Flavonoids and Triterpenoids Isolated From the Ethyl Acetate Extract of M. quadrangulata Leaves.

The new flavonoid (-)-4'-O-methylepicatechin 5-O-ß-D-glucopyranoside (1), along with four known triterpenes (2-5), a steroid (6), and a flavonoid (7) were isolated from the ethyl acetate extract of Maytenus quadrangulata leaves. The chemical structures of the isolated compounds were determined through analysis of 1D NMR (1H and 13C) spectroscopic data, in addition to 2D NMR and spectrometric (MS) data for compound 1. This is the first report of the isolation of daucosterol (6) and (-)-4'-O-methylepigallocatechin (7) from this species. Compounds 1 and 7 were evaluated against the bacteria Staphylococcus aureus and Klebsiella pneumoniae, but neither exhibited activity even at the highest concentration tested.

Oropouche virus infection induces ROS production and oxidative stress in liver and spleen of mice.

Oropouche virus (OROV) is the aetiological agent of Oropouche fever, the symptoms of which are common to most arboviruses, such as fever, headache, malaise, nausea and vomiting. More than half a million people have been infected with OROV since its isolation in 1955. Although Oropouche fever is classified as a neglected and emerging disease, to date, there are no antiviral drugs or vaccines available against the infection and little is known about its pathogenicity. Therefore, it is essential to elucidate the possible mechanisms involved in its pathogenesis. Since oxidative stress plays a pivotal role in the progression of various viral diseases, in this study, redox homeostasis in the target organs of OROV infection was evaluated using an animal model. Infected BALB/c mice exhibited reduced weight gain, splenomegaly, leukopenia, thrombocytopenia, anaemia, development of anti-OROV neutralizing antibodies, increased liver transaminases, and serum levels of pro-inflammatory cytokines tumour necrosis factor (TNF-α) and interferon-γ (IFN-γ). The OROV genome and infectious particles were detected in the liver and spleen of infected animals, with liver inflammation and an increase in the number and total area of lymphoid nodules in the spleen. In relation to redox homeostasis in the liver and spleen, infection led to an increase in reactive oxygen species (ROS) levels, increased oxidative stress biomarkers malondialdehyde (MDA) and carbonyl protein, and decreased activity of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT). Taken together, these results help elucidate some important aspects of OROV infection that may contribute to the pathogenesis of Oropouche.

Metabolic mitochondrial alterations prevail in the female rat heart 8 weeks after exercise cessation.

BACKGROUND: The consumption of high-caloric diets strongly contributes to the development of non-communicable diseases (NCDs), including cardiovascular disease, the leading cause of mortality worldwide. Exercise (along with diet intervention) is one of the primary non-pharmacological approaches to promote a healthier lifestyle and counteract the rampant prevalence of NCDs. The present study evaluated the effects of exercise cessation after a short period training on the cardiac metabolic and mitochondrial function of female rats. METHODS: Seven-week-old female Sprague-Dawley rats were fed a control or a high-fat, high-sugar (HFHS) diet and, after 7 weeks, the animals were kept on a sedentary lifestyle or submitted to endurance exercise for 3 weeks (6 days per week, 20-60 min/day). The cardiac samples were analysed 8 weeks after exercise cessation. RESULTS: The consumption of the HFHS diet triggered impaired glucose tolerance, whereas the HFHS diet and physical exercise resulted in different responses in plasma adiponectin and leptin levels. Cardiac mitochondrial respiration efficiency was decreased by the HFHS diet consumption, which led to reduced ATP and increased NAD(P)H mitochondrial levels, which remained prevented by exercise 8 weeks after cessation. Exercise training-induced cardiac adaptations in redox balance, namely increased relative expression of Nrf2 and downstream antioxidant enzymes persist after an eight-week exercise cessation period. CONCLUSIONS: Endurance exercise modulated cardiac redox balance and mitochondrial efficiency in female rats fed a HFHS diet. These findings suggest that exercise may elicit cardiac adaptations crucial for its role as a non-pharmacological intervention for individuals at risk of developing NCDs.

Untargeted-based metabolomics analysis and in vitro/in silico antiviral activity of extracts from Phyllanthus brasiliensis (Aubl.) Poir.

