Long daytime napping is associated with increased adiposity and type 2 diabetes in an elderly population with metabolic syndrome

Research examining associations between objectively-measured napping time and type 2 diabetes (T2D) is lacking. This study aimed to evaluate daytime napping in relation to T2D and adiposity measures in elderly individuals from the Mediterranean region. A cross-sectional analysis of baseline data from 2190 elderly participants with overweight/obesity and metabolic syndrome, in the PREDIMED-Plus trial, was carried out. Accelerometer-derived napping was measured. Prevalence ratios (PR) and 95% confidence intervals (CI) for T2D were obtained using multivariable-adjusted Cox regression with constant time. Linear regression models were fitted to examine associations of napping with body mass index (BMI) and waist circumference (WC). Participants napping ≥90 min had a higher prevalence of T2D (PR 1.37 (1.06, 1.78)) compared with those napping 5 to <30 min per day. Significant positive associations with BMI and WC were found in those participants napping ≥30 min as compared to those napping 5 to <30 min per day. The findings of this study suggest that longer daytime napping is associated with higher T2D prevalence and greater adiposity measures in an elderly Spanish population at high cardiovascular risk

Dietary diversity and nutritional adequacy among an older Spanish population with Metabolic Syndrome in the PREDIMED-Plus study: a cross-sectional analysis

Dietary guidelines emphasize the importance of a varied diet to provide an adequate nutrient intake. However, an older age is often associated with consumption of monotonous diets that can be nutritionally inadequate, increasing the risk for the development or progression of diet-related chronic diseases, such as metabolic syndrome (MetS). To assess the association between dietary diversity (DD) and nutrient intake adequacy and to identify demographic variables associated with DD, we cross-sectionally analyzed baseline data from the PREDIMED-Plus trial: 6587 Spanish adults aged 55–75 years, with overweight/obesity who also had MetS. An energy-adjusted dietary diversity score (DDS) was calculated using a 143-item validated semi-quantitative food frequency questionnaire (FFQ). Nutrient inadequacy was defined as an intake below 2/3 of the dietary reference intake (DRI) forat least four of 17 nutrients proposed by the Institute of Medicine (IOM). Logistic regression models were used to evaluate the association between DDS and the risk of nutritionally inadequate intakes. In the higher DDS quartile there were more women and less current smokers. Compared with subjects in the highest DDS quartile, those in the lowest DDS quartile had a higher risk of inadequate nutrient intake: odds ratio (OR) = 28.56 (95% confidence interval (CI) 20.80–39.21). When we estimated food varietyfor each of the food groups, participants in the lowest quartile had a higher risk of inadequate nutrient intake for the groups of vegetables, OR = 14.03 (95% CI 10.55–18.65), fruits OR = 11.62 (95% CI 6.81–19.81), dairy products OR = 6.54 (95% CI 4.64–9.22) and protein foods OR = 6.60 (95% CI 1.96–22.24). As DDS decreased, the risk of inadequate nutrients intake rose. Given the impact of nutrient intake adequacy on the prevention of non-communicable diseases, health policies should focus on the promotion of a healthy varied diet, specifically promoting the intake of vegetables and fruit among population groups with lower DDS such as men, smokers or widow(er)s. View Full-Tex

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Evaluation of Two Active System Encapsulant Matrices with Quercetin and <i>Bacillus clausii</i> for Functional Foods

Currently, demand for functional foods is increasing in the public interest in order to improve life expectations and general health. Food matrices containing probiotic microorganisms and active compounds encapsulated into carrier agents are essential in this context. Encapsulation via the lyophilisation method is widely used because oxidation reactions that affect physicochemical and nutritional food properties are usually avoided. Encapsulated functional ingredients, such as quercetin and Bacillus clausii, using two carrier agents’ matrices—I [inulin (IN), lactose (L) and maltodextrin (MX)] and II [arabic (A), guar (G), and xanthan (X) gums)]—are presented in this work. A D-optimal procedure involving 59 experiments was designed to evaluate each matrix’s yield, viability, and antioxidant activity (AA). Matrix I (33.3 IN:33.3 L:33.3 MX) and matrix II (33.3 A:33.3 G:33.3 X) exhibited the best yield; viability of 9.7 log10 CFU/g and 9.73 log10 CFU/g was found in matrix I (using a ratio of 33.3 IN:33.3 L:33.3 MX) and matrix II (50 G:50 X), respectively. Results for the antioxidant capacity of matrix I (100 IN:0 L:0M X) and matrix II (0 A:50 G:50 X) were 58.75 and 55.54 (DPPH* scavenging activity (10 µg/mL)), respectively. Synergy between matrices I and II with use of 100IN:0L:OMX and 0A:50G:50X resulted in 55.4 log10 CFU/g viability values; the antioxidant capacity was 9. 52 (DPPH* scavenging activity (10 µg/mL). The present work proposes use of a carrier agent mixture to produce a functional ingredient with antioxidant and probiotic properties that exceed the minimum viability, 6.0 log10 CFU/g, recommended by the FAO/WHO (2002) to be probiotic, and that contributes to the recommended daily quercetin intake of 10–16 mg/day or inulin intake of 10–20 g/day and dietary fibre intake of 25–38 g per day

