Relationship of dietary pattern with body composition and symptoms in patients with COPD

This study explored the relationship of dietary patterns with body composition and symptoms in patients with COPD. Data collection included: dietary pattern – n. meals/day; period of the day of highest food intake (morning [6 AM–12 PM], afternoon [12–18 PM], and evening [18 PM–6 AM]); the time interval between meals (3-4h, 5-6h, 9-10h), and daily energy and nutrient intake using a semiquantitative food frequency questionnaire (last 12 months); body composition – body mass index (BMI), % fat mass (%FM), % fat-free mass (%FFM), % total muscle mass (%MM), fat-free mass index (FFMI) and visceral fat index (VAT) (SECA mBCA 525); symptoms – dyspnoea (modified Medical Research Council Dyspnea Scale, mMRC), fatigue (Checklist of Individual Strength, CIS20-P total score), impact of COPD (COPD Assessment Test, CAT). Pearson’s (r) or Spearman’s (ρ) correlations were conducted. 18 patients participated (16 males, 68±7 years old, FEV1 43±20% predicted, BMI 25±5kg/m2, FFMI 18±3kg/m2). Most participants reported having 3-4 meals/day (n=14, 78%) with a 3-4-hour interval (n=15, 83%). Moderate correlations were found between %FM and carbohydrates (ρ=-.501) and between FFMI and monosaturated fat (r=.476) (p.05). Energy and nutrient intake are related to COPD symptoms and body composition. The nature of these relationships should be explored.info:eu-repo/semantics/publishedVersio

Foliar Spraying of Solanum tuberosum L. with CaCl2 and Ca(NO3)2: Interactions with Nutrients Accumulation in Tubers

Calcium is essential for plants, yet as its mobility is limited, the understanding of the rate of Ca2+ accumulation and deposition in tissues of tubers, as well as the interactions with other critical nutrients prompted this study. To assess the interactions and differential accumulation of micro and macronutrients in the tissues of tubers, Solanum tuberosum L. varieties Agria and Rossi were cultivated and, after the beginning of tuberization, four foliar sprayings (at 8–10 day intervals) with CaCl2 (3 and 6 kg ha1) or Ca(NO3)2 (2 and 4 kg ha1) solutions were performed. It was found that both fertilizers increased Ca accumulation in tubers (mostly in the parenchyma tissues located in the center of the equatorial region). The functioning of the photosynthetic apparatus was not affected until the 3rd application but was somewhat affected when approaching the end of the crop cycle (after the 4th application), although the lower dose of CaCl2 seemed to improve the photochemical use of energy, particularly when compared with the greater dose of Ca(NO3)2. Still, none of these impacts modified tuber height and diameter. Following the increased accumulation of Ca, in the tubers of both varieties, the mean contents of P, K, Na, Fe, and Zn revealed different accumulation patterns. Moreover, accumulation of K, Fe, Mn, and Zn prevailed in the epidermis, displaying a contrasting pattern relative to Ca. Therefore, Ca accumulation revealed a heterogeneous trend in the different regions analyzed, and Ca enrichment of tubers altered the accumulation of other nutrientsinfo:eu-repo/semantics/publishedVersio

Mineral Monitorization in Different Tissues of Solanum tuberosum L. during Calcium Biofortification Process