INTRODUCTION: This study describes the molecular profile and the potential antiviral activity of extracts from Phyllanthus brasiliensis, a plant widely found in the Brazilian Amazon. The research aims to shed light on the potential use of this species as a natural antiviral agent. METHODS: The extracts were analysed using liquid chromatography-mass spectrometry (LC-MS) system, a potent analytical technique to discover drug candidates. In the meantime, in vitro antiviral assays were performed against Mayaro, Oropouche, Chikungunya, and Zika viruses. In addition, the antiviral activity of annotated compounds was predicted by in silico methods. RESULTS: Overall, 44 compounds were annotated in this study. The results revealed that P. brasiliensis has a high content of fatty acids, flavones, flavan-3-ols, and lignans. Furthermore, in vitro assays revealed potent antiviral activity against different arboviruses, especially lignan-rich extracts against Zika virus (ZIKV), as follows: methanolic extract from bark (MEB) [effective concentration for 50% of the cells (EC50 ) = 0.80 µg/mL, selectivity index (SI) = 377.59], methanolic extract from the leaf (MEL) (EC50 = 0.84 µg/mL, SI = 297.62), and hydroalcoholic extract from the leaf (HEL) (EC50 = 1.36 µg/mL, SI = 735.29). These results were supported by interesting in silico prediction, where tuberculatin (a lignan) showed a high antiviral activity score. CONCLUSIONS: Phyllanthus brasiliensis extracts contain metabolites that could be a new kick-off point for the discovery of candidates for antiviral drug development, with lignans becoming a promising trend for further virology research.

Physical exercise positively modulates nonalcoholic steatohepatitis-related hepatic endoplasmic reticulum stress.

Obesity is a predictive factor for the development of nonalcoholic steatohepatitis (NASH). Although some of the mechanisms associated with NASH development are still elusive, its pathogenesis relies on a complex broad spectrum of (interconnected) metabolic-based disorders. We analyzed the effects of voluntary physical activity (VPA) and endurance training (ET), as preventive and therapeutic nonpharmacological strategies, respectively, against hepatic endoplasmic reticulum (ER) stress, ER-related proapoptotic signaling, and oxidative stress in an animal model of high-fat diet (HFD)-induced NASH. Adult male Sprague-Dawley rats were divided into standard control liquid diet (SCLD) or HFD groups, with sedentary, VPA, and ET subgroups in both (sedentary animals with access to SCLD [SS], voluntarily physically active animals with access to SCLD [SV], and endurance-trained animals with access to SCLD [ST] in the former and sedentary animals with access to liquid HFD [HS], voluntarily physically active animals with access to liquid HFD [HV], and endurance-trained animals with access to liquid HFD [HT] in the latter, respectively). Hepatic ER stress and ER-related proapoptotic signaling were evaluated by Western blot and reverse transcriptase-polymerase chain reaction; redox status was evaluated through quantification of lipid peroxidation, protein carbonyls groups, and glutathione levels as well as antioxidant enzymes activity. In SCLD-treated animals, VPA significantly decreased eukaryotic initiation factor-2 alpha (eIF2α). In HFD-treated animals, VPA significantly decreased eIF2α and phospho-inositol requiring enzyme-1 alpha (IRE1α) but ET significantly decreased eIF2α and significantly increased both spliced X-box binding protein 1 (sXBP1) and unspliced X-box binding protein 1; a significant increase of phosphorylated-eIF2α (p-eIF2α) to eIF2α ratio occurred in ET versus VPA. HS compared to SS disclosed a significant increase of total and reduced glutathione, HV compared to SV a significant increase of oxidized glutathione, HT compared to ST a significant increase of p-eIF2α to eIF2α ratio and sXBP1. Physical exercise counteracts NASH-related ER stress and its associated deleterious consequences through a positive and dynamical modulation of the hepatic IRE1α-X-box binding protein 1 pathway.

NS2B-NS3 protease inhibitors as promising compounds in the development of antivirals against Zika virus: A systematic review.

