Isotemporal substitution analysis of time between sedentary behavior, and physical activity on sleep quality in younger adults: a multicenter study.

OBJECTIVE: To evaluate the effects of replacing time spent in sedentary behavior (SB) with moderate to vigorous physical activity on sleep quality in young adults. METHODS: Multicenter cross-sectional study, carried out with students enrolled in undergraduate courses at universities in Brazil. Sleep quality was assessed using a question of the World Health Organization Quality of Life (WHOQOL-brief) and classified as good or poor sleep quality. SB was evaluated by self-reported total sitting time, and the level of leisure-time PA was classified according to the intensity of moderate-intensity physical activity (MPA) and vigorous-intensity physical activity (VPA), which were assessed using a self-reported questionnaire. An isotemporal replacement logistic model was used to evaluate the effects of different SB, MPA, and VPA sessions on sleep quality. RESULTS: A total of 8,059 study participants were evaluated, the majority had poor sleep quality (64.79%), were physically inactive (48.28%, defined as practicing < 150 min of MPA or < 75 min of VPA per week), and spent ≥ 9 h/day in SB (55.08%). The multivariate model showed an association between non-adherence to wake-based movement guidelines and poor sleep quality, where those with one altered behavior were 43% more likely to have poor sleep quality (OR:1.43;95%CI:1.27 to 1.60), while individuals with two altered behaviors were 97% more likely (OR:1.97;95%CI:1.73 to 2.24). In the isotemporal analysis, replacing MPA and VPA with equivalent time in SB increased the odds of poor sleep at all times assessed, with peaks of 56% for MPA and 68% for VPA. CONCLUSION: The results of the present study indicate that replacing SB with the same amount of MPA or VPA may reduce poor sleep quality.

Mindful eating questionnaire: Validation and reliability in Brazilian adults with type 2 diabetes mellitus.

OBJECTIVE: The objective was to evaluate the psychometric properties of the Mindful Eating Questionnaire (MEQ) in Brazilian subjects with type 2 diabetes mellitus (T2DM) and validate a Brazilian version of the MEQ for adults with T2DM (MEQ-DM). METHODOLOGY: Baseline data from the multicentre Nutritional Strategy for Glycaemic Control in Patients with Type 2 Diabetes Mellitus (NUGLIC) trial were used. Construct validity was assessed using exploratory factor analysis (EFA). The root mean square error of approximation (RMSEA), comparative fit index (CFI) and Tucker‒Lewis index (TLI) fit indices indicated the adequacy of the model. The reliability of the questionnaire was evaluated considering the different factor loadings. Criterion validity was tested by correlating the MEQ-DM with sociodemographic variables, body mass index (BMI) and physical activity levels. RESULTS: A total of 370 participants were included, who were mostly female (60.8 %) and had a median age of 61 (54-67) years. The EFA results supported the two-factor structure of the 25-item MEQ-DM: disinhibition and awareness. The results of the fit indices (RMSEA = 0.04; CFI = 0.95 and TLI = 0.94) and composite reliability (disinhibition = 0.84 and awareness = 0.81) were consistent. The criterion validity analysis indicated a significant association between MEQ-DM scores and age, sex, civil status, education level, BMI and physical activity (p < 0.05). CONCLUSION: When explored with Brazilian adults with T2DM, the MEQ-DM presented a factorial model with two dimensions: disinhibition and awareness. This model must be confirmed in future studies with Brazilians with T2DM.

Effects of acephate and glyphosate-based agrochemicals on the survival and flight of Plebeia lucii Moure, 2004 (Apidae: Meliponini).

The conservation of terrestrial ecosystems depends largely on the preservation of pollinators, mainly bees. Stingless bees are among the main pollinators of native plants and crops in tropical regions, where they can be exposed to agrochemicals while foraging on contaminated flowers. In the present study, we investigated the effects on stingless bees of both a commonly used insecticide and herbicide in Brazil. Plebeia lucii Moure, 2004 (Apidae: Meliponini) foragers were orally chronically exposed to food contaminated with different concentrations of commercial formulations of the insecticide acephate or the herbicide glyphosate. Bee mortality increased with increasing agrochemical concentrations. Depending on its concentration, the acephate-based formulation reduced the lifespan and impaired the flight ability of bees. The glyphosate-based formulation was toxic only under unrealistic concentrations. Our results demonstrate that realistic concentrations of acephate-based insecticides harm the survival and alter the mobility of stingless bees. The ingestion of glyphosate-based herbicides was safe for forager bees under realistic concentrations.

