding of the mechanisms behind how the transcription factor MeCP2 so profoundly affects the mammalian brain are yet to be determined. What is known, is that MeCP2 involvement in activity-dependent expression programs is a critical link between this protein and proper neuronal activity, which allows the correct maturation of connections in the brain. By using RNA-sequencing analysis, we found several immediate-early genes (IEGs, key mediators of activity-dependent responses) directly bound by MeCP2 at the chromatin level and upregulated in the hippocampus and prefrontal cortex of the Mecp2-KO mouse. Quantification of the IEGs response to stimulus both in vivo and in vitro detected an aberrant expression pattern in MeCP2-deficient neurons. Furthermore, altered IEGs levels were found in RTT patient's peripheral blood and brain regions of post-mortem samples, correlating with impaired expression of downstream myelination-related genes. Altogether, these data indicate that proper IEGs expression is crucial for correct synaptic development and that MeCP2 has a key role in the regulation of IEGs.

The influence of local market and household factors on aflatoxin presence in maize and symptoms of its exposure to children in Guatemala.

Recent evidence supports the hypothesis that aflatoxin exposure from maize can influence malnutrition rates among children. Therefore, in Guatemala we investigated two questions; which maize sources exposed households to higher risk of aflatoxin exposure symptoms and what the risk factors were for each maize source, pre- and post-maize harvest. Survey data and household maize samples were collected in October 2016 (pre-harvest) and February 2017 (post-harvest) in San Vicente, Guatemala. Structural equation modeling (SEM) and odds ratios were used to assess the data. The results suggested that households which purchased maize from the market had 3.64 higher odds of high levels of aflatoxin. The models identified that good market purchase habits were significant for market-based maize sources while improved post-harvest practices and improved types of maize storage were significant for subsistence-based maize sources. Cumulative results suggest multiple interventions may be effective but are dependent on time of year and source of maize.

Lower Cardiovascular Stress during Resistance Training Performed with Inter-Repetition Rests in Elderly Coronary Patients.

Background and Objectives: Hemodynamic stress during resistance training is often a reason why this training method is not used in cardiac patients. A lifting protocol that imposes rests between repetitions (IRRT) may provide less hemodynamic stress compared to traditional resistance training (TT). The aim of this study was to verify differences between set configurations on hemodynamic stress responses in resistance training. Materials and Methods: We compared hemodynamic (heart rate (HR), systolic blood pressure (SBP), and rate pressure product (RPP)) responses assessed with the auscultatory method in elderly (age = 75.3 ± 7.3 years) coronary male patients who were participating in a cardiac rehabilitation program allocated to either TT or IRRT with the same load (kg) and total number of repetitions (24) in the bilateral leg extension exercise. Results: IRRT resulted in significant lower values than TT for RPP at repetitions 8 (p = 0.024; G = 0.329; 95% CI: 0.061, 0.598) and 16 (p = 0.014; G = 0.483; 95% CI: 0.112, 0.854). Conclusions: IRRT appears to be a viable method of reducing the hemodynamic response (i.e., RPP) to resistance training and, thus, may contribute to the safety of cardiac rehabilitation programs. Further studies with more cardiac patients and other measurement techniques should be conducted to confirm these important findings.

Rehydration during exercise prevents the increase of homocysteine concentrations.