Zika virus (ZIKV) infections are associated with severe neurological complications and are a global public health concern. There are no approved vaccines or antiviral drugs to inhibit ZIKV replication. NS2B-NS3 protease (NS2B-NS3 pro), which is essential for viral replication, is a promising molecular target for anti-ZIKV drugs. We conducted a systematic review to identify compounds with promising effects against ZIKV; we discussed their pharmacodynamic and pharmacophoric characteristics. The online search, performed using the PubMed/MEDLINE and SCOPUS databases, yielded 56 articles; seven relevant studies that reported nine promising compounds with inhibitory activity against ZIKV NS2B-NS3 pro were selected. Of these, five (niclosamide, nitazoxanide, bromocriptine, temoporfin, and novobiocin) are currently available on the market and have been tested for off-label use against ZIKV. The 50% inhibitory concentration values of these compounds for the inhibition of NS2B-NS3 pro ranged at 0.38-21.6 µM; most compounds exhibited noncompetitive inhibition (66%). All compounds that could inhibit the NS2B-NS3 pro complex showed potent in vitro anti-ZIKV activity with a 50% effective concentration ranging 0.024-50 µM. The 50% cytotoxic concentration of the compounds assayed using A549, Vero, and WRL-69 cell lines ranged at 0.6-1388.02 µM and the selectivity index was 3.07-1698. This review summarizes the most promising antiviral agents against ZIKV that have inhibitory activity against viral proteases.

Fit mothers for a healthy future: Breaking the intergenerational cycle of non-alcoholic fatty liver disease with maternal exercise.

SPECIAL ISSUE: 'FOIEGRAS-Bioenergetic Remodelling in the Pathophysiology and Treatment of Non-Alcoholic Fatty Liver Disease'. BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) emerges as significant health burden worldwide. Lifestyle changes, unhealthy dietary habits and physical inactivity, can trigger NAFLD development. Persisting on these habits during pregnancy affects in utero environment and prompts a specific metabolic response in foetus resulting in offspring metabolic maladjustments potentially critical for developing NAFLD later in life. The increasing prevalence of NAFLD, particularly in children, has shifted the research focus towards preventive and therapeutic strategies. Yet, designing effective approaches that can break the NAFLD intergenerational cycle becomes even more complicated. Regular physical exercise (PE) is a powerful non-pharmacological strategy known to counteract deleterious metabolic outcomes. In this narrative review, we aimed to briefly describe NAFLD pathogenesis focusing on maternal nutritional challenge and foetal programming, and to provide potential mechanisms behind the putative intergenerational effect of PE against metabolic diseases, including liver diseases. METHODS: Following detailed electronic database search, recent existing evidence about NAFLD development, intergenerational programming and gestational exercise effects was critically analysed and discussed. RESULTS: PE during pregnancy could have a great potential to counteract intergenerational transmission of metabolic burden. The interplay between different PE roles-metabolic, endocrine and epigenetic-could offer a more stable in utero environment to the foetus, thus rescuing offspring vulnerability to metabolic disturbances. CONCLUSIONS: The better understanding of maternal PE beneficial consequences on offspring metabolism could reinforce the importance of PE during pregnancy as an indispensable strategy in improving offspring health.

Technical match actions and plasma stress markers in elite female football players during an official FIFA Tournament.

This study analyzed the impact of performing four consecutive football matches separated by 48-72 hours during a FIFA tournament on physical load, technical performance and plasma markers of redox state, muscle damage and inflammation in elite female players. Forty-eight players from three national teams were evaluated at seven time points: before (baseline) and throughout the tournament (after each match and before two training sessions). Only data from players who played all matches were included in the analyses (N = 13). The players were divided into high-rank (N = 6) and low-rank (N = 7) team players according to FIFA standards. Plasma creatine kinase (CK), C-reactive protein (CRP), total antioxidant status (TAS), and uric acid (UA) were analyzed at the selected time points. Technical performance and physical load were also quantified according to team rank. Players from low-rank teams played significantly more time than high-rank players (85 ± 10 vs 67 ± 15 minutes; P = .02; d = 1.51). Low-rank team players presented higher values in technical performance actions than the high-rank team players, but most of the differences were explained by the longer match time played. UA content differed across the matches, increasing from baseline (F(4,40)  = 3.90; P = .01) and more in the high-rank team players (F(1,10)  = 20.46; P = .001), while CRP only differed across the matches (F(4,36)  = 2.66; P = .05), also increasing from baseline. A large time effect was shown for UA only in the high-rank players (η2 p  = 0.50; P = .02). Four consecutive matches did not result in considerable alterations in plasma stress markers, physical load, and technical performance in elite female football players from distinct rank levels.

