Assessment of the adaptive capacity of Morada Nova ewes with different coat coloration.

Coat color is a factor affecting heat tolerance in tropical ruminant and a particular coat color can determine which is more resilient to environmental changes. The aim of this study was to measure the level of adaptation of Morada Nova sheep with different coat color by using an Adaptability Index (AI). Adult ewes were used, including two different coat colors of Morada Nova sheep (red and white) with mean of body weight of 28.02 ± 5.70 kg and 31.47 ± 3.41 kg, respectively. Physiology parameters, hematology, electrolytes, acid-base status, mineral, renal functions, metabolites, enzymes, and proteins were measured. AI was designed using a multivariate approach (principal component analysis) to "weigh" the influence of each variable in the animal responses. The variables more important for adaptive aspects of Red Morada Nova were: haematology, electrolytes and acid-base status. The hemoglobin (HG), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), sodium (Na+), oxygen pressure (PO2), glucose (GLU) and albumin (ALB) were significantly higher in Red Morada Nova sheep and hydrogen carbonate (HCO3), base excess (BE), total carbon dioxide concentration (TCO2) and URE were significantly higher in the white phenotype. The variables more important for adaptive aspects of White Morada Nova sheep were: (K+), total protein (TP), PO2, HG, cholesterol (CHO), rectal temperature (RT) and glucose (GLU). Both phenotypes showed a high adaptation level, however, a higher value was generated for the Red Morada Nova sheep (81.97). This study concludes that both phenotypes of the Morada Nova sheep breed are well adapted to the climatic condition of the Brazilian tropical region using different adaptive mechanisms.

The increase in core body temperature in response to exertional-heat stress can predict exercise-induced gastrointestinal syndrome.

Utilizing metadata from existing exertional and exertional-heat stress studies, the study aimed to determine if the exercise-associated increase in core body temperature can predict the change in exercise-induced gastrointestinal syndrome (EIGS) biomarkers and exercise-associated gastrointestinal symptoms (Ex-GIS). Endurance-trained individuals completed 2 h of running exercise in temperate (21.2-30.0°C) to hot (35.0-37.2°C) ambient conditions (n = 132 trials). Blood samples were collected pre- and post-exercise to determine the change in gastrointestinal integrity biomarkers and systemic inflammatory cytokines. Physiological and thermoregulatory strain variables were assessed every 10-15 min during exercise. The strength of the linear relationship between maximal (M-Tre) and change (Δ Tre) in rectal temperature and EIGS variables was determined via Spearman's rank correlation coefficients. While the strength of prediction was determined via simple and multiple linear regression analyses dependent on screened EIGS and Ex-GIS confounding factors. Significant positive correlations between Tre maximum (M-Tre) and change (Δ Tre) with I-FABP (rs = 0.434, p < 0.001; and rs = 0.305, p < 0.001; respectively), sCD14 (rs = 0.358, p < 0.001; and rs = 0.362, p < 0.001), systemic inflammatory response profile (SIR-Profile) (p < 0.001), and total Ex-GIS (p < 0.05) were observed. M-Tre and Δ Tre significantly predicted (adjusted R2) magnitude of change in I-FABP (R2(2,123)=0.164, p < 0.001; and R2(2,119)=0.058, p = 0.011; respectively), sCD14 (R2(2,81)=0.249, p < 0.001; and R2(2,77)=0.214, p < 0.001), SIR-Profile (p < 0.001), and total Ex-GIS (p < 0.05). Strong to weak correlations were observed between M-Tre and Δ Tre with plasma concentrations of I-FABP, sCD14, SIR-Profile, and Ex-GIS in response to exercise. M-Tre and Δ Tre can predict the magnitude of these EIGS variables and Ex-GIS in response to exercise.

The BALA project: A pioneering monitoring of Azorean forest invertebrates over two decades (1999-2022).

