The impact of delayed processing of chilled whole blood specimens on the measurement of nutritional biomarkers in the UK National Diet and Nutrition Survey rolling programme.

BACKGROUND: The logistics of timely processing of blood specimens remains a barrier in population health studies to the generation of micronutrient status data. OBJECTIVE: To test a blood specimen processing protocol that includes overnight postage with cooling and its effect on nutritional biomarker concentrations. METHODS: This study was embedded within the UK National Diet and Nutrition Survey (NDNS). Paired specimens were collected from 64 participants (16 y+). One set of specimens was processed within 2-hours of collection ["field"] and paired samples mailed in an insulated box with cold packs using an overnight postal service to a central laboratory ["postal"]. Specimen processing protocols were aligned across field sites and the central laboratory. Specimens were frozen and later analysed using established methods for vitamins, minerals, lipids, ferritin and C-reactive protein (CRP). Percent difference was calculated between protocols and compared with quality specifications determined from intra- and inter-individual variation. RESULTS: In the postal protocol, ferritin (6%(3, 8)) (geometric mean percent difference(95% CI)) (P=0.002) and zinc (4%(1, 6)) (P=0.004) were higher compared with the field protocol. Retinol (-3%(-4, -1) (P<0.0001)) and selenium (-3%(-5, -1) (P=0.003)) concentrations were lower in the postal protocol whereas total (2%(1, 3)) and HDL (4%(2, 5)) cholesterol were higher (P<0.0001) than in the field protocol. Percent differences were within the optimum quality specification for the majority of biomarkers, but ferritin, zinc and selenium fell outside of the optimum limits. Higher ferritin concentration in the postal protocol led to a decrease in the proportion of specimens with ferritin concentration <15 µg/L from 13% to 9%. CONCLUSIONS: The majority of micronutrient biomarkers, serum lipids and CRP were minimally affected by delayed processing when cooled. The study suggests acceptable stability of nutritional biomarkers within the described protocol, which can provide accurate data for nutritional biomarkers commonly measured in studies and surveys.

Assessment of Erythrocyte Transketolase, Whole Blood Thiamine Diphosphate, and Human Milk Thiamine Concentrations to Identify Infants and Young Children Responding Favorably to Therapeutic Thiamine Administration: Findings from the Lao Thiamine Study, a Prospective Cohort Study.

Background: There is limited information on relationships among biomarkers of thiamine status (whole blood thiamine diphosphate [ThDP], erythrocyte transketolase activity coefficient [ETKac], and human milk thiamine [MTh]) and clinical manifestations of thiamine deficiency. Objectives: This study aimed to explore correlations among these biomarkers and thiamine responsive disorders (TRDs), a diagnosis based on favorable clinical response to thiamine. Methods: Hospitalized infants and young children (aged 21 d to <18 mo) with respiratory, cardiac, and/or neurological symptoms suggestive of thiamine deficiency were treated with parenteral thiamine (100 mg daily) for ≥3 d alongside other treatments and re-examined systematically. Clinical case reports were reviewed by 3 pediatricians, who determined TRD or non-TRD status. Children in a community comparison group were matched by age, sex, and residence. Venous whole blood ThDP and MTh were determined by high-performance liquid chromatography fluorescence detection and ETKac in washed erythrocytes by ultraviolet spectrophotometry. Associations between biomarkers were assessed using Spearman correlations, and biomarker cutoffs predictive of TRD and ETKac >1.25 were explored using area under the receiver operating characteristic curve framework. Results: Thiamine biomarkers were available for 287 hospitalized children and 228 community children (mean age 4.7 mo; 59.4% male). Median (interquartile range [IQR]) ThDP and ETKac were 66.9 nmol/L (IQR: 41.4, 96.9 nmol/L) and 1.25 nmol/L (IQR: 1.11, 1.48 nmol/L), respectively, among hospitalized children, and 64.1 nmol/L (IQR: 50.0, 85.3 nmol/L) and 1.22 nmol/L (IQR: 1.12, 1.37 nmol/L) among 228 community children (P > 0.05 for both). Forty-five percent of breastfeeding mothers of infants <6 mo had MTh <90 µg/L. ThDP and ETKac, but not MTh, were significantly different between 152 children with TRD and 122 without TRD, but overlapping distributions undermined prediction of individual responses to thiamine. Conclusions: Although ETKac, ThDP, and MTh are useful biomarkers of population thiamine status, none of the biomarkers reliably identified individual children with TRD. ThDP is more practical for population assessment because preparing washed erythrocytes is not required.This trial was registered at clinicaltrials.gov as NCT03626337.

