Association of largest meal timing and eating frequency with body mass index and obesity.

BACKGROUND AND AIMS: The circadian pattern of eating behaviors has garnered increasing interest as a strategy for obesity prevention and weight loss. It is believed that the benefits stem from aligning food intake with the body's natural daily rhythms. However, the existing body of evidence is limited in scale and scope and there has been insufficient evaluation of temporal eating behaviors, such as the specific time of day in which the highest calorie consumption occurs, meal frequency, and distribution. This research aims to explore the association between the timing of the largest meal of the day and eating frequency with Body Mass Index (BMI) and obesity. METHODS: Participants (n = 2050, 18-65y) were part of an exploratory cross-sectional and population-based research, with data collection in a virtual environment. Linear regression analyses and restricted cubic splines evaluated differences in BMI associated with independent eating variables [timing of the largest meal, number of meals/day (as continuous and categorical: ≤3 or >3/day), and each largest meal of the day (breakfast/lunch/dinner)]. Logistic regression models were fitted to assess Odds Ratios (OR) and 95 % Confidence Intervals (CI) of obesity associated with the same independent variables. RESULTS: Our main findings were that the timing of the largest meal and reporting dinner as the largest meal were associated with higher values of BMI (respectively, 0.07 kg/m2 and 0.85 kg/m2) and increased odds of obesity [respectively OR(95%CI):1.04(1.01,1.08), and OR(95%CI):1.67(1.18,2.38)]. Those who realized more than 3 meals/day presented lower values of BMI (-0.14 kg/m2) and 32 % lower odds of having obesity [OR(95%CI):0.68(0.52,0.89)]. Reporting lunch as the largest meal also protected against obesity [OR(95%CI):0.71(0.54,0.93)]. These associations were statistically significant and independent of sex, age, marital status, education level, diet quality, sleep duration, and weekly frequency of physical exercise. CONCLUSION: Having the largest meal earlier in the day, concentrating the majority of caloric intake during lunch, and consuming more than three meals a day, may present a promising intervention for preventing and treating obesity/overweight.

Cytotoxic and molecular evaluation of spilanthol obtained from Acmella oleracea (L.) R. K. Jansen (jambu) in human gastric cancer cells.

Acmella oleracea (L.) is a plant popularly known as jambu in the Brazilian Amazon. This species has several biological properties, such as anaesthetic, antioxidant and anti-inflammatory activities, among others. However, there is limited information on its anticancer activity. In this context, this study aims to evaluate the effects of the hydroethanolic extract of jambu and its active compound (spilanthol) on gastric cancer cells. Hydroethanolic jambu inflorescence extract was obtained, and spilanthol was isolated by HPLC. Biological cytotoxicity assays were determined using MTT tests. In addition, an in silico study using molecular docking evaluated the inhibitory properties of spilanthol against JAK1 and JAK2 proteins. The results showed that the hydroethanolic extract and the isolated compound spilanthol exhibited cytotoxicity against cancer cells. Molecular docking revealed that spilanthol has inhibitory potential for JAK1 and JAK2 proteins. Thus, extract of jambu and spilanthol can be a possible candidate for the treatment of gastric carcinoma.

Association between sleep duration and latency, nocturnal awakenings, and body mass index among infants / Associação entre duração e latência do sono, despertares noturnos e índice de massa corporal de lactentes

ABSTRACT Objective: To investigate the association between sleep duration, nocturnal awakenings, and sleep latency with body mass index (BMI) at six and 12 months of age. Methods: 179 children from a birth cohort were enrolled. At six and 12 months of age, anthropometric data were obtained using standardized techniques and infants' mothers answered the Brief Infant Sleep Questionnaire for sleep data. The association of BMI with the independent variables (sleep duration, latency, and nocturnal awakenings) was assessed by linear regression models. Analyses were adjusted for potential confounders and a p-value<0.05 was adopted to define statistical significance. Results: For each additional hour of sleep duration, BMI was reduced by 0.15 kg/m² (95% confidence interval [CI] -0.28; -0.01; p=0.03) and each additional minute of sleep latency increased BMI by 0.01 kg/m² (95%CI -0.00; 0.03; p=0.02). These associations were independent of gestational age, child sex, birth weight, duration of exclusive breastfeeding, smoking during pregnancy, and mother's BMI, education, and marital status. Nocturnal awakenings showed no association with the outcome. Conclusions: Our findings suggest that sleep duration and sleep latency time are associated with BMI in the first year of life. Insights into the influence of sleep early in life on weight status may be helpful to complement future nutritional recommendations and prevent and treat obesity.

