Evaluation of urinary cysteinyl leukotrienes as biomarkers of severity and putative therapeutic targets in COVID-19 patients.

BACKGROUND: Cysteinyl leukotrienes (CysLT) are potent inflammation-promoting mediators, but remain scarcely explored in COVID-19. We evaluated urinary CysLT (U-CysLT) relationship with disease severity and their usefulness for prognostication in hospitalized COVID-19 patients. The impact on U-CysLT of veno-venous extracorporeal membrane oxygenation (VV-ECMO) and of comorbidities such as hypertension and obesity was also assessed. METHODS: Blood and spot urine were collected in "severe" (n = 26), "critically ill" (n = 17) and "critically ill on VV-ECMO" (n = 17) patients with COVID-19 at days 1-2 (admission), 3-4, 5-8 and weekly thereafter, and in controls (n = 23) at a single time point. U-CysLT were measured by ELISA. Routine markers, prognostic scores and outcomes were also evaluated. RESULTS: U-CysLT did not differ between groups at admission, but significantly increased along hospitalization only in critical groups, being markedly higher in VV-ECMO patients, especially in hypertensives. U-CysLT values during the first week were positively associated with ICU and total hospital length of stay in critical groups and showed acceptable area under curve (AUC) for prediction of 30-day mortality (AUC: 0.734, p = 0.001) among all patients. CONCLUSIONS: U-CysLT increase during hospitalization in critical COVID-19 patients, especially in hypertensives on VV-ECMO. U-CysLT association with severe outcomes suggests their usefulness for prognostication and as therapeutic targets.

Persistent weight gain between 0 and 4 years of age is associated with higher dehydroepiandrosterone sulphate levels at 7 years old: Data from the Generation XXI birth cohort.

OBJECTIVE: To assess the influence of longitudinal weight gain from 0 to 4 years old on dehydroepiandrosterone sulphate (DHEAS) levels at 7 years old. DESIGN: DHEAS levels were measured at 7 years old in a subsample of 587 children from the Generation XXI birth cohort. Weight trajectories (0-4 years of age) were identified using model-based clustering and categorized as "normal weight gain," "weight gain during infancy," "weight gain during childhood" and "persistent weight gain." MEASUREMENTS: Differences in DHEAS levels at age 7 between the four weight trajectories were analysed through analysis of covariance (ANCOVA), adjusted for birth weight (BW) and body mass index (BMI). RESULTS: In the crude analysis, compared with the "normal weight gain" trajectory (5.53 (95% CI: 5.10-5.98] µmol/L), DHEAS levels were significantly higher in children in the "persistent weight gain" (8.75 [95% CI: 7.23-10.49] µmol/L, p < .001] and in children in the "weight gain during infancy" trajectories (7.68 [95% CI: 6.22-9.49] µmol/L, p = .021] and marginally significantly higher in children in the "weight gain during childhood" trajectory (6.89 (95% CI: 5.98-8.00) µmol/L; p = .052). In BW- and BMI-adjusted model, a statistically significant difference in DHEAS levels was found between the "persistent weight gain" (7.93 [95% CI: 6.43-9.86] µmol/L) and the "normal weight gain" trajectories ([5.75 [95% CI: 5.32-6.23] µmol/L; p = .039). CONCLUSION: Higher DHEAS levels are found in 7-year-old children following a trajectory of persistent weight gain from 0 to 4 years, independently of their BW or current BMI, highlighting the impact of exposure to overweight in the first years of life on prepubertal adrenal androgen production.

Association of dehydroepiandrosterone sulfate, birth size, adiposity and cardiometabolic risk factors in 7-year-old children.