CoCl₂, a Mimic of Hypoxia, Induces Formation of Polyploid Giant Cells with Stem Characteristics in Colon Cancer

<div><p>The induction of polyploidy is considered the reproductive end of cells, but there is evidence that polyploid giant cancer cells (PGCCs) contribute to cell repopulation during tumor relapse. However, the role of these cells in the development, progression and response to therapy in colon cancer remains undefined. Therefore, the main objective of this study was to investigate the generation of PGCCs in colon cancer cells and identify mechanisms of formation. Treatment of HCT-116 and Caco-2 colon cancer cells with the hypoxia mimic CoCl₂ induced the formation of cells with larger cell and nuclear size (PGCCs), while the cells with normal morphology were selectively eliminated. Cytometric analysis showed that CoCl₂ treatment induced G2 cell cycle arrest and the generation of a polyploid cell subpopulation with increased cellular DNA content. Polyploidy of hypoxia-induced PGCCs was confirmed by FISH analysis. Furthermore, CoCl₂ treatment effectively induced the stabilization of HIF-1α, the differential expression of a truncated form of p53 (p47) and decreased levels of cyclin D1, indicating molecular mechanisms associated with cell cycle arrest at G2. Generation of PGCCs also contributed to expansion of a cell subpopulation with cancer stem cells (CSCs) characteristics, as indicated by colonosphere formation assays, and enhanced chemoresistance to 5-fluorouracil and oxaliplatin. In conclusion, the pharmacological induction of hypoxia in colon cancer cells causes the formation of PGCCs, the expansion of a cell subpopulation with CSC characteristics and chemoresistance. The molecular mechanisms involved, including the stabilization of HIF-1 α, the involvement of p53/p47 isoform and cell cycle arrest at G2, suggest novel targets to prevent tumor relapse and treatment failure in colon cancer.</p></div

PGCCs enrichment in colon cancer cells increases colonosphere formation capability.

<p>After enrichment in PGCCs by treatment for 48 µM CoCl₂, surviving cells were cultured at clonal density with serum free medium in low-adherence plates and the number of primary formed colonospheres was evaluated after seven days. Primary colonospheres were disaggregated and the resulting cell population was cultured again at clonal density for the formation of secondary colonospheres. Graphics show the numbers of primary (grey bars) and secondary (black bars) colonospheres formed by HCT-116 and Caco-2 cells after each treatment. The data represent the mean ± SD of three independent cultures (*p<0,05, compared to control).</p

Alteration of cell cycle in colon cancer exposed to CoCl₂.

<p>Both HCT-116 (A) and Caco-2 (B) cells were treated with the indicated doses of CoCl₂ for 6 or 48 hours. Next, a cell cycle analysis was performed by flow cytometry. The bar graphs on the right show the relative changes to control cells in the percentage of cells in different phases of the cell cycle. Data represent the mean ± SD of three independent cultures.</p

Morphological changes of colon cancer cells after treatment with CoCl₂.

<p>A) Both HCT-116 and Caco-2 cell lines were treated with 300 µM CoCl₂ for 48 hours. All photomicrographs were obtained using the same final magnification (×200). Scale bar corresponds to 20 microns. Staining of cell nuclei with DAPI was performed to evaluate the average nuclear size (Final magnification, ×200). Scale bars correspond to 20 microns. B) Changes in nuclear size after CoCl₂ treatment. Data represent the mean ± SD of three independent experiments (*p<0.05, compared with the control).</p

HIF-1α, p53, and cyclin D1 expression in colon cancer cells treated with CoCl₂.

<p>A) HCT-116 and Caco-2 cells were treated with the indicated doses of CoCl₂ for 6 hours and then the expression of HIF-1α, p53 and cyclin D1 proteins was evaluated using specific antibodies. B) The corresponding densitometric analyses of the protein bands detected in the immunoblots and normalized to the signal of β-actin are also shown. Data are means ± SD of three independent experiments. (*p<0.05, compared with the control).</p