RESUMO Objetivo: Investigar a associação entre duração do sono, despertares noturnos e latência do sono com o índice de massa corporal (IMC) aos seis e 12 meses de idade. Métodos: foram incluídas 179 crianças de uma coorte de nascimentos. Aos seis e 12 meses de idade, dados antropométricos foram obtidos por meio de técnicas padronizadas e as mães dos lactentes responderam ao Brief Infant Sleep Questionnaire para dados do sono. A associação do IMC com as variáveis independentes (duração do sono, latência e despertares noturnos) foi avaliada por modelos de regressão linear. As análises foram ajustadas para potenciais fatores de confusão e o p-valor<0,05 foi adotado para definir a significância estatística. Resultados: Para cada hora adicional de duração do sono, o IMC foi reduzido em 0,15 kg/m² (intervalo de confiança [IC]95% -0,28; -0,01; p=0,03) e cada minuto adicional no tempo de latência resultou em aumento de 0,01 kg/m² (IC95% -0,00; 0,03; p=0,02) no IMC. Essas associações foram independentes da idade gestacional, sexo da criança, peso ao nascer, duração do aleitamento materno exclusivo, tabagismo durante a gravidez e IMC, escolaridade e estado civil da mãe. Os despertares noturnos não apresentaram associação com o desfecho. Conclusões: Nossos achados sugerem que a duração e a latência do sono estão associadas ao IMC no primeiro ano de vida. Informações sobre a influência do sono no início da vida sobre o status do peso podem ser úteis para complementar futuras recomendações nutricionais e prevenir e tratar a obesidade.

Association between sleep duration and latency, nocturnal awakenings, and body mass index among infants.

OBJECTIVE: To investigate the association between sleep duration, nocturnal awakenings, and sleep latency with body mass index (BMI) at six and 12 months of age. METHODS: 179 children from a birth cohort were enrolled. At six and 12 months of age, anthropometric data were obtained using standardized techniques and infants' mothers answered the Brief Infant Sleep Questionnaire for sleep data. The association of BMI with the independent variables (sleep duration, latency, and nocturnal awakenings) was assessed by linear regression models. Analyses were adjusted for potential confounders and a p-value<0.05 was adopted to define statistical significance. RESULTS: For each additional hour of sleep duration, BMI was reduced by 0.15 kg/m² (95% confidence interval [CI] -0.28; -0.01; p=0.03) and each additional minute of sleep latency increased BMI by 0.01 kg/m² (95%CI -0.00; 0.03; p=0.02). These associations were independent of gestational age, child sex, birth weight, duration of exclusive breastfeeding, smoking during pregnancy, and mother's BMI, education, and marital status. Nocturnal awakenings showed no association with the outcome. CONCLUSIONS: Our findings suggest that sleep duration and sleep latency time are associated with BMI in the first year of life. Insights into the influence of sleep early in life on weight status may be helpful to complement future nutritional recommendations and prevent and treat obesity.

Molecular characterization and in silico evaluation of surfactins produced by endophytic bacteria from Phanera splendens.

