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OBJECTIVE: To study the impact of vigorous vs. moderate exercise on metabolic parameters in polycystic ovary syndrome (PCOS). DESIGN: Randomized controlled trial. SETTING: Unsupervised home-based exercise program. PATIENTS: Patients with PCOS on the basis of the Rotterdam criteria with insulin resistance. INTERVENTIONS: Participants were block randomized to a home-based exercise program of 75 minutes of vigorous exercise or 150 minutes of moderate exercise per week, for 8 weeks total. MAIN OUTCOME MEASURES: Changes in glucose, insulin, and insulin resistance. RESULTS: In total, 36 participants were randomized, of whom 20 completed the study. The percentage changes from baseline at 4 and 8 weeks for fasting glucose, insulin, and homeostatic model assessment for insulin resistance did not significantly differ between the groups, except for the change in the 8-week glucose level, which was more favorable in the moderate arm (8.06% [standard deviation, 6.44%] in the vigorous group compared with -0.32% [standard deviation, 4.91%] in the moderate group). The absolute values of the main outcomes (fasting glucose, insulin, and homeostatic model assessment for insulin resistance) at baseline and 4 and 8 weeks did not significantly differ between trial arms. When assessing the change from baseline at 4 and 8 weeks, overall and within each trial arm, only the 8-week fasting glucose level was significantly greater than the baseline value in the vigorous arm (93.5 [95% confidence interval, 88.7-98.3] vs. 86.8 [95% confidence interval, 81.1-92.4]). CONCLUSIONS: Unsupervised short-term exercise programs may not achieve significant metabolic improvements in patients with PCOS, regardless of vigorous vs. moderate intensity. Future studies should investigate this question in larger sample sizes and longer or structured exercise programs. CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.gov identifier, NCT02303470.

Abstract The use of antimicrobial drugs in food-producing animals contributes to the selection pressure on pathogenic and commensal bacteria to become resistant. This study aims to evaluate the existence of trade-offs between treatment effectiveness, cost, and the dynamics of resistance in gut commensal bacteria. We developed a within-host ordinary differential equation model to track the dynamics of antimicrobial drug concentrations and bacterial populations in the site of infection (lung) and the gut. The model was parameterized to represent enrofloxacin treatment for bovine respiratory disease (BRD) caused by Pastereulla multocida in cattle. Three approved enrofloxacin dosing regimens were compared for their effects on resistance on P. multocida and commensal E. coli: 12.5 mg/kg and 7.5 mg/kg as a single dose, and 5 mg/kg as three doses. Additionally, we explored non-FDA-approved regimes. Our results indicated that both 12.5 mg/kg and 7.5 mg/kg as a single dose scenario increased the most the treatment costs and prevalence of P. multocida resistance in the lungs, while 5 mg/kg as three doses increased resistance in commensal E. coli bacteria in the gut the most out of the approved scenarios. A proposed non-FDA-approved scenario (7.5 mg/kg, two doses 24 h apart) showed low economic costs, minimal P. multocida, and moderate effects on resistant E. coli. Overall, the scenarios that decrease P. multocida, including resistant P. multocida did not coincide with those that decrease resistant E. coli the most, suggesting a trade-off between both outcomes. The sensitivity analysis suggests that bacterial populations were the most sensitive to drug conversion factors into plasma ( $${\beta}$$ β ), elimination of the drug from the colon ( $$\vartheta$$ ϑ ), fifty percent sensitive bacteria (P. multocida) killing effect ( $${\text{L}}_{\text{s50}}$$ L s50 ), fifty percent of bacteria (E. coli) above ECOFF killing effect ( $${\text{C}}_{\text{r50}}$$ C r50 ), and net drug transfer rate in the lung ( $$\gamma$$ γ ) parameters.