Gestational Exercise Increases Male Offspring's Maximal Workload Capacity Early in Life.

Mothers' antenatal strategies to improve the intrauterine environment can positively decrease pregnancy-derived intercurrences. By challenging the mother-fetus unit, gestational exercise (GE) favorably modulates deleterious stimuli, such as high-fat, high-sucrose (HFHS) diet-induced adverse consequences for offspring. We aimed to analyze whether GE alters maternal HFHS-consumption effects on male offspring's maximal workload performance (MWP) and in some skeletal muscle (the soleus-SOL and the tibialis anterior-TA) biomarkers associated with mitochondrial biogenesis and oxidative fitness. Infant male Sprague-Dawley rats were divided into experimental groups according to mothers' dietary and/or exercise conditions: offspring of sedentary control diet-fed or HFHS-fed mothers (C-S or HFHS-S, respectively) and of exercised HFHS-fed mothers (HFHS-E). Although maternal HFHS did not significantly alter MWP, offspring from GE dams exhibited increased MWP. Lower SOL AMPk levels in HFHS-S were reverted by GE. SOL PGC-1α, OXPHOS C-I and C-IV subunits remained unaltered by maternal diet, although increased in HFHS-E offspring. Additionally, GE prevented maternal diet-related SOL miR-378a overexpression, while upregulated miR-34a expression. Decreased TA C-IV subunit expression in HFHS-S was reverted in HFHS-E, concomitantly with the downregulation of miR-338. In conclusion, GE in HFHS-fed dams increases the offspring's MWP, which seems to be associated with the intrauterine modulation of SM mitochondrial density and functional markers.

Building-up fit muscles for the future: Transgenerational programming of skeletal muscle through physical exercise.

'Special issue - In Utero and Early Life Programming of Aging and Disease'. Skeletal muscle (SM) adaptations to physical exercise (PE) have been extensively studied due, not only to the relevance of its in situ plasticity, but also to the SM endocrine-like effects in noncontractile tissues, such as brain, liver or adipocytes. Regular PE has been considered a pleiotropic nonpharmacological strategy to prevent and counteract the deleterious consequences of several metabolic, cardiovascular, oncological and neurodegenerative disorders. Additionally, PE performed by parents seems to have a direct impact in the offspring through the transgenerational programming of different tissues, such as SM. In fact, SM offspring programming mechanisms seems to be orchestrated, at least in part, by epigenetic machinery conditioning transcriptional or post-transcriptional processes. Ultimately, PE performed in the early in life is also a critical window of opportunity to positively modulate the juvenile and adult phenotype. Parental PE has a positive impact in several health-related offspring outcomes, such as SM metabolism, differentiation, morphology and ultimately in offspring exercise volition and endurance. Also, early-life PE counteracts conceptional-related adverse effects and induces long-lasting healthy benefits throughout adulthood. Additionally, epigenetics mechanisms seem to play a key role in the PE-induced SM adaptations. Despite the undoubtedly positive role of parental and early-life PE on SM phenotype, a strong research effort is still needed to better understand the mechanisms that positively regulate PE-induced SM programming.

Quantification of testosterone-dependent erythropoiesis during male puberty.

