Developing a foundation information and academic skills programme for potential Student Nursing Associates.

This article outlines the development of 'Prepare to Progress', a preapplication programme for potential Student Nursing Associate (SNA) applicants at Gloucestershire Hospitals NHS Foundation Trust. Created collaboratively by the Trust's Library and Knowledge Services and Professional Education teams, the programme aims to provide realistic course expectations, teach study skills and boost confidence in using library services. Evaluation results indicate increased understanding of the SNA course, improved application decision-making, and enhanced academic confidence among participants. The programme demonstrates the valuable role of library services in preparing healthcare support workers for further education and addressing library anxiety. The study suggests benefits for both participants and library services.

Effects of multiple fluid intake on Urolithiasis by mendelian randomization study.

Urolithiasis, a common and recurrent condition, imposes a significant global health burden. This study investigates the causal relationship between various types of fluid intake and urolithiasis using univariable and multivariable Mendelian randomization (MR) approaches. Genetic data for urolithiasis were obtained from the FinnGen Consortium (n = 400,681), while genetic measures for nine fluid types were sourced from meta-analyses of genome-wide association studies (GWAS). The analysis revealed that genetically predicted coffee intake (OR: 0.571, 95% confidence interval (CI): 0.341-0.958, p = 0.034) and ground coffee intake (OR: 0.219, 95% CI: 0.005-0.923, p = 0.038) were protective factors for upper urinary calculi. Additionally, a standard deviation (SD) increase in tea intake was associated with a 53% reduction in risk (OR: 0.473, 95% CI: 0.320-0.700, p < 0.001). Conversely, milk intake (OR: 1.072, 95% CI: 1.018-1.130) and alcohol intakefrequency (OR: 1.304, 95% CI: 1.083-1.570, p = 0.005) increased the risk of upper urinary calculi. These findings highlight the association of tea with reduced risk of urolithiasis, instead for milk and alcohol intake, in formulating prevention strategies for urolithiasis.

Associations of combined accelerated biological aging and genetic susceptibility with incident dementia: a prospective study in the UK Biobank.

BACKGROUND: Accelerated biological aging has been verified to be a critical risk factor for a number of age-related diseases, but its role in dementia remained unclear. Whether it modified the effects of genetic factors was also unknown. This study evaluated the associations between accelerated biological aging and dementia and the moderating role of accelerated biological aging in the genetic susceptibility to the disease. METHODS: We included 200,731 participants in the UK biobank. Nine clinical blood biomarkers and chronological age were used to calculate Phenotypic age acceleration (PhenoAgeAccel), which is a novel indicator for accelerated biological aging. The associations of PhenoAgeAccel with dementia, both young-onset and late-onset dementia, were assessed by Cox proportional hazard models. Apolipoprotein E (APOE) alleles and polygenic risk scores (PRS) were used to evaluate the genetic risk of dementia. The interactions between genetic susceptibility and biological aging were tested on both multiplicative and additive scales. RESULTS: These findings showed individuals who were in the highest quartile of PhenoAgeAccel had a higher risk with incidence of dementia compared to individuals in the lowest quartile of PhenoAgeAccel (HR: 1.145 (95% CI: 1.050, 1.249)). Individuals with biologically older had a higher risk of dementia than individuals with biologically younger (HR: 1.069 (95% CI: 1.004, 1.138)). Furthermore, compared to individuals with biologically younger and low APOE ε4-related genetic risk, individuals with biologically younger and high APOE ε4-related genetic risk (HR:3.048 (95% CI: 2.811, 3.305)) had a higher risk of dementia than individuals with biologically older and high APOE ε4-related genetic risk (HR: 2.765 (95% CI: 2.523, 3.029)). Meanwhile, referring to low dementia PRS and biologically younger, the risk of dementia increased by 72.7% (HR: 1.727 (95% CI: 1.538, 1.939) in the biologically younger and high PRS group and 58.7% (HR: 1.587 (95% CI: 1.404, 1.793) in the biologically older and high PRS group, respectively. The negative interactions between PhenoAgeAccel with APOE ε4 and PRS were also tested on the additive scale. CONCLUSIONS: Accelerated biological aging could bring the extra risk of dementia but attenuate the effects of genetic risk on dementia. These findings provide insights for precise prevention and intervention of dementia.