BACKGROUND: Low birth size (BS) and obesity have been associated with higher dehydroepiandrosterone sulfate (DHEAS) levels in childhood, insulin acting as a mediator, despite contradictory findings. To further explore these issues, we studied the associations between DHEAS, BS, adiposity, maternal characteristics, and cardiometabolic risk indicators, in participants of Generation XXI, a population-based birth cohort. METHODS: A sample of 700 children (mean age 7.1 yr) was randomly selected. Data on maternal characteristics, BS, body mass index (BMI), waist-to-height ratio, body fat (dual-energy X-ray absorptiometry), insulin, lipid profile, and high-sensitivity C-reactive protein were analyzed in relation to DHEAS. RESULTS: DHEAS was negatively associated with BS and positively associated with all adiposity indicators, with no sex differences. DHEAS was positively associated with insulinemia independently of the child's BS or BMI. No significant association was found between DHEAS, maternal characteristics, lipid profile, or high-sensitivity C-reactive protein. Including insulin in the model did not affect the association between BS and DHEAS but reduced the magnitude of the BMI effect by 24% for boys and 30% for girls. CONCLUSION: Higher DHEAS levels at 7 years old were associated with lower BS and higher adiposity. DHEAS levels were positively associated with insulinemia independently of BS or BMI. IMPACT: Low birth weight and obesity have been associated with higher dehydroepiandrosterone sulfate (DHEAS) levels in prepuberty. Insulin has been suggested as a mediator, despite previous studies failing to show an association between DHEAS and insulin levels. In a randomly selected population of 700 7-year-old children from the Generation XXI birth cohort, higher DHEAS levels were associated with a lower birth size and higher adiposity, with no sex differences. DHEAS was positively related to insulinemia independently of the child's birth size or body mass index. No association was found between DHEAS and other cardiometabolic risk factors.

The prostate health index and the percentage of [-2]proPSA maintain their diagnostic performance when calculated with total and free PSA from different manufacturers.

OBJECTIVES: To evaluate the diagnostic performance of the prostate health index (PHI) and of the percentage of [-2]proPSA (%[-2]proPSA) calculated with total and free PSA from non-Beckman Coulter manufacturers (Roche and Abbott), and compare it with the fully Beckman Coulter [-2]proPSA derivatives. METHODS: In this study, 237 men (PSA: 2-10 µg/L) scheduled for prostate biopsy were enrolled. %[-2]proPSA and PHI were calculated with total and free PSA from three manufacturers. Beckman Coulter PSA and [-2]proPSA were performed on the Access 2 analyzer (Hybritech calibration). Roche PSA was performed on the cobas e411 and the Abbott PSA on the Architect i2000sr. Statistical analysis was performed, considering prostate cancer (PCa) as the outcome. RESULTS: Univariate analysis showed that all indices were predictors of cancer, irrespective of the manufacturer (p<0.001). The AUC was similar for all manufacturers, both for %[-2]proPSA (Beckman Coulter: 0.756; Roche: 0.770; Abbott: 0.756) and PHI (Beckman Coulter: 0.776; Roche: 0.785; Abbott: 0.778). When considering the cutoffs that allowed 90% sensitivity, [-2]proPSA derivatives calculated with Roche and Abbott PSA had similar specificities and predictive values when compared to Beckman Coulter. The percentage of missed cancers (8-9%) was the same between manufacturers. The percentage of spared biopsies was significantly higher with Roche's PHI (21.0%) and Abbott's PHI (20.6%) than with Beckman Coulter's PHI (17.2%). CONCLUSIONS: In the PSA range between 2 and 10 µg/L, [-2]proPSA derivatives maintain their diagnostic performance in PCa detection when calculated with PSA from Roche and Abbott. This can lead to a broader implementation of these indices in clinical laboratories worldwide.

Inflammatory Response Assessment in Patients with COVID-19 Under Extracorporeal Membrane Oxygenation Support.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO), could be extremely helpful in the management of COVID-19 patients with refractory hypoxemic respiratory failure; however, to date, evidence on the true effecttiveness of ECMO in the COVID19 setting still hangs in the balance. METHODS: This was a prospective cohort study of 39 COVID-19 patients admitted to the intensive care unit (ICU) in an experienced ECMO center at a tertiary hospital during March/April 2020. Among the recruited participants, 10 (25.6%) required ECMO (ICU-ECMO group) and 29 (74.4%) did not have ECMO support (ICU group). Immunological parameters were assessed both at ICU admission and on a daily basis for 7 consecutive days. RESULTS: The absolute lymphocyte count increased significantly in the ICU-ECMO group compared to the ICU group in which it remained relatively stable: ß for the time variable was 127.1 [95% CI 68.9 - 185.3], p < 0.001 and for the interaction term -141.36 [-208.95 - -73.77], p < 0.001. On the other hand, globally, no significant differences were observed over time for the lymphocyte percentage, although it was higher in the ICU patients. Neutrophil counts were overall higher in the ICU-ECMO group (ß -4,275.38 [-6,845.21 - 1,705.55], p = 0.001). In regard to neutrophil percentage, a significant decrease over time was reported (ß -1.76 [-3.16 - -0.36], p = 0.014), namely in the ICU-ECMO group (ß for the interaction 2.09 [0.45 - 3.73], p = 0.013). CONCLUSIONS: Herein, we found ECMO support seems to provide a less aggressive immune response in COVID-19 patients with severe and refractory respiratory dysfunction.