Globally, there is a concerning decline in many insect populations, and this trend likely extends to all arthropods, potentially impacting unique island biota. Native non-endemic and endemic species on islands are under threat due to habitat destruction, with the introduction of exotic, and potentially invasive, species, further contributing to this decline. While long-term studies of plants and vertebrate fauna are available, long-term arthropod datasets are limited, hindering comparisons with better-studied taxa. The Biodiversity of Arthropods of the Laurisilva of the Azores (BALA) project has allowed gathering comprehensive data since 1997 in the Azorean Islands (Portugal), using standardised sampling methods across islands. The dataset includes arthropod counts from epigean (pitfall traps) and canopy-dwelling (beating samples) communities, enriched with species information, biogeographic origins, and IUCN categories. Metadata associated with the sample protocol and events, like sample identifier, archive number, sampled tree species, and trap type are also recorded. The database is available in multiple formats, including Darwin Core, which facilitates the ecological analysis of pressing environmental concerns, such as arthropod population declines and biological invasions.

Evaluation of the supply of Duddingtonia flagrans for the control of gastrointestinal parasites in sheep.

Parasitic resistance imposes alternative control methods, like nematophagous fungi. In this study, two experiments were conducted supplying Duddingtonia flagrans aiming to evaluate the biological control of parasites in sheep. In the first, 24 sheep naturally infected by gastrointestinal nematodes were allocated, in randomized blocks, following the treatments: control or treated group, 0.5g/animal product containing D. flagrans, chlamydospores. Weight, body score, Famacha©, egg count per gram of feces (EPG), and larval percentage were evaluated. In the second experiment, D. flagrans (0.25 and 0.5g product) was infested with manure, plus or not protein concentrate, in a completely randomized design. In both experiments the dose was intentionally lower than recommended. Recovery and larval identification were performed. The SAS analyzed the variables by the MIXED procedure, repeated measures in time. Weight, body score, hematocrit, and Famacha© did not show differences between treatments (p>0.05); however, EPG (p<0.001) and the percentage of larvae identified in coproculture were different. In the second experiment, the inclusion of the fungus did not influence the recovery of larvae (p>0.05). In both experiments, colonization and advancement of the fungus were visualized. Under the experimental conditions, the fungus D. flagrans was not effective in the biological control of parasitic infection in sheep.

The impact of 48 h high carbohydrate diets with high and low FODMAP content on gastrointestinal status and symptoms in response to endurance exercise, and subsequent endurance performance.

This study investigated the effects of a high carbohydrate diet, with varied fermentable oligo-, di-, and mono-saccharide and polyol (FODMAP) content, before endurance exercise on gastrointestinal integrity, motility, and symptoms; and subsequent exercise performance. Twelve endurance athletes were provided with a 48 h high carbohydrate (mean ± SD: 12.1 ± 1.8 g kg day-1) diet on two separate occasions, composed of high (54.8 ± 10.5 g day-1) and low FODMAP (3.0 ± 0.2 g day-1) content. Thereafter, participants completed a 2 h steady-state running exercise at 60% of V ˙ O 2 max (22.9 ± 1.2 °C, 46.4 ± 7.9% RH), followed by a 1 h distance performance test. Pre-exercise and every 20 min during steady-state exercise, 100 mL maltodextrin (10% w/v) solution was consumed. A 150 mL lactulose (20 g) solution was consumed 30 min into the distance performance test to determine orocecal transit time (OCTT) during exercise. Blood was collected pre- and post exercise to determine gastrointestinal integrity biomarkers (i.e., I-FABP, sCD14, and CRP). Breath hydrogen (H2) and gastrointestinal symptoms (GIS) were determined pre-exercise, every 15 min, during and throughout recovery. No differences in gastrointestinal integrity biomarkers, OCTT, or distance completed were observed between trials. Pre-exercise total-GIS (1.3 ± 2.9 vs. 4.3 ± 4.4), gut discomfort (9.9 ± 8.1 vs. 15.8 ± 9.0), and upper-GIS (2.8 ± 2.6 vs. 5.7 ± 4.8) during exercise were less severe on high carbohydrate low FODMAP (HC-LFOD) versus high carbohydrate high FODMAP (HC-HFOD) (p < 0.05). Gut discomfort (3.4 ± 4.4 vs. 0.2 ± 0.6) and total-GIS (4.9 ± 6.8 vs. 0.2 ± 0.6) were higher during recovery on HC-LFOD versus HC-HFOD (p < 0.05). The FODMAP content of a 48 h high carbohydrate diet does not impact gastrointestinal integrity or motility in response to endurance exercise. However, a high FODMAP content exacerbates GIS before and during exercise, but this does not impact performance outcomes.