Causal association between metabolites and upper gastrointestinal tumors: A Mendelian randomization study.

Upper gastrointestinal (UGI) tumors, notably gastric cancer (GC) and esophageal cancer (EC), are significant global health concerns due to their high morbidity and mortality rates. However, only a limited number of metabolites have been identified as biomarkers for these cancers. To explore the association between metabolites and UGI tumors, the present study conducted a comprehensive two­sample Mendelian randomization (MR) analysis using publicly available genetic data. In the present study, the causal relationships were examined between 1,400 metabolites and UGI cancer using methods such as inverse variance weighting and weighted medians, along with sensitivity analyses for heterogeneity and pleiotropy. Functional experiments were conducted to validate the MR results. The analysis identified 57 metabolites associated with EC and 58 with GC. Key metabolites included fructosyllysine [EC: Odds ratio (OR)=1.450, 95% confidence interval (CI)=1.087­1.934, P=0.011; GC: OR=1.728, 95% CI=1.202­2.483, P=0.003], 2'­deoxyuridine to cytidine ratio (EC: OR=1.464, 95% CI=1.111­1.929, P=0.007; GC: OR=1.464, 95% CI=1.094­1.957, P=0.010) and carnitine to protonylcarnitine (C3) ratio (EC: OR=0.655, 95% CI=0.499­0.861, P=0.002; GC: OR=0.664, 95% CI=0.486­0.906, P=0.010). Notably, fructosyllysine levels and the 2'­deoxyuridine to cytidine ratio were identified as risk factors for both EC and GC, while the C3 ratio served as a protective factor. Functional experiments demonstrated that fructosyllysine and the 2'­deoxyuridine to cytidine ratio promoted the proliferation of EC and GC cells, whereas carnitine inhibited their proliferation. In conclusion, the present findings provide insights into the causal factors and biomarkers associated with UGI tumors, which may be instrumental in guiding targeted dietary and pharmacological interventions, thereby contributing to the prevention and treatment of UGI cancer.

Interactions between muscle volume and body mass index on brain structure in the UK Biobank.

Background: Low skeletal muscle volume may increase dementia risk through mechanisms affecting brain structure. However, it is unclear whether this relationship exists outside of sarcopenia and/or varies by other factors. We aimed to study the interplay between skeletal muscle volume and factors, such as age, sex, and body mass index (BMI), in explaining brain structure at midlife in a cohort without sarcopenia. Methods: We used abdominal and brain magnetic resonance imaging (MRI) data from a population-based cohort enrolled in the UK Biobank. The following measures were derived: thigh fat-free muscle volume (FFMV), total brain volume (TBV), gray matter volume (GMV), white matter volume (WMV), total hippocampal volume (THV), and white matter hyperintensity volume (WMHV). Participants below sex-based grip strength thresholds suggesting probable sarcopenia were excluded. Linear regression analysis was used to study the interaction or mediation effects of age, sex, and BMI on the associations between FFMV and brain volumes. Results: Data were available for 20,353 participants (median age 64 years, 53% female). We found interactions between thigh FFMV, BMI, and age (all p < 0.05). Greater thigh FFMV was associated with better brain volumes in those aged <64 years with normal (TBV: ß = 2.0 ml/L, p = 0.004; GMV: ß = 0.8 ml/L, p = 0.04; WMV: ß = 1.1 ml/L, p = 0.006; WMHV: ß = -0.2 ml/L, p = 3.7 × 10-5) or low BMI (TBV: ß = 21.2 ml/L, p = 0.003; WMV: ß = 13.3 ml/L, p = 0.002, WMHV: ß = -1.1 ml/L, p = 0.04). Conclusion: Greater thigh muscle volume correlates with better brain volumes at midlife in people without sarcopenia, but this relationship weakens with greater age and BMI. Further study is required to investigate the underlying mechanisms to understand which components of body composition are potentially modifiable risk factors for dementia.

Plasma fatty acid levels and risk of non-small cell lung cancer: a large-scale prospective cohort study.