Predicted estimates of resting energy expenditure have limited clinical utility in patients with cirrhosis.

BACKGROUND & AIMS: Malnutrition is associated with adverse clinical outcomes in patients with cirrhosis. Accurate assessment of energy requirements is needed to optimize dietary intake. Resting energy expenditure (REE), the major component of total energy expenditure, can be measured using indirect calorimetry (mREE) or estimated using prediction equations (pREE). This study assessed the usefulness of predicted estimates of REE in this patient population. METHODS: Individual mREE data were available for 900 patients with cirrhosis (mean [±1 SD] age 55.7±11.6 years-old; 70% men; 52% south-east Asian) and 282 healthy controls (mean age 36.0±12.8 years-old; 52% men; 18% south-east Asian). Metabolic status was classified using thresholds based on the mean ± 1 SD of the mREE in the healthy controls. Comparisons were made between mREE and pREE estimates obtained using the Harris-Benedict, Mifflin, Schofield and Henry equations. Stepwise regression was used to build 3 new prediction models which included sex, ethnicity, body composition measures, and model for end-stage liver disease scores. RESULTS: The mean mREE was significantly higher in patients than controls when referenced to dry body weight (22.4±3.8 cf. 20.8±2.6 kcal/kg/24 hr; p <0.001); there were no significant sex differences. The mean mREE was significantly higher in Caucasian than Asian patients (23.1±4.4 cf. 21.7±2.9 kcal/kg/24 hr; p <0.001). Overall, 37.1% of Caucasian and 25.3% of Asian patients were classified as hypermetabolic. The differences between mREE and pREE were both statistically and clinically relevant; in the total patient population, pREE estimates ranged from 501 kcal/24 hr less to 548 kcal/24 hr more than the mREE. Newly derived prediction equations provided better estimates of mREE but still had limited clinical utility. CONCLUSIONS: Prediction equations do not provide useful estimates of REE in patients with cirrhosis. REE should be directly measured. LAY SUMMARY: People with cirrhosis are often malnourished and this has a detrimental effect on outcome. Provision of an adequate diet is very important and is best achieved by measuring daily energy requirements and adjusting dietary intake accordingly. Prediction equations, which use information on age, sex, weight, and height can be used to estimate energy requirements; however, the results they provide are not accurate enough for clinical use, particularly as they vary according to sex and ethnicity.

Lifestyle and eating habits before and during COVID-19 quarantine in Brazil.

OBJECTIVE: To assess changes in daily habits, food choices and lifestyle of adult Brazilians before and during the COVID-19 pandemic. DESIGN: This observational study was carried out with Brazilian adults through an online questionnaire 5 months after the social distance measures implementation. The McNemar, McNemar­Bowker and Wilcoxon tests were used to investigate differences before and during the COVID pandemic period, adopting the statistical significance of P < 0·05. SETTING: Brazil. PARTICIPANTS: Totally, 1368 volunteers aged 18+ years. RESULTS: The volunteers reported a lower frequency of breakfast, morning and lunch snacks (P < 0·05) and a higher frequency of evening snacks and other meal categories during the pandemic period (P < 0·05). The results showed an increase in the consumption of bakery products, instant meals and fast food, while the consumption of vegetables and fruits decreased (P < 0·005). There was a significant increase in the frequency of consumption of alcoholic beverages (P < 0·001), but a reduction in the dose (P < 0·001), increased frequency of smoking (P = 0·007), an increase in sleep and screen time in hours and decrease in physical activity (P < 0·001). CONCLUSIONS: It was possible to observe an increase in screen time, hours of sleep, smoking and drinking frequency. On the other hand, there was a reduction in the dose of alcoholic beverages but also in the practice of physical activity. Eating habits also changed, reducing the performance of daytime meals and increasing the performance of nighttime meals. The frequency of consumption of instant meals and fast food has increased, while consumption of fruits and vegetables has decreased.

Role of miRNAs in tumor and endothelial cell interactions during tumor progression.