Funding Information: This work received funding from PDR2020-101-030719 and the Fundação para a Ciência e a Tecnologia, I.P. (FCT), Portugal, through the research units UIDP/04035/2020 (GeoBioTec), UIDB/00239/2020 (CEF), and UID/FIS/04559/2013 (LIBPhys). This work was further supported by the grant of the Fundação para a Ciência e Tecnologia (FCT) UI/BD/150806/2020. Publisher Copyright: © 2022 by the authors.Calcium is one of the 16 essential elements for plants, being required as Ca2+ and being involved in several fundamental processes (namely, in the stability and integrity of the cell wall, the development of plant tissue, cell division, and in stress responses). Moreover, Ca plays an important role in potato production. In this context, this study aimed to monitor the culture development (in situ and using an unmanned aerial vehicle (UAV)) and the mineral content of four essential elements (Ca, P, K, and S) in different organs of Solanum tuberosum L. (roots, stems, leaves, and tubers) during a calcium biofortification process, carried out with two types of solutions (CaCl2 and Ca-EDTA) with two concentrations (12 and 24 kg∙ha−1). The calcium content generally increased in the S. tuberosum L. organs of both varieties and showed, after the last foliar application, an increase in Ca content that varied between 5.7–95.6% and 20.7–33%, for the Picasso and Agria varieties, respectively. The patterns of accumulation in both varieties during the biofortification process were different between the variety and mineral element. Regarding the quality analysis carried out during the development of the tubers, only the Agria variety was suitable for industrial processing after the last foliar application.publishersversionpublishe

Dysregulated RNA polyadenylation contributes to metabolic impairment in non-alcoholic fatty liver disease

Pre-mRNA processing is an essential mechanism for the generation of mature mRNA and the regulation of gene expression in eukaryotic cells. While defects in pre-mRNA processing have been implicated in a number of diseases their involvement in metabolic pathologies is still unclear. Here, we show that both alternative splicing and alternative polyadenylation, two major steps in pre-mRNA processing, are significantly altered in non-alcoholic fatty liver disease (NAFLD). Moreover, we find that Serine and Arginine Rich Splicing Factor 10 (SRSF10) binding is enriched adjacent to consensus polyadenylation motifs and its expression is significantly decreased in NAFLD, suggesting a role mediating pre-mRNA dysregulation in this condition. Consistently, inactivation of SRSF10 in mouse and human hepatocytes in vitro, and in mouse liver in vivo, was found to dysregulate polyadenylation of key metabolic genes such as peroxisome proliferator-activated receptor alpha (PPARA) and exacerbate diet-induced metabolic dysfunction. Collectively our work implicates dysregulated pre-mRNA polyadenylation in obesity-induced liver disease and uncovers a novel role for SRSF10 in this process

Liver RBFOX2 regulates cholesterol homeostasis via Scarb1 alternative splicing in mice

RNA alternative splicing (AS) expands the regulatory potential of eukaryotic genomes. The mechanisms regulating liver-specific AS profiles and their contribution to liver function are poorly understood. Here, we identify a key role for the splicing factor RNA-binding Fox protein 2 (RBFOX2) in maintaining cholesterol homeostasis in a lipogenic environment in the liver. Using enhanced individual-nucleotide-resolution ultra-violet cross-linking and immunoprecipitation, we identify physiologically relevant targets of RBFOX2 in mouse liver, including the scavenger receptor class B type I (Scarb1). RBFOX2 function is decreased in the liver in diet-induced obesity, causing a Scarb1 isoform switch and alteration of hepatocyte lipid homeostasis. Our findings demonstrate that specific AS programmes actively maintain liver physiology, and underlie the lipotoxic effects of obesogenic diets when dysregulated. Splice-switching oligonucleotides targeting this network alleviate obesity-induced inflammation in the liver and promote an anti-atherogenic lipoprotein profile in the blood, underscoring the potential of isoform-specific RNA therapeutics for treating metabolism-associated diseases

Causes of rail staff fatigue: results of qualitative analysis and a diary study

The purpose of this study was to investigate the causes of fatigue among rail staff by analysing qualitative data and conducting an online diary study. It had a closer look at the experience of fatigue among rail staff and brought a more detailed blueprint picture of fatigue and its causes in the rail staff’s real-life. Study 1 analysed 133 responses of qualitative data from rail staff, and Study 2 was a diary study examining fatigue and its related risk factors before and after work, on the first and the last day of a working week in 19 rail staff. The findings from the two studies, using different methodologies, showed similar results that fatigue among rail staff was a result of heavy workload and a high workload would further increase fatigue. Fatigue before work mainly resulted from sleep quality, length of sleep, and the time spent on commute, while fatigue after work resulted from the perceived workload and shift type. Evidence has demonstrated that overtime work, specific shift patterns, insufficient rest days between opposed shifts, and poor timing of breaks during work were also associated with fatigue