The Phanera splendens (Kunth) Vaz. is a medicinal plant that is used in traditional medicine for the treatment of various diseases, such as malaria. This plant presents highly efficient endophytic bacterial isolates with biocontrol properties. Bacillus sp. is responsible for the production of a variety of non-ribosomal synthesized cyclic lipopeptides which highlight the surfactins. Surfactins have a wide range of antimicrobial activity, including antiplasmodial activity. There is scientific evidence that surfactin structure 2d-01 can be a potent inhibitor against a Plasmodium falciparum sirtuin (Sir2) by acting on the Sir2A protein as the target. The Pf genome encodes two known sirtuins, PfSir2A and PfSir2B, where PfSir2A is a regulator of asexual growth and var gene expression. Herein, we have identified six surfactins produced by endophytic bacteria and performed in silico analysis to elucidate the binding mode of surfactins at the active site of the PfSir2A enzyme. Among the characterized surfactins, 1d-02 showed the highest affinity for the PfSir2A enzyme, with binding energy values equal to -45.08 ± 6.0 and -11.95 ± 0.8 kcal/mol, using MM/GBSA and SIE methods, respectively. We hope that the information about the surfactin structures obtained in this work, as well as the potential binding affinity with an important enzyme from P. falciparum, could contribute to the design of new compounds with antimalarial activity.

Antimicrobial Activity and Molecular Docking Studies of the Biotransformation of Diterpene Acanthoic Acid Using the Fungus Xylaria sp.

Biotransformations are reactions mediated by microorganisms, such as fungi. These bioreactions have high chemo- and stereoselectivity on organic substrates and can be applied in the search for new bioactive compounds. In this study, acanthoic acid (AA) was biotransformed using the fungus Xylaria sp., giving the novel compound 3ß,7ß-dihydroxyacanthoic acid (S1). Both the AA and the product S1 were tested against Gram-positive and Gram-negative bacteria. To identify and validate possible biological targets as enzymes or proteins involved in the activity observed in vitro, we used the molecular docking method. Hydroxylation at the C-3 and C-7 positions of the biotransformation product enhanced its activity against Escherichia coli as well as its binding affinity and interactions with superoxide dismutase 1 (SOD1; PDB ID 4A7G). Based on our results, the SOD1 enzyme was suggested to be a possible target for the antioxidant activity of product S1.

Beyond sleep duration: Sleep timing is associated with BMI among Brazilian adults.

Objectives: To examine the association of sleep duration and timing with BMI among adults. Also, to identify obesogenic and unhealthy behaviors (e.g.diet/sleep quality, physical activity, screen time, smoking) associated with short sleep duration and late bedtime. Participants: Participants (n=755) were part of exploratory, population-based research, with data collection in a virtual environment. Methods: For purposes of characterizing the population we considered short sleepers<7h/night, and the population bedtime median was used to stratify participants into early and late sleepers (before and after 23:08). Student's t-test and chi-square test were performed to assess differences in characteristics between groups. Linear regression analyses were conducted to determine the association of sleep duration, bedtime, and wake-up time with BMI. Quantile regression was estimated for the 25th, 50th, and 75th quantiles to identify the distributional correlations between BMI and sleep variables. Restricted cubic splines were also used to study the shape of the association between sleep-BMI. Analyses were adjusted for potential confounding variables. Results: BMI decreased by 0.40Kg/m2 for each additional hour of sleep duration [95%CI=-0.68,-0.12,p=0.005] and increased by 0.37 kg/m2 for each additional hour of bedtime [95%CI=0.12,0.61,p=0.003]. The association between bedtime and BMI remained even after adjustment for sleep duration. These effects were higher and stronger with higher BMI values (p75th). Wake-up time did not show statistically significant associations. Conclusions: Because we found that beyond sleep duration, bedtime was significantly associated with BMI, our data reflect the pertinence of assessing sleep timing patterns in disentangling sleep-obesity association. Insights into the characteristics, obesogenic and unhealthy behaviors related to short and late sleep may support specific strategies to prevent and treat excess body adiposity and other negative health outcomes.

Play into the domestic routine to promote child development: cross-sectional study.

OBJECTIVE: To analyze the association between the incorporation of play into the domestic routine of caregivers, and the child development of children under their care. METHOD: Cross-sectional study conducted with 129 caregiver-child dyads aged 12-23 months, living in the southern region of São Paulo. Child development was assessed using the Ages & Stages Questionnaire-3, and the incorporation of play into the domestic through a questionnaire and filming of the dyads in activities related to the domestic routine. RESULTS: Almost all the caregivers were the mother (98%), who, when answering the questionnaire, reported incorporating play into their domestic routine (93%), however in the video, only one third played with the child (34%). There was a positive association between playing in moments of domestic routine and domains of child development in children aged 18 months or less. CONCLUSIONS: A positive association was found between the incorporation of play into the domestic routine and child development.