Cancer is a multistep disease based on crucial interactions between tumor cells and the microenvironment (extracellular matrix and stroma/immune cells). In fact, during dissemination, tumor cells have to escape from the primary tumor mass, cross the basal membrane, interact with endothelial cells to enter blood vessels (intravasation), survive in the bloodstream, get in contact with endothelial cells again to exit the bloodstream (extravasation) and seed in distant organs. Interactions between tumor and stroma cells are strongly coordinated by microRNAs (miRNAs), small non-coding RNAs able to silence protein coding genes by binding to specific recognition sites, mostly located at the 3' UTR of mature mRNAs. Relevantly, miRNA expression is often altered (overexpression or downregulation) in tumor cells and influenced by stroma cells. At the same time, miRNAs are abundant and essential in stroma cells during tumor cell dissemination and their expression is influenced by tumor cells. In fact, for instance, conditional ablation of Dicer in the endothelium of tumor bearing-mice leads to reduced tumor growth and microvessel density. In this review, we specifically focus on the role of miRNAs in endothelial cells regarding their positive or negative intervention on tumor angiogenesis or lymphoangiogenesis or when tumor cells detach from the tumor mass and intravasate or extravasate in/out of the blood vessels. Examples of pro-angiogenic miRNAs are miR-9 or miR-494, often overexpressed in tumors, which accumulate in tumor cell microvescicles and, therefore, get transferred to endothelial cells where they induce migration and angiogenesis. Differently, miR-200 and miR-128 are often downregulated in tumors and inhibit angiogenesis and lymphoangiogenesis. Instead, miR-126 controls intravasation while miR-146a, miR-214, miR-148b govern extravasation, in a positive or negative manner. Finally, at the end, we summarize opportunities for therapeutic interventions based on miRNAs acting on endothelial cells.

Age- and Sex-Specific Plasticity in Dopamine Transporter Function Revealed by Food Restriction and Exercise in a Rat Activity-Based Anorexia Paradigm.

Eating disorders such as anorexia typically emerge during adolescence, are characterized by engagement in compulsive and detrimental behaviors, and are often comorbid with neuropsychiatric disorders and drug abuse. No effective treatments exist. Moreover, anorexia lacks adolescent animal models, contributing to a poor understanding of underlying age-specific neurophysiological disruptions. To evaluate the contribution of dopaminergic signaling to the emergence of anorexia-related behaviors during the vulnerable adolescent period, we applied an established adult activity-based anorexia (ABA) paradigm (food restriction plus unlimited exercise access for 4 to 5 days) to adult and adolescent rats of both sexes. At the end of the paradigm, measures of plasma volume, blood hormone levels, dopamine transporter (DAT) expression and function, acute cocaine-induced locomotion, and brain water weight were taken. Adolescents were dramatically more affected by the ABA paradigm than adults in all measures. In vivo chronoamperometry and cocaine locomotor responses revealed sex-specific changes in adolescent DAT function after ABA that were independent of DAT expression differences. Hematocrit, insulin, ghrelin, and corticosterone levels did not resemble shifts typically observed in patients with anorexia, though decreases in leptin levels aligned with human reports. These findings are the first to suggest that food restriction in conjunction with excessive exercise sex-dependently and age-specifically modulate DAT functional plasticity during adolescence. The adolescent vulnerability to this relatively short manipulation, combined with blood measures, evidence need for an optimized age-appropriate ABA paradigm with greater face and predictive validity for the study of the pathophysiology and treatment of anorexia. SIGNIFICANCE STATEMENT: Adolescent rats exhibit a distinctive, sex-specific plasticity in dopamine transporter function and cocaine response after food restriction and exercise access; this plasticity is both absent in adults and not attributable to changes in dopamine transporter expression levels. These novel findings may help explain sex differences in vulnerability to eating disorders and drug abuse during adolescence.

Inhibition of Epithelial-Mesenchymal Transition and Metastasis by Combined TGFbeta Knockdown and Metformin Treatment in a Canine Mammary Cancer Xenograft Model.