Abstract Indoor residual spraying (IRS) and insecticide-treated nets (ITNs) are the main methods used to control mosquito populations for malaria prevention. The efficacy of these strategies is threatened by the spread of insecticide resistance (IR), limiting the success of malaria control. Studies of the genetic evolution leading to insecticide resistance could enable the identification of molecular markers that can be used for IR surveillance and an improved understanding of the molecular mechanisms associated with IR. This study used a weighted gene co-expression network analysis (WGCNA) algorithm, a systems biology approach, to identify genes with similar co-expression patterns (modules) and hub genes that are potential molecular markers for insecticide resistance surveillance in Kenya and Benin. A total of 20 and 26 gene co-expression modules were identified via average linkage hierarchical clustering from Anopheles arabiensis and An. gambiae, respectively, and hub genes (highly connected genes) were identified within each module. Three specific genes stood out: serine protease, E3 ubiquitin-protein ligase, and cuticular proteins, which were top hub genes in both species and could serve as potential markers and targets for monitoring IR in these malaria vectors. In addition to the identified markers, we explored molecular mechanisms using enrichment maps that revealed a complex process involving multiple steps, from odorant binding and neuronal signaling to cellular responses, immune modulation, cellular metabolism, and gene regulation. Incorporation of these dynamics into the development of new insecticides and the tracking of insecticide resistance could improve the sustainable and cost-effective deployment of interventions.

Optimal control theory can be a useful tool to identify the best strategies for the management of infectious diseases. In most of the applications to disease control with ordinary differential equations, the objective functional to be optimized is formulated in monetary terms as the sum of intervention costs and the cost associated with the burden of disease. We present alternate formulations that express epidemiological outcomes via health metrics and reframe the problem to include features such as budget constraints and epidemiological targets. These alternate formulations are illustrated with a compartmental cholera model. The alternate formulations permit us to better explore the sensitivity of the optimal control solutions to changes in available budget or the desired epidemiological target. We also discuss some limitations of comprehensive cost assessment in epidemiology.

Mastery of quantitative skills is increasingly critical for student success in life sciences, but few curricula adequately incorporate quantitative skills. Quantitative Biology at Community Colleges (QB@CC) is designed to address this need by building a grassroots consortium of community college faculty to (1) engage in interdisciplinary partnerships that increase participant confidence in life science, mathematics, and statistics domains; (2) generate and publish a collection of quantitative skills--focused open education resources (OER); and (3) disseminate these OER and pedagogical practices widely, in turn expanding the network. Currently in its third year, QB@CC has recruited 70 faculty into the network and created 20 modules. Modules can be accessed by interested biology and mathematics educators in high school, 2-year, and 4-year institutions. Here, we use survey responses, focus group interviews, and document analyses (principles-focused evaluation) to evaluate the progress in accomplishing these goals midway through the QB@CC program. The QB@CC network provides a model for developing and sustaining an interdisciplinary community that benefits participants and generates valuable resources for the broader community. Similar network-building programs may wish to adopt some of the effective aspects of the QB@CC network model to meet their objectives.

Abstract Background Mexico has experienced a significant reduction in malaria cases over the past two decades. Certification of localities as malaria-free areas (MFAs) has been proposed as a steppingstone before elimination is achieved throughout the country. The Mexican state of Quintana Roo is a candidate for MFA certification. Monitoring the status of insecticide susceptibility of major vectors is crucial for MFA certification. This study describes the susceptibility status of Anopheles albimanus, main malaria vector, from historically important malaria foci in Quintana Roo, using both phenotypic and genotypic approaches. Methods Adult mosquito collections were carried out at three localities: Palmar (Municipality of Othon P. Blanco), Buenavista (Bacalar) and Puerto Morelos (Puerto Morelos). Outdoor human-landing catches were performed by pairs of trained staff from 18:00 to 22:00 during 3-night periods at each locality during the rainy season of 2022. Wild-caught female mosquitoes were exposed to diagnostic doses of deltamethrin, permethrin, malathion, pirimiphos-methyl or bendiocarb using CDC bottle bioassays. Mortality was registered at the diagnostic time and recovery was assessed 24 h after exposure. Molecular analyses targeting the Voltage-Gated Sodium Channel (vgsc) gene and acetylcholinesterase (ace-1) gene were used to screen for target site polymorphisms. An SNP analysis was carried out to identify mutations at position 995 in the vgsc gene and at position 280 in the ace-1 gene. Results A total of 2828 anophelines were collected. The main species identified were Anopheles albimanus (82%) and Anopheles vestitipennis (16%). Mortalities in the CDC bottle bioassay ranged from 99% to 100% for all the insecticides and mosquito species. Sequence analysis was performed on 35 An. albimanus across the three localities; of those, 25 were analysed for vgsc and 10 for ace-1 mutations. All individuals showed wild type alleles. Conclusion The results demonstrated that An. albimanus populations from historical malaria foci in Quintana Roo are susceptible to the main insecticides used by the Ministry of Health.

