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Alessandro Carvalho,1,2 Dannyel Barbirato,1 Narahyana Araujo,1 Jose Vicente Martins,3 Jose Luiz Sá Cavalcanti,3 Tony Meireles Santos,4 Evandro S Coutinho,5 Jerson Laks,1,2 Andrea C Deslandes1 1Centro de Doença de Alzheimer e Outros Transtornos da Velhice, Instituto de Psiquiatria, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil; 2Centro de Estudo de Pesquisa do Envelhecimento, Instituto Vital Brazil, Rio de Janeiro, Brazil; 3Instituto de Neurologia Deolindo Couto, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil; 4Departamento de Educação Física da Universidade Federal de Pernambuco, Pernambuco, Brazil; 5Departamento de Epidemiologia e Métodos Quantitativos em Saúde. Escola Nacional de Saúde Pública-FIOCRUZ, Rio de Janeiro, Brazil Introduction: Physical rehabilitation is commonly used in patients with Parkinson’s disease (PD) to improve their health and alleviate the symptoms. Objective: We compared the effects of three programs, strength training (ST), aerobic training (AT), and physiotherapy, on motor symptoms, functional capacity, and electroencephalographic (EEG) activity in PD patients. Methods: Twenty-two patients were recruited and randomized into three groups: AT (70% of maximum heart rate), ST (80% of one repetition maximum), and physiotherapy (in groups). Subjects participated in their respective interventions twice a week for 12 weeks. The assessments included measures of disease symptoms (Unified Parkinson’s Disease Rating Scale [UPDRS]), functional capacity (Senior Fitness Test), and EEG before and after 12 weeks of intervention. Results: The PD motor symptoms (UPDRS-III) in the group of patients who performed ST and AT improved by 27.5% (effect size [ES]=1.25, confidence interval [CI]=-0.11, 2.25) and 35% (ES=1.34, CI=-0.16, 2.58), respectively, in contrast to the physiotherapy group, which showed a 2.9% improvement (ES=0.07, CI=-0.85, 0.99). Furthermore, the functional capacity of all three groups improved after the intervention. The mean frequency of the EEG analysis mainly showed the effect of the interventions on the groups (F=11.50, P=0.0001). Conclusion: ST and AT in patients with PD are associated with improved outcomes in disease symptoms and functional capacity. Keywords: Parkinson’s disease, physical exercise, physical therapy, quality of life, functional capacity

Background: In simulation-based education, the effectiveness of observation or active participation on the retention of knowledge and skills is uncertain. The aim of the study was to investigate knowledge retention, technical and non-technical skills and self-efficacy among observers and active participants in a simulated palliative extubation., Method: We included medical and nursing undergraduates and residents. On the first day, participants were divided into observers and active participants, each with one participant from medical and nursing backgrounds. We presented a recorded lecture, followed by knowledge and self-efficacy tests for all participants before and after the simulation. After fourteen days, both groups actively participated in the scenario, without observers. We assessed technical and non-technical skills during the simulation and repeated the knowledge and self-efficacy tests after the training., Results: Forty-four individuals participated in this study, half from each training programme. Knowledge improved after the first training in both groups, with a significant drop only for active participants after 14 days. Self-efficacy increased in both groups, being higher for the active participants. After 14 days, active participants performed better in technical skills compared to observers, but it was similar in both groups for non-technical skills., Conclusions: Active participation seems superior to observation in the development of self-efficacy and the retention of technical skills. Observation may be superior to active participation in knowledge retention. Retention of non-technical skills appears to be similar with both observation and active participation. The findings have important implications for current simulation-based education, but further research is recommended.

Background: Home visiting programmes can support child development and reduce inequalities, but failure to identify the most vulnerable families can undermine such efforts. We examined whether there are strong predictors of poor child development that could be used to screen pregnant women in primary health care settings to target early interventions in a Brazilian population. Considering selected predictors, we assessed coverage and focus of a large-scale home visiting programme named Primeira Infância Melhor (PIM)., Methods: We undertook a prospective cohort study on 3603 children whom we followed from gestation to age four years. We then used 27 potential socioeconomic, psychosocial, and clinical risk factors measurable during pregnancy to predict child development, which was assessed by the Battelle Developmental Inventory (BDI) at the age of four years. We compared the results from a Bonferroni-adjusted conditional inference tree with exploratory linear regression and principal component analysis (PCA), and we conducted external validation using data from a second cohort from the same population. Lastly, we assessed PIM coverage and focus by linking 2015 cohort data with PIM databases., Results: The decision tree analyses identified maternal schooling as the most important variable for predicting BDI, followed by paternal schooling. Based on these variables, a group of 214 children who had the lowest mean BDI (BDI = -0.48; 95% confidence interval (CI) = -0.63, -0.33) was defined by mothers with ≤5 years and fathers with ≤4 years of schooling. Maternal and paternal schooling were also the strongest predictors in the exploratory analysis using regression and PCA, showing linear associations with the outcome. However, their capacity to explain outcome variance was low, with an adjusted R 2 of 5.3% and an area under the receiver operating characteristic curve of 0.62 (95% CI = 0.60, 0.64). External validation showed consistent results. We also provided an online screening tool using parental schooling data to support programme's targeting. PIM coverage during pregnancy was low, but the focus was adequate, especially among families with longer enrolment, indicating families most in need received higher dosage., Conclusions: Information on maternal and paternal schooling can improve the focus of home visiting programmes if used for initial population-level screening of pregnant women in Brazil. However, enrolment decisions require complementary information on parental resources and direct interactions with families to jointly decide on inclusion., Competing Interests: Disclosure of interest: The authors completed the ICMJE Disclosure of Interest Form (available upon request from the corresponding author) and disclose no relevant interests., (Copyright © 2024 by the Journal of Global Health. All rights reserved.)

Introduction: Femur fractures represent a significant public health concern for individuals over 60 years of age. In Brazil, the incidence of these fractures has shown a rising trend in line with population aging. Besides intrinsic risk factors like osteoporosis, seasonal and climatic variables have been suggested to significantly influence the occurrence of these fractures., Methods: Epidemiological data were sourced from the Hospital Information System of the Unified Health System (SIH-SUS) using the TABNET tool provided by the Department of Informatics of the Unified Health System (DATASUS). Information on hospital admissions for femur fractures in individuals over 60 years, categorized by diagnosis, region, and month, was collected from 2008 to 2023. Climatic data were obtained from the Brazilian National Institute of Meteorology (INMET) for the period from 1991 to 2020. Monthly average temperatures were compared with epidemiological data and analyzed to uncover correlations using ANOVA and Tukey's honestly significant difference (HSD) test., Results: During Brazil's winter months (June to August: 22.8 to 23.5º Celsius), average temperatures are at their lowest. This period also coincides with the peak incidence of femur fractures among the elderly. ANOVA revealed significant differences in fracture rates across various temperature ranges. Subsequent analysis using Tukey's HSD test identified significant differences between temperature ranges of 22-23°C and 25-26°C, as well as 23-24°C and 25-26°C. These results indicate that lower temperatures are associated with a higher incidence of femur fractures among the elderly., Conclusion: The analysis reveals a seasonal pattern in fracture incidence among older adults, with a notable increase during the colder months. To mitigate this risk, it is recommended to implement strategies such as heightened surveillance during colder months, targeted fall prevention measures, and effective osteoporosis management. These interventions aim to reduce the incidence of fractures in this vulnerable population., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Horita et al.)