Epithelial mesenchymal transition (EMT) is a process by which epithelial cells acquire mesenchymal properties, generating metastases. Transforming growth factor beta (TGF-ß) is associated with this malignancy by having the ability to induce EMT. Metformin, has been shown to inhibit EMT in breast cancer cells. Based on this evidence we hypothesize that treatment with metformin and the silencing of TGF-ß, inhibits the EMT in cancer cells. Canine metastatic mammary tumor cell line CF41 was stably transduced with a shRNA-lentivirus, reducing expression level of TGF-ß1. This was combined with metformin treatment, to look at effects on cell migration and the expression of EMT markers. For in vivo study, unmodified or TGF-ß1sh cells were injected in the inguinal region of nude athymic female mice followed by metformin treatment. The mice's lungs were collected and metastatic nodules were subsequently assessed for EMT markers expression. The migration rate was lower in TGF-ß1sh cells and when combined with metformin treatment. Metformin treatment reduced N-cadherin and increased E-cadherin expression in both CF41 and TGF-ß1sh cells. Was demonstrated that metformin treatment reduced the number of lung metastases in animals bearing TGF-ß1sh tumors. This paralleled a decreased N-cadherin and vimentin expression, and increased E-cadherin and claudin-7 expression in lung metastases. This study confirms the benefits of TGF-ß1 silencing in addition to metformin as potential therapeutic agents for breast cancer patients, by blocking EMT process. To the best of our knowledge, we are the first to report metformin treatment in cells with TGF-ß1 silencing and their effect on EMT.

Melatonin decreases breast cancer metastasis by modulating Rho-associated kinase protein-1 expression.

The occurrence of metastasis, an important breast cancer prognostic factor, depends on cell migration/invasion mechanisms, which can be controlled by regulatory and effector molecules such as Rho-associated kinase protein (ROCK-1). Increased expression of this protein promotes tumor growth and metastasis, which can be restricted by ROCK-1 inhibitors. Melatonin has shown oncostatic, antimetastatic, and anti-angiogenic effects and can modulate ROCK-1 expression. Metastatic and nonmetastatic breast cancer cell lines were treated with melatonin as well as with specific ROCK-1 inhibitor (Y27632). Cell viability, cell migration/invasion, and ROCK-1 gene expression and protein expression were determined in vitro. In vivo lung metastasis study was performed using female athymic nude mice treated with either melatonin or Y27832 for 2 and 5 wk. The metastases were evaluated by X-ray computed tomography and single photon emission computed tomography (SPECT) and by immunohistochemistry for ROCK-1 and cytokeratin proteins. Melatonin and Y27632 treatments reduced cell viability and invasion/migration of both cell lines and decreased ROCK-1 gene expression in metastatic cells and protein expression in nonmetastatic cell line. The numbers of 'hot' spots (lung metastasis) identified by SPECT images were significantly lower in treated groups. ROCK-1 protein expression also was decreased in metastatic foci of treated groups. Melatonin has shown to be effective in controlling metastatic breast cancer in vitro and in vivo, not only via inhibition of the proliferation of tumor cells but also through direct antagonism of metastatic mechanism of cells rendered by ROCK-1 inhibition. When Y27632 was used, the effects were similar to those found with melatonin treatment.

Prospective evaluation of metabolic syndrome and its components among long-term liver recipients.

BACKGROUND & AIMS: Survival after liver transplantation (LTx) has increased. Metabolic syndrome (MS) is widely reported in patients in the early years after LTx; few studies have researched this condition in relatively long-term liver recipients. To describe, prospectively, the prevalence of MS, its components and its associated factors in relatively long-term liver recipients. METHODS: A total of 117 patients were evaluated in 2008 (median of 3 years after LTx, range 0-13 years) and in 2012 (median of 7 years after LTx, range 3-17 years) for the presence of MS [using modified NCEP Adult Treatment Panel III and International Diabetes Federation (IDF) criteria]; its components; and its associated factors, including demographic, socioeconomic, lifestyle, clinical, body composition (measured using bioelectric impedance) and dietetic factors. RESULTS: MS increased over the years (IDF, 43.1-53.3%, P=0.12; and NCEP, 34.3-44.8%, P=0.03). Blood glucose increased over the years (98.8±24.7 to 109.2±33.3 mg/dl, P<0.01), which resulted in an increased prevalence of glucose intolerance (34.2-48.6%, P<0.01). Waist circumference (93.3±14.3 to 99.4±14.9 cm, P<0.01) and body fat (30.3±8.9 to 31.8±10.3%, P=0.03) also increased. The MS associated factors (P<0.05) were age [Odds ratio (OR) 1.05, confidence interval (CI) 1.02-1.11], family history of diabetes (OR 3.38, CI 1.19-9.61), body mass index (BMI) prior to liver disease (OR 1.39, CI 1.19-1.63) and body fat (OR 1.09, CI 1.03-1.14). The MS components were associated (P<0.05) with greater age, family history of diabetes, current and previous BMI, body fat, current corticosteroid use, lack of exercise and greater carbohydrate and fat intakes. CONCLUSION: MS prevalence increased over the years after LTx because of the increases in waist circumference and blood glucose. MS and its components are associated with modifiable factors, such as greater BMI, body fat and carbohydrate and fat intake.