Flavonoids and phenolic acids from sugarcane: Distribution in the plant, changes during processing, and potential benefits to industry and health.

Sugarcane (Saccharum sp.) plants are grown in warmer climates throughout the world and processed to produce sugar as well as other useful byproducts such as molasses and bagasse. Sugarcane is rich in (poly)phenols, but there has been no attempt to critically evaluate the published information based on the use of suitable methodologies. The objective of this review is to evaluate the quantitative and qualitative (poly)phenolic profiles of individual parts of the sugarcane plant and its multiple industrial products, which will help develop new processes and uses for sugarcane (poly)phenols. The quantitative analysis involves the examination of extraction, concentration, and analytical techniques used in each study for each plant part and product. The qualitative analysis indicates the identification of various (poly)phenols throughout the sugarcane processing chain, using only compounds elucidated through robust analytical methodologies such as mass spectrometry or nuclear magnetic resonance. In conclusion, sugarcane (poly)phenols are predominantly flavonoids and phenolic acids. The main flavonoids, derivatives of apigenin, luteolin, and tricin, with a substantial proportion of C-glycosides, are consistently found across all phases of sugarcane processing. The principal phenolic acids reported throughout the process include chlorogenic acids, as well as ferulic and caffeic acids mostly observed after hydrolysis. The derivation of precise quantitative information across publications is impeded by inconsistencies in analytical methodologies. The presence of multiple (poly)phenols with potential benefits for industrial applications and for health suggests sugarcane could be a useful provider of valuable compounds for future use in research and industrial processes.

Performance, feed efficiency, feeding behavior, and cortisol concentration of lambs ranked for Residual Feed Intake and Residual Intake and Gain.

This study aimed to evaluate the performance, feed efficiency, feeding behavior, and cortisol concentrations of lambs ranked into different groups of Residual Feed Intake (RFI) and Residual Intake and Gain (RIG). Forty Santa Inês lambs with a mean initial age of 120 ± 30 days and mean initial (IBW) and final body weight (FBW) of 28.9 ± 3.2 and 43.7 ± 3.9 kg, respectively, were used. The animals were fed at an automatic feed and water station (Intergado®) for 60 days and classified at the end of the experiment as low-RFI/RIG, medium-RFI/RIG, and high-RFI/RIG according to RFI and RIG. Performance, feed efficiency measures, ingestive behavior, temperament, and cortisol concentrations were measured, and Pearson's correlation analysis was performed to evaluate the relationship between the variables studied. The variables that differed most between RFI groups were dry matter intake, feed conversion, and feed efficiency, with better values in efficient animals (RFI-). Regarding the RGI groups, the average daily gain of animals classified as RIG- was 19.37% lower than that of animals classified as RIG± and 39.28% lower than that of animals classified as RIG+. Only the hourly feeding rate per day (p = 0.04) differed significantly between RFI and RIG classes, while no differences were observed for the ingestive behavior variables or cortisol. The number of visits to the feed bunk (total, with or without intake) showed no correlation with any performance or efficiency measure. Identifying animals ranked into different RFI and RIG classes shows that more efficient animals have a lower feed intake for the same weight gain and spend less time at the feed bunk.

Does Age Influence Gastrointestinal Status Responses to Exertional-heat Stress?

This meta-data exploration aimed to determine the impact of exertional-heat stress (EHS) on gastrointestinal status of masters age and young adult endurance athletes. Sixteen MASTERS (mean: 44y) and twenty-one YOUNG (26y) recreational endurance athletes completed 2 h of running at 60% ˙V O2max in 35˚C ambient conditions. Blood samples were collected pre-, immediately and 1 h post-EHS, and analyzed for markers of exercise-induced gastrointestinal syndrome (EIGS). Thermo-physiological measures and gastrointestinal symptoms (GIS) were recorded every 10-20 min during EHS. Peak Δ pre- to post-EHS did not substantially differ (p>0.05) between MASTERS and YOUNG for intestinal epithelial injury [I-FABP: 1652pg/ml vs. 1524pg/ml, respectively], bacterial endotoxic translocation [sCD14: -0.09µg/mL vs. 0.84µg/mL, respectively], lipopolysaccharide-binding protein [LBP: 0.26µg/mL vs. 1.76µg/mL, respectively], and systemic inflammatory response profile (SIR-Profile: 92.0arb.unit vs. 154arb.unit, respectively). A significantly higher peak Δ pre- to post-EHS in endogenous endotoxin anti-body IgM (p=0.042), and pro-inflammatory cytokine IL-1ß (p=0.038), was observed in YOUNG compared to MASTERS. No difference was observed between incidence (81% and 80%, respectively) and severity (summative accumulation: 21 and 30, respectively) of reported GIS during EHS between MASTERS and YOUNG. Pathophysiology of EIGS in response to EHS does not substantially differ with age progression, since masters and younger adult endurance athletes responded comparably.