Stress, infections, and psychological and social well-being can affect the reproductive system. Activation of the hypothalamic-pituitary-adrenal axis can disrupt ovarian cyclicity. Estrogens can modulate stress responsiveness and mood. Thus, understanding this interaction and how it modulates the menstrual cycle is crucial for women's reproductive health., Purpose: The objective of this study was to analyze the influence of a stressor, a period of the Covid-19 pandemic when there were no vaccines available yet, on the psychological state of women aged 18 to 45 years; as well as the influence of mental health on the menstrual cycle, considering the influence of age and hormonal contraceptives., Method: Online questionnaire using the Google Forms platform was used., Results: There is a high prevalence of the onset of new psychosocial symptoms. Moreover, most women reported some type of change in their menstrual cycles. The women who were using hormonal contraceptives demonstrated a higher frequency of spotting and menstrual color alterations, while women without hormonal contraceptives demonstrated a higher frequency of cycle duration and menstrual odor alterations. Women without hormonal contraceptives were more susceptible to the development of psychosocial symptoms. Younger adult women were more affected by menstrual changes and psychosocial symptoms. Close to 90% of women who reported several psychosocial symptoms had changes in their menstrual cycles., Conclusion: These data suggest the impact of stressors, such as a period of the pandemic, on mental health and menstrual cycles, and younger adult women can be more susceptible. This reflects the relationship between mental and reproductive health., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Introduction: Hospital-associated infections (HAIs) are associated with increased mortality and prolonged hospital length-of-stay (LOS). Although some studies have shown that HAIs are associated with increased costs, these studies only used cost estimates, were carried out in a small number of centres, or only in high-income countries., Methods: We carried out a prospective cohort study in ten Brazilian intensive care units (ICUs) selected from a collaborative platform study (IMPACTO MR). We included all patients aged 18 years or older admitted from October 2019 to December 2021 and who had an ICU LOS of at least two days. The costs were adjusted for official inflation until December 2022 and converted into international dollars using the 2021 purchasing power parity (PPP) conversion rate. We used a propensity score matching method to compare patients with HAIs and patients without HAIs, and patients with and without ventilator-associated pneumonia (VAP), central-line bloodstream infection (CLABSI), catheter-associated urinary tract infection (CA-UTI) and multidrug-resistant (MDR) HAIs., Results: We included 7,953 patients in the study, of whom 574 (7.2%) had an HAI during their ICU stay. After propensity-score matching, patients with HAIs had ICU costs that were more than three times higher than those of patients without HAIs [$ 19,642 (IQR; 12,884-35,134) vs. 6,086 (IQR; 3,268-12,550); p <0.001). Patients with VAP, CLABSI, and CA-UTI, but not with MDR-HAIs also had higher total ICU costs., Conclusions: HAIs acquired in the ICU are associated with higher ICU costs. These findings were consistent across specific types of infection., (Copyright © 2024. Published by Elsevier Ltd.)

Introduction: Pollution harms the health of people with asthma. The effect of the anti-inflammatory cholinergic pathway in chronic allergic inflammation associated to pollution is poorly understood., Methods: One hundred eight animals were divided into 18 groups (6 animals). Groups included: wild type mice (WT), genetically modified with reduced VAChT (VAChTKD), and those sensitized with ovalbumin (VAChTKDA), exposed to metal powder due to iron pelletizing in mining company (Local1) or 3.21 miles away from a mining company (Local2) in their locations for 2 weeks during summer and winter seasons. It was analyzed for hyperresponsivity, inflammation, remodeling, oxidative stress responses and the cholinergic system., Results: During summer, animals without changes in the cholinergic system revealed that Local1 exposure increased the hyperresponsiveness (%Rrs, %Raw), and inflammation (IL-17) relative to vivarium animals, while animals exposed to Local2 also exhibited elevated IL-17. During winter, animals without changes in the cholinergic system revealed that Local2 exposure increased the hyperresponsiveness (%Rrs) relative to vivarium animals. Comparing the exposure local of these animals during summer, animals exposed to Local1 showed elevated %Rrs, Raw, and IL-5 compared to Local 2, while in winter, Local2 exposure led to more IL-17 than Local1. Animals with VAChT attenuation displayed increased %Rrs, NFkappaB, IL-5, and IL-13 but reduced alpha-7 compared to animals without changes in the cholinergic system WT. Animals with VAChT attenuation and asthma showed increased the hyperresponsiveness, all inflammatory markers, remodeling and oxidative stress compared to animals without chronic lung inflammation. Exposure to Local1 exacerbated the hyperresponsiveness, oxidative stressand inflammation in animals with VAChT attenuation associated asthma, while Local2 exposure led to increased inflammation, remodeling and oxidative stress., Conclusions: Reduced cholinergic signaling amplifies lung inflammation in a model of chronic allergic lung inflammation. Furthermore, when associated with pollution, it can aggravate specific responses related to inflammation, oxidative stress, and remodeling., (© 2024. The Author(s).)

Urban children are more likely to be vaccinated than rural children, but that advantage is not evenly distributed. Children living in poor urban areas face unique challenges, living far from health facilities and with lower-quality health services, which can impact their access to life-saving vaccines. Our goal was to compare the prevalence of zero-dose children in poor and non-poor urban and rural areas of low- and middle-income countries (LMICs). Zero-dose children were those who failed to receive any dose of a diphtheria-pertussis-tetanus (DPT) containing vaccine. We used data from nationally representative household surveys of 97 LMICs to investigate 201,283 children aged 12-23 months. The pooled prevalence of zero-dose children was 6.5% among the urban non-poor, 12.6% for the urban poor, and 14.7% for the rural areas. There were significant differences between these areas in 43 countries. In most of these countries, the non-poor urban children were at an advantage compared to the urban poor, who were still better off or similar to rural children. Our results emphasize the inequalities between urban and rural areas, but also within urban areas, highlighting the challenges faced by poor urban and rural children. Outreach programs and community interventions that can reach poor urban and rural communities-along with strengthening of current vaccination programs and services-are important steps to reduce inequalities and ensure that no child is left unvaccinated., (© 2024. The Author(s).)

The peptide derived from E. contortisiliquum trypsin inhibitor (Pep-3-EcTI), peptide derived from kallikrein inhibitor isolated from B. bauhinioides (Pep-BbKI), and B. rufa peptide modified from B. bauhinioides (Pep-BrTI) peptides exhibit anti-inflammatory and antioxidant activities, suggesting their potential for treating asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO). We compared the effects of these peptides with dexamethasone (DX) treatment in an ACO model. In this study, 11 groups of male BALB/c mice were pre-treated under different conditions, including sensitization with intraperitoneal injection and inhalation of ovalbumin (OVA), intratracheal instillation of porcine pancreatic elastase (ELA), sensitization with intraperitoneal injection, and various combinations of peptide treatments with Pep-3-EcTI, Pep-BbKI, Pep-BrTI, dexamethasone, and non-treated controls (SAL-saline). Respiratory system resistance, airway resistance, lung tissue resistance, exhaled nitric oxide, linear mean intercept, immune cell counts in the bronchoalveolar lavage fluid, cytokine expression, extracellular matrix remodeling, and oxidative stress in the airways and alveolar septa were evaluated on day 28. Results showed increased respiratory parameters, inflammatory markers, and tissue remodeling in the ACO group compared to controls. Treatment with the peptides or DX attenuated or reversed these responses, with the peptides showing effectiveness in controlling hyperresponsiveness, inflammation, remodeling, and oxidative stress markers. These peptides demonstrated an efficacy comparable to that of corticosteroids in the ACO model. However, this study highlights the need for further research to assess their safety, mechanisms of action, and potential translation to clinical studies before considering these peptides for human use., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 João, Silva Barbosa, Sales da Silva, Fukuzaki, de Campos, Camargo, Santos, Moreira Bezerra, de Almeida, Saraiva-Romanholo, Lopes, Bonturi, Righetti, Oliva, Tibério and Leick.)

Fourth-generation synchrotron storage rings represent a significant milestone in synchrotron technology, offering outstandingly bright and tightly focused X-ray beams for a wide range of scientific applications. However, due to their inherently tight magnetic lattices, these storage rings have posed critical challenges for accessing lower-energy radiation, such as infrared (IR) and THz. Here the first-ever IR beamline to be installed and to operate at a fourth-generation synchrotron storage ring is introduced. This work encompasses several notable advancements, including a thorough examination of the new IR source at Sirius, a detailed description of the radiation extraction scheme, and the successful validation of our optical concept through both measurements and simulations. This optimal optical setup has enabled us to achieve an exceptionally wide frequency range for our nanospectroscopy experiments. Through the utilization of synchrotron IR nanospectroscopy on biological and hard matter samples, the practicality and effectiveness of this beamline has been successfully demonstrated. The advantages of fourth-generation synchrotron IR sources, which can now operate with unparalleled stability as a result of the stringent requirements for producing low-emittance X-rays, are emphasized., (open access.)