Climatic fluctuations alter the preference of stingless bees (Apidae, Meliponini) towards food contaminated with acephate and glyphosate.

The global decline of pollinators has become a major concern for the scientific community, policymakers, and the general public. Among the main drivers of diminishing bee populations is the widespread use of agrochemicals. To gain a comprehensive understanding of the foraging dynamics of bees at agrochemical-contaminated areas, it is essential to consider both environmental conditions and the specific foraging ecology of bee species. For the first time, we conducted a semi-field study to investigate whether stingless bees exhibit a preference for food contaminated with agrochemicals compared to non- contaminated food, under natural weather conditions. Colonies of Plebeia lucii Moure, 2004 were placed in a greenhouse and subjected to a preference test, where bees were given the freedom to choose between contaminated or non-contaminated food sources following a preliminary training period. Within the greenhouse, we placed feeders containing realistic concentrations of an insecticide (acephate: 2 mg a.i./L), a herbicide (glyphosate: 31.3 mg a.i./L), or a mixture of both, alongside non-contaminated food. Environmental variables (temperature, humidity, and light intensity) were monitored throughout the experiment. At higher temperatures, the foragers preferred food containing the mixture of both agrochemicals or uncontaminated food over the other treatments. At lower temperatures, by contrast, the bees preferred food laced with a single agrochemical (acephate or glyphosate) over uncontaminated food or the agrochemical mixture. Our findings indicate that agrochemical residues in nectar pose a significant threat to P. lucii colonies, as foragers do not actively avoid contaminated food, despite the detrimental effects of acephate and glyphosate on bees. Furthermore, we demonstrate that even minor, natural fluctuations in environmental conditions can alter the colony exposure risk. Despite the interplay between temperature and bees' preference for contaminated food, foragers consistently collected contaminated food containing both agrochemicals, whether isolated or in combination, throughout the whole experiment.

A pilot study of mitochondrial genomic ancestry in admixed Brazilian patients with type 1 diabetes.

Interactions between multiple genes and environmental factors could be related to the pathogenesis of type 1 diabetes (T1D). The Brazilian population results from different historical miscegenation events, resulting in a highly diverse genetic pool. This study aimed to analyze the mtDNA of patients with T1D and to investigate whether there is a relationship between maternal ancestry, self-reported color and the presence of T1D. The mtDNA control region of 204 patients with T1D residing in three geographic regions of Brazil was sequenced following the International Society for Forensic Genetics (ISFG) recommendations. We obtained a frequency of Native American matrilineal origin (43.6%), African origin (38.2%), and European origin (18.1%). For self-declared color, 42.6% of the patients with diabetes reported that they were White, 50.9% were Brown, and 5.4% were Black. Finally, when we compared the self-declaration data with maternal ancestral origin, we found that for the self-declared White group, there was a greater percentage of haplogroups of Native American origin (50.6%); for the self-declared Black group, there was a greater percentage of African haplogroups (90.9%); and for the Brown group, there was a similar percentage of Native American and African haplogroups (42.3% and 45.2%, respectively). The Brazilian population with diabetic has a maternal heritage of more than 80% Native American and African origin, corroborating the country's colonization history.

Prevalence of autoimmune diseases in an admixed population of patients with type 1 diabetes: a multicenter study in Brazil.