The BEM Program: An innovative online parenting program for socioeconomically disadvantaged caregiver-child dyads in Brazil.

Objective: To describe the BEM Program, an innovative online parenting program for socioeconomically disadvantaged caregiver-child dyads in Brazil. Methods: The Template for Intervention Description and Replication checklist was used to describe the BEM Program in detail. Results: The BEM Program (an acronym for Brincar Ensina Mudar in Portuguese, "Play Teaches Change" in English) refers to the change in adult, child, and dyad outcomes that can be observed through incorporating playful interactions between the caregiver and their child into their daily household chores. Content consisting of 8 videos and 40 text and audio messages was sent entirely online through WhatsApp®. Thus, the Program could be accessed wherever caregivers wanted, if they had their smartphone and Internet access. Conclusions: The detailed description of an innovative online parenting program focused on caregiver-child interaction and child development contributes to the scarce evidence on this type of programs. Adherence to the program continues to represent one of the main challenges to overcome.

Alkaloid from Geissospermum sericeum Benth. & Hook.f. ex Miers (Apocynaceae) Induce Apoptosis by Caspase Pathway in Human Gastric Cancer Cells.

Gastric cancer is among the major causes of death from neoplasia leading causes of death worldwide, with high incidence rates and problems related to its treatment. Here, we outline how Geissospermum sericeum exerts antitumor activity on the ACP02 cell line (human gastric adenocarcinoma) and the mechanism of cell death. The ethanol extract and fractions, neutral fraction and alkaloid fraction, were characterized by thin-layer chromatography and HPLC-DAD, yielding an alkaloid (geissoschizoline N4-methylchlorine) identified by NMR. The cytotoxicity activity of the samples (ethanol extract, neutral fraction, alkaloid fraction, and geissoschizoline N4-methylchlorine) in HepG2 and VERO cells was determined by MTT. The ACP02 cell line was used to assess the anticancer potential. Cell death was quantified with the fluorescent dyes Hoechst 33342, propidium iodide, and fluorescein diacetate. The geissoschizoline N4-methylchlorine was evaluated in silico against caspase 3 and 8. In the antitumor evaluation, there was observed a more significant inhibitory effect of the alkaloid fraction (IC50 18.29 µg/mL) and the geissoschizoline N4-methylchlorine (IC50 12.06 µg/mL). However, geissoschizoline N4-methylchlorine showed lower cytotoxicity in the VERO (CC50 476.0 µg/mL) and HepG2 (CC50 503.5 µg/mL) cell lines, with high selectivity against ACP02 cells (SI 39.47 and 41.75, respectively). The alkaloid fraction showed more significant apoptosis and necrosis in 24 h and 48 h, with increased necrosis in higher concentrations and increased exposure time. For the alkaloid, apoptosis and necrosis were concentration- and time-dependent, with a lower necrosis rate. Molecular modeling studies demonstrated that geissoschizoline N4-methylchlorine could occupy the active site of caspases 3 and 8 energetically favorably. The results showed that fractionation contributed to the activity with pronounced selectivity for ACP02 cells, and geissoschizoline N4-methylchlor is a promising candidate for caspase inhibitors of apoptosis in gastric cancer. Thus, this study provides a scientific basis for the biological functions of Geissospermum sericeum, as well as demonstrates the potential of the geissoschizoline N4-methylchlorine in the treatment of gastric cancer.

Does the use of a diving mask adapted for non-invasive ventilation in hypoxemic acute respiratory failure in individuals with and without COVID-19 increase the ratio of arterial oxygen partial pressure to fractional inspired oxygen? A randomized clinical trial.