Saprotrophic fungi, key players in global carbon cycling, have been identified as methane (CH4) sources not yet accounted for in the global CH4 budget. This study, for the first time, explores the influence of oxygen (O2) and temperature on CH4 production by two fungi, Laetiporus sulphureus and Pleurotus sapidus. To explore the relationship between these parameters and fungal CH4 formation, we examined CH4 formation under varying O2 levels (0 to 98%) and temperatures (17, 27, and 40 °C) during fungal growth on pine wood, beech wood, and grass under sterile conditions. Our findings show that fungal CH4 formation strongly depends on O2 levels. Methane formation was highest when O2 levels exceeded 5%, whilst no CH4 formation was observed after complete O2 consumption. Reintroducing O2 immediately resumed fungal CH4 production. Methane formation normalized to O2 consumption (CH4_norm) showed a different pattern. L. sulphureus showed higher CH4_norm rates with higher O2 levels, whereas P. sapidus showed elevated rates between 0 and 5%. Temperature also significantly influenced CH4 and CH4_norm rates, with the highest production at 27 °C, and comparatively lower rates at 17 and 40 °C. These findings demonstrate the importance of O2 levels and temperature in fungal CH4 emissions, which are essential for refining CH4 source predictions.

Abstract Vector control is one of the principal strategies used for reducing malaria transmission. Long-lasting insecticidal bed nets (LLINs) are a key tool used to protect populations at risk of malaria, since they provide both physical and chemical barriers to prevent human-vector contact. This study aimed to assess the physical durability and insecticidal efficacy of LLINs distributed in Cruzeiro do Sul (CZS), Brazil, after 4 years of use. A total of 3000 LLINs (PermaNet 2.0) were distributed in high malaria risk areas of CZS in 2007. After 4 years of use, 27 ‘rectangular’ LLINs and 28 ‘conical’ LLINs were randomly selected for analysis. The evaluation of physical integrity was based on counting the number of holes and measuring their size and location on the nets. Insecticidal efficacy was evaluated by cone bioassays, and the amount of residual insecticide remaining on the surface of the LLINs was estimated using a colorimetric method. After 4 years of use, physical damage was highly prevalent on the rectangular LLINs, with a total of 473 holes detected across the 27 nets. The upper portion of the side panels sustained the greatest damage in rectangular LLINs. The overall mosquito mortality by cone bioassay was

Abstract Background Insecticide resistance (IR) is one of the major threats to malaria vector control programs in endemic countries. However, the mechanisms underlying IR are poorly understood. Thus, investigating gene expression patterns related to IR can offer important insights into the molecular basis of IR in mosquitoes. In this study, RNA-Seq was used to characterize gene expression in Anopheles gambiae surviving exposure to pyrethroids (deltamethrin, alphacypermethrin) and an organophosphate (pirimiphos-methyl). Results Larvae of An. gambiae s.s. collected from Bassila and Djougou in Benin were reared to adulthood and phenotyped for IR using a modified CDC intensity bottle bioassay. The results showed that mosquitoes from Djougou were more resistant to pyrethroids (5X deltamethrin: 51.7% mortality; 2X alphacypermethrin: 47.4%) than Bassila (1X deltamethrin: 70.7%; 1X alphacypermethrin: 77.7%), while the latter were more resistant to pirimiphos-methyl (1.5X: 48.3% in Bassila and 1X: 21.5% in Djougou). RNA-seq was then conducted on resistant mosquitoes, non-exposed mosquitoes from the same locations and the laboratory-susceptible An. gambiae s.s. Kisumu strain. The results showed overexpression of detoxification genes, including cytochrome P450s (CYP12F2, CYP12F3, CYP4H15, CYP4H17, CYP6Z3, CYP9K1, CYP4G16, and CYP4D17), carboxylesterase genes (COEJHE5E, COE22933) and glutathione S-transferases (GSTE2 and GSTMS3) in all three resistant mosquito groups analyzed. Genes encoding cuticular proteins (CPR130, CPR10, CPR15, CPR16, CPR127, CPAP3-C, CPAP3-B, and CPR76) were also overexpressed in all the resistant groups, indicating their potential role in cross resistance in An. gambiae. Salivary gland protein genes related to ‘salivary cysteine-rich peptide’ and ‘salivary secreted mucin 3’ were also over-expressed and shared across all resistant groups. Conclusion Our results suggest that in addition to metabolic enzymes, cuticular and salivary gland proteins could play an important role in cross-resistance to multiple classes of insecticides in Benin. These genes warrant further investigation to validate their functional role in An. gambiae resistance to insecticides.