Exertional Stress-induced Pathogenic Luminal Content Translocation - Friend or Foe?

The incidence of perturbed gastrointestinal integrity, as well as resulting systemic immune responses and gastrointestinal symptoms, otherwise known as exercised-induced gastrointestinal syndrome (EIGS), is common among individuals who partake in prolonged exercise. EIGS may cause the translocation of pathogenic material, including whole bacteria and bacterial endotoxins, from the lumen into circulation, which may progress into clinical consequences such as sepsis, and potentially subsequent fatality. However, further investigation is warranted to assess the possibility of food allergen and/or digestive enzyme luminal to circulatory translocation in response to exercise, and the clinical consequences. Findings from this narrative literature review demonstrate evidence that whole bacteria and bacterial endotoxins translocation from the gastrointestinal lumen to systemic circulation occurs in response to exercise stress, with a greater propensity of translocation occurring with accompanying heat exposure. It has also been demonstrated that food allergens can translocate from the lumen to systemic circulation in response to exercise stress and initiate anaphylaxis. To date, no research investigating the effect of exercise on the translocation of digestive enzymes from the lumen into systemic circulation exists. It is evident that EIGS and consequential pathogenic translocation presents life-threatening clinical implications, warranting the development and implementation of effective management strategies in at-risk populations.

Effect of Personalized Sodium Replacement on Fluid and Sodium Balance and Thermophysiological Strain During and After Ultraendurance Running in the Heat.

PURPOSE: To investigate the effect of personalized sweat sodium replacement on drinking behavior, sodium and water balance, and thermophysiological responses during and after ultraendurance running in hot conditions. METHODS: Nine participants (7 male, 2 female) completed two 5-hour treadmill runs (60% maximum oxygen uptake, 30°C ambient temperature), in a double-blind randomized crossover design, consuming sodium chloride (SODIUM) capsules to replace 100% of previously assessed losses or placebo (PLACEBO). Fluid was consumed ad libitum. RESULTS: No effect of SODIUM was observed for ad libitum fluid intake or net fluid balance (P > .05). Plasma sodium concentration increased in both trials, but to a greater extent in SODIUM at 2.5 hours (mean [SD]: 4 [4] mmol·L-1 vs 1 [5] mmol·L-1; P < .05) and postexercise (4 [3] mmol·L-1 vs 1 [5] mmol·L-1; P < .05). Plasma volume change was not different between trials (P > .05) but was strongly correlated with sodium balance in SODIUM (r = .880, P < .01). No effect of sodium replacement was observed for heart rate, rectal temperature, thermal comfort, perceived exertion, or physiological strain index. During the 24 hours postexercise, ad libitum fluid intake was greater following SODIUM (2541 [711] mL vs 1998 [727] mL; P = .04), as was urinary sodium excretion (NaCl: 66 [35] mmol, Pl: 21 [12] mmol; P < .01). CONCLUSIONS: Personalized sweat sodium replacement during ultraendurance running in hot conditions, with ad libitum fluid intake, exacerbated the rise in plasma sodium concentration compared to no sodium replacement but did not substantially influence overall body-water balance or thermophysiological strain. A large sodium deficit incurred during exercise leads to substantial renal sodium conservation postexercise.