Background: Non-small cell lung cancer (NSCLC) ranks among the most prevalent and lethal malignancies globally. Fatty acids (FAs) play a significant role in diverse physiological and pathological mechanisms, yet their precise involvement in NSCLC remains poorly understood. Methods: This study utilized a large-scale prospective cohort of 249,132 participants, observed over an average of 12 years, to investigate the relationship between different FAs and NSCLC risk. Analytical approaches included Cox proportional hazards regression, Kaplan-Meier survival analysis, accelerated failure time (AFT) modeling, and restricted cubic spline (RCS) analysis. Results: During the follow-up period, 1,460 participants were diagnosed with NSCLC. Cox regression analysis demonstrated that elevated levels of docosahexaenoic acid (DHA), linoleic acid (LA), and omega-3 were inversely associated with NSCLC risk. Kaplan-Meier curves, along with AFT models, corroborated that elevated concentrations of DHA and LA significantly delayed NSCLC onset. Additionally, RCS analysis uncovered nuanced dose-response relationships between these FAs and NSCLC. Stratified analyses highlighted variability based on smoking status, gender, and body mass index subgroups. Conclusion: The concentration of specific FAs exhibits a significant association with NSCLC risk. These results offer a foundation for devising dietary FA composition adjustments aimed at reducing NSCLC risk.

Plasma Proteomic Insights for Identification of Novel Predictors and Potential Drug Targets in Atrial Fibrillation: A Prospective Cohort Study and Mendelian Randomization Analysis.

BACKGROUND: Currently, there are no reliable methods for predicting and preventing atrial fibrillation (AF) in its early stages. This study aimed to identify plasma proteins associated with AF to discover biomarkers and potential drug targets. METHODS: The UK Biobank Pharma Proteomics Project examined 2923 circulating proteins using the Olink platform, forming the basis of this prospective cohort study. The UK Biobank Pharma Proteomics Project included a randomly selected discovery cohort and the consortium-selected replication cohort. The study's end point was incident AF, identified using International Classification of Diseases, Tenth Revision codes. The association between plasma proteins and incident AF was evaluated using Cox proportional hazard models in both cohorts. Proteins present in both cohorts underwent Mendelian randomization analysis to delineate causal connections, utilizing cis-protein quantitative trait loci as genetic tools. The predictive efficacy of the identified proteins for AF was assessed using the area under the receiver operating characteristic curve, and their druggability was explored. RESULTS: Data from 53 032 participants were included in this study. Incident AF cases were identified in the discovery cohort (1894; 5.5%) within a median follow-up of 14.5 years and in the replication cohort (451; 10.6%) within a median follow-up of 14.4 years. Twenty-one proteins linked to AF were identified in both cohorts. Specifically, COL4A1 (collagen IV α-1; odds ratio, 1.11 [95% CI, 1.04-1.19]; false discovery rate, 0.016) and RET (proto-oncogene tyrosine-protein kinase receptor Ret; odds ratio, 0.96 [95% CI, 0.94-0.98]; false discovery rate, 0.013) demonstrated a causal link with AF, and RET is druggable. COL4A1 improved the short- and long-term predictive performance of established AF models, as evidenced by significant enhancements in the area under the receiver operating characteristic, integrated discrimination improvement, and net reclassification index, all with P values below 0.05. CONCLUSIONS: COL4A1 and RET are associated with the development of AF. RET is identified as a potential drug target for AF prevention, while COL4A1 serves as a biomarker for AF prediction. Future studies are needed to evaluate the effectiveness of targeting these proteins to reduce AF risk.

Association of a composite trait for anthropometrics, adiposity and energy expenditure with cardiometabolic diseases: An age-stratified cohort and genetic risk score analysis.

