Bridging the technological divide: Stigmas and challenges with technology in digital brain health studies of older adults

The COVID-19 pandemic has increased adoption of remote assessments in clinical research. However, longstanding stereotypes persist regarding older adults\u27 technology familiarity and their willingness to participate in technology-enabled remote studies. We examined the validity of these stereotypes using a novel technology familiarity assessment

Dietary influence on systolic and diastolic blood pressure in the TwinsUK cohort

Nutrition plays a key role in blood pressure (BP) regulation. Here, we examine associations between nutrient intakes and BP in a large predominantly female population-based cohort. We assessed the correlation between 45 nutrients (from food frequency questionnaires) and systolic BP/diastolic BP (SBP/DBP) in 3889 individuals from TwinsUK not on hypertensive treatments and replicated in an independent subset of monozygotic twins discordant for nutrient intake (17–242 pairs). Results from both analyses were meta-analysed. For significant nutrients, we calculated heritability using structural equation modelling. We identified and replicated 15 nutrients associated with SBP, 9 also being associated with DBP, adjusting for covariates and multiple testing. 14 of those had a heritable component (h2: 27.1–57.6%). Strong associations with SBP were observed for riboflavin (Beta(SE) = −1.49(0.38), P = 1.00 × 10−4) and tryptophan (−0.31(0.01), P = 5 × 10−4), while with DBP for alcohol (0.05(0.07), P = 1.00 × 10−4) and lactose (−0.05(0.0), P = 1.3 × 10−3). Two multivariable nutrient scores, combining independently SBP/DBP-associated nutrients, explained 22% of the variance in SBP and 13.6% of the variance in DBP. Moreover, bivariate heritability analysis suggested that nutrients and BP share some genetic influences. We confirm current understanding and extend the panel of dietary nutrients implicated in BP regulation underscoring the value of nutrient focused dietary research in preventing and managing hypertension

Patterns of Exposure to Cumulative Risk Through Age 2 and Associations with Problem Behaviors at Age 4.5: Evidence from Growing Up in New Zealand.

Exposure to cumulative risk (CR) has important implications for child development, yet little is known about how frequency, persistence, and timing of CR exposure during early childhood predict behavioral problems already before school start. We examine prospective longitudinal associations between patterns of CR exposure from third trimester through 2 years and subsequent behavior problems at 4.5 years. In 6156 diverse children in the Growing Up in New Zealand longitudinal study, the presence of 12 risk factors, spanning maternal health, social status, and home and neighborhood environment, defined CR and were assessed at last trimester and 9 months and 2 years of age. At child age 4.5 years, mothers completed the Strengths and Difficulties Questionnaire, where a score ≥ 16 indicated an abnormal level of problem behaviors (ALPB). Children exposed to a CR ≥ 1 at least once in early development, compared to those with consistent CR = 0, showed a significantly higher likelihood of ALPB at 4.5 years. Consistent high exposure to CR ≥ 4 across all three assessments had the highest prevalence (44%) of ALPB at age 4.5. Children with high CR exposure on two of three, compared to on all three, time points in early development did not evidence a significantly reduced prevalence (32%-41%) of ALPB. The common co-occurrence of risk factors and their significant developmental impact when accumulated early in life underscore the need for systematic multisector intervention and policy implementation during pregnancy and shortly after birth to improve outcomes for vulnerable children

Increased potassium intake from fruit and vegetables or supplements does not lower blood pressure or improve vascular function in UK men and women with early hypertension: a randomised controlled trial

K-rich fruit and vegetables may lower blood pressure (BP) and improve vascular function. A randomised controlled trial (ISRCTN50011192) with a cross-over design was conducted in free-living participants with early stages of hypertension (diastolic BP . 80 and , 100 mmHg, not receiving BP-lowering medication) to test this hypothesis. Following a 3-week run-in period on a control diet, each subject completed four dietary 6-week dietary interventions (control þ placebo capsules, an additional 20 or 40 mmol K þ /d from fruit and vegetables or 40 mmol potassium citrate capsules/d) using a Latin square design with a washout period $ 5 weeks between the treatment periods. Out of fifty-seven subjects who were randomised, twenty-three male and twenty-five female participants completed the study; compliance to the intervention was corroborated by food intake records and increased urinary K þ excretion; plasma lipids, vitamin C, folate and homocysteine concentrations, urinary Na excretion, and body weight remained were unchanged. On the control diet, mean ambulatory 24 h systolic/diastolic BP were 132·3 (SD 12·0)/81·9 (SD 7·9) mmHg, and changes (Bonferroni's adjusted 95 % CI) compared with the control on the diets providing 20 and 40 mmol K þ /d as fruit and vegetables were 0·8 (23·5, 5·3)/0·8 (21·9, 3·5) and 1·7 (2 3·0, 5·3)/1·5 (2 1·5, 4·4), respectively, and were 1·8 (2 2·1, 5·8)/1·4 (2 1·6, 4·4) mmHg on the 40 mmol potassium citrate supplement, and were not statistically significant. Arterial stiffness, endothelial function, and urinary and plasma isoprostane and C-reactive protein (CRP) concentrations did not differ significantly between the diets. The present study provides no evidence to support dietary advice to increase K intake above usual UK intakes in the subjects with early stages of hypertension

Laser Capture and Deep Sequencing Reveals the Transcriptomic Programmes Regulating the Onset of Pancreas and Liver Differentiation in Human Embryos.