This study aimed to assess the effect of rehydration during and after acute aerobic submaximal exercise on total homocysteine (tHcy) concentrations and related parameters in physically active adult males. Twenty trained males (29.4 ± 7.9 years old) completed four exercise tests: two without rehydration during exercise (NH1 and NH2), one with rehydration during exercise using water (H1) and one with rehydration during exercise using an isotonic sports drink (H2). After finishing the exercise tests, subjects followed a rehydration protocol for 2 h. Serum tHcy, vitamin B12, folate, creatine and creatinine were analysed before, after and at 2, 6 and 24 h after exercise. Data were analysed with and without correcting for haemoconcentration to assess the changes in tHcy related. The methylenetetrahydrofolate reductase (MTHFR) 677TT genotype was also analysed. THcy (uncorrected by haemoconcentration) increased significantly after exercise (P < 0.05) in the NH1 and NH2 tests [mean increase ± SD: 1.55 ± 0.33 (15.18%) and 1.76 ± 0.25 (17.69%) µmol/L, respectively], while no significant differences were found in the H1 and H2 tests [mean increase: 0.65 (6.29%) and 0.90 (8.69%) µmol/L, respectively]. The increase was partly due to haemoconcentration and partly due to the metabolism underlying acute exercise. THcy concentrations recovered to baseline after 24 h in all tests. In conclusion, adequate rehydration during acute aerobic exercise using either water or a sports drink maintains tHcy concentrations at baseline and for up to 2 h after exercise in physically active male adults and prevents further increases when compared to no rehydration.

Association of aflatoxin exposure and height-for-age among young children in Guatemala.

Aflatoxin exposure has been proposed to affect child height-for-age. The following hypothesized associations were tested in Guatemala: (1) aflatoxin (B1, B2, G1, G2) exposure and environmental enteric dysfunction (EED) and child height-for-age z-score; and (2) aflatoxin exposures and subsequent symptoms of aflatoxins. Maize consumption data, health data, and samples of maize from households were collected from mothers and their children - under five - in October 2016 (n = 320) and February 2017 (n = 120). Maize samples were tested for aflatoxin levels and maize consumption data were used to compute an aflatoxin exposure level. Results suggest that there was a significant negative correlation between the putative aflatoxin exposure level and child height-for-age z-score (-0.073, p = 0.030), but not for EED. Furthermore, aflatoxin exposure was significantly correlated with aflatoxin symptoms only at the same time point (0.123, p = 0.026). These results support the potential need for engineered solutions to household aflatoxin transmission problems in rural communities of Guatemala.

What do we know about homocysteine and exercise? A review from the literature.

High total homocysteine (tHcy) concentrations contribute to an increased risk of cardiovascular diseases and neurodegenerative disorders. Several investigations have focused on the effect of exercise on tHcy concentrations, but results remain controversial. The differences among the methodologies in the investigations make difficult the interpretation of results. This review differentiates the effects of exercise on tHcy and establishes the relation with the implicated biomarkers on tHcy metabolism related to exercise. The electronic database MEDLINE (http://www.ncbi.nlm.nih.gov) was used for searching studies published between years 2002 and 2015. 'Homocysteine', 'Training ', 'Exercise', 'Physical Activity' as well as combinations out of these terms were entered in the database. Articles were grouped in: 1) Acute effect of exercise on tHcy, 2) chronic exercise and tHcy, 3) relationship of physical activity (PA) level and cardiorespiratory fitness with tHcy, and 4) biomarkers related to tHcy and exercise. From a total of 30 articles, most of the studies analyzing the acute effect of exercise showed an increase on tHcy concentrations. Studies analyzing the chronic effect on tHcy concentrations showed contradictory results and no consensus exists probably due to the differences in the methodology, exercise interventions and participants characteristics. Low cardiorespiratory fitness seems to be associated with high tHcy; in contrast, the relation of PA levels and tHcy needs further research. Regarding biomarkers related to tHcy and exercise, some studies showed an increase of folate, vitamin B12, and creatine after acute exercise that could to be due to requirement of protein turnover and an increased metabolic demand of vitamin-B.

Elderly patients treated with psychotropic medicines admitted to hospital: associated characteristics and inappropriate use.