Serum lipids and prostate cancer.

BACKGROUND: Conflicting results are found in the literature relating serum lipids levels and prostate cancer. Some results imply a relationship between them; others contradict this association. The purpose of this study was to investigate a possible association between serum lipids levels and prostate cancer, at time of diagnosis. METHODS: We measured serum levels of total cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides in 237 patients submitted to a prostate biopsy, with PSA between 2 and 10 ng/ml. Patients without cancer at biopsy were used as controls, and the others were considered as cases. No information about lipid-lowering therapy, including statins, was available neither in cases nor in controls. Cases were divided into risk groups, according to the disease severity, based on staging. Lipids levels were compared between groups, using parametric and nonparametric tests. Logistic regression analysis and odds ratios were calculated. RESULTS: LDL and total cholesterol levels were lower in patients with cancer, with the difference being statistically significant for LDL cholesterol (p = 0.010) and borderline for total cholesterol (p = 0.050). No significant differences were found between the several risk groups. Odds ratios for low LDL cholesterol (<130 mg/dl) and low total cholesterol (<200 mg/dl), with prostate cancer as the outcome, were 1.983 and 1.703, respectively. There were no significant differences between cases and controls for the other lipids. CONCLUSION: Lower LDL cholesterol (<130 mg/dl) and lower total cholesterol (<200 mg/dl) serum levels seem to associate with prostate cancer, at time of diagnosis.

Chromosome 6p SNP microhaplotypes and IgG3 levels in hemochromatosis probands with HFE p.C282Y homozygosity.

Subnormal IgG1 or IgG3 levels occurred in 30% of hemochromatosis probands with HFE p.C282Y homozygosity and were concordant in HLA-identical siblings. We sought to identify factors associated with IgG subclasses in Alabama probands with p.C282Y homozygosity evaluated for 500 kb microhaplotypes AAT and GGG defined by SNPs in chromosome 6p genes PGBD1, ZNF193, and ZNF165. In regressions on IgG subclasses, we used: age; sex; GGG (dichotomous); iron removed to achieve depletion; CD8+ T-lymphocytes; and other IgG subclasses. Among 49 probands, AAT and GGG occurred in 95.9% and 16.3%, respectively. Thirteen probands (26.5%) had subnormal IgG1; 11 probands (22.4%) had subnormal IgG3. Mean IgG3 was higher in probands with than without GGG (75 mg/dL [95% confidence interval 63, 89] vs. 58 mg/dL [49, 71], respectively; p = 0.0321). Regression on IgG3 revealed: GGG positivity (p = 0.0106); and IgG1 (p = 0.0015). In a replication cohort of 22 Portugal probands with p.C282Y homozygosity, mean IgG3 was higher in probands with than without GGG (46 ±â€¯16 vs. 31 ±â€¯12 mg/dL, respectively; p = 0.0410). We conclude that mean IgG3 levels are higher in hemochromatosis probands with p.C282Y homozygosity with chromosome 6p microhaplotype GGG than in probands homozygous for microhaplotype AAT.

Chronic consumption of the dietary polyphenol chrysin attenuates metabolic disease in fructose-fed rats.

