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BackgroundIrritable bowel syndrome (IBS) is a common functional gastrointestinal disorder in adults. Systematic reviews with meta-analyses have demonstrated the efficacy and safety of probiotics in improving symptoms of IBS.AimThe aim of the study was to demonstrate the efficacy and safety of Limosilactobacillus reuteri (L. reuteri) DSM 17938 combined with L. reuteri ATCC PTA 6475 regarding improving the symptoms associated with IBS in adults.MethodsA randomized, double-blind, placebo-controlled clinical trial was conducted in 140 adults aged 18 years to 65 years with a diagnosis of IBS (based on the Rome IV criteria). After 2 weeks of washout, subjects were randomized to receive either 2 × 108 colony-forming units (CFUs) of L. reuteri DSM 17938 combined with L. reuteri ATCC PTA 6475 plus standard of care or placebo plus standard of care for 14 weeks, followed by a post-intervention period of 2 additional weeks. Changes in gastrointestinal symptoms (as measured with the GSRS-IBS), stool pattern (as measured with the Bristol scale), quality of life, depression and anxiety, frequency of adverse events, and fecal calprotectin concentrations were evaluated.ResultsIn total, 70 subjects were allocated to receive L. reuteri and 70 were allocated to receive placebo. During the pre-randomization phase, no differences were observed between the groups in terms of IBS-associated symptoms and stool consistency. Starting at week 6 of the intervention, subjects in group L. reuteri showed a significant improvement in IBS-associated symptoms (p < 0.01). A significant improvement was also observed in fecal calprotectin concentration in the L. reuteri group at the end of interventions (30.2 ± 11.8 mg/g of stool in the L. reuteri group and 41.6 mg/g ± 10.7 mg/g in the placebo group; p = 0.019). The frequency of adverse events was similar between groups.ConclusionsA twice-a-day intervention for 14 weeks is safe and effective, reduces the symptoms associated with IBS in adults aged 18 years to 65 years, improves stool consistency, and reduces symptoms associated with anxiety after 6 weeks.

The hypocaloric Mediterranean diet (MD) mainly reduces fat mass but inevitably causes a loss of skeletal muscle mass. High-intensity interval training (HIIT) seems to have advantages in preserving muscle mass during a hypocaloric regime. Our study compares body composition and metabolic changes in overweight and obese Chilean women and men after 3 months of weight loss treatment with a Mediterranean-type hypocaloric diet, HIIT, or a combination of both. The study included 83 overweight or obese women and men between the ages of 25 and 50. The subjects were randomly assigned to one of the three intervention groups: (1) MD, (2) EX, and (3) MD + EX. Baseline and post-intervention measurements included: (a) body composition by dual-beam densitometry, muscle, and fat measurements by thigh ultrasound and computed tomography; (b) handgrip and quadriceps muscle strength; (c) exercise performance by peak oxygen consumption, peak load, work efficiency, and exercise energy expenditure; and (d) metabolic parameters. Out of 83 participants, the retention rate was 49% due to low compliance with the interventions. As expected, the MD group resulted in significantly greater weight loss (MD −7%, EX −0.6% and MD + EX −5.3%) and appendicular fat mass loss (MD −11.1%, EX −2.9, MD + EX −10.2%) but was associated with significant lean tissue loss (2.8%), which was prevented by HIIT (EX −0.1 and MD + EX −0.6%). Metabolic and glycoxidative parameters remained unchanged, irrespective of changes in body composition. Hypocaloric diets remain the most effective means to lose weight and body fat. However, it induces a loss of lean body mass when not accompanied by exercise training. This study shows that HIIT prevents the loss of muscle mass caused by a hypocaloric Mediterranean diet.