Leprosy in children under fifteen years of age in the most hyperendemic municipality in Brazil / Hanseníase em menores de quinze anos no município mais hiperendêmico do Brasil

ABSTRACT Objective: To describe leprosy involvement and physical disability profiles in children and adolescents under 15 years old. Methods: Ecological time series study, based on data from the Brazilian Notifiable Diseases Information System, including new cases of leprosy residing in Palmas (TO), from 2001 to 2020. Results: A total of 471 notified cases in children and adolescents under 15 years of age were evaluated, resulting in a detection coefficient of 26.5 per 100,000 inhabitants. Of these, 52% (n=243) were women, 5% (n=24) corresponded to grade two disability, and 36% (n=168) were diagnosed through spontaneous demand. The temporal trend analysis showed a 0.5% reduction in the detection coefficient. There was a significant decrease in the diagnosis of the undetermined and tuberculoid clinical forms and a significant increase in the dimorphous form. Diagnosis through contact examination increased significantly by 13.1% and that through spontaneous demand decreased by 4.9%. The detection coefficient of cases with grade two disability reduced significantly by 7.4% while those with grade one increased by 16.8%. Conclusions: Despite the downward trend in the detection coefficient in children and adolescents under 15 years of age and in cases with grade two disability, other factors indicate failure in the adequate management of leprosy in Palmas.

RESUMO Objetivo: Descrever os perfis de acometimento de hanseníase e incapacidade física em menores de 15 anos. Métodos: Estudo ecológico de série temporal, baseado em dados do Sistema Nacional de Agravos de Notificação, incluindo casos novos de hanseníase residentes em Palmas (TO), no período de 2001 a 2020. Resultados: Foram avaliados 471 casos notificados em crianças e adolescentes menores de 15 anos, resultando em um coeficiente de detecção de 26,5 por cem mil habitantes. Destes, 52% (n=243) eram do gênero feminino, 5% (n=24) correspondiam ao grau dois de incapacidade física, e 36% (n=168) foram diagnosticados por demanda espontânea. A análise de tendência temporal mostrou queda do coeficiente de detecção em 0,5%. Houve queda significativa no diagnóstico das formas clínicas indeterminada e tuberculoide e aumento significativo da dimorfa. O diagnóstico por exame de contato teve um aumento significativo de 13,1% e o por demanda espontânea, queda significativa de 4,9%. O coeficiente de detecção de casos com grau dois de incapacidade apresentou uma queda significativa de 7,4%, enquanto o de casos com grau um, apresentou um aumento de 16,8%. Conclusões: Apesar da tendência de queda do coeficiente de detecção em menores de 15 anos e do coeficiente de detecção de casos com grau dois de incapacidade, outros fatores indicam falha no manejo adequado da hanseníase em Palmas.

Pediatric COVID-19: clinical and epidemiological data of 1303 cases in a general hospital in Brazil / COVID-19 pediátrico: dados clínicos e epidemiológicos de 1303 casos em um hospital geral no Brasil

ABSTRACT Objective: This study aimed to describe the clinical characteristics of the pediatric population with COVID-19 in an Emergency Department (ED) of a Brazilian general hospital. Methods: Epidemiological and clinical data of patients younger than 20 years old were collected from patients' medical records from February 2020 to July 2021. Most of the epidemiological data described pertains to hospitalized patients. We also reviewed coinfections, treatment, and outcomes and compared the first and second waves of COVID-19. Results: We identified a total of 1303 episodes of SARS-CoV-2 infection. The median time from symptom onset to diagnosis was three days. Symptoms were present in 92.3% of the patients. The most common symptoms were fever (45.2%), nasal congestion/discharge (44.2%), and cough (39.4%). Chest radiography and tomography were performed in 7.7 and 3.3% of cases, with abnormal findings in 29.7 and 53.4%, respectively. Hospital admissions occurred in 3.5% of patients, mainly in the presence of comorbidities, in children under five years old and in those who presented to the ED during the first wave of COVID-19. Coinfection with a viral agent was identified in 20% of the 71 cases tested in this study, and a positive rapid test for Streptococcus pyogenes was found in 8% of the 174 cases tested, with no impact of these coinfections on hospitalization. Conclusions: We found that COVID-19 was a mild disease in most children in our study population, with most hospitalizations and readmissions occurring during the first wave of COVID-19.