PURPOSE: Metabolic syndrome (MS) is a major public health issue worldwide and fructose consumption has been associated with MS development. Recently, we showed that the dietary polyphenol chrysin is an effective inhibitor of fructose uptake by human intestinal epithelial cells. Therefore, our aim was to investigate if chrysin interferes with the development of MS induced by fructose in an animal model. METHODS: Adult male Sprague-Dawley rats (220-310 g) were randomly divided into four groups: (A) tap water (control), (B) tap water and a daily dose of chrysin (100 mg/kg) by oral administration (chrysin) (C) 10% fructose in tap water (fructose), and (D) 10% fructose in tap water and a daily dose of chrysin (100 mg/kg) by oral administration (fructose + chrysin). All groups were fed ad libitum with standard laboratory chow diet and dietary manipulation lasted 18 weeks. RESULTS: Fructose-feeding for 18 weeks induced an increase in serum triacylglycerols, insulin and angiotensin II levels and in hepatic fibrosis and these changes did not occur in fructose + chrysin rats. Moreover, the increase in both systolic and diastolic blood pressure which was found in fructose-fed animals from week 14th onwards was not observed in fructose + chrysin animals. In contrast, the increase in energy consumption, liver/body, heart/body and right kidney/body weight ratios, serum proteins, serum leptin and liver triacylglycerols observed in fructose-fed rats was not affected by chrysin. CONCLUSIONS: Chrysin was able to protect against some of the MS features induced by fructose-feeding.

Parental education associated with immune function in adolescence.

BACKGROUND: The immune system is affected and shaped by several internal and external factors. Among the external variables, the socioeconomic status is known to influence the immune system since the early years of life and throughout life. METHODS: In this study, we assessed the relationship between parental education with the white blood cells and its subtypes in 1213 adolescents from the EPITeen cohort, assessed at the age of 13. Beta coefficients (ß) and 95% confidence intervals (CI) were fitted using linear regression models to quantify the association and were adjusted for sex, body mass index and chronic disease. RESULTS: After adjustment, parental education presented a negative association with white blood cells, which was significant among those with higher high-sensitivity C-reactive protein (hs-CRP) median levels [-0.05 mg/l (95% CI -0.08, -0.01)]. On the contrary, a positive association with lymphocytes was observed, which was, significant among those with lower hs-CRP [0.17 mg/l (95% CI 0.02, 0.32)]. A neutrophil-to-lymphocyte ratio significant decrease was also observed with the increment of parental education (P<0.001). CONCLUSION: We found that parental education was positively associated with a higher proportion of lymphocytes and a lower proportion of neutrophils, suggesting that parental education is associated with offsprinǵs innate immune system regulation. These results may contribute to clarify the relationships between childhood socioeconomic status and increased risk of adverse cardiovascular outcomes and other immune-related diseases.

Association between insulin resistance and haematological parameters: A cohort study from adolescence to adulthood.

BACKGROUND: The aim of this study was to quantify the relationship between insulin resistance and haematological parameters from adolescence to adulthood. METHODS: Participants from the EPITeen cohort were evaluated at 13, 17, and 21 years, through standardized procedures. A fasting blood sample was obtained, and insulin resistance was evaluated by the homeostatic model assessment (HOMA-IR). The cross-sectional association between HOMA-IR and haematological parameters at 21 years was quantified in 1671 participants by multivariate linear regression coefficients (ß) and 95% confidence intervals (95%CI). For the longitudinal analysis (n = 496), trajectories of insulin and glucose were estimated using model-based clustering, and haematological parameters were compared according to trajectories using ANOVA. RESULTS: At 21 years, after adjustment for BMI, positive associations (ß [95%CI]) were found between HOMA-IR and red blood count (0.05 [0.03;0.07] in females; 0.02 [0.00;0.04] in males); and haematocrit (0.29 [0.12;0.46] in females; 0.21 [0.04,0.38] in males). In females, HOMA-IR was inversely associated with packed cell volume (PCV) (-0.35 [-0.66;-0.05]) and iron levels (-3.98 [-6.94,-1.03]) but positively associated with white blood cells (0.31 [0.19;0.43]) and platelets (7.66 [3.93;11.39]). In males, a higher HOMA-IR was significantly associated with higher haemoglobin (0.09 [0.03;0.16]). Regarding the longitudinal analysis, similar trends were found, but statistical significance was not reached. CONCLUSIONS: Both longitudinal and cross-sectional analyses support the hypothesis that insulin resistance is associated with increased red blood cells count and haematocrit in young adults, even within normal ranges of insulin and glucose.

Central and peripheral body fat distribution: Different associations with low-grade inflammation in young adults?

