Prenatal and childhood exposure to per-/polyfluoroalkyl substances (PFASs) and its associations with childhood overweight and/or obesity: a systematic review with meta- analyses

Background. Per-/polyfluoroalkyl substances (PFASs) are persistent organic pollutants and suspected endocrine disrupters. Objective. The aim of this work was to conduct a systematic review with meta-analysis to summarise the associations between prenatal or childhood exposure to PFASs and childhood overweight/obesity. Methods. The search was performed on the bibliographic databases PubMed and Embase with text strings containing terms related to prenatal, childhood, overweight, obesity, and PFASs. Only papers describing a biomonitoring study in pregnant women or in children up to 18 years that assessed body mass index (BMI), waist circumference (WC), or fat mass in children were included. When the estimates of the association between a PFAS and an outcome were reported from at least 3 studies, a meta-analysis was conducted; moreover, to correctly compare the studies, we developed a method to convert the different effect estimates and made them comparable each other. Results. In total, 354 and 565 articles were retrieved from PubMed and Embase, respectively, resulting in a total of 613 articles after merging duplicates. The papers included in this systematic review were 31: 18 evaluating prenatal exposure to PFASs, 11 childhood exposure, and 2 both. Overall, results were conflicting, with positive, negative, and null associations. 17 papers were included in meta-analyses (12 prenatal, 3 children, and 2 both). The method implemented for data conversion allowed a suitable comparison of different effect estimates. Meta-analyses evaluating the associations between prenatal exposure to PFOA, PFOS, PFNA, PFHxS, and the outcomes BMI, WC, and Dual-Energy X-ray Absorptiometry (DXA) showed no significant results. Meta-analyses for the associations between childhood exposure to PFASs and the outcomes BMI showed no significant results except for a negative association between PFNA and BMI (pooled estimate from a random effect model: -0.045; 95%CI: -0.087, -0.002), however, more studies are required to confirm the strength of this association. Conclusion. To increase the reliability of meta-analyses in environmental epidemiology we suggest the conversion of effect estimates to compare different studies. The pooled evidence of the meta-analyses of the present study suggests that there is no overall association between exposure to PFASs and childhood overweight/obesity

Development and Application of an LC-MS/MS Untargeted Exposomics Method with a Separated Pooled Quality Control Strategy

Pooled quality controls (QCs) are usually implemented within untargeted methods to improve the quality of datasets by removing features either not detected or not reproducible. However, this approach can be limiting in exposomics studies conducted on groups of exposed and nonexposed subjects, as compounds present at low levels only in exposed subjects can be diluted and thus not detected in the pooled QC. The aim of this work is to develop and apply an untargeted workflow for human biomonitoring in urine samples, implementing a novel separated approach for preparing pooled quality controls. An LC-MS/MS workflow was developed and applied to a case study of smoking and non-smoking subjects. Three different pooled quality controls were prepared: mixing an aliquot from every sample (QC-T), only from non-smokers (QC-NS), and only from smokers (QC-S). The feature tables were filtered using QC-T (T-feature list), QC-S, and QC-NS, separately. The last two feature lists were merged (SNS-feature list). A higher number of features was obtained with the SNS-feature list than the T-feature list, resulting in identification of a higher number of biologically significant compounds. The separated pooled QC strategy implemented can improve the nontargeted human biomonitoring for groups of exposed and nonexposed subjects

A Metabolomics-Based Investigation of the Effects of a Short-Term Body Weight Reduction Program in a Cohort of Adolescents with Obesity: A Prospective Interventional Clinical Study

Metabolomics applied to assess the response to a body weight reduction program (BWRP) may generate valuable information concerning the biochemical mechanisms/pathways underlying the BWRP-induced cardiometabolic benefits. The aim of the present study was to establish the BWRP-induced changes in the metabolomic profile that characterizes the obese condition. In particular, a validated liquid chromatography–tandem mass spectrometry (LC–MS/MS) targeted metabolomic approach was used to determine a total of 188 endogenous metabolites in the plasma samples of a cohort of 42 adolescents with obesity (female/male = 32/10; age = 15.94 ± 1.33 year; body mass index standard deviation score (BMI SDS) = 2.96 ± 0.46) who underwent a 3-week BWRP, including hypocaloric diet, physical exercise, nutritional education, and psychological support. The BWRP was capable of significantly improving body composition (e.g., BMI SDS, p < 0.0001), glucometabolic homeostasis (e.g., glucose, p < 0.0001), and cardiovascular function (e.g., diastolic blood pressure, p = 0.016). A total of 64 metabolites were significantly reduced after the intervention (at least p < 0.05), including 53 glycerophospholipids (23 PCs ae, 21 PCs aa, and 9 lysoPCs), 7 amino acids (tyrosine, phenylalanine, arginine, citrulline, tryptophan, glutamic acid, and leucine), the biogenic amine kynurenine, 2 sphingomyelins, and (free) carnitine (C0). On the contrary, three metabolites were significantly increased after the intervention (at least p < 0.05)—in particular, glutamine, trans-4-hydroxyproline, and the octadecenoyl-carnitine (C18:1). In conclusion, when administered to adolescents with obesity, a short-term BWRP is capable of changing the metabolomic profile in the plasma