RESUMO Objetivo: Este estudo teve como objetivo descrever as características clínicas da população pediátrica com COVID-19 no setor de emergência de um hospital geral brasileiro. Métodos: Os dados epidemiológicos e clínicos de pacientes idade inferior a 20 anos foram coletados dos prontuários dos pacientes de fevereiro de 2020 a julho de 2021. A maior parte dos dados epidemiológicos descritos refere-se a pacientes hospitalizados. Também foram revisados as coinfecções, o tratamento e os desfechos de internação e comparadas a primeira e a segunda ondas de COVID-19. Resultados: Foi identificado o total de 1.303 episódios de infecção por SARS-CoV-2. A mediana de tempo desde o início dos sintomas até o diagnóstico foi de três dias. Os sintomas estiveram presentes em 92,3% dos pacientes. Os sintomas mais comuns foram febre (45,2%), congestão/secreção nasal (44,2%) e tosse (39,4%). Radiografia e tomografia de tórax foram realizadas em 7,7 e 3,3% dos casos, com achados anormais em 29,7 e 53,4%, respectivamente. As internações hospitalares ocorreram em 3,5% dos pacientes, principalmente na presença de comorbidades, em crianças menores de cinco anos e naqueles que se apresentaram no pronto-socorro durante a primeira onda de COVID-19. Foi identificada coinfecção viral em 20% dos 71 casos testados e teste rápido positivo para Streptococcus pyogenes em 8% dos 174 casos testados, não havendo impacto dessas coinfecções quanto à internação hospitalar. Conclusões: Observamos que a COVID-19 foi uma doença leve na maioria das crianças de nossa população, com a maior parte das hospitalizações e readmissões ocorrendo durante a primeira onda de COVID-19.

Pediatric COVID-19: clinical and epidemiological data of 1303 cases in a general hospital in Brazil.

OBJECTIVE: This study aimed to describe the clinical characteristics of the pediatric population with COVID-19 in an Emergency Department (ED) of a Brazilian general hospital. METHODS: Epidemiological and clinical data of patients younger than 20 years old were collected from patients' medical records from February 2020 to July 2021. Most of the epidemiological data described pertains to hospitalized patients. We also reviewed coinfections, treatment, and outcomes and compared the first and second waves of COVID-19. RESULTS: We identified a total of 1303 episodes of SARS-CoV-2 infection. The median time from symptom onset to diagnosis was three days. Symptoms were present in 92.3% of the patients. The most common symptoms were fever (45.2%), nasal congestion/discharge (44.2%), and cough (39.4%). Chest radiography and tomography were performed in 7.7 and 3.3% of cases, with abnormal findings in 29.7 and 53.4%, respectively. Hospital admissions occurred in 3.5% of patients, mainly in the presence of comorbidities, in children under five years old and in those who presented to the ED during the first wave of COVID-19. Coinfection with a viral agent was identified in 20% of the 71 cases tested in this study, and a positive rapid test for Streptococcus pyogenes was found in 8% of the 174 cases tested, with no impact of these coinfections on hospitalization. CONCLUSIONS: We found that COVID-19 was a mild disease in most children in our study population, with most hospitalizations and readmissions occurring during the first wave of COVID-19.

Historical line of airglow observations at Comandante Ferraz Brazilian Station: measurements of temperature and studies on gravity waves.

The thermal dynamics of the upper atmosphere, especially in the mesosphere, have been improving our understanding about the effects of climate change, as well as how the dynamics and general circulation in the upper atmosphere are driven by different types of waves, such as the atmospheric gravity waves, planetary waves and atmospheric tides. In order to study the upper atmospheric temperature variability and gravity waves, several research groups have been employing the remote technique of observing the airglow emissions originated in the upper mesosphere and lower thermosphere, besides emissions from the ionosphere. INPE's airglow group started the studies on emissions from the upper atmosphere to investigate temperature and dynamics in the mesosphere, thermosphere/ionosphere at the end of 70's. However, only in 2001 this group sent the first airglow experiment to the Brazilian Antarctic Station Comandante Ferraz (EACF) to measure the OH (8-3) emission and temperature. From that year to 2014, several other experiments were carried out at EACF, not only to measure the temperature and airglow intensities, but also to observe gravity waves, winds and other related phenomena. This paper presents airglow experiments at EACF from 2001 to the present, including illustrations, examples of already published results, and unpublished data.