BACKGROUND AND AIMS: Evidence regarding the impact of regional body fat distribution on low-grade inflammation is limited. The current study examined the association of central and peripheral body fat distribution and low-grade inflammation levels in young adults, considering collinearity between variables. METHODS AND RESULTS: A cross-sectional analysis of 809 adults (aged 27 years) was conducted as part of the EPITeen cohort, Porto, Portugal. Regional body fat was measured by dual-energy X-ray absorptiometry scan (DXA) and serum high-sensitivity C-reactive protein (hsCRP) was measured in a fasting blood sample. OLS (ordinary least squares) and LASSO (least absolute shrinkage and selection operator) regression models were fitted to estimate the association of trunk and peripheral fat with hsCRP, stratified by sex. Using OLS regression, trunk fat in females was positively associated with ln(hsCRP) (ß1 = 0.064, 95% CI 0.018; 0.109). The effect of peripheral fat on ln(hsCRP) was shown not to be significantly different from trunk fat (ß2 = -0.011, 95% CI -0.110; 0.089), but no statistically significant association was observed (ß3 = 0.053, 95% CI -0.004; 0.110) between peripheral fat and ln(hsCRP). In males, trunk fat also showed a positive association with ln(hsCRP) (ß1 = 0.104, 95% CI 0.055; 0.154), and the effect of peripheral fat on ln(hsCRP) was shown to be significantly different from trunk fat (ß2 = -0.124, 95% CI -0.237;-0.011). However, the association between peripheral fat and ln(hsCRP) did not reach statistical significance (ß3 = -0.020, 95% CI -0.086; 0.046). The results of OLS were confirmed by LASSO regression. CONCLUSION: A higher fat deposited in the trunk was positively associated with hsCRP, whereas no statistically significant effect was observed for peripheral fat.

Xanthohumol impairs glucose uptake by a human first-trimester extravillous trophoblast cell line (HTR-8/SVneo cells) and impacts the process of placentation.

In this study, we aimed to investigate modulation of glucose uptake by the HTR-8/SVneo human first-trimester extravillous trophoblast cell line by a series of compounds and to study its consequences upon cell proliferation, viability and migration. We observed that uptake of (3)H-deoxy-d-glucose ((3)H-DG; 10 nM) was time-dependent, saturable, inhibited by cytochalasin B (50 and 100 µM), phloretin (0.5 mM) and phloridzin (1 mM), insulin-insensitive and sodium-independent. In the short term (30 min), neither 5-HT (100-1000 µM), melatonin (10 nM) nor the drugs of abuse ethanol (100 mM), nicotine (100 µM), cocaine (25 µM), amphetamine (10-25 µM) and 3,4-methylenedioxy-N-methamphetamine (10 µM) affected (3)H-DG uptake, while dexamethasone (100-1000 µM), fluoxetine (100-300 µM), quercetin, epigallocatechin-3-gallate (30-1000 µM), xanthohumol (XH) and resveratrol (1-500 µM) decreased it. XH was the most potent inhibitor [IC50 = 3.55 (1.37-9.20) µM] of (3)H-DG uptake, behaving as a non-competitive inhibitor of (3)H-DG uptake, both after short- and long-term (24 h) treatment. The effect of XH (5 µM; 24 h) upon (3)H-DG uptake involved mammalian target of rapamycin, tyrosine kinases and c-Jun N-terminal kinases intracellular pathways. Moreover, XH appeared to decrease cellular uptake of lactate due to inhibition of the monocarboxylate transporter 1. Additionally, XH (24 h; 5 µM) decreased cell viability, proliferation, culture growth and migration. The effects of XH upon cell viability and culture growth, but not the antimigratory effect, were mimicked by low extracellular glucose conditions and reversed by high extracellular glucose conditions. We thus suggest that XH, by inhibiting glucose cellular uptake and impairing HTR-8/SVneo cell viability and proliferation, may have a deleterious impact in the process of placentation.

The chemopreventive effect of the dietary compound kaempferol on the MCF-7 human breast cancer cell line is dependent on inhibition of glucose cellular uptake.