Genetic determinants of risk in pulmonary arterial hypertension: international genome-wide association studies and meta-analysis

Background Rare genetic variants cause pulmonary arterial hypertension, but the contribution of common genetic variation to disease risk and natural history is poorly characterised. We tested for genome-wide association for pulmonary arterial hypertension in large international cohorts and assessed the contribution of associated regions to outcomes. Methods We did two separate genome-wide association studies (GWAS) and a meta-analysis of pulmonary arterial hypertension. These GWAS used data from four international case-control studies across 11744 individuals with European ancestry (including 2085 patients). One GWAS used genotypes from 5895 whole-genome sequences and the other GWAS used genotyping array data from an additional 5849 individuals. Cross-validation of loci reaching genome-wide significance was sought by meta-analysis. Conditional analysis corrected for the most significant variants at each locus was used to resolve signals for multiple associations. We functionally annotated associated variants and tested associations with duration of survival. All-cause mortality was the primary endpoint in survival analyses. Findings A locus near SOX17 (rs10103692, odds ratio 1·80 [95% CI 1·55–2·08], p=5·13×10– ¹⁵) and a second locus in HLA-DPA1 and HLA-DPB1 (collectively referred to as HLA-DPA1/DPB1 here; rs2856830, 1·56 [1·42–1·71], p=7·65×10– ²⁰) within the class II MHC region were associated with pulmonary arterial hypertension. The SOX17 locus had two independent signals associated with pulmonary arterial hypertension (rs13266183, 1·36 [1·25–1·48], p=1·69×10– ¹²; and rs10103692). Functional and epigenomic data indicate that the risk variants near SOX17 alter gene regulation via an enhancer active in endothelial cells. Pulmonary arterial hypertension risk variants determined haplotype-specific enhancer activity, and CRISPR-mediated inhibition of the enhancer reduced SOX17 expression. The HLA-DPA1/DPB1 rs2856830 genotype was strongly associated with survival. Median survival from diagnosis in patients with pulmonary arterial hypertension with the C/C homozygous genotype was double (13·50 years [95% CI 12·07 to >13·50]) that of those with the T/T genotype (6·97 years [6·02–8·05]), despite similar baseline disease severity. Interpretation This is the first study to report that common genetic variation at loci in an enhancer near SOX17 and in HLA-DPA1/DPB1 is associated with pulmonary arterial hypertension. Impairment of SOX17 function might be more common in pulmonary arterial hypertension than suggested by rare mutations in SOX17. Further studies are needed to confirm the association between HLA typing or rs2856830 genotyping and survival, and to determine whether HLA typing or rs2856830 genotyping improves risk stratification in clinical practice or trials. Funding UK NIHR, BHF, UK MRC, Dinosaur Trust, NIH/NHLBI, ERS, EMBO, Wellcome Trust, EU, AHA, ACClinPharm, Netherlands CVRI, Dutch Heart Foundation, Dutch Federation of UMC, Netherlands OHRD and RNAS, German DFG, German BMBF, APH Paris, INSERM, Université Paris-Sud, and French ANR

GWAS meta-analysis of intrahepatic cholestasis of pregnancy implicates multiple hepatic genes and regulatory elements

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disorder affecting 0.5–2% of pregnancies. The majority of cases present in the third trimester with pruritus, elevated serum bile acids and abnormal serum liver tests. ICP is associated with an increased risk of adverse outcomes, including spontaneous preterm birth and stillbirth. Whilst rare mutations affecting hepatobiliary transporters contribute to the aetiology of ICP, the role of common genetic variation in ICP has not been systematically characterised to date. Here, we perform genome-wide association studies (GWAS) and meta-analyses for ICP across three studies including 1138 cases and 153,642 controls. Eleven loci achieve genome-wide significance and have been further investigated and fine-mapped using functional genomics approaches. Our results pinpoint common sequence variation in liver-enriched genes and liver-specific cis-regulatory elements as contributing mechanisms to ICP susceptibility