Protocol for a seamless phase 2A-phase 2B randomized double-blind placebo-controlled trial to evaluate the safety and efficacy of benfotiamine in patients with early Alzheimer's disease (BenfoTeam).

BACKGROUND: Benfotiamine provides an important novel therapeutic direction in Alzheimer's disease (AD) with possible additive or synergistic effects to amyloid targeting therapeutic approaches. OBJECTIVE: To conduct a seamless phase 2A-2B proof of concept trial investigating tolerability, safety, and efficacy of benfotiamine, a prodrug of thiamine, as a first-in-class small molecule oral treatment for early AD. METHODS: This is the protocol for a randomized, double-blind, placebo-controlled 72-week clinical trial of benfotiamine in 406 participants with early AD. Phase 2A determines the highest safe and well-tolerated dose of benfotiamine to be carried forward to phase 2B. During phase 2A, real-time monitoring of pre-defined safety stopping criteria in the first approximately 150 enrollees will help determine which dose (600 mg or 1200 mg) will be carried forward into phase 2B. The phase 2A primary analysis will test whether the rate of tolerability events (TEs) is unacceptably high in the high-dose arm compared to placebo. The primary safety endpoint in phase 2A is the rate of TEs compared between active and placebo arms, at each dose. The completion of phase 2A will seamlessly transition to phase 2B without pausing or stopping the trial. Phase 2B will assess efficacy and longer-term safety of benfotiamine in a larger group of participants through 72 weeks of treatment, at the selected dose. The co-primary efficacy endpoints in phase 2B are CDR-Sum of Boxes and ADAS-Cog13. Secondary endpoints include safety and tolerability measures; pharmacokinetic measures of thiamine and its esters, erythrocyte transketolase activity as blood markers of efficacy of drug delivery; ADCS-ADL-MCI; and MoCA. CONCLUSION: The BenfoTeam trial utilizes an innovative seamless phase 2A-2B design to achieve proof of concept. It includes an adaptive dose decision rule, thus optimizing exposure to the highest and best-tolerated dose. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT06223360, registered on January 25, 2024. https://classic.clinicaltrials.gov/ct2/show/NCT06223360.

A Predictive Model for Thiamine Responsive Disorders Among Infants and Young Children: Results from a Prospective Cohort Study in Lao People's Democratic Republic.

OBJECTIVE: To develop a predictive model for thiamine responsive disorders (TRDs) among infants and young children hospitalized with signs or symptoms suggestive of thiamine deficiency disorders (TDDs) based on response to therapeutic thiamine in a high-risk setting. STUDY DESIGN: Children aged 21 days to <18 months hospitalized with signs or symptoms suggestive of TDD in northern Lao People's Democratic Republic were treated with parenteral thiamine (100 mg daily) for ≥3 days in addition to routine care. Physical examinations and recovery assessments were conducted frequently for 72 hours after thiamine was initiated. Individual case reports were independently reviewed by three pediatricians who assigned a TRD status (TRD or non-TRD), which served as the dependent variable in logistic regression models to identify predictors of TRD. Model performance was quantified by empirical area under the receiver operating characteristic curve. RESULTS: A total of 449 children (median [Q1, Q3] 2.9 [1.7, 5.7] months old; 70.3% exclusively/predominantly breastfed) were enrolled; 60.8% had a TRD. Among 52 candidate variables, those most predictive of TRD were exclusive/predominant breastfeeding, hoarse voice/loss of voice, cyanosis, no eye contact, and no diarrhea in the previous 2 weeks. The area under the receiver operating characteristic curve (95% CI) was 0.82 (0.78, 0.86). CONCLUSIONS: In this study, the majority of children with signs or symptoms of TDD responded favorably to thiamine. While five specific features were predictive of TRD, the high prevalence of TRD suggests that thiamine should be administered to all infants and children presenting with any signs or symptoms consistent with TDD in similar high-risk settings. The usefulness of the predictive model in other contexts warrants further exploration and refinement. TRIAL REGISTRATION: Clinicaltrials.gov NCT03626337.