Our aim was to investigate the effect of several dietary polyphenols on glucose uptake by breast cancer cells. Uptake of (3)H-deoxy-D-glucose ((3)H-DG) by MCF-7 cells was time-dependent, saturable, and inhibited by cytochalasin B plus phloridzin. In the short-term (26 min), myricetin, chrysin, genistein, resveratrol, kaempferol, and xanthohumol (10-100 µM) inhibited (3)H-DG uptake. Kaempferol was found to be the most potent inhibitor of (3)H-DG uptake [IC50 of 4 µM (1.6-9.8)], behaving as a mixed-type inhibitor. In the long-term (24 h), kaempferol (30 µM) was also able to inhibit (3)H-DG uptake, associated with a 40% decrease in GLUT1 mRNA levels. Interestingly enough, kaempferol (100 µM) revealed antiproliferative (sulforhodamine B and (3)H-thymidine incorporation assays) and cytotoxic (extracellular lactate dehydrogenase activity determination) properties, which were mimicked by low extracellular (1 mM) glucose conditions and reversed by high extracellular (20 mM) glucose conditions. Finally, exposure of cells to kaempferol (30 µM) induced an increase in extracellular lactate levels over time (to 731 ± 32% of control after a 24 h exposure), due to inhibition of MCT1-mediated lactate cellular uptake. In conclusion, kaempferol potently inhibits glucose uptake by MCF-7 cells, apparently by decreasing GLUT1-mediated glucose uptake. The antiproliferative and cytotoxic effect of kaempferol in these cells appears to be dependent on this effect.

Metabolic score: insights on the development and prediction of remission of metabolic syndrome after gastric bypass.

INTRODUCTION: Metabolic syndrome (MetS) clusters the most dangerous cardiovascular disease risk factors. Although insulin resistance and central obesity play an important role in the pathogenesis, the factors that determine its development and ultimate remission after Roux-en-Y gastric bypass (RYGB) are not fully understood. METHODS: We recruited a prospective cohort of 210 consecutive patients after RYGB between January 2010 and December 2011. Patients were evaluated clinically and with a biochemical profile preoperatively and at 12 months after surgery. Visceral adipose tissue and subcutaneous abdominal adipose tissue samples were collected at surgical intervention. We aimed to identify factors associated with MetS in morbidly obese patients and predictors of its remission 12 months after RYGB. RESULTS: Increasing age (>40 years), male sex, alanine aminotransferase levels and visceral adipose tissue/subcutaneous adipocyte size ratio were independently related to the expression of MetS at the moment of surgery.One year after RYGB, there was a significant decrease in the prevalence of MetS (63.3%-10%; P < 0.001) and in each of its components. A multivariable analysis for the remission of MetS identified that only fasting glucose levels (OR = 13.4; P = 0.01) and duration of obesity (OR = 1.08; P = 0.04) were independently related to the persistence of MetS. A metabolic score (scale of 1-10), consisting of duration of obesity, fasting blood glucose levels, the presence of high blood pressure and low levels of high-density lipoprotein identified 4 different risk categories for the persistence of MetS (area under the curve = 0.848). CONCLUSIONS: The metabolic score can be used to predict the remission of MetS after RYGB with high accuracy. Patients in high-risk groups might be managed more aggressively and low-risk patients may have their medication discontinued earlier with extra safety.

Persistent organic pollutant levels in human visceral and subcutaneous adipose tissue in obese individuals--depot differences and dysmetabolism implications.

BACKGROUND: The role of persistent organic pollutants (POPs) with endocrine disrupting activity in the aetiology of obesity and other metabolic dysfunctions has been recently highlighted. Adipose tissue (AT) is a common site of POPs accumulation where they can induce adverse effects on human health. OBJECTIVES: To evaluate the presence of POPs in human visceral (vAT) and subcutaneous (scAT) adipose tissue in a sample of Portuguese obese patients that underwent bariatric surgery, and assess their putative association with metabolic disruption preoperatively, as well as with subsequent body mass index (BMI) reduction. METHODS: AT samples (n=189) from obese patients (BMI ≥ 35) were collected and the levels of 13 POPs were determined by gas chromatography with electron-capture detection (GC-ECD). Anthropometric and biochemical data were collected at the time of surgery. BMI variation was evaluated after 12 months and adipocyte size was measured in AT samples. RESULTS: Our data confirm that POPs are pervasive in this obese population (96.3% of detection on both tissues), their abundance increasing with age (RS=0.310, p<0.01) and duration of obesity (RS=0.170, p<0.05). We observed a difference in AT depot POPs storage capability, with higher levels of ΣPOPs in vAT (213.9 ± 204.2 compared to 155.1 ± 147.4 ng/g of fat, p<0.001), extremely relevant when evaluating their metabolic impact. Furthermore, there was a positive correlation between POP levels and the presence of metabolic syndrome components, namely dysglycaemia and hypertension, and more importantly with cardiovascular risk (RS=0.277, p<0.01), with relevance for vAT (RS=0.315, p<0.01). Finally, we observed an interesting relation of higher POP levels with lower weight loss in older patients. CONCLUSION: Our sample of obese subjects allowed us to highlight the importance of POPs stored in AT on the development of metabolic dysfunction in a context of obesity, shifting the focus to their metabolic effects and not only for their recognition as environmental obesogens.