AIM: Various anthropometric measures capture distinct as well as overlapping characteristics of an individual's body composition. To characterize independent body composition measures, we aimed to reduce easily-obtainable individual measures reflecting adiposity, anthropometrics and energy expenditure into fewer independent constructs, and to assess their potential sex- and age-specific relation with cardiometabolic diseases. METHODS: Analyses were performed within European ancestry participants from UK Biobank (N = 418,963, mean age 58.0 years, 56% women). Principal components (PC) analyses were used for the dimension reduction of 11 measures of adiposity, anthropometrics and energy expenditure. PCs were studied in relation to incident type 2 diabetes mellitus (T2D) and coronary artery disease (CAD). Multivariable-adjusted Cox regression analyses, adjusted for confounding factors, were performed in all and stratified by age. Genome-wide association studies were performed in half of the cohort (N = 156,295) to identify genetic variants as instrumental variables. Genetic risk score analyses were performed in the other half of the cohort stratified by age of disease onset (N = 156,295). RESULTS: We identified two PCs, of which PC1 reflected lower overall adiposity (negatively correlated with all adiposity aspects) and PC2 reflected more central adiposity (mainly correlated with higher waist-hip ratio, but with lower total body fat) and increased height, collectively capturing 87.8% of the total variance. Similar to that observed in the multivariable-adjusted regression analyses, we found associations between the PC1 genetic risk score and lower risks of CAD and T2D [CAD cases <50 years, odds ratio: 0.91 (95% confidence interval 0.87, 0.94) per SD; T2D cases <50 years, odds ratio: 0.76 (0.72, 0.81)], which attenuated with higher age (p-values 8.13E-4 and 2.41E-6, respectively). No associations were found for PC2. CONCLUSIONS: The consistently observed weaker associations of the composite traits with cardiometabolic disease suggests the need for age-specific cardiometabolic disease prevention strategies.

High-content phenotypic analysis of a C. elegans recombinant inbred population identifies genetic and molecular regulators of lifespan.

Lifespan is influenced by complex interactions between genetic and environmental factors. Studying those factors in model organisms of a single genetic background limits their translational value for humans. Here, we mapped lifespan determinants in 85 C. elegans recombinant inbred advanced intercross lines (RIAILs). We assessed molecular profiles-transcriptome, proteome, and lipidome-and life-history traits, including lifespan, development, growth dynamics, and reproduction. RIAILs exhibited large variations in lifespan, which correlated positively with developmental time. We validated three longevity modulators, including rict-1, gfm-1, and mltn-1, among the top candidates obtained from multiomics data integration and quantitative trait locus (QTL) mapping. We translated their relevance to humans using UK Biobank data and showed that variants in GFM1 are associated with an elevated risk of age-related heart failure. We organized our dataset as a resource that allows interactive explorations for new longevity targets.

Genomic Validation in the UK Biobank Cohort Suggests a Role of C8B and MFG-E8 in the Pathogenesis of Trigeminal Neuralgia.

Trigeminal neuralgia (TN) is a severe facial pain disease of uncertain pathophysiology and unclear genetic background. Although recent research has reported a more important role of genetic factors in TN pathogenesis, few candidate genes have been proposed to date. The present study aimed to identify independent genetic variants in the protein-coding genes associated with TN. We focused on genes previously linked to TN based on the results of four proteomic studies conducted by our research team. The goal was to validate these findings on the genetic level to enhance our understanding of the role of genetics in TN. The study is based on the participants from UK Biobank cohort. Following quality control, 175 independent single nucleotide polymorphisms (SNPs) in 17 genes were selected. The study sample comprised of diagnosed TN cases (N = 555) and randomly matched controls (N = 6245) based on specific criteria. Two SNPs corresponding to C8B rs706484 [odds ratio (OR) (95% confidence interval (CI)): 1.357 (1.158-1.590); p: 0.00016] and MFG-E8 rs2015495 [OR (95% CI): 1.313 (1.134-1.521); p: 0.00028] showed significant positive association with TN, indicating a positive effect of the SNP alleles on gene expression and disease risk. Interestingly, both SNPs are Expression Quantitative Trait Loci (eQTLs), and are associated with changes in the expression activity of their corresponding gene. Our findings suggest novel genetic associations between C8B, a key component of the complement system, and MFG-E8, which plays a role in regulating neuroinflammation, in relation to TN. The identified genetic variations may help explain why some individuals develop TN while others do not, indicating a potential genetic predisposition to the condition.

Conceptualising food banking in the UK from drivers of use to impacts on health and wellbeing: A systematic review and directed content analysis.