Abstract Background Effective vector control is key to malaria prevention. However, this is now compromised by increased insecticide resistance due to continued reliance on insecticide-based control interventions. In Kenya, we have observed heterogenous resistance to pyrethroids and organophosphates in Anopheles arabiensis which is one of the most widespread malaria vectors in the country. We investigated the gene expression profiles of insecticide resistant An. arabiensis populations from Migori and Siaya counties in Western Kenya using RNA-Sequencing. Centers for Disease Control and Prevention (CDC) bottle assays were conducted using deltamethrin (DELTA), alphacypermethrin (ACYP) and pirimiphos-methyl (PMM) to determine the resistance status in both sites. Results Mosquitoes from Migori had average mortalities of 91%, 92% and 58% while those from Siaya had 85%, 86%, and 30% when exposed to DELTA, ACYP and PMM, respectively. RNA-Seq analysis was done on pools of mosquitoes which survived exposure (‘resistant’), mosquitoes that were not exposed, and the insecticide-susceptible An. arabiensis Dongola strain. Gene expression profiles of resistant mosquitoes from both Migori and Siaya showed an overexpression mainly of salivary gland proteins belonging to both the short and long form D7 genes, and cuticular proteins (including CPR9, CPR10, CPR15, CPR16). Additionally, the overexpression of detoxification genes including cytochrome P450s (CYP9M1, CYP325H1, CYP4C27, CYP9L1 and CYP307A1), 2 carboxylesterases and a glutathione-S-transferase (GSTE4) were also shared between DELTA, ACYP, and PMM survivors, pointing to potential contribution to cross resistance to both pyrethroid and organophosphate insecticides. Conclusion This study provides novel insights into the molecular basis of insecticide resistance in An. arabiensis in Western Kenya and suggests that salivary gland proteins and cuticular proteins are associated with resistance to multiple classes of insecticides.

BackgroundIndividuals living in rural communities experience substantial geographic and infrastructure barriers to attaining health equity in accessing tobacco use cessation treatment. Social media and other digital platforms offer promising avenues to improve access and overcome engagement challenges in tobacco cessation efforts. Research has also shown a positive correlation between faith-based involvement and a lower likelihood of smoking, which can be used to engage rural communities in these interventions. ObjectiveThis study aimed to develop and beta test a social intervention prototype using a Facebook (Meta Platforms, Inc) group specifically designed for rural smokers seeking evidence-based smoking cessation resources. MethodsWe designed a culturally aligned and faith-aligned Facebook group intervention, FaithCore, tailored to engage rural people who smoke in smoking cessation resources. Both intervention content and engagement strategies were guided by community-based participatory research principles. Given the intervention’s focus on end users, that is, rural people who smoked, we conducted a beta test to assess any technical or usability issues of this intervention before any future trials for large-scale implementation. ResultsNo critical beta test technical and usability issues were noted. Besides, the FaithCore intervention was helpful, easy to understand, and achieved its intended goals. Notably, 90% (9/10) of the participants reported that they tried quitting smoking, while 90% (9/10) reported using or seeking cessation resources discussed within the group. ConclusionsThis study shows that social media platform with culturally aligned and faith-aligned content and engagement strategies delivered by trained moderators are promising for smoking cessation interventions in rural communities. Our future step is to conduct a large pilot trial to evaluate the intervention’s effectiveness on smoking cessation outcomes.

Metabolic dysfunction-associated steatohepatitis (MASH) is the progressive form of liver steatosis, the most common liver disease, and substantially increases the mortality rate. However, limited therapies are currently available to prevent MASH development. Identifying potential pharmacological treatments for the condition has been hampered by its heterogeneous and complex nature. Here, we identified a hepatic nonneuronal cholinergic signaling pathway required for metabolic adaptation to caloric overload. We found that cholinergic receptor nicotinic alpha 2 subunit (CHRNA2) is highly expressed in hepatocytes of mice and humans. Further, CHRNA2 is activated by a subpopulation of local acetylcholine-producing macrophages during MASH development. The activation of CHRNA2 coordinates defensive programs against a broad spectrum of MASH-related pathogenesis, including steatosis, inflammation, and fibrosis. Hepatocyte-specific loss of CHRNA2 signaling accelerates the disease onset in different MASH mouse models. Activation of this pathway via pharmacological inhibition of acetylcholine degradation protects against MASH development. Our study uncovers a hepatic nicotinic cholinergic receptor pathway that constitutes a cell-autonomous self-defense route against prolonged metabolic stress and holds therapeutic potential for combatting human MASH.