PURPOSE: The purpose of this study is to describe the characteristics of older patients treated with psychotropic medicines and the associated factors and to assess their inappropriate use. METHODS: An observational, prospective study was carried out in 672 elderly patients admitted to seven hospitals for a year. A comparison of sociodemographic characteristics, geriatric variables, multimorbidity and the number of prescribed medicines taken in the preceding month before hospitalization between patients treated with psychotropics and those not treated was performed. To assess factors associated with psychotropics, multivariate logistic regression analyses were performed. Inappropriate use was assessed using the Beers and the STOPP criteria. RESULTS: A total of 57.5 % patients (median [Q1-Q3] age 81.7 [78.2-86.1], 65.7 % female) were treated with psychotropics (44.2 % anxiolytics, 22.6 % antidepressants and 10.8 % antipsychotics). Independent factors associated with the use of psychotropics were female gender (OR = 2.3; CI 95 %,1.6-3.5), some degree of disability on admission (slight [OR = 2.2; 1.2-4.2], moderate [OR = 3.2, 1.6-6.6], severe [OR = 3.4; 1.4-8] and very severe [OR = 5.1; 2.0-12.8]) and polypharmacy (5-9 medicines [OR = 3.0; 1.3-6.9] and ≥10 medicines [OR = 6.0; 2.7-13.6]). The associated factors varied depending on the different types of psychotropics. In patients treated with psychotropics, the percentage of those with at least one Beers (61.6 %) or at least one STOPP (71.4 %) criteria was significantly higher in comparison with those not treated with psychotropics (30.7 and 47.7 %, respectively, p < 0.001). CONCLUSIONS: Psychotropics are widely used in the elderly population and often their use is inappropriate. Female gender, a poor functional status and polypharmacy, are the characteristics linked to their use. Interventional strategies should be focused on patients with these characteristics.

Inappropriate prescribing to the oldest old patients admitted to hospital: prevalence, most frequently used medicines, and associated factors.

BACKGROUND: Scientific evidence on treatments of chronic diseases in patients 85 years old or older is very limited, as is available information on inappropriate prescription (IP) and its associated factors. The study aimed to describe medicine prescription, potentially inappropriate medicines (PIM) and potentially prescribing omissions (PPO) and their associated factors on this population. METHODS: In the context of an observational, prospective and multicentric study carried out in elderly patients admitted to seven Spanish hospitals for a year, a sub-analysis of those aged 85 years and over was performed. To assess PIMs, the Beers and STOPP criteria were used, and to assess PPOs, the START and the ACOVE-3 criteria were used. To assess factors associated with IP, a multivariate logistic regression analysis was performed. Patients were selected randomly every week on consecutive days from the hospitalization lists. RESULTS: A total of 336 patients were included in the sub-analysis with a median (Q1-Q3) age of 88 (86-90) years. The median medicines taken during the month prior to admission was 10 (7-13). Forty-seven point two per cent of patients had at least one Beers-listed PIM, 63.3% at least one STOPP-listed PIM, 53.6% at least one START-listed PPO, and 59.4% at least one ACOVE-3-listed PPO. Use of benzodiazepines in patients who are prone to falls (18.3%) and omission of calcium and vitamin D supplements in patients with osteoporosis (13.3%) were the most common PIM and PPO, respectively. The main factor associated with the Beers-listed and the STOPP-listed PIM was consumption of 10 or more medicines (OR = 5.7, 95% CI 1.8-17.9 and OR = 13.4, 95% CI 4.0-44.0, respectively). The main factors associated with the START-listed PPO was a non-community dwelling origin (OR 2.3, 95% CI 1.0-5.0), and multimorbidity (OR1.8, 95% CI 1.0-3.1). CONCLUSIONS: Prescribed medicines and PIM and PPO prevalence were high among patients 85 years and over. Benzodiazepine use in those who are prone to falls and omission of calcium and vitamin D in those with osteoporosis were the most frequent PIM and PPO, respectively. Factors associated with PIM and PPO differed with polypharmacy being the most important factor associated with PIM.

Prevalence of cleft lip and cleft palate in rural north-central guatemala.