Food banks have become commonplace in the UK as an emergency response to food insecurity. However, food banks are not a long-term solution to food insecurity and are often not accessed by those in need. In the context of the cost-of-living crisis, and increased food insecurity, this systematic review applied market/government failure theory, voluntary failure theory, and Radimer et al.'s (1990) domains of food insecurity to explore three important aspects relevant to the food banking experience: the drivers of food bank use; the limitations of the current food bank model; and the impacts of the food banking model for food bank clients. Empirical, peer-reviewed articles written in English with a UK food bank context and reporting relevant data to these aspects were eligible for inclusion. In total, 221 titles were identified using four databases (Web of Science, SCOPUS, PubMed, CINHAL Plus) in July 2022. The final sample of 41 articles (comprising qualitative, quantitative and mixed methods studies), were quality assessed using the Mixed Methods Appraisal Tool. Data were extracted and analysed through directed content analysis. Market and government failures were widely reported to drive food bank use. Insufficiency, paternalism and particularism represented key limitations of the food bank model. Negative health and psychological impacts of food bank use were prominent, yet social impacts were largely positive. Consequently, new solutions are needed to promote positive health and psychological impacts for food bank clients in the UK. The application of these findings to other high-income countries experiencing food insecurity should be determined.

Accelerated biological aging, mediating amino acids, and risk of incident type 2 diabetes: a prospective cohort study.

PURPOSE: Aging plays an important role in type 2 diabetes mellitus (T2DM). But the association between accelerated biological age and T2DM, and the mechanisms underlying this association remains unclear. Thus, this study aimed to examine the associations of biological aging with T2DM, and explore the potential mediation effect of amino acids. METHODS: This prospective cohort study included 95,773 participants in the UK Biobank who were free of diabetes at baseline. Biological age was measured from clinical traits using PhenoAgeAccel. Cox proportional hazard models were used to estimate the hazard ritios (HRs) and 95% confidence intervals (CIs), and mediation analysis was used to explore the mediation effect of amino acids. RESULTS: During a median follow-up of 14.02 years, 6,347 incident T2DM cases were recorded. After multivariable adjustment for sociodemographic characteristics, lifestyle factors, and other risk factors of T2DM, participants with older biological age were at increased risk of incident T2DM (30% increase per standard deviation of PhenoAgeAccel, 95% CI: 28.0-33.0%). Additionally, higher branched chain amino acids (BCAAs) including isoleucine and leucine, aromatic amino acids (AAAs) including phenylalanine and tyrosine, were associated with increased PhenoAgeAccel and risk of incident T2DM; while glutamine and glycine were inversely associated. Alanine, glutamine, glycine, phenylalanine, tyrosine, isoleucine, leucine, and total concentration of branched-chain amnio acids could partially explain the associations between PhenoAgeAccel and T2DM. CONCLUSION: Accelerated biological aging was associated with increased risk of incident T2DM independent of chronological age and may be a risk factor of T2DM, partially mediated by several amino acids.

Incidence and outcomes of vasa praevia in the United Kingdom.

Background: Vasa praevia is an obstetric condition in which the fetal vessels run through the membrane over the internal cervical os, unprotected by the placenta or umbilical cord. It is associated with perinatal mortality if not diagnosed antenatally. We investigated the incidence and outcomes of vasa praevia in the UK. Methods: We conducted a population-based descriptive study using the UK Obstetric Surveillance System (UKOSS). Cases were identified prospectively through monthly UKOSS submissions form all UK hospitals with obstetrician-led maternity units. All women diagnosed with vasa praevia who gave birth between 1 st December 2014 and 30 th November 2015 were included. The main outcome was incidence of vasa praevia with 95% confidence intervals, using 2015 maternities as the denominator. Results: Fifty-one women met the case definition. The incidence of diagnosed vasa praevia was 6.64 per 100,000 maternities (95% CI 5.05-8.73). Of 198 units, 10 (5%) had a vasa praevia screening programme; one of these 10 units identified 25% of the antenatally diagnosed cases. Among women who had vasa praevia diagnosed or suspected antenatally (n=28, 55%), there were no perinatal deaths or hypoxic ischaemic encephalopathy (HIE). Twenty-four women with antenatal diagnosis were hospitalised at a median gestation of 32 weeks and caesarean section was scheduled at a median gestation of 36 weeks. When vasa praevia was diagnosed peripartum (n=23, 45%), the perinatal mortality rate was 37.5% and 47% of survivors developed HIE. Conclusions: The incidence of diagnosed vasa praevia was lower than anticipated. There was high perinatal mortality and morbidity for cases not diagnosed antenatally. The incidence of antenatally identified cases was much higher in the few centres that actively screened for this condition, and the perinatal outcomes were better. However, this group were all delivered by caesarean section and may include women who would not have experienced any adverse perinatal outcome.