BACKGROUND/OBJECTIVES: The primary aim of this study was to evaluate the prevalence of autoimmune diseases (AIDs) and its associated factors in an admixed Brazilian population of patients with type 1 diabetes (T1D). The secondary one was to determine the relationship between AIDs and the occurrence of diabetes-related chronic complications (DRCC). METHODS: This cross-sectional, nationwide survey was conducted in 13 public clinics in 11 Brazilian cities. Overall, 1,760 patients were included; 967 females (55.9%), 932 (54%) Caucasians, aged 29.9 ± 11.9 years, age at diagnosis 14.8 ± 8.9 years, diabetes duration 15.5 ± 9.3 years and 12.2 ± 3.8 years of school attendance. AIDs were retrieved from medical records or self-report and stratified as follows: absence of AIDs, only autoimmune thyroid disease (AITD), and other AIDs including the combination with AITD (hyper or hypothyroidism). RESULTS: The prevalence of AIDs was 19.5% being AITDs (16.1%), the most frequently found. A higher prevalence of hypertension, dyslipidemia and overweight or obesity was found in patients who had exclusively AITDs. A higher prevalence of diabetic retinopathy (DR) was observed in patients with AITDs and patients with other AIDs in combination with AITDs. Chronic kidney disease (CKD) was more prevalent in patients with only AITDs. Lower levels of HbA1C, were observed in patients with isolated AITDs or with other AIDs, regardless of the presence of AITD. Hierarchical multivariate analysis, showed that AIDs were associated with female gender, older age, and longer diabetes duration, self-reported color-race (White and Brown), geographic region (Brazilian North/Northeast region) and higher anti-TPO levels (≥ 35 UI/ml). CONCLUSIONS: In conclusion, Brazilian patients with T1D, belonging to a highly ethnically admixed population, had an important prevalence of AIDs, mostly AITDs, that was associated with female gender, self-reported color-race, older age and longer diabetes duration. Moreover, these patients also had a higher prevalence of DRCC. Even though we highlight the importance of investigating the presence of AIDs at diagnosis and at regular intervals, it is unclear whether screening and early detection of additional AIDs may improve the clinical outcomes in individuals with T1D. Future prospective studies are necessary to establish the interplay between T1D, AIDs and DRCC.

Sociodemographic, economic, and academic factors linked with resilience in university students during covid-19 pandemic: a Brazilian cross-sectional study.

BACKGROUND: Resilience is a crucial factor in students' mental health, playing an important role in their successful adaptation to the academic environment. However, there is a lack of understanding about resilience and its associated factors in students from different undergraduate courses. This study aimed to describe the resilience profile of undergraduate students from various courses in Brazil and identify sociodemographic, economic, and academic factors associated with resilience. METHODS: This study has data from a cross-sectional multicenter study involving undergraduate students from eight Federal Institutions of Higher Education in Minas Gerais, Brazil. The dependent variable was resilience, measured using the Connor-Davidson Resilience Scale (CD-RISC) 10-item version, with sociodemographic, economic, and academic factors considered independent variables. Data was collected virtually via a self-administered questionnaire between October 2021 and February 2022 (during the covid-19 pandemic). Independent samples t-tests and ANOVAs were conducted to compare resilience scores between independent variables, and Tukey's post-hoc test was performed when necessary. Multiple linear regression was performed to create three models. RESULTS: 8,650 undergraduate students were included in this study. The average score on the resilience scale was 19.86 ± 8.15, with a normal distribution. The respondents ranged from 18 to 71 years old, averaging 23.9 ± 6.33. Being female, not having a religious belief, having low per capita family income, having had a decrease in the family income, not being heterosexual, or having the head of the family with a low education level were the main factors associated, individually, with low resilience scores in the sociodemographic and economic multiple linear regression model constructed. Being from linguistics, letters and arts courses, being enrolled in fewer subjects, or being from UFMG were the main factors associated, individually, with low resilience scores in the academic multiple linear regression model constructed. CONCLUSIONS: The study's findings revealed that sociodemographic, economic, and academic variables were significantly associated with resilience scores in undergraduates from Minas Gerais during the covid-19 pandemic. These findings can help universities develop target strategies to promote students' resilience and reduce the risk of poor mental health among this population.

Mid-arm muscle circumference cutoff points in patients with cirrhosis: Low muscle mass related to malnutrition predicts mortality.