OBJECTIVE: To estimate the number of new cases of cleft lip and cleft palate in the department (state) of Alta Verapaz, Guatemala, in 2012. DESIGN: Cross-sectional survey of midwives from communities identified through a two-stage cluster-sampling process. Midwives were asked how many babies they had delivered in the past year and how many of those newborns had various types of birth defects, as illustrated in pictures. SETTING: Indigenous Mayan communities in rural north-central Guatemala. PARTICIPANTS: Midwives (n = 129) who had delivered babies in the previous year. MAIN OUTCOME MEASURE: Reports of babies born with cleft lip and cleft palate. RESULTS: A 1-year prevalence rate of 18.9 per 10,000 for cleft lip and 4.7 per 10,000 for cleft palate was estimated for Alta Verapaz. None of the cases of cleft lip also had cleft palate. CONCLUSION: The indigenous communities in north-central Guatemala might have a relatively high cleft lip prevalence rate compared with the global average.

Photochemical pump and NMR probe: chemically created NMR coherence on a microsecond time scale.

We report pump-probe experiments employing laser-synchronized reactions of para-hydrogen (para-H2) with transition metal dihydride complexes in conjunction with nuclear magnetic resonance (NMR) detection. The pump-probe experiment consists of a single nanosecond laser pump pulse followed, after a precisely defined delay, by a single radio frequency (rf) probe pulse. Laser irradiation eliminates H2 from either Ru(PPh3)3(CO)(H)2 1 or cis-Ru(dppe)2(H)2 2 in C6D6 solution. Reaction with para-H2 then regenerates 1 and 2 in a well-defined nuclear spin state. The rf probe pulse produces a high-resolution, single-scan (1)H NMR spectrum that can be recorded after a pump-probe delay of just 10 µs. The evolution of the spectra can be followed as the pump-probe delay is increased by micro- or millisecond increments. Due to the sensitivity of this para-H2 experiment, the resulting NMR spectra can have hydride signal-to-noise ratios exceeding 750:1. The spectra of 1 oscillate in amplitude with frequency 1101 ± 3 Hz, the chemical shift difference between the chemically inequivalent hydrides. The corresponding hydride signals of 2 oscillate with frequency 83 ± 5 Hz, which matches the difference between couplings of the hydrides to the equatorial (31)P nuclei. We use the product operator formalism to show that this oscillatory behavior arises from a magnetic coherence in the plane orthogonal to the magnetic field that is generated by use of the laser pulse without rf initialization. In addition, we demonstrate how chemical shift imaging can differentiate the region of laser irradiation thereby distinguishing between thermal and photochemical reactivity within the NMR tube.

Dietary, socioeconomic, and maize handling practices associated with aflatoxin and fumonisin exposure among women tortilla makers in 5 departments in Guatemala.

Previous research has demonstrated human exposure to mycotoxins among Guatemalans, with high levels of mycotoxins being found in blood and urine samples as well as in maize for human consumption. Mishandling of crops such as maize during pre- and post-harvest has been associated with mycotoxin contamination. The overarching goal of this study was to identify risk factors for aflatoxin and fumonisin exposure in Guatemala. A cross-sectional survey of 141 women tortilla makers was conducted in the departments of Guatemala, Sololá, Suchitepéquez, Izabal, and Zacapa in February 2022. Maize and tortilla samples were collected and analyzed for aflatoxin B1 (AFB1) and fumonisin B1, B2, and B3 contamination (FB1, FB2, FB3). Urine samples were collected and analyzed for urinary FB1 (uFB1) contamination. A questionnaire was administered to collect data on sociodemographic characteristics, dietary intake of maize-based foods the week prior to the study, and maize handling practices. Descriptive statistics were used to describe common maize handling practices. A univariable analysis was conducted to identify predictors of low/high AFB1, total fumonisins, and uFB1. Multivariable logistic regression was used to calculate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). During tortilla processing, a reduction in the AFB1 and total fumonisin levels was observed. The presence of AFB1 in maize was associated with department and mean total fumonisin level in maize (OR: 1.705, 95% CI: 1.113-2.613). The department where the tortilleria was located was significantly associated with the presence of fumonisins in tortillas. Increased consumption of Tortrix was significantly associated with the presence of FB1 in urine (OR: 1.652, 95% CI: 1.072-2.546). Results of this study can be used in the development and implementation of supply chain management practices that mitigate mycotoxin production, reduce food waste and economic loss, and promote food security.