Early dietary treated patients with phenylketonuria can achieve normal growth and body composition.

BACKGROUND: In the past, overtreatment may have resulted in growth impairment in patients with phenylketonuria. OBJECTIVE: The paper aims to investigate height and body composition in early treated patients with phenylketonuria who were diagnosed between 1981 and 2008. DESIGN: A cross-sectional study of 89 patients with phenylketonuria and 78 controls aged (mean ± SD, in years) 14.4 ± 6.6 and 15.9 ± 7.1, respectively, was undertaken, including anthropometric and body composition evaluation using bioelectrical impedance. Median Phe concentrations in the last year before study enrollment were used as a measure of metabolic control. Natural protein and amino acid mixture intakes were recorded in patients. RESULTS: No statistically significant differences were found on height z-scores between patients and controls aged less than 19 years (p=0.301), although all patients with classical phenylketonuria revealed negative height z-scores, resulting in a mean ± SD of -0.65 ± 0.41. Among participants aged 19 years or more, median (p25-p75) of height was significantly higher in controls [168.0 cm (159.2-174.8)] than in patients [160.5 cm (151.9-167.5)] (p=0.017). No significant differences were found between patients and controls regarding fat mass, fat free mass, muscular mass, body cell mass index and phase angle. CONCLUSION: Our results suggest that early and continuously treated patients with phenylketonuria born after 1992 can achieve normal growth and body composition, although the negative height z-score in patients with classical phenylketonuria strengthens the continuous need to optimize the quality of their protein intake.

Sociodemographic determinants of prevalence and incidence of Helicobacter pylori infection in Portuguese adults.

BACKGROUND: Understanding the determinants of Helicobacter pylori infection in adults is essential to predict the burden of H. pylori-related diseases. We aimed to estimate the prevalence and incidence of H. pylori infection and to identify its major sociodemographic correlates in an urban population from the North of Portugal. MATERIAL AND METHODS: A representative sample of noninstitutionalized adult inhabitants of Porto (n = 2067) was evaluated by ELISA (IgG) and a subsample (n = 412) was tested by Western Blot to assess infection with CagA-positive strains. Modified Poisson and Poisson regression models were used to estimate crude and sex-, age-, and education-adjusted prevalence ratios (PR) and incidence rate ratios (RR), respectively. RESULTS: The prevalence of H. pylori infection was 84.2% [95% confidence interval (95%CI): 82.4-86.1]. It increased across age-groups in the more educated subjects, (18-30 years: 72.6%; ≥71 years: 88.1%; p for trend <0.001) and decreased with education in the younger (≤4 schooling years: 100.0%; ≥10 schooling years: 72.6%; p for trend <0.001). Living in a more deprived neighborhood was associated with a higher prevalence of infection, only in the younger (PR = 1.20, 95%CI: 1.03-1.38) and more educated participants (PR = 1.15, 95%CI: 1.03-1.29). Among the infected, the proportion with CagA-positive strains was 61.7% (95%CI: 56.6-66.9). The incidence rate was 3.6/100 person-years (median follow-up: 3 years; 95%CI: 2.1-6.2), lower among the more educated (≥10 vs ≤9: RR = 0.25, 95%CI: 0.06-0.96). The seroreversion rate was 1.0/100 person-years (95%CI: 0.6-1.7). CONCLUSIONS: The prevalence of infection among adults is still very high in Portugal, suggesting that stomach cancer rates will remain high over the next few decades.

Xanthohumol modulates inflammation, oxidative stress, and angiogenesis in type 1 diabetic rat skin wound healing.