Prolonged exposure to iron powder and other mineral dusts can threaten the health of individuals, especially those with COPD. The goal of this study was to determine how environmental exposure to metal dust from two different mining centers in Brazil affects lung mechanics, inflammation, remodeling and oxidative stress responses in healthy and elastase-exposed mice. This study divided 72 male C57Bl/6 mice into two groups, the summer group and the winter group. These groups were further divided into six groups: control, nonexposed (SAL); nonexposed, given elastase (ELA); exposed to metal powder at a mining company (SAL-L1 and ELA-L1); and exposed to a location three miles away from the mining company (SAL-L2 and ELA-L2) for four weeks. On the 29th day of the protocol, the researchers assessed lung mechanics, bronchoalveolar lavage fluid (BALF), inflammation, remodeling, oxidative stress, macrophage iron and alveolar wall alterations (mean linear intercept-Lm). The Lm was increased in the ELA, ELA-L1 and ELA-L2 groups compared to the SAL group (p < 0.05). There was an increase in the total number of cells and macrophages in the ELA-L1 and ELA-L2 groups compared to the other groups (p < 0.05). Compared to the ELA and SAL groups, the exposed groups (ELA-L1, ELA-L2, SAL-L1, and SAL-L2) exhibited increased expression of IL-1β, IL-6, IL-10, IL-17, TNF-α, neutrophil elastase, TIMP-1, MMP-9, MMP-12, TGF-β, collagen fibers, MUC5AC, iNOS, Gp91phox, NFkB and iron positive macrophages (p < 0.05). Although we did not find differences in lung mechanics across all groups, there were low to moderate correlations between inflammation remodeling, oxidative stress and NFkB with elastance, resistance of lung tissue and iron positive macrophages (p < 0.05). Environmental exposure to iron, confirmed by evaluation of iron in alveolar macrophages and in air, exacerbated inflammation, initiated remodeling, and induced oxidative stress responses in exposed mice with and without emphysema. Activation of the iNOS, Gp91phox and NFkB pathways play a role in these changes., (© 2024. The Author(s).)

Introduction and Objective: p62 is a human multifunctional adaptor protein involved in key cellular processes such as tissue homeostasis, inflammation, and cancer. It acts as a negative regulator of inflammasome complexes. It may thus be considered a good candidate for therapeutic use in inflammatory bowel diseases (IBD), such as colitis. Probiotics, including recombinant probiotic strains producing or delivering therapeutic biomolecules to the host mucosal surfaces, could help prevent and mitigate chronic intestinal inflammation. The objective of the present study was to combine the intrinsic immunomodulatory properties of the probiotic Lactococcus lactis NCDO2118 with its ability to deliver health-promoting molecules to enhance its protective and preventive effects in the context of ulcerative colitis (UC)., Material and Methods: This study was realized in vivo in which mice were supplemented with the recombinant strain. The intestinal barrier function was analyzed by monitoring permeability, secretory IgA total levels, mucin expression, and tight junction genes. Its integrity was evaluated by histological analyses. Regarding inflammation, colonic cytokine levels, myeloperoxidase (MPO), and expression of key genes were monitored. The intestinal microbiota composition was investigated using 16S rRNA Gene Sequencing., Results and Discussion: No protective effect of L. lactis NCDO2118 pExu: p62 was observed regarding mice clinical parameters compared to the L. lactis NCDO2118 pExu: empty . However, the recombinant strain, expressing p62, increased the goblet cell counts, upregulated Muc2 gene expression in the colon, and downregulated pro-inflammatory cytokines Tnf and Ifng when compared to L. lactis NCDO2118 pExu: empty and inflamed groups. This recombinant strain also decreased colonic MPO activity. No difference in the intestinal microbiota was observed between all treatments. Altogether, our results show that recombinant L. lactis NCDO2118 delivering p62 protein protected the intestinal mucosa and mitigated inflammatory damages caused by dextran sodium sulfate (DSS). We thus suggest that p62 may constitute part of a therapeutic approach targeting inflammation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Laguna, Freitas, Barroso, De Jesus, De Vasconcelos, Quaresma, Américo, Campos, Glória, Dutra, Da Silva, Vital, Fernandes, Souza, Martins, Ferreira, Santos, Birbrair, De Oliveira, Faria, Carvalho, Venanzi, Le Loir, Jan, Guédon and Azevedo.)

Target delivery of therapeutic agents with anti-inflammatory properties using probiotics as delivery and recombinant protein expression vehicles is a promising approach for the prevention and treatment of many diseases, such as cancer and intestinal immune disorders. Lactococcus lactis, a Lactic Acid Bacteria (LAB) widely used in the dairy industry, is one of the most important microorganisms with GRAS status for human consumption, for which biotechnological tools have already been developed to express and deliver recombinant biomolecules with anti-inflammatory properties. Cytokines, for  example, are immune system communication molecules present at virtually all levels of the immune response. They are essential in cellular and humoral processes, such as hampering inflammation or adjuvating in the adaptive immune response, making them good candidates for therapeutic approaches. This review discusses the advances in the development of new therapies and prophylactic approaches using LAB to deliver/express cytokines for the treatment of inflammatory and autoimmune diseases in the future., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Identification of unvaccinated children is important for preventing deaths due to infections. Number of siblings and birth order have been postulated as risk factors for zero-dose prevalence., Methods: We analysed nationally representative cross-sectional surveys from 85 low and middle-income countries (2010-2020) with information on immunisation status of children aged 12-35 months. Zero-dose prevalence was defined as the failure to receive any doses of DPT (diphtheria-pertussis-tetanus) vaccine. We examined associations with birth order and the number of siblings, adjusting for child's sex, maternal age and education, household wealth quintiles and place of residence. Poisson regression was used to calculate zero-dose prevalence ratios., Findings: We studied 375,548 children, of whom 13.7% (n = 51,450) were classified as zero-dose. Prevalence increased monotonically with birth order and with the number of siblings, with prevalence increasing from 11.0% for firstborn children to 17.1% for birth order 5 or higher, and from 10.5% for children with no siblings to 17.2% for those with four or more siblings. Adjustment for confounders attenuated but did not eliminate these associations. The number of siblings remained as a strong risk factor when adjusted for confounders and birth order, but the reverse was not observed. Among children with the same number of siblings, there was no clear pattern in zero-dose prevalence by birth order; for instance, among children with two siblings, the prevalence was 13.0%, 14.7%, and 13.3% for firstborn, second, and third-born, respectively. Similar results were observed for girls and boys. 9513 families had two children aged 12-35 months. When the younger sibling was unvaccinated, 61.9% of the older siblings were also unvaccinated. On the other hand, when the younger sibling was vaccinated, only 5.9% of the older siblings were unvaccinated., Interpretation: The number of siblings is a better predictor than birth order in identifying children to be targeted by immunization campaigns. Zero-dose children tend to be clustered within families., Funding: Gavi, the Vaccine Alliance., Competing Interests: TM and DHR are employed by Gavi, the Vaccine Alliance, funder of this research. All other authors declare no competing interests., (© 2024 The Authors.)