Non-invasive ventilation (NIV) can be used in acute hypoxemic respiratory failure (AHRF); however, verifying the best interface for its use needs to be evaluated in the COVID-19 pandemic scenario. The objective of this study was to evaluate the behavior of the ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2 ratio) in patients with AHRF with and without COVID-19 undergoing NIV with the conventional orofacial mask and the adapted diving mask. This is a randomized clinical trial in which patients were allocated into four groups: i) group 1: COVID-19 + adapted mask (n=12); ii) group 2: COVID-19 + conventional orofacial mask (n=12); iii) group 3: non-COVID-19 + adapted mask (n=2); iv) group 4: non-COVID-19 + conventional orofacial mask (n=12). The PaO2/FiO2 ratio was obtained 1, 24, and 48 hours after starting NIV, and the success of NIV was evaluated. This study followed the norms of the Consolidated Standards of Reporting Trials statement and was registered in the Brazilian Registry of Clinical Trials under registration RBR-7xmbgsz. Both the adapted diving mask and the conventional orofacial mask increased the PaO2/FiO2 ratio. The interfaces differed in terms of the PaO2/FiO2 ratio in the first hour [309.66 (11.48) and 275.71 (11.48), respectively] (p=0.042) and 48 hours [365.81 (16.85) and 308.79 (18.86), respectively] (p=0.021). NIV success was 91.7% in groups 1, 2, and 3, and 83.3% in group 4. No adverse effects related to interfaces or NIV were observed. NIV through the conventional orofacial mask interfaces and the adapted diving mask was effective in improving the PaO2/FiO2 ratio; however, the adapted mask presented a better PaO2/FiO2 ratio during use. There was no significant difference between interfaces regarding NIV failure.

Effects of an Online Play-Based Parenting Program on Child Development and the Quality of Caregiver-Child Interaction: A Randomized Controlled Trial.

Background: Studies assessing the effects of parenting programs have focused on interventions delivered through face-to-face modalities. There is a need for research to evaluate the effects of online parenting programs on child development, such as the BEM Program ('Play Teaches Change' in English), an online play-based parenting program that teaches caregivers on how to introduce playful interactions into their daily household chores. Objective: To assess the effects of the BEM Program on child development and the quality of caregiver-child interaction. Method: A two-arm randomized controlled trial was conducted in a socioeconomically disadvantaged district of São Paulo city in Brazil. 129 children aged 12-23 months and their caregiver were randomly assigned to receive either the BEM Program for 8 weeks (intervention, n = 66) or standard child care (control, n = 63). Data were collected at baseline and endline of the intervention through home visits and online interviews. An intention-to-treat analysis was conducted. Results: The intervention showed positive effects on child development, by improving language development (Cohen's d = 0.20, 95%CI 0.08-0.47) and reduced intrusiveness (Cohen's d = 0.35, 95%CI 0.06-0.65) of caregiver-child interaction. No significant differences were observed in caregiver's repertoire and engagement in age-appropriate play activities with the child while doing the household chores, parenting sense of competence and perceived stress. Conclusions: Despite the small size and low adherence to the program, such promising results advance evidences for fully remote parenting programs and their effects on child development.

Play into the domestic routine to promote child development: cross-sectional study / El juego en la rutina doméstica para la promoción del desarrollo infantil: estudio transversal / O brincar na rotina doméstica para a promoção do desenvolvimento infantil: estudo transversal

ABSTRACT Objective: To analyze the association between the incorporation of play into the domestic routine of caregivers, and the child development of children under their care. Method: Cross-sectional study conducted with 129 caregiver-child dyads aged 12-23 months, living in the southern region of São Paulo. Child development was assessed using the Ages & Stages Questionnaire-3, and the incorporation of play into the domestic through a questionnaire and filming of the dyads in activities related to the domestic routine. Results: Almost all the caregivers were the mother (98%), who, when answering the questionnaire, reported incorporating play into their domestic routine (93%), however in the video, only one third played with the child (34%). There was a positive association between playing in moments of domestic routine and domains of child development in children aged 18 months or less. Conclusions: A positive association was found between the incorporation of play into the domestic routine and child development.