A Cohort Study of the Antitumor Efficacy and Toxicity Profile of Alpelisib for Metastatic or Locally Advanced HR+, HER2- Breast Cancer: A Single-Institution Experience.

INTRODUCTION: Alpelisib is approved in combination with endocrine therapy (ET) to treat patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) progressive metastatic breast cancer (MBC). The SOLAR-1 trial demonstrated the efficacy of this oral agent and showed that, while alpelisib improves outcomes compared to placebo, it is also associated with clinically relevant adverse events (AEs). There is a pressing need for improved knowledge on the effectiveness and tolerability of this agent in real-world patient populations. METHODS: We conducted a retrospective cohort study of patients with HR+, HER2- MBC treated with alpelisib and ET. We assessed the safety, tolerability, and effectiveness of alpelisib in a real-world population. Deidentified patient-, tumor-, and outcome-related data, including AEs, were collected and summarized. Kaplan-Meier methods were applied for survival analyses, and stratified analyses of interest were conducted. A p value <0.05 was considered statistically significant. RESULTS: A total of 76 women treated with alpelisib + ET were included in our cohort. Most had been previously treated with cyclin-dependent kinase (CDK) 4/6 inhibitors and chemotherapy for MBC. The estimated median progression-free survival was 5.2 months (95% CI, 4.1-8.0). The median overall survival was longer among patients without prior everolimus therapy (hazard ratio, 4.28 [95% CI, 1.64-11.16]; p = 0.0012), and no significant outcome differences were observed between patients treated with different starting doses of alpelisib. Approximately 31.6% of patients permanently discontinued alpelisib due to AEs, and 32.9% had at least one dose reduction. The most common grade 3/4 AEs were hyperglycemia (21%), fatigue (13.2%), and diarrhea (10.5%). CONCLUSIONS: For progressive HR+, HER2- MBC, alpelisib + ET showed effectiveness in a real-world patient population that was comparable to published clinical trial data, regardless of starting dose. However, the effectiveness of alpelisib following previous everolimus exposure may be limited and, hence, should be a consideration to decide sequencing of therapy in these patients. Patients treated with alpelisib are at risk for clinically relevant AEs and require close monitoring.

Gender-Based Clinical, Therapeutic Strategies and Prognosis Differences in Atrial Fibrillation.

BACKGROUND: There are limited data on gender-based differences in atrial fibrillation (AF) treatment and prognosis. We aimed to examine gender-related differences in medical attention in an emergency department (ED) and follow-up (FU) among patients diagnosed with an AF episode and to determine whether there are gender-related differences in clinical characteristics, therapeutic strategies, and long-term adverse events in this population. METHODS: We performed a retrospective observational study of patients who presented to a tertiary hospital ER for AF from 2010 to 2015, with a minimum FU of one year. Data on medical attention received, mortality, and other adverse outcomes were collected and analyzed. RESULTS: Among the 2013 patients selected, 1232 (60%) were female. Women were less likely than men to be evaluated by a cardiologist during the ED visit (11.5% vs. 16.6%, p = 0.001) and were less likely to be admitted (5.9% vs. 9.5%, p < 0.05). Electrical cardioversion was performed more frequently in men, both during the first episode (3.4% vs. 1.2%, p = 0.001) and during FU (15.9% vs. 10.6%, p < 0.001), despite a lower AF recurrence rate in women (9.9% vs. 18.1%). During FU, women had more hospitalizations for heart failure (26.2% vs. 16.1%, p < 0.001). CONCLUSIONS: In patients with AF, although there were no gender differences in mortality, there were significant differences in clinical outcomes, medical attention received, and therapeutic strategies. Women underwent fewer attempts at cardioversion, had a lower probability of being evaluated by cardiologists, and showed a higher probability of hospitalization for heart failure. Being alert to these inequities should facilitate the adoption of measures to correct them.

Weighted single-step genome-wide association study and functional enrichment analyses for gastrointestinal nematode resistance traits in Santa Ines sheep.