Purpose: To compare the effects of 12-week high-intensity interval (HIIT), moderate-intensity continuous (MICT), and self-selected intensity training (SSIT) on health outcomes and affective responses. Methods: Seventy-three overweight/obese inactive adults (62% woman; age, 31.4 ± 7.2 years; height, 1.66 ± 0.09 cm; Body mass index, 28.9 ± 2.7 kg.m -2 ) who were randomized into HIIT (n = 23), MICT (n = 24) and SSIT (n = 26) groups. The training was conducted three times per week in an outdoor environment, with 4 weeks under direct supervision and 8 weeks with semi-supervision. Cardiorespiratory fitness, body composition, and metabolic profile were evaluated at baseline and at the end of the 4 th and 12 th weeks. Core affect was measured during all training sessions. Results: Peak oxygen uptake improved in all groups after 4 and 12 weeks compared with baseline. Only the SSIT had reductions in body fat throughout the intervention. No improvements were observed in the metabolic profile across all groups. SSIT was perceived as more pleasurable than HIIT; however, there were no differences in affective responses between SSIT and MICT. Affective responses in-task (e.g. negative and positive peak, rate of change and affect at the end of the exercise session) predicted the HIIT and SSIT exercises attendance rate. Conclusion: Regardless of the exercise training protocol, overweight/obese inactive adults improved health outcomes, which suggests the prescribing HIIT, MICT, and SSIT in outdoor environments. SSIT should be considered in order to optimize the pleasure during training sessions. Affective response more positive in-task of the HIIT and SSIT is associated with greater attendance rate in these exercise protocols.

Mental fatigue reduces exercise performance through an impaired psychological response such as increased perceived exertion. Carbohydrate (CHO) mouth rinses improve exercise performance and perceived exertion likely due to an improved activation in cerebral reward areas, then we investigated if the CHO mouth rinse-improved exercise performance in mentally fatigued individuals was associated with ameliorated reward-related psychological responses. We hypothesised that CHO mouth rinse would be beneficial for mentally fatigued cyclists mainly in high-metabolic disturbance intensities. After familiarization and baseline sessions, well trained cyclists (n = 20) performed a maximal incremental test (MIT) after mental fatigue induction. They completed the MIT either without mouth rinse (MF) or rinsing their mouth with CHO (MF+CHO) or placebo (FM+PLA) solutions at every 25 % of the MIT. Psychological responses such as ratings of perceived exertion (RPE), affective valence, emotional arousal, and motivation were assessed throughout the MIT, while performance was assessed as peak power output and time of exercise. Mental fatigue reduced MIT performance (P < 0.05), but CHO mouth rinse was effective to counteract this deleterious mental fatigue effect (P < 0.05). However, we found null effects of CHO mouth rinses in psychological responses above the VT 2 (P > 0.05) such as RPE, affective valence, emotional arousal, and motivation. Correlational analysis showed a significant, but moderate negative correlation between motivation and time of exercise above the VT 2 when participants used CHO mouth rinse. In conclusion, the ergogenic CHO mouth rinse effects on MIT performance of mentally fatigued cyclists were irrespective of ameliorated psychological responses to exercise., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023. Published by Elsevier Inc.)

Introduction: The development of clinical skills requires the appropriate use of self-regulated learning (SRL). Students' use of key SRL processes as they perform a clinical skill can be identified by SRL microanalysis and used to provide feedback. SRL-microanalysis feedback only on students' key SRL processes has not been previously researched for developing clinical skills. The aim of this study was to investigate whether SRL-microanalysis feedback only on students' key SRL processes can improve both their use of SRL and their clinical skill performance., Methods: Twenty-three final year medical students with no experience in the clinical skill required for mechanical ventilation participated in this study. Key SRL processes and clinical skill performance were measured before and after SRL microanalysis feedback., Results: Overall, we found an improvement in the key SRL processes of planning and monitoring of performance, with a significant difference in monitoring. We also found an increase in students' clinical skill performance., Discussion: This study, which is the first in clinical skills, demonstrated that SRL microanalysis feedback only on key SRL processes can improve both students' SRL and their clinical skill performance. studies are recommended with a great number of students and across a variety of clinical skills.

Introduction: Zika virus (ZIKV) is a flavivirus transmitted through the bites of infected Aedes mosquitoes. These viruses can also be transmitted through sexual contact, vertical transmission, and possibly transfusion. Most cases are asymptomatic, but symptoms can include rash, conjunctivitis, fever, and arthralgia, which are characteristic of other arboviruses. Zika infection can lead to complications such as microcephaly, miscarriage, brain abnormalities, and Guillain-Barré syndrome (GBS)., Objective: The aim is to determine the inhibitory potential of the algae Kappaphycus alvarezii (K. alvarezii) on ZIKV replication., Methodology: Cytotoxicity experiments were performed using Vero cells to determine the CC 50 , and ZIKV replication inhibition assays (ATCC ® VR-1839™) were conducted to determine the EC 50 . The mechanism of action was also studied to assess any synergistic effect with Ribavirin., Results: K. alvarezii demonstrated low toxicity with a CC 50 of 423 μg/mL and a potent effect on ZIKV replication with an EC 50 of 0.65 μg/mL and a Selectivity Index (SI) of 651, indicating the extract's safety. Virucidal effect assays were carried out to evaluate the possible mechanism of action, and the compound addition time was studied, showing the potential to delay the treatment of infected cells by up to 6 hours. A potential synergistic effect was observed when K. alvarezii extract was combined with suboptimal concentrations of Ribavirin, resulting in 99% inhibition of viral replication., Conclusion: Our data demonstrate the significant potential of K. alvarezii extract and highlight the need for further studies to investigate its mechanism of action. We propose this extract as a potential anti-Zika compound., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Introduction: Shorter courses of antimicrobials have been shown to be non-inferior to longer, "traditional" duration of therapies, including for some severe healthcare-associated infections, with a few exceptions. However, evidence is lacking regarding shorter regimes against severe infections by multidrug-resistant Gram-negative bacteria (MDR-GNB), which are often caused by distinct strains and commonly treated with second-line antimicrobials. In the duratiOn of theraPy in severe infecTIons by MultIdrug-reSistant gram-nEgative bacteria (OPTIMISE) trial, we aim to assess the non-inferiority of 7-day versus 14-day antimicrobial therapy in critically ill patients with severe infections caused by MDR-GNB., Methods: This is a randomized, multicenter, open-label, parallel controlled trial to assess the non-inferiority of 7-day versus 14-day of adequate antimicrobial therapy for intensive care unit (ICU)-acquired severe infections by MDR-GNB. Adult patients with severe infections by MDR-GNB initiated after 48 h of ICU admission are screened for eligibility. Patients are eligible if they proved to be hemodynamically stable and without fever for at least 48 h on the 7th day of adequate antimicrobial therapy. After consenting, patients are 1:1 randomized to discontinue antimicrobial therapy on the 7th (± 1) day or to continue for a total of 14th (± 1) days., Planned Outcomes: The primary outcome is treatment failure, defined as death or relapse of infection within 28 days after randomization. Non-inferiority will be achieved if the upper edge of the two-tailed 95% confidence interval of the difference between the clinical failure rate in the 7-day and the 14-day group is not higher than 10%., Conclusion: The OPTIMISE trial is the first randomized controlled trial specifically designed to assess the duration of antimicrobial therapy in patients with severe infections by MDR-GNB., Trial Registration: ClinicalTrials.gov, NCT05210387. Registered on 27 January 2022. Seven Versus 14 Days of Antibiotic Therapy for Multidrug-resistant Gram-negative Bacilli Infections (OPTIMISE)., (© 2023. The Author(s).)

Importance: Giant viruses are noteworthy not only due to their enormous particles but also because of their gigantic genomes. In this context, a fundamental question has persisted: how did these genomes evolve? Here we present the discovery of cedratvirus pambiensis, featuring the largest genome ever described for a cedratvirus. Our data suggest that the larger size of the genome can be attributed to an unprecedented number of duplicated genes. Further investigation of this phenomenon in other viruses has illuminated gene duplication as a key evolutionary mechanism driving genome expansion in diverse giant viruses. Although gene duplication has been described as a recurrent event in cellular organisms, our data highlights its potential as a pivotal event in the evolution of gigantic viral genomes., Competing Interests: The authors declare no conflict of interest.

The world is not on track to achieve universal access to safely managed water by 2030, and access is substantially lower in rural areas. This Sustainable Development Goal target and many other global indicators rely on the classification of improved water sources for monitoring access. We aimed to investigate contamination in drinking water sources, comparing improved and unimproved sources in urban and rural settings. We used data from Multiple Indicator Cluster Surveys, which tested samples from the household water source and a glass of water for Escherichia coli contamination across 38 countries. Contamination was widespread and alarmingly high in almost all countries, settings, and water sources, with substantial inequalities between and within countries. Water contamination was found in 51.7% of households at the source and 70.8% in the glass of water. Some improved sources (e.g., protected wells and rainwater) were as likely to be contaminated as unimproved sources. Some sources, like piped water, were considerably more likely to be contaminated in rural than urban areas, while no difference was observed for others. Monitoring water contamination along with further investigation in water collection, storage, and source classification is essential and must be expanded to achieve universal access to safely managed water.