Abstract Background Sedentariness may be an important risk factor for sarcopenia. The aim of this work was to assess the association between muscle mass and strength and markers of usual physical activity such as activity energy expenditure and peak oxygen uptake. Methods Young and old participants were assessed measuring body composition by DEXA (double beam X ray absorptiometry), handgrip strength, peak oxygen consumption and workload during an exercise calorimetry in a braked cycle ergometer and a 72 h activity energy expenditure using Actiheart actigraphs. A heart rate/energy expenditure curve derived from the exercise calorimetry was used to calibrate each actigraph. Sarcopenia was defined as having an appendicular fat free mass index below 7.5 kg/m2 and 5.6 kg/m2 in men and women respectively, or a handgrip strength z score below 1, using local normal data or having both parameters below the cutoff points. Results We analyzed data from 192 assessments performed in participants aged 22 to 88 years (106 women). Sarcopenic participants (as determined by muscle mass, strength or both) had a significantly lower peak oxygen uptake and work load and a significantly lower activity energy expenditure. When analyzing lean mass and strength as continuous variables, peak oxygen consumption was a significant predictor of fat free mass in men. Among women, the association was observed only when percentage of muscle mass was expressed as a z score. Conclusions Activity energy expenditure and peak oxygen consumption are associated with a lower muscle mass and the presence of sarcopenia and should be considered as risk factors for this condition.

Abstract Background Changes in DNA methylation, one of the most studied epigenetic mechanisms, are considered an initial marker for early cancer detection. We evaluated how availability of dietary factors (folates and vitamin B12) involved in one-carbon metabolism may contribute to DNA methylation changes of cancer-related genes in human subjects. Methods We studied, by pyrosequencing, the methylation of tumor suppressor gene p16, DNA repair genes MLH1 and MGMT, and the repetitive element LINE-1 (as a surrogate for global DNA methylation), in blood of elderly individuals (n = 249) who had been exposed to folic acid (FA) through FA-fortified wheat flour during the last 12 years. Results We found that serum folate and to a lesser extent, vitamin B12 concentrations, were significantly correlated with DNA methylation of p16, MLH1, and MGMT, but not with LINE-1. High serum folate concentrations (>45.3 nmol/L) were present in 31.1% of the participants. Although the methylated fraction of CpG sites in p16, MLH1, and MGMT was low (1.17–3.8%), high folate concentrations were significantly associated with methylation at the 3rd tertile of specific CpG sites in all genes with OR between 1.97 and 4.17. Conclusions This study shows that a public policy, like food fortification with FA that increases circulating serum folate levels, could affect methylation levels of specific genes linked to cancer risk. Our present results deserve additional studies to clarify the real impact of high FA levels for risk of cancer in a whole population chronically exposed to a fortified food such as wheat flour. Trial registration ISRCTN 48153354 and ISRCTN 02694183

An inexpensive and simple method to determine non-alcoholic fatty liver disease (NAFLD) is the abdominal ultrasound, but there are still doubts about its accuracy. We assessed the precision of a semi-quantitative ultrasound method to determine liver fat infiltration, using magnetic resonance spectroscopy (MRS) as the reference. The study was conducted in youths from an ongoing cohort study. Clinical validation was performed, using receiver operating characteristic analysis, in n = 60 participants (22.6y; 50% males). Abdominal ultrasound was carried out with liver brightness (score 0–3), diaphragm attenuation (0–2) and liver vessel blurring (0–1) scored by two observers. Liver fat was estimated using MRS. Then, analytical validation was conducted in the remaining participants (n = 555; 22.7y; 51% males) using effects size estimates. An ultrasound score ≥4.0 had the highest sensitivity (78%) and specificity (85%) for NAFLD diagnosis. An area under the curve of 86% denotes a good diagnostic performance of the test, whereas a Kappa of 0.63 suggests substantial agreement of ultrasound vs. MRS. The analytical validation showed that participants having NAFLD according to ultrasound had an unhealthier cardiometabolic profile than participants without the condition. Abdominal ultrasound, combined with a semi-quantitative score system, is a reliable method to determine liver fat infiltration in young adults and should be encouraged whenever MRS is unavailable.