Vasa praevia is a pregnancy complication in which the blood vessels that connect the mother and fetus run across the opening of the womb, without protection from the placenta or umbilical cord. During birth, the vessels can tear. This can result in rapid blood loss from the baby and in some cases, death of the baby. We investigated how common vasa praevia is in the UK, and how women with the condition and their babies fared. The UK Obstetric Surveillance System (UKOSS) collects anonymous information from all maternity units in the UK about pregnant women who have certain medical conditions. UKOSS reporters provided information about all women with vasa praevia who gave birth between December 2014 and November 2015. We identified 51 women with vasa praevia, meaning vasa praevia was diagnosed less often in the UK than we had expected based on studies from other countries. Twenty-eight women were diagnosed during the antenatal period, while 23 were diagnosed during labour or after giving birth. Pregnant women in the UK are not screened for vasa praevia as standard, and some women may have had vasa praevia that was not diagnosed. A small number (5%) of maternity units in our study did offer screening for vasa praevia in their pregnant population. One of these units identified a quarter of all the women who had vasa praevia diagnosed during pregnancy. Babies born to women whose vasa praevia was diagnosed during pregnancy had good outcomes. All of these women gave birth by planned caesarean section, and they and their babies survived. Babies born to women whose vasa praevia was suspected or diagnosed during labour or after birth had worse outcomes. Around 40% were stillborn or died shortly after birth, and about half of those who survived had brain damage caused by lack of oxygen.

Associations of metabolic syndrome with cognitive function and dementia risk: Evidence from the UK Biobank cohort.

AIM: To investigate the associations of metabolic syndrome (MetS) with cognitive function, dementia and its subtypes. METHODS: Based on the participants recruited by UK Biobank, this study aims to investigate the associations of MetS with cognitive function, dementia and its subtypes. Generalized estimating equations, Cox proportional risk models, and multiple linear regression models were respectively used to assess associations between MetS and dementia-related outcomes. RESULTS: Among the 363,231 participants, 95,713 had MetS at baseline. The results showed that MetS was significantly associated with cognitive function related to fluid intelligence and prospective memory at follow-up. Among participants aged ≥60 years, MetS was correlated with elevated risk of all-cause dementia, particularly vascular dementia (VaD) [hazard ratio 1.115 (95% confidence interval: 1.047, 1.187), hazard ratio 1.393 (95% confidence interval: 1.233, 1.575), respectively]. With increasing MetS components, the risk of all-cause dementia and VaD tended to be elevated. MetS has also been associated with dementia-related structural changes in the brain, including alterations in overall brain volume, white matter volume, grey matter volume and white matter integrity. CONCLUSION: MetS was associated with poorer cognitive performance and might increase the risk of all-cause dementia as well as VaD, but the effect on Alzheimer's disease was not significant. Holistic control of the MetS may benefit the prevention and control of cognitive impairment and dementia.

Ultra-processed food intake in toddlerhood and mid-childhood in the UK: cross sectional and longitudinal perspectives.

PURPOSE: (i) Characterize ultra-processed food (UPF) intakes in toddlerhood and mid-childhood, including identifying principal UPF sub-groups and associations with nutrient profile; (ii) explore stability and change in UPF intake between toddlerhood and mid-childhood. METHODS: Data were from children in the UK Gemini twin cohort at 21 months (n = 2,591) and 7 years (n = 592) of age. UPF intakes were estimated using diet diaries and Nova classification. Complex samples general linear or logistic regression models were used to explore associations between UPF intake, UPF sub-groups and nutrients, and changes in intake over time. RESULTS: The contribution of UPF to total energy was 46.9% (± 14.7) at 21 months and 59.4% (± 12.5) at 7 years. Principal UPF sub-groups were yogurts, higher-fiber breakfast cereals, and wholegrain breads in toddlerhood, and puddings and sweet cereal products and white breads in mid-childhood. At both ages, mean free sugar and sodium intakes exceeded recommended maximums and higher UPF consumption was associated with consuming more of each nutrient (P < 0.001). UPF intake was negatively associated with fat, saturated fat and protein intake in toddlerhood, and fiber intake in mid-childhood (P < 0.001). Being in the highest UPF intake quintile in toddlerhood was predictive of being in the highest quintile in mid-childhood (OR 9.40, 95%CI 3.94-22.46). CONCLUSIONS: UPF accounted for nearly half of toddlers' energy, increasing to 59% in mid-childhood. Higher UPF consumers had higher intakes of free sugar and sodium. UPF intake in toddlerhood was predictive of mid-childhood intake. Effective policies are needed to reduce UPF intakes in the early years.