Quinolinic acid (QUIN) is a toxic compound with pro-oxidant, pro-inflammatory, and pro-apoptotic actions found at high levels in the central nervous system (CNS) in several pathological conditions. Due to the toxicity of QUIN, it is important to evaluate strategies to protect against the damage caused by this metabolite in the brain. In this context, coenzyme Q 10 (CoQ 10 ) is a provitamin present in the mitochondria with a protective role in cells through several mechanisms of action. Based on these, the present study was aimed at evaluating the possible neuroprotective role of CoQ 10 against damage caused by QUIN in the striatum of young Wistar rats. Twenty-one-day-old rats underwent a 10-day pretreatment with CoQ 10 or saline (control) intraperitoneal injections and on the 30th day of life received QUIN intrastriatal or saline (control) administration. The animals were submitted to behavior tests or euthanized, and the striatum was dissected to neurochemical studies. Results showed that CoQ 10 was able to prevent behavioral changes (the open field, object recognition, and pole test tasks) and neurochemical parameters (alteration in the gene expression of IL-1β, IL-6, SOD, and GPx, as well as in the immunocontent of cytoplasmic Nrf2 and nuclear p-Nf-κβ) caused by QUIN. These findings demonstrate the promising therapeutic effects of CoQ 10 against QUIN toxicity., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: IL-17 is a modulator of the inflammatory response and is implicated in lung remodeling in both asthma and chronic obstructive pulmonary disease (COPD). Well as and probably in patients with asthma-COPD overlap (ACO)., Methods: In this study, we evaluated the response of the airways and alveolar septa to anti-IL-17 treatment in an ACO model. Fifty-six male BALB/c mice were sensitized with ovalbumin (OVA group), received porcine pancreatic elastase (PPE group), or both (ACO group). Mice were then treated with either anti-IL-17 monoclonal antibody or saline. We evaluated hyperresponsiveness, bronchoalveolar lavage fluid (BALF) cell counts, and mean alveolar diameter. We quantified inflammatory, response, extracellular matrix remodeling, oxidative stress markers, and signaling pathway markers., Results: Anti-IL-17 treatment in the ACO anti-IL-17 group reduced the maximum response of respiratory system Rrs, Ers, Raw, Gtis, this when compared to the ACO group (p<0.05). There was a reduction in the total number of inflammatory cells, neutrophils, and macrophages in the BALF in the ACO anti-IL-17 group compared to the ACO group (p<0.05). There was attenuated dendritic cells, CD4+, CD8+, FOXP3, IL-1β, IL-2, IL-6, IL-13, IL-17, IL-33 in ACO anti-IL-17 group in airway and alveolar septum compared to the ACO group (p<0.05). We observed a reduction of MMP-9, MMP-12, TIMP-1, TGF-β, collagen type I in ACO anti-IL-17 group in airway and alveolar septum compared to the ACO group (p < 0.05). We also observed a reduction of iNOS and 8-iso-PGF2α in the airways and in the alveolar septum was reduced in the ACO anti-IL-17group compared to the ACO group (p < 0.05). Regarding the signaling pathways, NF-kB, ROCK-1, and ROCK-2 in the airway and alveolar septum were attenuated in the ACO anti-IL-17 group when compared to the ACO group (p<0.05)., Conclusions: Our results suggest that inhibiting IL-17 modulates cell-associated cytokine production in lung tissue, extracellular matrix remodeling, and oxidative stress in ACO through the modulation of NF-kB and FOXP3., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Camargo, Righetti, de Almeida, Santos, Fukuzaki, Martins, Barbeiro, Saraiva-Romanholo, Lopes, Leick, Prado and Tibério.)

The synthesized peptide derived from Enterolobium contortisiliquum (pep3-EcTI) has been associated with potent anti-inflammatory and antioxidant effects, and it may be a potential new treatment for asthma-COPD overlap-ACO). Purpose: To investigate the primary sequence effects of pep3-EcTI in an experimental ACO. BALB/c mice were divided into eight groups: SAL (saline), OVA (ovalbumin), ELA (elastase), ACO (ovalbumin + elastase), ACO-pep3-EcTI (treated with inhibitor), ACO-DX (treated with dexamethasone), ACO-DX-pep3-EcTI (treated with dexamethasone and inhibitor), and SAL-pep3-EcTI (saline group treated with inhibitor). We evaluated the hyperresponsiveness to methacholine, exhaled nitric oxide, bronchoalveolar lavage fluid (BALF), mean linear intercept (Lm), inflammatory markers, tumor necrosis factor (TNF-α), interferon (IFN)), matrix metalloproteinases (MMPs), growth factor (TGF-β), collagen fibers, the oxidative stress marker inducible nitric oxide synthase (iNOS), transcription factors, and the signaling pathway NF-κB in the airways (AW) and alveolar septa (AS). Statistical analysis was conducted using one-way ANOVA and t -tests, significant when p < 0.05. ACO caused alterations in the airways and alveolar septa. Compared with SAL, ACO-pep3-EcTI reversed the changes in the percentage of resistance of the respiratory system (%Rrs), the elastance of the respiratory system (%Ers), tissue resistance (%Gtis), tissue elastance (%Htis), airway resistance (%Raw), Lm, exhaled nitric oxide (ENO), lymphocytes, IL-4, IL-5, IL-6, IL-10, IL-13, IL-17, TNF-α, INF-γ, MMP-12, transforming growth factor (TGF)-β, collagen fibers, and iNOS. ACO-DX reversed the changes in %Rrs, %Ers, %Gtis, %Htis, %Raw, total cells, eosinophils, neutrophils, lymphocytes, macrophages, IL-1β, IL-6, IL-10, IL-13, IL-17, TNF-α, INF-γ, MMP-12, TGF-β, collagen fibers, and iNOS. ACO-DX-pep3-EcTI reversed the changes, as was also observed for the pep3-EcTI and the ACO-DX-pep3-EcTI. Significance: The pep3-EcTI was revealed to be a promising strategy for the treatment of ACO, asthma, and COPD.