Type 1 diabetes mellitus is responsible for metabolic dysfunction, accompanied by chronic inflammation, oxidative stress, and endothelium dysfunction, and is often associated with impaired wound healing. Phenol-rich food improves vascular function, contributing to diabetes prevention. This study has evaluated the effect of phenol-rich beverage consumption in diabetic rats on wound healing, through angiogenesis, inflammation, and oxidative stress modulation. A wound-healing assay was performed in streptozotocin-induced diabetic Wistar rats drinking water, 5% ethanol, and stout beer with and without 10 mg/L xanthohumol (1), for a five-week period. Wounded skin microvessel density was reduced to normal values upon consumption of 1 in diabetic rats, being accompanied by decreased serum VEGF-A and inflammatory markers (IL-1ß, NO, N-acetylglucosaminidase). Systemic glutathione and kidney and liver H2O2, 3-nitrotyrosine, and protein carbonylation also decreased to healthy levels after treatment with 1, implying an improvement in oxidative stress status. These findings suggest that consumption of xanthohumol (1) by diabetic animals consistently decreases inflammation and oxidative stress, allowing neovascularization control and improving diabetic wound healing.

Adding protein to a carbohydrate pre-exercise beverage does not influence running performance and metabolism.

BACKGROUND: To analyze whether pre-exercise CHO+PRO vs. CHO intake distinctly influences running performance and metabolic biomarkers along a various of exercise intensities. METHODS: In a randomized, double blind, counterbalanced, crossover and placebo control design, 10 middle distance runners were tested in 3 occasions. After 10 h of fasting, participants ingested isovolumic beverages (0.75+0.25g·BW-1 of CHO+PRO, 1.0g·BW-1 of CHO and placebo control) 30 min before a treadmill running incremental protocol of 4 min steps until exhaustion. Venous blood was collected at fasting, 30 min after beverage ingestion and after the 3rd and 7th running steps. Oxygen uptake-related variables, including respiratory exchange ratio, heart rate, plasma glucose, insulin, glucagon, free fatty acids, blood lactate concentrations, gastrointestinal discomfort and rate of perceived exertion were measured. RESULTS: The addition of PRO to CHO had no influence on the measured variables, which did not differ between conditions along all incremental protocol intensities. The intake of CHO+PRO (compared to CHO) tended to decrease glycemia (106.5±21.3 vs. 113.6±26.5) and to increase insulinemia (14.4±15.1 vs. 12.7±10.8) at intensities close to maximum oxygen uptake. CONCLUSIONS: The addition of PRO to a pre-exercise CHO beverage had no impact on running performance and related metabolic variables at a wide spectrum of exercise intensities.

Xanthohumol-supplemented beer modulates angiogenesis and inflammation in a skin wound healing model. Involvement of local adipocytes.

Angiogenesis and inflammation are two intermingled processes that play a role in wound healing. Nevertheless, whenever exacerbated, these processes result in nonhealing wounds. Xanthohumol (XN), a beer-derived polyphenol, inhibits these processes in many physiopathological situations. This study aimed at examining whether XN ingestion affects wound healing. Wistar rats drinking water, 5% ethanol, stout beer (SB) or stout beer supplemented with 10 mg/L XN (Suppl SB) for 4 weeks, were subjected to a 1.5 cm full skin-thickness longitudinal incision, and further maintained under the same beverage conditions for another week. No differences in beverage consumption or body weight were found throughout the study but food intake decreased in every group relative to controls. Consumption of Suppl SB resulted in decreased serum VEGF levels (18.42%), N-acetylglucosaminidase activity (27.77%), IL1ß concentration (9.07%), and NO released (77.06%), accompanied by a reduced redox state as observed by increased GSH/GSSG ratio (to 198.80%). Also, the number of blood vessels within the wound granulation tissue seems to reduce in animals drinking Suppl SB (23.08%). Interestingly, SB and primarily Suppl SB showed a tendency to increase adipocyte number (to 194.26% and 156.68%, respectively) and reduce adipocyte size (4.60% and 24.64%, respectively) within the granuloma. Liver function and metabolism did not change among the animal groups as analyzed by plasma biochemical parameters, indicating no beverage toxicity. This study shows that XN intake in its natural beer context reduced inflammation, oxidative stress, and angiogenesis, ameliorating the wound healing process, suggesting that this polyphenol may exert beneficial effect as a nutritional supplement.