RESUMEN Objetivo: Analizar la asociación entre la incorporación del juego en la rutina doméstica, por parte de cuidadoras, y el desarrollo infantil de niños bajo su cuidado. Método: Estudio transversal con 129 díadas cuidadora-niño de 12-23 meses, en la ciudad de São Paulo. El desarrollo infantil se evaluó con el Ages & Stages Questionnaire-3 y la incorporación del juego a la rutina doméstica a través de cuestionario y filmaciones de las díadas en actividades relacionadas con la rutina doméstica. Resultados: Casi todas las cuidadoras fueron la madre (98%) que, al responder al cuestionario, refirieron incorporar el juego en su rutina doméstica (93%), pero en el video, solo un tercio jugó con el niño (34%). Hubo asociación positiva entre jugar en momentos de rutina doméstica y dominios del desarrollo de niños de 18 meses o menos. Conclusiones: Se encontró una asociación positiva entre la incorporación del juego en la rutina doméstica y el desarrollo infantil.

RESUMO Objetivo: Analisar a associação entre a incorporação do brincar na rotina doméstica de cuidadoras e o desenvolvimento infantil de crianças sob seu cuidado. Método: Estudo transversal conduzido com 129 díades cuidadora-criança de 12-23 meses, na região sul de São Paulo. O desenvolvimento infantil foi avaliado com a utilização do Ages & Stages Questionnaire-3, e a incorporação do brincar na rotina doméstica, por meio de questionário e filmagem das díades em atividades relacionadas à rotina doméstica. Resultados: Quase a totalidade das cuidadoras era a mãe (98%) que, ao responder ao questionário, referiu incorporar o brincar na rotina doméstica (93%), porém, no vídeo, apenas um terço brincou com a criança (34%). Verificou-se associação positiva entre brincadeiras em momentos da rotina doméstica e domínios do desenvolvimento em crianças com idade igual ou inferior a 18 meses. Conclusões: Constatou-se associação positiva entre a incorporação do brincar na rotina doméstica e o desenvolvimento infantil.

Efficacy of resistance exercise during hemodialysis on improving lower limb muscle strength in patients with chronic kidney disease: a meta-analysis of randomized clinical trials.

INTRODUCTION: Patients with chronic kidney disease (CKD) on hemodialysis (HD) have muscle weakness in addition to a high risk of falls, motor impairment and immobilization. OBJECTIVE: To conduct a systematic review with meta-analysis of randomized clinical trials regarding the effectiveness of resistance exercises on muscle strengthening and lower limb endurance in patients with CKD on HD. METHODOLOGY: The study was conducted in the PubMed, EMBASE, SciELO, LILACS and Cochrane databases, without linguistic restrictions or year of publication. RESULTS: Of the 824 studies found, only 6 were included for analysis. Studies were allocated to some concern or high risk of bias regarding the reporting of outcomes. The low quality of outcome evidence can mainly be observed due to the severe level of inconsistency owing to the high degree of heterogeneity. A significant reduction in heterogeneity was observed after the sensitivity analysis, demonstrating an improvement in the muscle strength of the lower limbs (p = .002). CONCLUSION: It is concluded that most studies demonstrate benefits in carrying out resistance training programs in increasing muscle strength of the lower limbs, however, it is necessary that randomized clinical trials (RCTs) with greater methodological rigor are performed to confirm these findings.

Breakfast skipping and timing of lunch and dinner: Relationship with BMI and obesity.

OBJECTIVE: To determine whether breakfast-skipping, late-lunch, and late-dinner eating are cross-sectionally associated with higher BMI and obesity. Also, to identify obesogenic behaviors and circadian-related variables, associated with late eating. METHODS: Participants(n = 776) were part of exploratory, population-based research, with data collection in a virtual environment. They were grouped into breakfast-eaters (first meal until 10:00) and skippers (first meal after 10:00), and the population median for the lunch and dinner timing was used to stratify participants into early (lunch/dinner-time before 12:34/20:55) and late (lunch/dinner-time after 12:34/20:55) eaters. Student's t-test and chi-square test were performed to assess differences in characteristics and lifestyle traits between groups. Logistic regression models were used to assess differences in obesity between groups. Linear regression analysis was conducted to determine the association of the clock time of meals with BMI. Analyses were adjusted for potential confounders variables. RESULTS: BMI raised of 0.74 Kg/m2 for each additional hour of lunch-time [95 %CI= 0.31;1.18,P ≤ 0.001]. Breakfast-skippers [OR(95 % CI):1.84(1.02;3.31);P ≤ 0.05] and late-lunch eaters [OR(95 % CI):1.61(1.04;2.49),P ≤ 0.05] had higher odds of having obesity, compared with breakfast-eaters and early-lunch eaters, respectively. These associations were independent of age, gender, diet quality, physical activity duration, and region. No statistically significant differences were found in the comparison between early and late-dinner eaters. CONCLUSIONS: Our results suggest that skipping breakfast and eating late-lunch are associated with BMI and higher odds of having obesity. Insights into the obesogenic behaviors/characteristics related to breakfast-skipping and late-eating may be helpful for future nutritional recommendations and obesity prevention and treatment.