Risk Factors Associated with Antibiotic Exposure Variability in Critically Ill Patients: A Systematic Review.

(1) Background: Knowledge about the behavior of antibiotics in critically ill patients has been increasing in recent years. Some studies have concluded that a high percentage may be outside the therapeutic range. The most likely cause of this is the pharmacokinetic variability of critically ill patients, but it is not clear which factors have the greatest impact. The aim of this systematic review is to identify risk factors among critically ill patients that may exhibit significant pharmacokinetic alterations, compromising treatment efficacy and safety. (2) Methods: The search included the PubMed, Web of Science, and Embase databases. (3) Results: We identified 246 observational studies and ten clinical trials. The most studied risk factors in the literature were renal function, weight, age, sex, and renal replacement therapy. Risk factors with the greatest impact included renal function, weight, renal replacement therapy, age, protein or albumin levels, and APACHE or SAPS scores. (4) Conclusions: The review allows us to identify which critically ill patients are at a higher risk of not reaching therapeutic targets and helps us to recognize the extensive number of risk factors that have been studied, guiding their inclusion in future studies. It is essential to continue researching, especially in real clinical practice and with clinical outcomes.

Eating Behavior Disorders and Disordered Eating Habits in Spanish High-Performance Women's Olympic Wrestling Athletes.

Eating disorders (EDs) are a significant health issue in combat sports. This study investigated the differences between the different types of female wrestlers and the frequency at which EDs occur in the elite population, and it also sought to establish which factors are predictors of EDs. This study was comprised of 22 elite, female wrestlers who were selected based on the following inclusion criteria: having previously been the Spanish champion, being part of the Spanish national team, participating in at least one international championship, and having a history of ED. Data collection involved five questionnaires: demographic data, the Eating Attitudes Test-26 (EAT-26), the Bulimic Investigatory Test, the Edinburgh (BITE), the Eating Disorders Inventory (EDI-3), and the Depression, Anxiety, and Stress Scale (DASS-21). The results revealed diverse levels of depression, anxiety, and stress, with BITE scores indicating abnormal eating patterns. Group comparisons exposed significant distinctions in eating behaviors based on competition and training experience. Regression analyses showed competition and training experience as predictors of bulimia severity and symptoms. The study revealed prevalent extreme weight-control practices, including fasting, diuretic and laxative use, and binge eating. This research emphasizes the importance of EDs in Olympic wrestling, urging a comprehensive approach involving education, support, and policy implementation by coaches, health professionals, and sports organizations to prioritize athletes' well-being and discourage unhealthy weight-control practices.

Reversible insertion of carbenes into ruthenium-silicon bonds.

The five-coordinate carbene complexes [Ru{κP,P,Si-Si(Me)(C6H4-2-PiPr2)2}Cl(═CHR)] (2, R = Ph; 3, R = SiMe3), analogues of the Grubbs catalyst, were prepared from the dimer [Ru(µ-Cl){κP,P,Si-Si(Me)(C6H4-2-PiPr2)2}]2 (1) and the corresponding diazoalkane N2CHR. The particular structural features that result from the presence of a strongly trans directing silyl group at the pincer ligand of these complexes are discussed on the basis of NMR information and the crystal structure of the vinylidene analogue [Ru{κP,P,Si-Si(Me)(C6H4-2-PiPr2)2}Cl(═C═CHPh)] (4), which was also obtained from 1 and phenylacetylene. The reactions of 3 with reagents such as P(OMe)3, CO, NCMe, and K(acac) illustrate that the first response of these carbene complexes to an increase of the coordination number around ruthenium is the insertion of the carbene ligand into the Ru-Si bond. These reactions also indicate that the insertion process is reversible and allows typical transformations of carbene ligands such as C-H functionalizations via carbene insertion (in the acac ligand) or the formation of ketene from CO. In addition, the reactions of 3 with terminal alkynes such as phenylacetylene or 3,3-dimethyl-1-butyne show that the inserted carbenes can also undergo reactions typical of metal-bound alkyls such as alkyne insertion and C-H reductive elimination.