This study aimed to identify genomic regions, pathways, and putative candidate genes associated with resistance to gastrointestinal nematode in Santa Ines sheep. The phenotypic information comprised 5529 records from 1703 naturally infected animals. After genomic data quality control, 37,511 SNPs from 589 animals were available. The weighted single-step approach for genome-wide association study was performed to estimate the SNP effects and variances accounted by 10-SNP sliding windows. Confirming the polygenic nature of the studied traits, 20, 22, 21, and 19 genomic windows that explained more than 0.5% of the additive genetic variance were identified for fecal egg counts (FEC), Famacha© (FAM), packed cell volume (PCV), and total plasma protein (TPP), respectively. A total of 81, 122, 106, and 101 protein-coding genes were found in windows associated with FEC, FAM, PCV, and TPP, respectively. Several protein-coding genes related to the immune system and inflammatory response functions were identified within those genomic regions, such as ADCY9, ADRB2, BRAF, CADM1, CCL20, CD70, CREBBP, FNBP1, HTR4, IL16, IL22, IL26, MAPK8, NDFIP1, NLRC3, PAK5, PLCB1, PLCB4, ROCK1, TEK, TNFRSF12A, and VAV1. Functional enrichment analysis by DAVID tool also revealed many significant (P < 0.05) pathways and Gene Ontology terms that could be related to resistance to gastrointestinal nematode in Santa Ines sheep, such as chemokine signaling pathway (oas04062), cAMP signaling pathway (oas04024), cGMP-PKG signaling pathway (Oas04022), platelet activation (Oas04611), Rap1 signaling pathway (oas04015), and oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen (GO:0016705). These results contribute to improving the knowledge of the genetic architecture of resistance to gastrointestinal nematode in Santa Ines sheep.

Plasma measurements of the dual sugar test reveal carbohydrate immediately alleviates intestinal permeability caused by exertional heat stress.

The aim of this set of randomised cross-over studies was to determine the impact of progressive heat exposure and carbohydrate or protein feeding during exertional stress on small intestine permeability using a dual sugar test. In our previous work, and typically in the field, recovery of lactulose and l-rhamnose is measured cumulatively in urine. This follow-up study exploits our novel high-performance anion exchange chromatography with pulsed amperometric detection (HPAEC-PAD) protocol to accurately quantify the sugars in plasma. Endurance-trained participants completed experimental trial A (ET-A; n = 8), consisting of 2 h running at 60% V ̇ O 2 max ${\dot V_{{{\mathrm{O}}_{\mathrm{2}}}{\mathrm{max}}}}$ in temperate, warm and hot ambient conditions, and/or experimental trial B (ET-B; n = 9), consisting of 2 h running at 60% V ̇ O 2 max ${\dot V_{{{\mathrm{O}}_{\mathrm{2}}}{\mathrm{max}}}}$ in the heat while consuming water, carbohydrate or protein. Blood samples were collected and plasma lactulose (L) and l-rhamnose (R) appearance, after dual sugar solution ingestion at 90 min of exercise, was quantified by HPAEC-PAD to measure plasma L/R and reveal new information about intestinal permeability immediately post-exercise and during recovery. In ET-A, plasma L/R increased immediately post-exercise in hot compared with temperate and warm conditions, while, in ET-B, carbohydrate alleviated this, and this information was otherwise missed when measuring urine L/R. Consuming carbohydrate or protein before and during exercise attenuated small intestine permeability throughout recovery from exertional heat stress. We recommend using the dual sugar test with quantification of plasma sugars by HPAEC-PAD at intervals to maximise intestinal permeability data collection in exercise gastroenterology research, as this gives additional information compared to urinary measurements. KEY POINTS: Intestinal permeability is typically assessed using a dual sugar test, by administering a drink containing non-metabolisable sugars (e.g. lactulose (L) and l-rhamnose (R)) that can enter the circulation by paracellular translocation when the epithelium is compromised, and are subsequently measured in urine. We demonstrate that our recently developed ion chromatography protocol can be used to accurately quantify the L/R ratio in plasma, and that measuring L/R in plasma collected at intervals during the post-exercise recovery period reveals novel acute response information compared to measuring 5-h cumulative urine L/R. We confirm that exercising in hot ambient conditions increases intestinal epithelial permeability immediately after exercise, while consuming carbohydrate or protein immediately before and during exercise attenuates this. We recommend using our dual sugar absorption test protocol to maximise intestinal epithelial permeability data collection in exercise gastroenterology research and beyond.