NEW FINDINGS: What is the central question of this study? To what extent does testosterone influence haemoglobin formation during male puberty? What is the main finding and its importance? In boys, testosterone might be responsible for about 65% of the increase in haemoglobin mass during puberty. The underlying mechanisms are assumed to be twofold: (i) indirectly, mediated by the increase in lean body mass, and (ii) directly by immediate testosterone effects on erythropoiesis. Thereby, an increase in testosterone of 1 ng/ml is associated with an increase in haemoglobin mass of ∼65 g. These processes are likely to determine endurance performance in adulthood. ABSTRACT: The amount of haemoglobin during puberty is related to endurance performance in adulthood. During male puberty, testosterone stimulates erythropoiesis and could therefore be used as a marker for later endurance performance. This cross-sectional study aimed to determine the relationship between serum testosterone concentration and haemoglobin mass (Hbmass) in both male and female children and adolescents and to evaluate the possible influences of altitude and training. Three-hundred and thirteen differentially trained boys and girls aged from 9 to 18 years and living at altitudes of 1000 and 2600 m above sea level entered the study. The stage of sexual maturation was determined according to the classification of Tanner. Testosterone was measured by ELISA. Hbmass was determined by CO-rebreathing. Haemoglobin concentration did not change during maturation in girls and was 11% higher during puberty in boys, while Hbmass was elevated by 33% in Tanner stage V compared to stage II in girls (498 ± 77 vs. 373 ± 88 g) and by 95% in boys (832 ± 143 vs. 428 ± 95 g). This difference can most likely be attributed to indirect testosterone influences through an increase in lean body mass (LBM) and to direct testosterone effects on erythropoiesis, which increase the Hbmass by ∼65 g per 1 ng/ml. Altitude and training statuses were not associated with testosterone, but with an increase in Hbmass (altitude by 1.1 g/kg LBM, training by 0.8 g/kg LBM). Changes in Hbmass are closely related to testosterone levels during male puberty. Further studies will show whether testosterone and Hbmass during childhood and adolescence can be used as diagnostic tools for endurance talents.

A methanol extract and N,N-dimethyltryptamine from Psychotria viridis Ruiz & Pav. inhibit Zika virus infection in vitro.

Zika virus (ZIKV) is a public health problem due to its association with serious fetal and neurological complications and the lack of antiviral agents and licensed vaccines against this virus. Surveillance studies have alerted about the potential occurrence of a new South American epidemic episode due to the recent circulation of an African ZIKV strain detected in Brazil. Therefore, it is essential to discover antiviral agents, including natural substances, that are capable of neutralizing the action of ZIKV. Several Psychotria species have antimicrobial and anti-inflammatory properties. Thus, a methanol extract and dimethyltryptamine from Psychotria viridis were evaluated for their ability to inhibit ZIKV infection in vitro by measuring the effective concentration that protects 50% of cells and investigating their possible mechanisms of action. The tested samples showed antiviral activity against ZIKV. The extract showed virucidal activity, affecting viral and non-cellular elements, inactivating the virus before infection or when it becomes extracellular after the second cycle of infection. It was also observed that both extract and dimethyltryptamine could inhibit the virus at intracellular stages of the viral cycle. In addition to dimethyltryptamine, it is believed that other compounds also contribute to the promising virucidal effect observed for the methanol extract. To our knowledge, this is the first report of the activity of a methanolic extract and dimethyltryptamine from Psychotria viridis against cellular ZIKV infection. These two samples, extracted from natural sources, are potential candidates for use as antiviral drugs to inhibit ZIKV infections.

"Body & Brain": effects of a multicomponent exercise intervention on physical and cognitive function of adults with dementia - study protocol for a quasi-experimental controlled trial.

BACKGROUND: Dementia is a leading cause of death and disability that was declared as one of the greatest health and social care challenges of the twenty-first century. Regular physical activity and exercise have been proposed as a non-pharmacological strategy in disease prevention and management. Multicomponent Training (MT) combines aerobic, strength, balance and postural exercises and might be an effective training to improve both functional capacity and cognitive function in individuals with dementia (IwD). Nevertheless, data on the effects of MT in IwD are still limited and the extent to which IwD can retain improvements after an exercise intervention still needs to be elucidated. The aim of "Body & Brain" study is to investigate the effects of a 6-month MT intervention and 3-month detraining on the physical and cognitive function of IwD. Additionally, we aim to explore the impact of this intervention on psychosocial factors and physiologic markers related to dementia. METHODS: This study is a quasi-experimental controlled trial using a parallel-group design. The study sample consists of community-dwelling individuals aged ≥60 years who are clinically diagnosed with dementia or major neurocognitive disorder. Participants will be either allocated into the intervention group or the control group. The intervention group will participate in MT biweekly exercise sessions, whereas the control group will receive monthly sessions regarding physical activity and health-related topics for 6 months. The main outcomes will be physical function as measured by the Short Physical Performance Battery (SPPB) and cognitive function evaluated using the Alzheimer Disease Assessment Scale - Cognitive (ADAS-Cog) at baseline, after 6-months and 3-months after the end of intervention. Secondary outcomes will be body composition, physical fitness, daily functionality, quality of life, neuropsychiatric symptoms and caregiver's burden. Cardiovascular, inflammatory and neurotrophic blood-based biomarkers, and arterial stiffness will also be evaluated in subsamples. DISCUSSION: If our hypothesis is correct, this project will provide evidence regarding the efficacy of MT training in improving physical and cognitive function and give insights about its impact on novel molecular biomarkers related to dementia. This project may also contribute to provide guidelines on exercise prescription for IwD. TRIAL REGISTRATION: ClinicalTrials.gov - identifier number NCT04095962 ; retrospectively registered on 19 September 2019.