Objective: To assess the individual variability of HOMA and QUICKI indexes for the assessment of insulin resistance, using three fasting blood samples obtained within 30 minutes. Research methods & procedures: Data from 80 participants aged 41.5 ± 15 years (26 females), who underwent an oral glucose tolerance test to calculate Matsuda index, were used. Every participant had three fasting blood samples obtained within 30 minutes and four blood samples obtained at 30, 60, 90 and 120 minutes after a 75 g oral glucose load. Insulin and glucose were measured in each sample. HOMA and QUICKI indexes were calculated using the nine possible combinations of the three fasting blood samples. Matsuda index was calculated with all samples obtained. Results: Median values of HOMA-IR, HOMA-β, QUICKI and Matsuda indexes were 1.9, 117.9, 0.35 and 3.71 arbitrary units, respectively. The individual variation coefficients of HOMA-IR, HOMA-β and QUICKI were 11.8 (7.8-18.9), 15 (10.2-22.9) and 1.8 (8.8-21.9) % respectively. When compared with Matsuda index, the R squared values of HOMA-IR, HOMA-β and QUICKI were 0.46, 0.2 and 0.71, respectively. Conclusions: Among fasting indexes for insulin resistance, QUICKI had the lower variation coefficient and the higher correlation with Matsuda index.

Background: Obesity has long been associated with an increased risk of cardiovascular disease (CVD). The aim of this study was to evaluate the impact of substantial weight loss induced by bariatric surgery on carotid intima media thickness (C-IMT) (surrogate marker of early atherosclerosis) and classic factors of cardiovascular risk (CVRFs). Methods: thirty-one obesity patients were evaluated for bariatric surgery. Twenty-seven were undergone surgery, 14 Roux-en-Y gastric bypass surgery (GBS) and 13 sleeve gastrectomy. The four obese patients who did not undergo surgery, were performed the same evaluations. Measurements: Body weight, BMI, blood pressure, total cholesterol, TC levels, LDL-C, HDL-C, TG, fasting plasma glucose and insulin, HOMA IR, and US B-mode C-IMT was measured. Results: After 354 ± 92 days follow up, 27 patients that underwent bariatric surgery evidenced a mean body mass index decrease from 38 to 27 k/m² (p < 0.001), simultaneously was observed improvement in CVRFs, 10 years Framingham risk and a significant reduction of therapeutic requirements. C-IMT diminished from a mean of 0.58 ± 0.14 mm to 0.49 ± 0.09 mm (p = 0.0001). Four patients that did not undergo surgery increased C-IMT from 0.52 ± 0.12 to 0.58 ± 0.13 mm (p = 0.03) with no significant changes in CVRFs. Conclusion: Weight loss, one year after bariatric surgery, GBS and sleeve gastrectomy, decreases C-IMT; improve CVRFs and 10 years Framingham risk.

Aim: To test the variability within and between subject of glycemic response test following the ingestion of a standard food. Material and methods: Glucose and insulin response of a standard meal (white bread) was performed in ten healthy volunteers and repeated under identical conditions for 6 times. Blood glucose and insulin levels were measured in the fasted state and over the 180 min following commencement of consumption of the foods The Area Under the Curve (AUC) for glucose and insulin was calculated for the values above baseline for the 3hour period following the standard meal. Within and between coefficient of variation was calculated. Results: The total intra-individual variation of the gAUC was 51.8% range 24.9 to 91.4%. The inter-individual variation of the gAUC in the complete study was 75.2% . The total intra-individual variation of the iAUC was 51.9%. ranged: 7.7 to 103%. The inter-individual variation in the complete study was 86%. Conclusion: Glucose and insulin response to a reference food has low reliability, therefore limits its clinical utility for individual dietary prescription.

Background: Functional limitations may be a mortality risk among older people. The aim of this work is to determine if body composition and strength are risk factors related to mortality in older Chilean people. Methods: In a retrospective study, 306 independent elderly Chileans (age: 61–91 years) were followed for a median of 7.2 years. Baseline information was obtained, including gender, living conditions, smoking and drinking habits, educational status, history of chronic diseases, cognitive function, and depression. Body composition was assessed using dual-energy X-ray absorptiometry (DXA). Functionality was assessed by determining isometric handgrip strength and 12-minute walking capacity. The associations between all of these parameters and mortality were assessed using univariate and multivariate models. Results: During follow-up, 23 (30.7%) male and 34 (14.7%) female participants died (p