Homocysteine (Hcy) is a risk factor for neurodegenerative diseases, such as Alzheimer's Disease, and is related to cellular and tissue damage. In the present study, we verified the effect of Hcy on neurochemical parameters (redox homeostasis, neuronal excitability, glucose, and lactate levels) and the Serine/Threonine kinase B (Akt), Glucose synthase kinase-3β (GSK3β) and Glucose transporter 1 (GLUT1) signaling pathway in hippocampal slices, as well as the neuroprotective effects of ibuprofen and rivastigmine alone or in combination in such effects. Male Wistar rats (90 days old) were euthanized and the brains were dissected. The hippocampus slices were pre-treated for 30 min [saline medium or Hcy (30 µM)], then the other treatments were added to the medium for another 30 min [ibuprofen, rivastigmine, or ibuprofen + rivastigmine]. The dichlorofluorescein formed, nitrite and Na+, K+-ATPase activity was increased by Hcy at 30 µM. Ibuprofen reduced dichlorofluorescein formation and attenuated the effect of Hcy. The reduced glutathione content was reduced by Hcy. Treatments with ibuprofen and Hcy + ibuprofen increased reduced glutathione. Hcy at 30 µM caused a decrease in hippocampal glucose uptake and GLUT1 expression, and an increase in Glial Fibrillary Acidic Protein-protein expression. Phosphorylated GSK3β and Akt levels were reduced by Hcy (30 µM) and co-treatment with Hcy + rivastigmine + ibuprofen reversed these effects. Hcy toxicity on glucose metabolism can promote neurological damage. The combination of treatment with rivastigmine + ibuprofen attenuated such effects, probably by regulating the Akt/GSK3β/GLUT1 signaling pathway. Reversal of Hcy cellular damage by these compounds may be a potential neuroprotective strategy for brain damage., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Multiple studies have focused on the effect of long-term weathering processes on oils after spill events, without considering the chemical compositional changes occurring shortly after the release of oil into the environment. Therefore, the present study provides a broad chemical characterization for understanding of the changes occurring in the chemical compositions of intermediate (°API = 27.0) and heavy (°API = 20.9) oils from the Sergipe-Alagoas basin submitted to two simulated situations, one under marine conditions and the other in a riverine environment. Samples of the oils were collected during the first 72 h of contact with the simulated environments, followed by evaluation of their chemical compositions. SARA fractionation was used to isolate the resins, which were characterized at the molecular level by UHRMS. The evaporation process was highlighted, with the GC-FID chromatographic profiles showing the disappearance of compounds from n-C 10 until n-C 16 , as well as changes in the weathering indexes and pristane + n-C 17 /phytane + n-C 18 ratios for the crude oils submitted to the riverine conditions. Analysis of the resins fraction showed that basic polar compounds underwent little or no alterations during the early stages of weathering. The marine environment was shown to be much less oxidative than the riverine environment. For both environments, a feature highlighted was an increase of acidic oxygenated compounds with the increase of weathering, especially for the crude oil with °API = 27.0., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Clinical vignette-type multiple choice questions (CV-MCQs) are widely used in assessment and identifying the response process validity (RPV) of questions with low and high integration of knowledge is essential. Answering CV-MCQs of different levels of knowledge application and integration can be understood from a cognitive workload perspective and this can be identified by using eye-tracking. The aim of the pilot study was to identify the cognitive workload and RPV of CV-MCQs of different levels of knowledge application and integration by the use eye-tracking., Methods: Fourteen fourth-year medical students answered a test with 40 CV-MCQs, which were equally divided into low-level and high-level complexity (knowledge application and integration). Cognitive workload was measured using screen-based eye tracking, with the number of fixations and revisitations for each area of interest., Results: We found a higher cognitive workload for high-level complexity ( M  = 121.74) compared with lower-level complexity questions ( M  = 51.94) and also for participants who answered questions incorrectly ( M  = 94.31) compared with correctly ( M  = 79.36)., Conclusion: Eye-tracking has the potential to become a useful and practical approach for helping to identify the RPV of CV-MCQs. This approach can be used for improving the design and development of CV-MCQs, and to provide feedback to inform teaching and learning.[Box: see text].

(1) There are several patients with asthma-COPD overlap (ACO). A peptide derived from the primary sequence of a kallikrein inhibitor isolated from Bauhinia bauhinioides (pep-BbKI) has potent anti-inflammatory and antioxidant effects. Purpose: To investigate the effects of pep-BbKI treatment in an ACO model and compare them with those of corticosteroids. (2) BALB/c mice were divided into groups: SAL (saline), OVA (ovalbumin), ELA (elastase), ACO (ovalbumin + elastase), ACO-pep-BbKI (treated with inhibitor), ACO-DX (dexamethasone treatment), ACO-DX-pep-BbKI (both treatments), and SAL-pep-BbKI (saline group treated with inhibitor). We evaluated: hyperresponsiveness to methacholine, bronchoalveolar lavage fluid (BALF), exhaled nitric oxide (eNO), IL-1β, IL-4, IL-5, IL-6, IL-10, IL-13, IL-17, IFN-γ, TNF-α, MMP-9, MMP-12, TGF-β, collagen fibers, iNOS, eNO, linear mean intercept (Lm), and NF-κB in airways (AW) and alveolar septa (AS). (3) ACO-pep-BbKI reversed ACO alterations and was similar to SAL in all mechanical parameters, Lm, neutrophils, IL-5, IL-10, IL-17, IFN-γ, TNF-α, MMP-12 (AW), collagen fibers, iNOS (AW), and eNO ( p > 0.05). ACO-DX reversed ACO alterations and was similar to SAL in all mechanical parameters, Lm, total cells and differentials, IL-1β(AS), IL-5 (AS), IL-6 (AS), IL-10 (AS), IL-13 (AS), IFN-γ, MMP-12 (AS), TGF-β (AS), collagen fibers (AW), iNOS, and eNO ( p > 0.05). SAL was similar to SAL-pep-BbKI for all comparisons ( p > 0.05). (4) Pep-BbKI was similar to dexamethasone in reducing the majority of alterations of this ACO model.

Interoception refers to the competence in perceiving and interpreting internal sensations emerging from the body. The most common approach to assess interoception is through cardiac interoceptive tests like the heartbeat tracking task (HTT), which measures the accuracy on perceive and counting heartbeats during a period. However, the literature is scarce in providing adequate reliability evidence for this measure so that the interoception assessment may be threaten. In addition to HTT accuracy, it is possible to determine sensibility (self-reported confidence) and interoceptive awareness (correspondence between accuracy and sensibility). Thus, we measured the test-retest reliability of HTT and also investigated the behavior of HTT outcomes along the task. Therefore, 31 healthy adults (16 males) with 27.8 (9.4) years old performed two consecutive HTT interspersed by one day. Intraclass correlation coefficient (ICC), standard error of measurement (SEM) and minimal detectable difference (MD) analyzes showed 'Good' relative reliability for interoceptive accuracy (ICC = 0.880; SEM = 0.263; MD = 0.728; p < 0.001) and 'Moderate' for sensibility (ICC = 0.617; SEM = 0.648; MD = 1.797; p < 0.001) and awareness (ICC = 0.593; SEM = 0.227; MD = 0.628; p < 0.001). The absolute reliability shows low threshold values for observing true effects in HTT outcomes. The results also showed that reducing the number of HTT blocks did not impact the outcomes. The HTT showed to be reliable in determine the interoceptive competences in healthy adults., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Promising evidence points to gestational physical exercise as the key to preventing various disorders that affect the offspring neurodevelopment, but there are no studies showing the impact of resistance exercise on offspring health. Thus, the aim of this study was to investigate whether resistance exercise during pregnancy is able to prevent or to alleviate the possible deleterious effects on offspring, caused by early life-stress (ELS). Pregnant rats performed resistance exercise throughout the gestational period:they climbed a sloping ladder with a weight attached to their tail, 3 times a week. Male and female pups, on the day of birth (P0), were divided into 4 experimental groups: 1) rats of sedentary mothers (SED group); 2) rats of exercised mothers (EXE group); 3) rats of sedentary mothers and submitted to maternal separation (ELS group) and 4) rats of exercised mothers and submitted to MS (EXE + ELS group). From P1 to P10, pups from groups 3 and 4 were separated from their mothers for 3 h/day. Maternal behavior was assessed. From P30, behavioral tests were performed and on P38 the animals were euthanized and prefrontal cortex samples were collected. Oxidative stress and tissue damage analysis by Nissl staining were performed. Our results demonstrate that male rats are more susceptible to ELS than females, showing impulsive and hyperactive behavior similar to that seen in children with ADHD. This behavior was attenuated by the gestational resistance exercise. Our results demonstrate, for the first time, that resistance exercise performed during pregnancy seems to be safe for the pregnancy and offspring's neurodevelopment and are effective in preventing ELS-induced damage only in male rats. Interestingly, resistance exercise during pregnancy improved maternal care and it is reasonable to propose that this finding may be related to the protective role on the animals neurodevelopment, observed in our study., Competing Interests: Conflict of interest The authors affirm that they have no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Non-linear analyzes such as Approximated Entropy (ApEn) and Sample Entropy (SampEn) could show the adaptability of the autonomic nervous system in relation to the dynamic changes caused by exercise. The aims of the study were: a) Investigate the effects of different Self-Selected based Interval Exercises (SSIE) configurations on Heart Rate (HR) entropy; b) Determine whether the stimuli time promote different entropy responses; c) Observe whether exercises with passive self-selected recovery time (SSRT) promote different HR entropy responses compared to those with imposed time and active recovery; and d) Determine whether post-training entropy responses quickly return to baseline. Fifteen older women were randomized to perform six sessions of SSIE and one session of Self-Selected Continuous Exercise (SSCE), with approximately 24 min duration each. The results showed increases on ApEn during the exercises compared to the moments of rest Pre (p < 0.001), Post 6 min (p = 0.003) and Post 12 min (p < 0.001). Results demonstrated that interval exercises (IE) with SSRT, present lower values of ApEn and SampEn regarding the continuous activity (p < 0.05). It was also observed that the entropy values after training returned quickly to levels close to those of pre-exercise rest with a tendency to decrease more pronounced for the continuous. The SSIE were able to promote greater complexity in the HR entropy of older women, allowing greater stabilization of the cardiovascular system, including after training.