Modifiable predictors to maternal visceral adipose tissue during pregnancy: A clinical, demographic, and nutritional study.

AIM: Higher amounts of maternal visceral adipose tissue were related to abnormal outcomes in pregnancy. Our objective was to evaluate the impact of modifiable and nonmodifiable predictors related to abnormal amounts of maternal visceral fat during three trimesters of pregnancy. METHODS: Visceral fat thickness was evaluated by ultrasound during three trimesters centered in the maternal epigastrium (preperitoneal m-VAT) and additionally fat thickness evaluation centered at maternal periumbilical region (periumbilical m-VAT) among cases with gestational age below 20 weeks. The fourth quartile was considered abnormal m-VAT and the first three quartiles as normal m-VAT. Nonmodifiable characteristics included maternal age, past term pregnancies, and ethnicity. Modifiable characteristics included pre-pregnancy body mass index (BMI), weight gain, usual macronutrients, and sugar consumption during pregnancy. RESULTS: Preperitoneal m-VAT was assessed in 270 pregnant women and m-VAT periumbilical assessment in 154. The fourth quartile measurement was 15 mm and 53 mm, respectively. Nonmodifiable predictors including maternal age and past term pregnancies significantly impacted the primary study outcome of abnormal periumbilical m-VAT. Having a non-Caucasian ethnicity had a significant impact on the amount of normal preperitoneal m-VAT. Among the modifiable characteristics, both pre-pregnancy BMI and pre-pregnancy obesity impacted the amount of abnormal preperitoneal and periumbilical m-VAT. CONCLUSION: Abnormal amounts of maternal visceral fat during pregnancy are related to nonmodifiable predictors and those present before pregnancy. No impact was found among weight gain during pregnancy or macronutrients and sugar consumption at pregnancy.

Maternal adipose tissue to early preeclampsia risk detection: Is the time to maternal ultrasound beyond fetal evaluation?

INTRODUCTION: This study aims to determine the predictive capacity of isolated maternal periumbilical and epigastric fat measurements during pregnancy to hypertensive outcomes. METHODS: A cohort study was conducted with pregnant women in any trimester and followed until delivery to identify the outcomes of interest, preeclampsia (PE) and gestational hypertension (GH). The predictive capacity of fourth quartile measurements was compared with the first three quartiles of maternal subcutaneous and visceral adipose tissue from the periumbilical site (periumbilical m-SAT and m-VAT) (n = 155) and maternal adipose tissue from the epigastric site (preperitoneal m-SAT and m-VAT) (n = 261). The predictive ability of prepregnant body mass index (BMI) above 30 kg/m2 for PE and GH was also assessed. RESULTS: Fourth quartiles for the periumbilical ultrasound measurements were m-VAT 52.7 mm and m-SAT 21.7 mm. Preperitoneal site presents fourth quartiles m-VAT 15.2 mm and m-SAT 18.6 mm. Both m-VAT and m-SAT maternal periumbilical and preperitoneal sites are unable to predict PE, with the utmost sensitivity attributed to the periumbilical site m-SAT at 54%. The best PE predictor odds ratio (OR) found was the prepregnant BMI consistent with obesity, with an OR of 3.2 (95% CI 1.1-9.4), whereas the best OR to GH predictor was preperitoneal m-SAT with 8.9 (95% CI 2.3-34.6). CONCLUSION: PE pathogenic mechanisms related to maternal abdominal adipose tissue include differences in molecular, cytological, and tissue levels not detected by ultrasound in a quantified gray scale assessment. Periumbilical or epigastric m-VAT use is not able to predict PE during pregnancy.