Folate deficiency during pregnancy has been related to low birth weight, preterm (PT) birth and other health risks in the offspring; however, it is unknown whether prematurity is related to low folate transport through the placenta due to altered expression of specific folate transporters. We determined placental expression (mRNA and protein concentrations by RT-qPCR and WB respectively) of specific folate transporters: RFC, PCFT/HCP1 and FOLR1 in chorionic (fetal) and basal (maternal) plates of placentas of PT pregnancies (PT, 32-36 weeks, n = 51). Term placentas were used as controls (T, 37-41 weeks, n = 47). Folates and vitamin B12 levels were measured by electrochemiluminescence in umbilical cord blood of newborns. FOLR1 mRNA expression was lower and protein concentration higher in PT placentas (both plates) relative to the control group (p

In the placenta, 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) limits fetal glucocorticoid exposure and its inhibition has been associated to low birth weight. Its expression, encoded by the HSD11B2 gene is regulated by DNA methylation. We hypothesized that maternal diets supplemented with folic acid (FA) during pregnancy modify the expression of placental HSD11B2 through gene methylation. Wistar rats were fed with high (8 mg/kg) or normal low (1mg/kg, control) levels of FA during pregnancy. Concentrations of mRNA and protein in placentas were determined by qRT-PCR and Western blot respectively. Methylation in five CpG sites of the placental HSD11B2 promoter (-378 to -275) was analyzed by bacterial cloning and subsequent sequencing. In the FA-supplemented group, mRNA and protein levels of 11β-HSD2 decreased by 58% and increased by 89%, respectively, only in placentas attached to males. In controls, most CpG sites were not methylated except for the CpG2 site which was 80% methylated. CpG2 methylation level increased under the FA treatment; however, only in placentas attached to females was this increase significant (113%). This change was not related to HSD11B2 expression. Fetal weight of females from FA- supplemented mothers was 6% higher than females from control mothers. In conclusion, this is the first study reporting that FA over supplementation during pregnancy modifies the placental HSD11B2 gene expression and methylation in a sex-dependent manner, suggesting that maternal diets with high content of FA can induce early sex-specific responses, which may lead to long-term consequences for the offspring.

Aim: In response to DNA damage the serine/threonine-specific protein kinase checkpoint kinase 1 (CHK1) is activated allowing cells to enter S phase (S) and G2 phase (G2) cell-cycle arrest. CHK1 inhibitors are expected to prevent cells from entering such arrest, thereby enhancing DNA damage-induced cytotoxicity. In contrast, normal cells with intact ataxia–telangiectasia mutated (ATM), CHK2 and tumour suppressor protein 53 (P53) signalling are still able to enter cell-cycle arrest using the functioning G1/S checkpoint, thereby being rescued from enhanced cytotoxicity. The main objective of this work is to investigate the in vitro effects of the novel CHK1 inhibitor SRA737 on pairs of non-small cell lung cancer (NSCLC) and colorectal cancer (CRC) cell lines, all with genetic aberrations rendering them susceptible to replication stress but of differing tumour protein 53 (TP53) gene status, focusing on DNA damage induction and the subsequent effects on cell proliferation and viability. Methods: NSCLC cell lines H23 [TP53 mutant (MUT)] and A549 [TP53 wild-type (WT)] and CRC cell lines HT29 (TP53 MUT) and HCT116 (TP53 WT) were incubated with differing micromolar concentrations of SRA737 for 24 h and then analysed using alkaline comet and phosphorylated H2A.X variant histone (γH2AX)-foci assays to assess mostly DNA single strand break and double strand break damage, respectively. Cell-counting/trypan blue staining was also performed to assess cell proliferation/viability. Results: Clear concentration-dependent increases in comet formation and γH2AX-foci/cell were noted for the TP53 MUT cells with no or lower increases being noted in the corresponding TP53 WT cells. Also, greater anti-proliferative and cell killing effects were noted in the TP53 MUT cells than in the TP53 WT cells. Conclusions: This study’s data suggests that P53 status/functioning is a key factor in determining the sensitivity of NSCLC and CRC cancer cells towards CHK1 inhibition, even in circumstances conducive to high replicative stress.