Phenolic profile and antioxidant activity of different raisin (Vitis vinifera L.) samples

In the last years, the interest in non-alcoholic grape products, aa potential alternative sources of phenolic compounds, has considerably increased. Raisins are dried grapes largely consumed in the Mediterranean area for the positive pattern of nutrients, and for recent data describing potential benefits on human health. Among the health-promoting substances contained in raisins, flavonoids seem the most interesting. The aim of this study was the application of in vitromethods for the characterization of the phenolic fraction of five samples of raisins, and, in parallel, the evaluation of their antioxidant activity. The methods were: 1) Folin-Cocalteau's assay for the quantification of total polyphenol content; 2) vanillin assay for the measure of flavan-3-ols content; 3) DPPH (1,1,-diphenil-2\u2014picrylhydrazyl) spectrophotometric assay for the assessment of radical scavenging activity; 4) High Performance Thin Layer Chromatography for separation of phenolic substances and assessment of their antioxidant activity; 5) chromatographic separation and quantification of main active substances was performed by HPLC-DAD. Although raisins showed a high variability in their composition, they can be considered as a promising source of phenolic compounds with a significant antioxidant activity for the human diet

Towards a map of the Upper Pleistocene loess of the Po Plain Loess Basin (Northern Italy)

Upper Pleistocene (MIS 4-2) loess sequences occur in most of continental Europe and in Northern Italy along the Po Plain Loess Basin. Loess is distributed along the flanks of the Po Plain and was deposited on glacial deposits, fluvial terraces, uplifted isolated hills, karst plateaus, slopes and basins of secondary valleys. Loess bodies are generally tiny and affected by pedogenesis, being locally slightly reworked by slope processes and bioturbation. Notwithstanding, loess in the Po Plain is an important archive of paleoenviron-mental record and its mapping provides new insights in paleoenvironmental and palaeoseismic reconstructions of Northern Ital

Evaluation of the Anti-Inflammatory Activity of Raisins (Vitis vinifera L.) in Human Gastric Epithelial Cells: A Comparative Study

Raisins (Vitis vinifera L.) are dried grapes largely consumed as important source of nutrients and polyphenols. Several studies report health benefits of raisins, including anti-inflammatory and antioxidant properties, whereas the anti-inflammatory activity at gastric level of the hydro-alcoholic extracts, which are mostly used for food supplements preparation, was not reported until now. The aim of this study was to compare the anti-inflammatory activity of five raisin extracts focusing on Interleukin (IL)-8 and Nuclear Factor (NF)-\u3baB pathway. Raisin extracts were characterized by High Performance Liquid Chromatography-Diode Array Detector (HPLC-DAD) analysis and screened for their ability to inhibit Tumor necrosis factor (TNF)\u3b1-induced IL-8 release and promoter activity in human gastric epithelial cells. Turkish variety significantly inhibited TNF\u3b1-induced IL-8 release, and the effect was due to the impairment of the corresponding promoter activity. Macroscopic evaluation showed the presence of seeds, absent in the other varieties; thus, hydro-alcoholic extracts from fruits and seeds were individually tested on IL-8 and NF-\u3baB pathway. Seed extract inhibited IL-8 and NF-\u3baB pathway, showing higher potency with respect to the fruit. Although the main effect was due to the presence of seeds, the fruit showed significant activity as well. Our data suggest that consumption of selected varieties of raisins could confer a beneficial effect against gastric inflammatory disease

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure &lt; 100 mmHg (n = 1127), estimated glomerular filtration rate &lt; 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Development and Application of an LC-MS/MS Untargeted Exposomics Method with a Separated Pooled Quality Control Strategy

Pooled quality controls (QCs) are usually implemented within untargeted methods to improve the quality of datasets by removing features either not detected or not reproducible. However, this approach can be limiting in exposomics studies conducted on groups of exposed and nonexposed subjects, as compounds present at low levels only in exposed subjects can be diluted and thus not detected in the pooled QC. The aim of this work is to develop and apply an untargeted workflow for human biomonitoring in urine samples, implementing a novel separated approach for preparing pooled quality controls. An LC-MS/MS workflow was developed and applied to a case study of smoking and non-smoking subjects. Three different pooled quality controls were prepared: mixing an aliquot from every sample (QC-T), only from non-smokers (QC-NS), and only from smokers (QC-S). The feature tables were filtered using QC-T (T-feature list), QC-S, and QC-NS, separately. The last two feature lists were merged (SNS-feature list). A higher number of features was obtained with the SNS-feature list than the T-feature list, resulting in identification of a higher number of biologically significant compounds. The separated pooled QC strategy implemented can improve the nontargeted human biomonitoring for groups of exposed and nonexposed subjects

Alternating recombinant and natural alpha-interferon helps to prevent clinical resistance to interferon in cutaneous T-cell lymphoma treatment.

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