Duodenal lymphangiectasias - The first sign of pancreatic adenocarcinoma.

A 41-year-old caucasian female, with past medical history of pituitary adenoma medicated with cabergoline, presented with worsening dyspepsia and unintentional weight loss of 5%. Physical exam and laboratory results were unremarkable for pathological findings. Esophagogastroduodenoscopy revealed an oedematous and exuberant lymphangiectasia appearance in the duodenum, with no ulceration or suspected infiltration component. However, duodenal biopsies revealed infiltration by poorly differentiated carcinoma. In the meantime, infection and inflammatory/autoimmune causes were ruled out. A CT scan was performed revealing a thickened and enlarged pancreas with ill-defined limits and several intra-abdominal adenopathies, raising suspicion of pancreatic lymphoproliferative disease. EUS with FNB was performed with biopsy of the pancreas and one of the larger adenopathy. EUS also revealed an enlarged, non-nodular pancreas and a thickened duodenal wall. Mild ascites was detected. Both EUS-biopsies were concordant on the diagnosis of carcinoma with gastric or pancreatic-biliary origin, highly aggressive (Ki67 > 80 %). Therefore, the diagnosis of pancreatic adenocarcinoma was assumed (cT4N1Mx). The patient is currently on palliative chemotherapy and remains paucisymptomatic.

Anthropometrical measurements and maternal visceral fat during first half of pregnancy: a cross-sectional survey.

BACKGROUND: Determining anthropometric measures that indicate different fat deposits can be useful to predict metabolic risk and set specific treatment goals, reducing negative consequences for maternal and fetal health. In cases where pre-gestational weight measure and subsequent body mass index (BMI) values cannot be determined, other anthropometric measurements may be ideal for measuring the nutritional status of pregnant women, especially in low- and middle-income countries. This study aims to identify which anthropometric measurements correlate better with the maternal fat deposits measured by ultrasound. METHODS: A cross-sectional study was conducted with pregnant women from the city of Porto Alegre (city), capital of Rio Grande do Sul (state), southern Brazil, from October 2016 until January 2018. Anthropometrical variables (weight, height, mid-upper arm circumference [MUAC], circumferences of calf and neck and triceps skinfolds [TSF] and subscapular skinfolds [SBSF]), and ultrasound variables (visceral adipose tissue [VAT] and total adipose tissue [TAT]) were collected. To verify the correlation of anthropometric and ultrasound measurements, a non-adjusted and adjusted Spearman correlation was used. The study was approved by the ethics committees. RESULTS: The age median of the 149 pregnant women was 25 years [21-31], pre-pregnancy BMI was 26.22 kg/m² [22.16-31.21] and gestational age was 16.2 weeks [13.05-18.10]. The best measurements correlated with VAT and TAT were MUAC and SBSF, both of which showed a higher correlation than pre-pregnancy BMI. CONCLUSIONS: It is possible to provide a practical and reliable estimate of VAT and TAT from the anthropometric evaluation (MUAC or SBSF) that is low cost, efficient and replicable in an outpatient clinic environment, especially in low- and middle-income countries.

High-intensity interval versus moderate-intensity continuous half-marathon training programme for middle-aged women.