OBJECTIVES: Muscle loss is one of the phenotypic criteria of malnutrition, is highly prevalent in patients with cirrhosis, and is associated with adverse outcomes. Mid-arm muscle circumference (MAMC) estimates the skeletal muscle mass and is especially helpful in cases of fluid overload. This study aimed to propose MAMC cutoff points for patients with cirrhosis and demonstrate its association with 1-year mortality. METHODS: This is an analysis of cohort databases from five reference centers in Brazil that included inpatients and outpatients with cirrhosis aged ≥18 y. The nutritional variables obtained were the MAMC (n = 1075) and the subjective global assessment (n = 629). We established the MAMC cutoff points stratified by sex based on the subjective global assessment as a reference standard for malnutrition diagnosis, considering the sensitivity, specificity, and Youden index. An adjusted Cox regression model was used to test the association of MAMC cutoff points and 1-year mortality. RESULTS: We included 1075 patients with cirrhosis, with a mean age of 54.8 ± 11.3 y; 70.4% (n = 757) male. Most patients had alcoholic cirrhosis (47.1%, n = 506) and were classified as Child-Pugh B (44.7%, n = 480). The MAMC cutoff points for moderate and severe depletion were ≤21.5 cm and ≤24.2 cm; ≤20.9 cm and ≤22.9 cm for women and men, respectively. According to these cutoff points, 13.8% (n = 148) and 35.1% (n = 377) of the patients had moderate or severe MAMC depletion, respectively. The 1-year mortality rate was 17.3% (n = 186). In the multivariate analysis adjusted for sex, age, MELD-Na, and Child-Pugh scores, a severe depletion in MAMC was an independent increased risk factor for 1-year mortality (HR: 1.71, 95% CI: 1.24-2.35, P < 0.001). Each increase of 1 cm in MAMC values was associated with an 11% reduction in 1-year mortality risk (HR: 0.89, 95% CI: 0.85-0.94, P < 0.001). CONCLUSIONS: Low MAMC classified according to the new cutoff points predicts mortality risk in patients with cirrhosis and could be used in clinical practice.

The role of BmoR, a MarR Family Regulator, in the survival of Bacteroides fragilis during oxidative stress.

The intestinal opportunistic pathogen Bacteroides fragilis is among the most aerotolerant species of strict anaerobic bacteria and survives exposure to atmospheric oxygen for up to 72h. Under these circumstances, a strong oxygen stress response (OSR) mechanism is activated and the expression of as much as 45% of B. fragilis genes is altered. One of the most important regulators of this response is the product of the oxyR gene, but other regulation systems are in place during the OSR. The MarR family of transcriptional regulators has been shown to control several physiological events in bacteria, including response to stress conditions. In B. fragilis, at least three homologs of MarR regulators are present, one of which, bmoR, is upregulated during oxidative stress independently of oxyR. In this study, we demonstrate that the inactivation of the bmoR gene in B. fragilis diminishes its ability to withstand oxidative stress caused either by exposure to atmospheric oxygen or hydrogen peroxide. Recovery of growth rate on pre-oxidized media under anaerobiosis is slower than that observed in parental strain. Addition of hydrogen peroxide has a similar effect on the growth rate. Complementation of the mutant strain partially recovered the oxygen resistance phenotype, but the overexpression of the gene in the parental strain was also deleterious to a lesser extent. Our results indicate that BmoR has a role in the OSR in B. fragilis, particularly in the initial stages of oxygen exposure.

The Mini Nutritional Assessment-Short Form is more effective in predicting clinical outcomes among hospitalised patients with overweight than the Nutritional Risk Screening-2002.

Understanding of the association between nutritional risk and clinical outcomes in hospitalised patients with overweight is still at an early stage. Given the lack of specific tools for the patient with overweight, the objective of this study was to compare two of the main general screening instruments for assessing nutritional risk in predicting clinical outcomes in a population of hospitalised patients with overweight. A retrospective study was carried out in a medium-sized hospital in Brazil, with patients ≥20 years old admitted between July 2017 and December 2019. Patients who were overweight and had records of Nutritional Risk Screening-2002 (NRS-2002) and Mini-Nutritional Assessment-Short Form (MNA-SF) in their medical files were included in the study. Clinical outcomes data (longer length of stay, readmission during the study period and mortality before the end of study or during hospitalisation) were obtained. The Kappa coefficient assessed agreement between both tools, and their performance for predicting outcomes was analysed using characteristic receiver operating curves (ROC). Data were collected from 643 patients. The prevalence of nutritional risk was 17.7% and 36.1% according to the NRS-2002 and MNA-SF (k = 0.390; p < 0.001), respectively. According to both tools, all clinical outcomes were significantly more common among individuals at nutritional risk (p < 0.05). Only the MNA-SF showed a significant percentage of predictions for readmission (57.2%) and death during hospitalisation (65.7%). For mortality until the end of the study, the area under the ROC curve was similar for MNA-SF (60.5%) and NRS-2002 (60.7%; p = 0.057). The MNA-SF detected a greater proportion of nutritional risk among hospitalised patients with overweight and better predicted all clinical outcomes compared to the NRS-2002 and should be used to screen patients with overweight for nutritional risk.