Proinflammatory Diet Increases the Risk of Irritable Bowel Syndrome: A Prospective Study of 129,408 UK Biobank Participants and Mendelian Randomization Analysis.

BACKGROUND: Patients with irritable bowel syndrome (IBS) often have chronic low-grade inflammation in the intestinal mucosa. Some dietary components are known to be associated with inflammation. However, there is currently limited research on the relationship between dietary inflammatory potential and the risk of IBS. METHODS: A total of 129,408 participants in the UK Biobank were included in this study. Energy-Adjusted Dietary Inflammatory Index (E-DII) based on 26 nutrients and the Empirical Dietary Inflammatory Pattern (EDIP) based on 17 food groups were constructed, and on the basis of the tertiles, the continuous score was categorized into proinflammatory, neutral, and antiinflammatory categories. Associations between IBS and E-DII and EDIP were investigated by multivariable Cox proportional hazard models. Potential confounders including sociodemographic, lifestyle, body mass index (BMI), psychological state, type 2 diabetes, and thyroiditis were adjusted. In addition, subgroup analysis and sensitivity analysis were also performed. Finally, a two-sample Mendelian randomization (MR) analysis was employed to explore the independent causality of nutrients and dietary-derived serum antioxidants with IBS. RESULTS: In the cohort study, over a median follow-up period of 13.26 years, 2421(1.87%) participants developed IBS. In the E-DII categories, after adjusting for the confounders, individuals in the proinflammatory diet category had a higher risk of IBS compared with the antiinflammatory category (HR 1.15, 95% CI 1.03-1.28, p = 0.015, p trend = 0.017) and neutral category (HR 1.13, 95% CI 1.01-1.26, p = 0.030, p trend = 0.017). In the EDIP categories, after adjusting for the confounders, individuals in the proinflammatory diet category had a higher risk of IBS compared with antiinflammatory category (HR 1.19, 95% CI 1.06-1.33, p = 0.002, p trend = 0.002) but no significant association compared with neutral category (HR 1.10, 95% CI 0.99-1.23, p = 0.067, p trend = 0.002). In the MR analysis, genetically determined intake levels of 16 nutrients and 6 dietary sources of circulating antioxidants did not have a causal effect on IBS. CONCLUSIONS: Our findings indicate that proinflammatory dietary components are independent risk factors for IBS. However, there is no causal relationship between individual nutrient intake or serum antioxidants from dietary sources and IBS.

Back to the future: Retrograde alcohol calculations an uncertain science.

Retrograde extrapolations, known as back calculations are widely used in forensic toxicology to estimate the blood alcohol concentration of an individual at some prior time. In the UK guidelines have been issued by the United Kingdom and Ireland Association of Forensic Toxicologists) and the Organization of Scientific Area Committees (OSAC) for Forensic Science. However, these guidelines are not fully agreed and open tointerpretation. Alcohol elimination rates have been discussed in numerous publications since Widmark's original data was published. The current guidance from UKIAFT, is to report the most likely back calculated result together with a range of results based on the 95% confidence limit elimination rates (9 to 29 mg/100 mL/hour).The Divisional Court, upheld by the House of Lords, ruled that in order to convict someone for being over the prescribed limit on the basis of any back calculation, the case must be proven beyond reasonable doubt. A 99.73% confidence interval increased to 3 standard deviations at the lower end would provide a greater factual basis for the court and cover alarger proportion of the population, this can be achieved by increasing the elimination range to 8 to 29 mg/100 mL/hour. Retrograde extrapolations also rely on the subject being post absorptive at the prior time. In the UK, back calculations are validif the subject has not eaten or consumed alcohol withinonehour ofthe back calculation time. Where the subject has eatenprior to the back calculation, experts are instructed to consider whether the back calculation is applicable. In Germany and the United States back calculations are not permitted to a time within 2 h after last drink consumed. The 2 h limit would better meet the highest standard of 'beyond reasonable doubt' burden of proof, and should be used. These proposed changes would decrease the uncertainty associated with retrograde calculations carried out by UK toxicologists.