Assessment of aflatoxin exposure, growth faltering and the gut microbiome among children in rural Guatemala: protocol for an observational prospective cohort and bioreactor simulations.

INTRODUCTION: Aflatoxin B1 (AFB1) is a carcinogen produced by Aspergillus flavus and Aspergillus parasiticus which grow on maize. Given the high prevalence of child stunting (ie, impaired growth) and other nutritional disorders in low-income and middle-income countries, where maize is consumed, the role of aflatoxin exposure may be significant. Observational reports have demonstrated associations between aflatoxin exposure and impaired child growth; however, most have been cross-sectional and have not assessed seasonal variations in aflatoxin, food preparation and dynamic changes in growth. Biological mechanistic data on how aflatoxin may exert an impact on child growth is missing. This study incorporates a prospective cohort of children from rural Guatemala to assess (1) temporal associations between aflatoxin exposure and child growth and (2) possible mediation of the gut microbiome among aflatoxin exposure, inflammation and child growth. METHODS AND ANALYSIS: We will prospectively evaluate aflatoxin exposure and height-for-age difference trajectories for 18 months in a cohort of 185 children aged 6-9 months at enrolment. We will assess aflatoxin exposure levels and biomarkers of gut and systemic inflammation. We will examine the faecal microbiome of each child and identify key species and metabolic pathways for differing AFB1 exposure levels and child growth trajectories. In parallel, we will use bioreactors, inoculated with faeces, to investigate the response of the gut microbiome to varying levels of AFB1 exposure. We will monitor key microbial metabolites and AFB1 biotransformation products to study nutrient metabolism and the impact of the gut microbiome on aflatoxin detoxification/metabolism. Finally, we will use path analysis to summarise the effect of aflatoxin exposure and the gut microbiome on child growth. ETHICS AND DISSEMINATION: Ethics approval was obtained from Arizona State University Institutional Review Board (IRB; STUDY00016799) and Wuqu' Kawoq/Maya Health Alliance IRB (WK-2022-003). Findings will be disseminated in scientific presentations and peer-reviewed publications.

Pelvic Floor Muscle Training Interventions in Female Athletes: A Systematic Review and Meta-analysis.

CONTEXT: Athletes are almost 3 times more at risk of experiencing urinary incontinence (UI) than sedentary women, with prevalence rates varying from 10.9% in low-impact sports such as cycling to 80% when engaging in high-impact sports such as trampoline gymnastics. To treat UI, pelvic floor muscle (PFM) training (PFMT) is recommended as a first line of treatment. OBJECTIVE: The aim of the present study was to perform a meta-analysis of the available literature on the efficacy of PFMT interventions in young, nulliparous female athletes. DATA SOURCES: A literature research was conducted using PubMed, Sport Discus, and Web of Science. STUDY SELECTION: The inclusion criteria were studies with PFMT intervention in female athletes or recreationally active women. Interventions could be carried out for treatment or prevention of pelvic floor dysfunctions. STUDY DESIGN: Systematic review with meta-analysis. LEVEL OF EVIDENCE: Level 5. DATA EXTRACTION: A descriptive analysis of the articles included in the systematic review was carried out. Meta-analyses could be performed on 6 of the included articles, evaluating the maximal voluntary contraction (MVC) of the PFMs, the amount of urinary leakage (AUL), and the vaginal resting pressure (VRP). Random-effects model and standardized mean differences (SMD) ± 95% CI were reported. RESULTS: The meta-analysis showed that PFMT produced a significant increase in MVC (SMD, 0.60; 95% CI, 0.11 to 1.08; P = 0.02) and a significant reduction of AUL (SMD, -1.13; 95% CI, -1.84 to -0.41; P < 0.01) in female athletes. No effects were shown in VRP (SMD, -0.05; 95% CI, -1.27 to 1.17; P = 0.93). CONCLUSION: PFMT is shown to be effective in increasing PFM strength and reducing urine leakage in female athletes, being a powerful tool to prevent and treat pelvic floor dysfunction in this population.