PURPOSE: To test the effectiveness on recreational female middle-aged runners of a programme of high-intensity interval training (HIIT) for a half-marathon race contrasted to a conventional moderate-intensity continuous training (MICT). METHODS: Twenty recreational female runners (40 ± 7 years) followed MICT or HIIT schedules for training a half-marathon. The MICT group trained a mean of 32 km/week at intensities below 80% VO2max. The HIIT group ran 25 km/week at intensities between 80 and 100% VO2max, combined with uphill running and resistance training. Women following HIIT ran 21% less distance and invested 17% less time than those from MICT group. All the women were evaluated at the beginning and end of the training and participated in the same half-marathon run. RESULTS: Women following both schedules reduced their previous finishing times by 2-3%, which for HIIT group would have meant rising up to 90 positions out of 1454 participants in the local half-marathon race. The high intensity performed during series of high power output (200 m and 400 m) and resistance sessions in HIIT programme promoted changes that allowed modifying efficiency at high workloads. At the same time, the HIIT training programme elicited changes in oxygen uptake and transport as indicated the cardiorespiratory parameters obtained during recovery in lab tests. Moreover, HIIT registered a 14% baseline decrease in heart rate contrasting to the not significant 6% decrease in MICT. CONCLUSIONS: Runners following HIIT training obtained similar registers as with a traditional MICT schedule, expending less time and running shorter distances, yet improving their anaerobic and aerobic power.

Peripherally administered melanocortins induce mice fat browning and prevent obesity.

BACKGROUND/OBJECTIVES: The browning of white adipose tissue (WAT) has been in the spotlight during the last years, becoming an attractive approach to combat obesity. Melanocortin neuropeptides, such as α-melanocyte-stimulating hormone (α-MSH), are well-known regulators of appetite at the central nervous system, but its role in adipocyte metabolism is poorly elucidated. This study sought to verify if α-MSH can induce transdifferentiation of white to brown/beige adipocytes and to determine whether it can ameliorate the obesity phenotype. METHODS: The browning effect of α-MSH was determined in isolated adipocytes using the 3T3-L1 cell line and in inguinal subcutaneous adipose tissue (ingWAT) of diet-induced obese (DIO) mice by quantifying the expression of browning hallmark genes, oxygen consumption, and mitochondrial biogenesis. α-MSH protection from diet-induced obesity was evaluated by analyzing mice body weight, fat mass, and lipid and glucose serum profiles. RESULTS: Here, we report that α-MSH activates a thermogenic gene program and increases the mitochondrial respiratory rate in 3T3-L1 adipocytes and ingWAT of DIO mice. Without affecting food intake, peripheral administration of α-MSH decreases body weight and ingWAT mass, promoting a significant rise in the number of smaller adipocytes, whereas it lowered the larger ones. Additionally, there was an increase in the mass of brown adipose tissue. Browning activation occurs concomitantly with improvement on serum lipid profile, insulin resistance, and glucose homeostasis. CONCLUSIONS: This study highlights the anti-obesity properties of melanocortins by promoting ingWAT browning and provides new perspectives for future designing of more effective therapeutic strategies.

Maximal heart rate assessment in recreational football players: A study involving a multiple testing approach.

This study aimed at examining the suitability of a standard treadmill test (TT), popular intermittent field tests, and small-sided football matches to induce maximal heart rate (HRmax ) in recreational football players. Sixty-six inactive untrained male subjects (age: 39.3 ± 5.8 years, VO2max : 41.2 ± 6.2 mL kg-1  min-1 , body mass: 81.9 ± 10.8 kg, height: 173.2 ± 6.4 cm) were evaluated. On separate occasions, the players were randomly submitted to a progressive VO2max TT, to the Yo-Yo intermittent endurance level 1 (YYIE1) and level 2 (YYIE2) tests, to the Yo-Yo intermittent recovery level 1 (YYIR1) test, and to 7v7 (43 × 27 m pitch, 83 m2 /player) football matches (45 minutes; 2-4 matches/player). To ensure data consistency, exercise HR was recorded using the same HR monitors in all the experimental conditions. A total of 73%, 24%, 18%, 17%, and 30% of the players achieved their HRmax during the YYIE1, YYIE2, YYIR1, TT, and the small-sided football matches, respectively. The probability of achieving HRmax increased proportionally to test duration, with 7.8 minutes as the cutoff time. Variations in HRpeak of ±2 b min-1 should be regarded as of practical relevance. YYIE1 HRpeak provided the most accurate estimation of a subject's individual HRmax and much higher probability of reaching HRmax . Nevertheless, the results of this study suggest caution in considering a reference test for HRmax assessment in this population. The use of confirmation tests is still highly advisable when the test duration is shorter than 7.8 minutes. In this regard, field tests seem to be suitable and accurate for individual HRmax assessment in recreational football players.