To interrogate the alternative fates of pancreas and liver in the earliest stages of human organogenesis, we developed laser capture, RNA amplification, and computational analysis of deep sequencing. Pancreas-enriched gene expression was less conserved between human and mouse than for liver. The dorsal pancreatic bud was enriched for components of Notch, Wnt, BMP, and FGF signaling, almost all genes known to cause pancreatic agenesis or hypoplasia, and over 30 unexplored transcription factors. SOX9 and RORA were imputed as key regulators in pancreas compared with EP300, HNF4A, and FOXA family members in liver. Analyses implied that current in vitro human stem cell differentiation follows a dorsal rather than a ventral pancreatic program and pointed to additional factors for hepatic differentiation. In summary, we provide the transcriptional codes regulating the start of human liver and pancreas development to facilitate stem cell research and clinical interpretation without inter-species extrapolation.This project received support from the UK Medical Research Council (MRC) (R.E.J. was a clinical research training fellow; additional funding from MR/L009986/1 to N.B. and N.A.H.; and MR/J003352/1 to K.P.H.), the Academy of Medical Sciences (supported by Wellcome Trust, MRC, British Heart Foundation, Arthritis Research UK, the Royal College of Physicians and Diabetes UK) (R.E.J.), the Society for Endocrinology (R.E.J.), the Wellcome Trust (N.A.H. was a senior fellow in clinical science, 088566; additional support from grant 105610/Z/14/Z), and the British Council and JDRF (14BX15NHBG to N.A.H.)

In vitro and in vivo modeling of lipid bioaccessibility and digestion from almond muffins: the importance of the cell-wall barrier mechanism

This study compares in vitro and in vivo models of lipid digestion from almond particles within a complex food matrix (muffins) investigating whether the cell-wall barrier regulates the bioaccessibility of nutrients within this matrix. Muffins containing small (AF) or large (AP) particles of almond were digested in triplicate using an in vitro dynamic gastric model (DGM, 1 h) followed by a static duodenal digestion (8 h). AF muffins had 97.1 ± 1.7% of their lipid digested, whereas AP muffins had 57.6 ± 1.1% digested. In vivo digestion of these muffins by an ileostomy volunteer (0–10 h) gave similar results with 96.5% and 56.5% lipid digested, respectively. The AF muffins produced a higher postprandial triacylglycerol iAUC response (by 61%) than the AP muffins. Microstructural analysis showed that some lipid remained encapsulated within the plant tissue throughout digestion. The cell-wall barrier mechanism is the main factor in regulating lipid bioaccessibility from almond particles

Phenotypic and functional analyses show stem cell-derived hepatocyte-like cells better mimic fetal rather than adult hepatocytes

Background & Aims: Hepatocyte-like cells (HLCs), differentiated from pluripotent stem cells by the use of soluble factors, can model human liver function and toxicity. However, at present HLC maturity and whether any deficit represents a true fetal state or aberrant differentiation is unclear and compounded by comparison to potentially deteriorated adult hepatocytes. Therefore, we generated HLCs from multiple lineages, using two different protocols, for direct comparison with fresh fetal and adult hepatocytes. Methods: Protocols were developed for robust differentiation. Multiple transcript, protein and functional analyses compared HLCs to fresh human fetal and adult hepatocytes. Results: HLCs were comparable to those of other laboratories by multiple parameters. Transcriptional changes during differentiation mimicked human embryogenesis and showed more similarity to pericentral than periportal hepatocytes. Unbiased proteomics demonstrated greater proximity to liver than 30 other human organs or tissues. However, by comparison to fresh material, HLC maturity was proven by transcript, protein and function to be fetal-like and short of the adult phenotype. The expression of 81% phase 1 enzymes in HLCs was significantly upregulated and half were statistically not different from fetal hepatocytes. HLCs secreted albumin and metabolized testosterone (CYP3A) and dextrorphan (CYP2D6) like fetal hepatocytes. In seven bespoke tests, devised by principal components analysis to distinguish fetal from adult hepatocytes, HLCs from two different source laboratories consistently demonstrated fetal characteristics. Conclusions: HLCs from different sources are broadly comparable with unbiased proteomic evidence for faithful differentiation down the liver lineage. This current phenotype mimics human fetal rather than adult hepatocytes