To our knowledge, no study has investigated the reliability of the time to exhaustion (TTE) test during constant-load trials in Olympic distance cross-country mountain bike (XCO-MTB) athletes. Thus, the aim was to analyze the reliability of the TTE test at intensities above peak oxygen uptake (VO 2peak ) in trained XCO-MTB athletes. Fifteen male XCO-MTB athletes (mean ± SD: age 31.5 ± 6.6 years, stature 174.0 ± 5.4 cm, body mass 67.2 ± 5.1 kg, VO 2peak 64.5 ± 4.7 mL·kg -1 ·min -1 ) completed 2 TTE tests on the cycle ergometer with 4 different intensities above the maximal work rate in the incremental test (W max ) (105%, 120%, 130%, and 140% of W max ). There was moderate reliability between TTE tests at 105% (intraclass correlation coefficient (ICC) = 0.81, p ≤ 0.001; coefficient of variation (CV) = 9.1%; standard error of measurement (SEM) = 18.3%), and 120% (ICC = 0.88, p ≤ 0.001; CV = 6.6%; SEM = 9.3%) W max . For intensities of 130% (ICC = 0.53, p = 0.018; CV = 9.2%; SEM = 15.8%) and 140% (ICC = 0.56, p = 0.012; CV = 12.2%; SEM = 13.5%) W max , the reliability results proved to be questionable. In addition, no significant differences were found between the 2 TTE tests in all intensities ( p > 0.05). Caution should be taken when assessing TTE above VO 2peak or when using it as a performance indicator, given its moderate to questionable reliability.

Several studies have investigated the interaction between acute physical exercise and cognitive performance. However, few studies have investigated this issue during acute high-intensity exercise. In the present study, we evaluated executive functions (EFs) during incremental exercise in three different intensities [below lactate threshold (LT), at LT, and above LT], measuring EFs performance, gaze behavior, and pupil diameter. Twenty subjects were familiarized with the EFs test and participated in a graded maximal exercise test on a cycle ergometer on the first visit. On the second visit, they performed the EFs task at rest and while exercising at three different intensities using mobile eye-tracking glasses. Our results showed that the psychophysiological measures differed between the conditions. Regarding EFs performance, during exercise above LT, the subjects showed worse accuracy when compared with rest (p < .001) and below LT (p < .001). In addition, the response time (RT) at LT and above LT was shorter than in the rest condition (p < .050). Further, RT was faster (p = .002) in the above LT than in the below LT condition. In addition, the gaze behavior measures indicated that exercise, independently of the intensity, improves the number of fixations with shorter fixation durations compared to the rest condition (p < .050). Additionally, we found no significant differences in average and peak pupil diameter between conditions. In conclusion, exercise at LT improves the EFs performance while exercising above LT worsens EFs performance. However, there were no significant differences in average and peak pupil diameter between conditions., (© 2022 Society for Psychophysiological Research.)

Background: Repurposed drugs for treatment of new onset disease may be an effective therapeutic shortcut. We aimed to evaluate the efficacy of repurposed antivirals compared to placebo in lowering SARS-CoV2 viral load of COVID-19 patients., Methods: REVOLUTIOn is a randomised, parallel, blinded, multistage, superiority and placebo controlled randomised trial conducted in 35 centres in Brazil. We include patients aged 18 years or older admitted to hospital with laboratory-confirmed SARS-CoV-2 infection, symptoms onset 9 days or less and SpO 2 94% or lower at room air were eligible. All participants were randomly allocated to receive either atazanavir, daclatasvir or sofosbuvir/daclatasvir or placebo for 10 days. The primary outcome was the decay rate (slope) of the SARS-CoV-2 viral load logarithm assessed in the modified intention to-treat population. This trial was registered with ClinicalTrials.gov, number NCT04468087., Findings: Between February 09, 2021, and August 04, 2021, 255 participants were enrolled and randomly assigned to atazanavir (n = 64), daclatasvir (n = 66), sofosbuvir/daclatasvir (n = 67) or placebo (n = 58). Compared to placebo group, the change from baseline to day 10 in log viral load was not significantly different for any of the treatment groups (0.05 [95% CI, -0.03 to 0.12], -0.02 [95% CI, -0.09 to 0.06], and -0.03 [95% CI, -0.11 to 0.04] for atazanavir, daclatasvir and sofosbuvir/daclatasvir groups respectively). There was no significant difference in the occurrence of serious adverse events between treatment groups., Interpretation: No significant reduction in viral load was observed from the use of atazanavir, daclatasvir or sofosbuvir/daclatasvir compared to placebo in hospitalised COVID-19 patients who need oxygen support with symptoms onset 9 days or less., Funding: Ministério da Ciência, Tecnologia e Inovação (MCTI) - Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPQ); Cia Latino-Americana de Medicamentos (Clamed); Cia Industrial H. Carlos Schneider (Ciser); Hospital Research Foundation Incorporation, Australia, HCor São Paulo; Blanver Farmoquímica; Instituto de Tecnologia em Fármacos (Farmanguinhos) da Fundação Oswaldo Cruz (Fiocruz); Coordenação Geral de Planejamento Estratégico (Cogeplan)/Fiocruz; and Fundação de apoio a Fiocruz (Fiotec, VPGDI-054-FIO-20-2-13)., Competing Interests: ISM reports devices supply from Fisher & Paykel outside the submitted work; ISM and ABC reports funding paid to HCor by Ministerio da Ciência, Tecnologia e Inovação (MCTIC)/Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPQ), Cia Latino Americana de Medicamentos (Clamed); Cia Industrial H. Carlos Schneider (Ciser); Hospital Research Foundation Incorporation, Australia, HCor São Paulo; Blanver Farmoquímica; Instituto de Tecnologia em Fármacos (Farmanguinhos) da Fundação Oswaldo Cruz (Fiocruz); Coordenação Geral de Planejamento Estratégico (Cogeplan)/Fiocruz; and Fundação de apoio a Fiocruz; LPD reports personal statistical Consulting fees from Servier Laboratories, Aché Laboratory and Astra Zeneca; FGZ reports grants for investigator initiated trials paid to his institution from Bactiguard, Ionis Pharmaceuticals and statistical Consulting from Bactiguard; RGR reported research grants from Pfizer and Brazilian Ministry of Health-PROADI-SUS; LCPA reported participation on advisory board of COVID-19 drugs for MSD; OB reported grants or contracts from: AstraZeneca, Amgen, Bayer, Pfizer, BMS Servier, Novartis Boehringer-Ingelheim, RDL reports grants or contracts from Bristol-Myers Squibb, Glaxo Smith Kline, Medtronic, Pfizer, Sanofi with payments to his institution, payment or honoraria for lectures, presentations, speakers, manuscript writing from Pfizer, Participation on a Data Safety Monitoring Board or Advisory Board of Glaxo Smith Kline and Consulting fees from Bayer, Boehringer Ingleheim, Bristol-Myers Squibb, Daiichi Sankyo, Glaxo Smith Kline, Medtronic, Merck, Pfizer, Portola and Sanofi; AA reports grants form Population Health Research Institute, EMS and Bayer as funding to his institution, payment for lectures for EMS and Bayer. All other authors declare no competing interests., (© 2023 The Authors.)