Global Leadership Initiative on Malnutrition criteria for the diagnosis of malnutrition and prediction of mortality in patients awaiting liver transplant: A validation study.

OBJECTIVES: The Global Leadership Initiative on Malnutrition (GLIM) is a framework aiming to standardize malnutrition diagnosis. However, it still needs to be validated, in particular for patients with chronic liver disease. This study aimed to validate the GLIM criteria in patients with liver cirrhosis awaiting liver transplant (LTx). METHODS: This was a retrospective observational study carried out with adult patients on the waiting list for LTx, consecutively evaluated between 2006 and 2021. The phenotypic criteria were unintentional weight loss, low body mass index, and reduced muscle mass (midarm muscle circumference [MAMC]). The etiologic criteria were high Model for End-Stage Liver Disease (MELD) and MELD adjusted for serum sodium (MELD-Na) scores, the Child-Pugh score, low serum albumin, and low food intake and/or assimilation. Forty-three GLIM combinations were tested. Sensitivity (SE), specificity (SP), positive and negative predictive values, and machine learning (ML) techniques were used. Survival analysis with Cox regression was carried out. RESULTS: A total of 419 patients with advanced liver cirrhosis were included (median age, 52.0 y [46-59 y]; 69.2% male; 68.8% malnourished according to the Subjective Global Assessment [SGA]). The prevalence of malnutrition by the GLIM criteria ranged from 3.1% to 58.2%, and five combinations had SE or SP >80%. The MAMC as a phenotypic criterion with MELD and MELD-Na as etiologic criteria were predictors of mortality. The MAMC and the presence of any phenotypic criteria associated with liver disease parameters and low food intake or assimilation were associated with malnutrition prediction in ML analysis. CONCLUSIONS: The MAMC and liver disease parameters were associated with malnutrition diagnosis by SGA and were also predictors of 1-y mortality in patients with liver cirrhosis awaiting LTx.

Construction and validation of simulated scenarios in the emergency care of patients with chest pain.

OBJECTIVE: To construct and validate clinical simulation scenarios for emergency care for patients with chest pain. METHODS: A methodological study carried out in two stages: construction and validity. The construction took place through the survey of evidence from national and international literature. The validity stage took place through instrument assessment by judges, according to the Content Validity Index and application of a pilot test with the target audience. Fifteen judges with expertise in simulation, teaching and/or care participated in the research, in addition to 18 nursing students, in the pilot test. RESULTS: Two scenarios of clinical simulation were constructed, and all the assessed items obtained a value above 0.80, showing evidence of validity, being considered instruments suitable for application. CONCLUSION: The research contributed to the development and validity of instruments that can be applied for teaching, assessment and training in clinical simulation in emergency care for patients with chest pain.

Acute cannabidiol treatment enhances social interaction in adult male mice.

Cannabidiol (CBD) is a non-intoxicating phytochemical from Cannabis sativa that is increasingly used to manage pain. The potential for CBD to ameliorate dimensional behavior symptoms occurring in multiple psychiatric disorders was suggested, including social interaction impairments. To test this hypothesis, adult male BTBRT+Itpr3tf/J (BTBR) mice, a model of idiopathic autism exhibiting social preference deficits and restrictive repetitive behaviors, were acutely treated with vehicle or 0.1, 1, or 10 mg/kg CBD. Social interaction preference was assessed 50 min after treatment, followed by social novelty preference at 60 min, marble burying at 75 min and social dominance at 120 min. CBD (10 mg/kg) enhanced BTBR social interaction but not social novelty preference, marble burying or dominance, with serum levels = 29 ± 11 ng/mg at 3 h post-injection. Next, acute 10 mg/kg CBD was compared to vehicle treatment in male serotonin transporter (SERT) knock-out mice, since SERT deficiency is an autism risk factor, and in their wildtype background strain controls C57BL/6J mice. CBD treatment generally enhanced social interaction preference and attenuated social novelty preference, yet neither marble burying nor dominance was affected. These findings show acute treatment with as little as 10 mg/kg purified CBD can enhance social interaction preference in male mice that are otherwise socially deficient.