Objetivos: Descrever a atuação do farmacêutico clínico, perfil dos pacientes, medicamentos, exames, taxa de óbito e tempo de internação de pacientes internados em unidade de terapia intensiva (UTI) por Covid-19. Métodos: Estudo de coorte retrospectivo não-comparado de pacientes adultos internados em UTI por Covid-19 no período de seis meses. Foram coletados os dados de dose, frequência e tempo de tratamento de antimicrobianos, corticosteroides, anticoagulantes, colchicina, ivermectina e bloqueadores neuromusculares e resultados dos exames de creatinina, D-dímeros, ALT (alanina aminotransferase), AST (aspartato aminotransferase) e bilirrubina. Bem como, o motivo, quantidade e o desfecho das intervenções farmacêuticas realizadas. Os dados referem-se aos primeiros 15 dias de internação e foram coletados do prontuário eletrônico, portal Scola® de exames laboratoriais e do sistema de inteligência artificial NoHarm®. Resultados: Incluiu-se 174 pacientes, a média de idade foi de 61,8 ± 14,1 anos, tempo de internação de 17,3 ± 14,4 dias, sexo masculino (58,0%), com comorbidades prévias (95,4%), em uso de ventilação mecânica (75,4%) e mortalidade de 58,0%. Os antimicrobianos foram mais utilizados, seguido de corticosteroides e anticoagulantes. Idade, uso de ventilação mecânica, indicação para uso de anticoagulante, alteração de creatinina e ALT foram associados com o óbito. Foi realizada uma intervenção farmacêutica a cada 13,1 prescrições avaliadas, com uma taxa de aceitação de 86,8%. Conclusões: As intervenções farmacêuticas e seus desfechos mostraram a importância do farmacêutico no cuidado do paciente crítico com Covid-19 em conjunto com a equipe multiprofissional.

During large scale outbreaks of infectious diseases, it is imperative that media report about the potential risks. Because media reporting plays a vital role in disseminating crucial information about diseases and its associated risk, understanding how media reports could influence individuals’ behavior and its potential impact on disease transmission dynamics is important. A mathematical model within an optimal control framework of a generic disease, accounting for treatment and media reporting of disease-induced deaths is formulated. Due to the complexity of choosing the best media function, our goal is to attempt to address the following research question: what is the effect of the media-induced functional response on mitigating the spread of the disease? Connecting the functional forms to the control problem is an approach that is not very developed in the literature. Thus, this study analyses the effect of different incidence functions on disease transmission, and the qualitative nature of epidemic dynamics by carrying out optimal control analysis using three different contact rates and a media function that is dependent on the number of deaths. Theoretical analyses show that the functional forms of the effective contact rate have no effect on initial disease transmission. Time-dependent controls for treatment and vaccination with a constant effective contact rate are incorporated to determine optimal control strategies. Numerical simulations show the short-term impact of media coverage on mitigating the spread of the disease, and it is observed that with three incidence functions used, the qualitative nature of the controls remains the same. The effective contact rates are graphically shown to have a population-level effect on the disease dynamics as the number of treated and recovered individuals could be significantly different. Finally, it is shown that treatment of infectives should be at its maximum rate for a longer period compared to vaccination, while concurrent implementation of vaccination and treatment is more impactful in mitigating the spread of the disease. Thus, it is imperative that media reports and health policy decision making on infectious diseases are contextualized.

This paper explores the affordances and constraints of STEM faculty members' instructional data-use practices and how they engage students (or not) in reflection around their own learning data. We found faculty used a wide variety of instructional data-use practices. We also found several constraints that influenced their instructional data-use practices, including perceived lack of time, standardized curriculum and assessments predetermined in scope and sequence, and a perceived lack of confidence and competence in their instructional data-use practices. Novel findings include faculty descriptions of instructional technology that afforded them access to immediate and nuanced instructional data. However, faculty described limited use of instructional data that engaged students in reflecting on their own learning data. We consider implications for faculty's instructional data-use practices on departmental and institutional policies and procedures, professional development experts, and for faculty themselves.