Phomoxanthone A, Compound of Endophytic Fungi Paecilomyces sp. and Its Potential Antimicrobial and Antiparasitic.

The present work reports the isolation and biological evaluation of three dimeric xanthones from Paecilomyces sp. EJC01.1 isolated as endophytic from Schnella splendens, a typical plant of the Amazon. The compounds phomoxanthone A (1), phomoxanthone B (2) and dicerandrol B (3) were isolated by chromatographic procedures and identified by spectroscopic methods of 1D and 2D NMR and MS. The extracts and compound 1 showed antimicrobial activities against Bacillus subtilis, Escherichia coli, Staphylococcus aureus, Salmonella typhimurium and Pseudomonas aeruginosa. The compound phomoxanthone A (1) showed greater inhibitory activity against B. subtilis (MIC of 7.81 µg mL-1); in addition, it also pronounced inhibitory effect against promastigote forms of Leishmania amazonensis (IC50 of 16.38 ± 1.079 µg mL-1) and epimastigote forms Trypanosoma cruzi (IC50 of 28.61 ± 1.071 µg mL-1). To provide more information about the antibacterial activity of compound 1, an unprecedented molecular docking study was performed using S-ribosyl-homocysteine lyase (LuxS) (PDB ID 2FQO), which showed a possible interaction of phomoxanthone A with two of the residues (His58 and Cys126) that are fundamental for the catalysis mechanism in B. subtilis, which may be associated with the higher activity, when compared to other bacteria, observed in experimental studies. Additionally, quantum studies (DFT) were performed, for which a low gap value (5.982 eV) was observed, which corroborates the reactivity of phomoxanthone A. Thus, phomoxanthone A can be a good agent against pathogenic bacteria.

Monomethylsulochrin isolated from biomass extract of Aspergillus sp. against Leishmania amazonensis: In vitro biological evaluation and molecular docking.

Leishmaniasis represents a serious world health problem, with 1 billion people being exposed to infection and a broad spectrum of clinical manifestations with a potentially fatal outcome. Based on the limitations observed in the treatment of leishmaniasis, such as high cost, significant adverse effects, and the potential for drug resistance, the aim of the present study was to evaluate the leishmanicidal activity of the compounds pseurotin A and monomethylsulochrin isolated from the biomass extract of Aspergillus sp. The chromatographic profiles of the extract were determined by high-performance liquid chromatography coupled with a diode-array UV-Vis detector (HPLC-DAD-UV), and the molecular identification of the pseurotin A and monomethylsulochrin were carried out by electrospray ionization mass spectrometry in tandem (LC-ESI-MS-MS) and nuclear magnetic resonance (NMR). Antileishmanial activity was assayed against promastigote and intracellular amastigote of Leishmania amazonensis. As a control, cytotoxicity assays were performed in non-infected BALB/c peritoneal macrophages. Ultrastructural alterations in parasites were evaluated by transmission electron microscopy. Changes in mitochondrial membrane potential were determined by flow cytometry. Only monomethylsulochrin inhibited the promastigote growth (IC50 18.04 ± 1.11 µM), with cytotoxicity to peritoneal macrophages (CC50 5.09 91.63 ± 1.28 µM). Activity against intracellular amastigote forms (IC50 5.09 ± 1.06 µM) revealed an increase in antileishmanial activity when compared with promastigotes. In addition to a statistically significant reduction in the evaluated infection parameters, monomethylsulochrin altered the ultrastructure of the promastigote forms with atypical vacuoles, electron-dense corpuscles in the cytoplasm, changes at the mitochondria outer membrane and abnormal disposition around the kinetoplast. It was showed that monomethylsulochrin leads to a decrease in the mitochondrial membrane potential (25.9%, p = 0.0286). Molecular modeling studies revealed that monomethylsulochrin can act as inhibitor of sterol 14-alpha-demethylase (CYP51), a therapeutic target for human trypanosomiasis and leishmaniasis. Assessed for its drug likeness, monomethylsulochrin follows the Lipinski Rule of five and Ghose, Veber, Egan, and Muegge criteria. Furthermore, monomethylsulochrin can be used as a reference in the development of novel and therapeutically useful antileishmanial agents.