The joint associations of physical activity and ultra-processed food consumption with depression: A cohort study in the UK Biobank.

BACKGROUND: Despite substantial evidence regarding independent associations between physical activity (PA) and ultra-processed foods (UPF) consumption with depression, the joint effects of these two factors remain unknown. METHODS: This study included 99,126 participants without depression in the UK Biobank at baseline. A 24-h recall method was used to assess UPF consumption, and self-reported total physical activity (TPA), moderate-to-vigorous physical activity (MVPA), and vigorous physical activity (VPA) were assessed by metabolic equivalent task (MET). A series of Cox proportional hazard regression models were used to explore the independent and joint effects of TPA, MVPA, VPA and UPF consumption on depression. RESULTS: The incidence rate of depression was 1.94 % [95 % confidence interval (CI): 1.80 %-2.10 %] per 1000 person-years after an average follow-up of 12.10 years. We found that MVPA and UPF consumption had additive interactions on depression risk (p < 0.05). Participants in Q1 of TPA and Q4 of UPF consumption (HR: 1.83, 95%CI: 1.45-2.31) showed a higher risk for depression than those in Q4 of TPA and Q1 of UPF consumption. Compared with the participants with WHO guideline-recommended MVPA and the lowest UPF consumption, those below recommended MVPA (HR: 1.51, 95%CI: 1.20-1.89) or above recommended MVPA (HR: 1.40, 95%CI: 1.10-1.78) and with the highest UPF consumption had a higher risk for depression. LIMITATIONS: Study limitations include use of self-reported data, observational study and concerns regarding generalizability. CONCLUSION: Higher UPF consumption, accompanied by lower PA levels regardless of TPA, MVPA, and VPA, is associated with a higher risk of depression. Our study offers insights on public health priorities to decrease the risk of depression in the population by addressing both PA and UPF consumption together.

Genetic Variance in Heparan Sulfation Is Associated With Salt Sensitivity.

BACKGROUND: High heritability of salt sensitivity suggests an essential role for genetics in the relationship between sodium intake and blood pressure (BP). The role of glycosaminoglycan genes, which are crucial for salinity tolerance, remains to be elucidated. METHODS: Interactions between 54 126 variants in 130 glycosaminoglycan genes and daily sodium excretion on BP were explored in 20 420 EPIC-Norfolk (European Prospective Investigation Into Cancer in Norfolk) subjects. The UK Biobank (n=414 132) and the multiethnic HELIUS study (Healthy Life in an Urban Setting; n=2239) were used for validation. Afterward, the urinary glycosaminoglycan composition was studied in HELIUS participants (n=57) stratified by genotype and upon dietary sodium loading in a time-controlled crossover intervention study (n=12). RESULTS: rs2892799 in NDST3 (heparan sulfate N-deacetylase/N-sulfotransferase 3) showed the strongest interaction with sodium on mean arterial pressure (false discovery rate 0.03), with higher mean arterial pressure for the C allele in high sodium conditions. Also, rs9654628 in HS3ST5 (heparan sulfate-glucosamine 3-sulfotransferase 5) showed an interaction with sodium on systolic BP (false discovery rate 0.03). These interactions were multiethnically validated. Stratifying for the rs2892799 genotype showed higher urinary expression of N-sulfated heparan sulfate epitope D0S0 for the T allele. Conversely, upon dietary sodium loading, urinary D0S0 expression was higher in participants with stable BP after sodium loading, and sodium-induced effects on this epitope were opposite in individuals with and without BP response to sodium. CONCLUSIONS: The C allele of rs2892799 in NDST3 exhibits higher BP in high sodium conditions when compared with low sodium conditions, whereas no differences were detected for the T allele. Concomitantly, both alleles demonstrate distinct expressions of D0S0, which, in turn, correlates with sodium-mediated BP elevation. These findings underscore the potential significance of genetic glycosaminoglycan variation in human BP regulation.