SARS-CoV-2 infection depend on the binding of the viral Spike glycoprotein (S) to the human receptor Angiotensin Converting Enzyme 2 (ACE2) to induce virus-cell membrane fusion. S protein evolved diverse amino acid changes that are possibly linked to more efficient binding to human ACE2, which might explain part of the increase in frequency of SARS-CoV-2 Variants Of Concern (VOCs). In this work, we investigated the role of ACE2 protein variations that are naturally found in human populations and its binding affinity with S protein from SARS-CoV-2 representative genotypes, based on a series of in silico approaches involving molecular modelling, docking and molecular dynamics simulations. Our results indicate that SARS-CoV-2 VOCs bind more efficiently to the human receptor ACE2 than the ancestral Wuhan genotype. Additionally, variations in the ACE2 protein can affect SARS-CoV-2 binding and protein-protein stability, mostly making the interaction weaker and unstable in some cases. We show that some VOCs, such as B.1.1.7 and P.1 are much less sensitive to ACE2 variants, while others like B.1.351 appear to be specifically optimized to bind to the widespread wild-type ACE2 protein.Communicated by Ramaswamy H. Sarma.

Substantial progress in maternal and neonatal tetanus elimination has been made in the past 40 years, with dramatic reductions in neonatal tetanus incidence and mortality. However, twelve countries have still not achieved maternal and neonatal tetanus elimination, and many countries that have achieved elimination do not meet key sustainability thresholds to ensure long-lasting elimination. As maternal and neonatal tetanus is a vaccine-preventable disease (with coverage of the infant conferred by maternal immunization during and prior to pregnancy), maternal tetanus immunization coverage is a key metric for monitoring progress towards, equity in, and sustainability of tetanus elimination. In this study, we examine inequalities in tetanus protection at birth, a measure of maternal immunization coverage, across 76 countries and four dimensions of inequality via disaggregated data and summary measures of inequality. We find that substantial inequalities in coverage exist for wealth (with lower coverage among poorer wealth quintiles), maternal age (with lower coverage among younger mothers), maternal education (with lower coverage among less educated mothers), and place of residence (with lower coverage in rural areas). Inequalities existed for all dimensions across low- and lower-middle-income countries, and across maternal education and place of residence across upper-middle-income countries. Though global coverage changed little over the time period 2001-2020, this obscured substantial heterogeneity across countries. Notably, several countries had substantial increases in coverage accompanied by decreases in inequality, highlighting the need for equity considerations in maternal and neonatal tetanus elimination and sustainability efforts.

Purpose: This study aimed to investigate the acute effects of tDCS combined with caffeine intake on training volume and pain perception in the bench press in resistance-trained males. The correlation between training volume and pain perception was also assessed in all interventions. Methods: Sixteen healthy males (age = 25.2 ± 4.7 years, body mass = 82.8 ± 9.1 kg, and height = 178.3 ± 5.7 cm), advanced in RT, were randomized and counterbalanced for the following experimental conditions: Sham tDCS with placebo intake (Sham+Pla), Sham tDCS with caffeine intake (Sham+Caff), anodal tDCS with placebo intake (a-tDCS+Pla), and anodal tDCS with caffeine intake (a-tDCS+Caff) . The caffeine or placebo ingestion (both with 5 mg.kg -1 ) occurred 40 minutes before the tDCS sessions. The tDCS was applied over the left DLPFC for 20 minutes, with a 2 mA current intensity . After the tDCS sessions, participants performed the bench press with an 80% of 1RM load, where training volume and pain perception were measured. Results: Training volume was higher in the 1 st and 2 nd sets in both a-tDCS+Caff and Sham+Caff conditions, compared to the Sham+Pla condition ( P < .05). Both a-tDCS+Caff and a-tDCS+Pla showed an increased pain perception during the third set compared to the first set. Also, no correlation was found between the number of repetitions and pain perception in any condition ( P > .05). Conclusion: This research revealed that caffeine intake alone could be used as an ergogenic aid during resistance training programs in resistance-trained males.

We estimated the associations between age at first marriage and recent intimate partner violence (IPV) among women young women aged 20-24 years using data from demographic and health surveys (DHS) conducted at 48 low- and middle-income countries (LMICs). We fitted a multilevel logistic regression model controlling for sociodemographic covariates. Our pooled analyses revealed that age at marriage is strongly associated with past year IPV in a non-linear way, with steep reductions in violence when young women marry after age 15 and a continued decline in IPV for every year marriage is delayed up to age 24. The risk of physical IPV was 3.3 times higher among women married at age 15 (24.4%, 95% CI 19.7; 29.2%) compared to young women married at age 24 (7.5%, 95% CI 5.8; 9.2%). For sexual IPV, girls married at 15 had 2.2 times higher risk compared to those married at 24 (7.5%, 95% CI 5.6; 9.5% vs. 3.4%, 95% CI 2.7; 4.2%, respectively). For psychological IPV, the relative risk was 3.4 for the same comparison (married at 15: 20.1%, 95% CI 14.6; married at 24: 25.5% vs. 6.0%, 95% CI 3.4; 8.6%). Country specific analyses showed that, age at marriage was negatively associated with physical and psychological IPV in nearly half of the countries (n/48) and with sexual IPV in ten countries. Our findings underscore the importance of integrating violence prevention and response interventions into efforts to prevent child marriage, as well as the health, educations and social services young women access.

The inverse relationship between exercise intensity and affective valence is well established for continuous exercise but not for high-intensity interval exercise (HIIE). The objective was to verify the dose-response relationship between exercise intensity and affective valence in HIIE sessions. Eleven young men underwent a vigorous-intensity continuous exercise (VICE) and three HIIE sessions at the same average intensity (70% of peak power-W Peak ) and duration (20 min) but with different amplitudes: 10 × [1 min at 90% W Peak /1 min at 50% W Peak ]-HIIE-90/50; 10 × [1 min at 100% W Peak /1 min at 40% W Peak ]-HIIE-100/40; 10 × [1 min at 110% W Peak /1 min at 30% W Peak ]-HIIE-110/30. During the exercise sessions, psychophysiological variables were recorded (VO 2 , VCO 2 , heart rate, perceived exertion CR10, and Feeling Scale (FS)). Higher correlations were found between CR10 and FS for all conditions (VICE = -0.987; HIIE-90/50 = -0.873; HIIE-100/40 = -0.908; HIIE-110/30 = -0.948). Regarding the physiological variables, the %HR Max presented moderate inverse correlations with FS for all exercise conditions (VICE = -0.867; HIIE-90/50 = -0.818; HIIE-100/40 = -0.837; HIIE-110/30 = -0.828) while the respiratory variables (%VO 2Peak and %VCO 2Peak ) presented low-to-moderate correlations only for VICE, HIIE-90/50, and HIIE-100/40 (ranging from -0.523 to -0.805). Poor correlations were observed between the %VO 2Peak (r = -0.293) and %VCO 2Peak (r = -0.020) with FS. The results indicated that perceived exertion is more sensible than physiological variables to explain the intensity-affective valence relationship in HIIE sessions. RPE should be used for HIIE prescription with a focus on affect.

Prolonged mechanical ventilation (PMV) is common among critically ill septic patients and leads to serious adverse effects. Transthoracic echocardiography (TTE) is an efficient tool for the assessment of septic shock. Our study investigated the relationship between TTE parameters and PMV in mechanically ventilated septic shock patients. TTE was performed in the first 24 h of intensive care unit admission, acquiring data on cardiac output (CO), cardiac index (CI), s' wave (s'), E wave (E), e' wave (e') and E/e' ratio. We compared data on patients who met the criteria for PMV with data on patients who did not. Sixty-four patients were included, 26 of whom met the criteria for PMV. CO, CI and s' were higher in patients who required PMV (5.49 vs. 4.20, p = 0.02; 2.95 vs. 2.34, p = 0.04; and 12.56 vs. 9.81, p = 0.01, respectively). CI correlated with s' (r = 0.37, p < 0.01). The areas under the receiver operating characteristic curves for CO, CI and s' in assessing the need for PMV were, respectively, 0.7 (fair results), 0.69 and 0.68 (poor results). Despite a lack of a prognostic model, the observed differences suggest that hemodynamic TTE could provide information on the risk of PMV in septic shock., (Copyright © 2022 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)