Relationship between quadriceps thickness and 60-second sit-to-stand test in patients with chronic kidney disease / Relação entre espessura do quadríceps e o teste sit-to-stand de 60 segundos em pacientes com doença renal crônica

Abstract Background: This study aimed to evaluate the relationship between quadriceps muscle thickness and functional performance on the 60s sit-to-stand test (60s-STS), the six-minute walk test (6MWT), and handgrip strength in non-dialytic stage 4 and 5 chronic kidney disease (CKD) patients. Methods: This was a cross-sectional study that evaluated 40 CKD patients aged between 30-70 years. Participants were submitted to an assessment that included quadriceps muscle thickness evaluated by a portable ultrasound. Functional performance tests included the 60s-STS, distance walked in the 6MWT, and handgrip strength. Also, body composition evaluated using electrical bioimpedance analysis and physical activity level through the short version of International Physical Activity were measured. Multiple linear regression was used to investigate the relationship between the quadriceps thickness and functional performance. Results: Quadriceps muscle thickness was correlated to 60s-STS (R2 = 43.6%; 95% CI = 0.022 - 0.665; β = 0.34; p = 0.037). Also, a moderate correlation between this muscle thickness and appendicular skeletal muscle (ALM) was found in CKD patients (r = 0.603, p <0.001). No relationship was found between quadriceps muscle thickness with the 6MWT and handgrip strength. Conclusion: Quadriceps muscle thickness is associated to 60s-STS, thus our results demonstrate the repercussions of the disease on the musculoskeletal system.

Resumo Antecedentes: Este estudo teve como objetivo avaliar a relação entre espessura muscular do quadríceps e desempenho funcional no teste sit-to-stand de 60s (STS-60s), no teste de caminhada de seis minutos (TC6M), e na força de preensão manual em pacientes não dialíticos com doença renal crônica (DRC) estágios 4 e 5. Métodos: Este foi um estudo transversal que avaliou 40 pacientes com DRC com idades entre 30-70 anos. Os participantes foram submetidos a uma avaliação que incluiu a espessura muscular do quadríceps avaliada por um ultrassom portátil. Os testes de desempenho funcional incluíram o STS-60s, a distância percorrida no TC6M e a força de preensão manual. Além disso, foram medidos a composição corporal, avaliada usando a análise de bioimpedância elétrica e o nível de atividade física por meio da versão curta do International Physical Activity. A regressão linear múltipla foi usada para investigar a relação entre a espessura do quadríceps e o desempenho funcional. Resultados: A espessura muscular do quadríceps foi correlacionada com o STS-60s (R2 = 43,6%; IC 95% = 0,022 - 0,665; β = 0,34; p = 0,037). Também foi encontrada uma correlação moderada entre esta espessura muscular e a massa muscular esquelética apendicular (MEA) em pacientes com DRC. (r = 0,603, p <0,001). Nenhuma relação foi encontrada entre a espessura muscular do quadríceps com o TC6M e a força de preensão manual. Conclusão: A espessura muscular do quadríceps está associada ao STS-60s, assim nossos resultados demonstram as repercussões da doença sobre o sistema músculo-esquelético.