Risk factors for anaemia among women and their young children hospitalised with suspected thiamine deficiency in northern Lao PDR.

Anaemia among women and young children remains a major public health concern. This secondary study describes the anaemia prevalence among young hospitalised children and their mothers in northern Lao People's Democratic Republic and explores possible nutritional causes and risk factors for anaemia. Hospitalised children (ages 21 days to <18 months) with clinical symptoms suggestive of thiamine deficiency disorders were eligible along with their mothers. Venous blood was collected for determination of haemoglobin, ferritin, soluble transferrin receptor (sTfR), retinol-binding protein (RBP), erythrocyte glutathione reductase activation coefficient (EGRac), thiamine diphosphate (ThDP) and acute phase proteins. Risk factors for anaemia were modelled using minimally adjusted logistic regression controlling for age. Haemoglobin results were available for 436 women (mean ± SD age 24.7 ± 6.4 years; 1.6% pregnant) and 427 children (4.3 ± 3.5 months; 60.3% male). Anaemia prevalence (Hb < 120 g/L for nonpregnant women and <110 g/L for pregnant women and children) was 30.7% among women and 55.2% among children. In bivariate analyses, biomarkers significantly associated with anaemia in women were ferritin, sTfR, RBP, EGRac and ThDP. Other risk factors for women were lower BMI, mid-upper arm circumference < 23.5 cm, lower education, lower socioeconomic index, food insecurity, Hmong ethnicity, not/rarely having attended antenatal care, not having taken antenatal iron-containing supplements and not meeting minimum dietary diversity. Risk factors for anaemia among children were older age, male sex, stunting, sTfR, ThDP and alpha-1-acid-glycoprotein. Anaemia was common among women and their hospitalised children and was associated with micronutrient deficiencies and socioeconomic, dietary and health care-seeking risk factors, suggesting that multiple strategies are required to prevent anaemia among women and children.

Quantification and reporting of vitamin D concentrations measured in human milk by LC-MS/MS.

Vitamin D is essential for optimal bone health, and vitamin D deficiency has been associated with an increased risk of adverse pregnancy, growth and developmental outcomes. In early life, and in the absence of endogenous vitamin D production from UVB light, infants are reliant on vitamin D stores established in utero and the vitamin D supply from human milk (HM). However, comprehensive data on vitamin D in HM is lacking. Thus, in this review we explore the application of liquid-chromatography tandem mass spectrometry (LC-MS/MS) to the assessment of vitamin D in HM. We discuss the challenges of extracting and measuring multiple vitamin D metabolites from HM including the frequent requirement for a large sample volume, and inappropriate poor sensitivity. Shortcomings in the reporting of experimental procedures and data analysis further hinder advances in the field. Data collated from all studies that have applied LC-MS/MS reveal that, in general, cholecalciferol concentration is greater and more variable than 25-hydroxyvitamin D concentration, and that the vitamin D content of HM is low and less than the currently recommended dietary requirement of infants, although maternal supplementation can increase the vitamin D content of HM. Improvements in analytical methods and their validation and larger, more representative studies are required to better characterize HM milk vitamin D metabolite concentrations and their relationship with maternal status. These data are essential to understand relationships with infant health and to inform public health policies around vitamin D fortification and supplementation.

Protocol for measuring erythrocyte glutathione reductase activity coefficient to assess riboflavin status.

Riboflavin (vitamin B2) is a component of the co-enzyme flavin adenine dinucleotide (FAD). The activity coefficient of erythrocyte glutathione reductase (EGRAC), a FAD-dependent enzyme, is a biomarker of riboflavin status. Here, we describe a protocol for measuring unstimulated (basal) and FAD-stimulated (activated) erythrocyte glutathione reductase activity to calculate EGRAC. We describe the steps for preparing washed red blood cells and hemolysates; preparing reagents; loading, incubating, and reading the 96-well plate; and calculating the results. For complete details on the use and execution of this protocol, please refer to Hess et al.1.

Nursing students experiences of end-of-life care.

BACKGROUND: Undergraduate nursing students spend a significant amount of time in clinical placements where they are involved in care at the end of a person's life and care after death. While their role is to provide compassionate care, some students feel wholly unprepared. AIMS: The aim of this qualitative study was to explore student nurses' experiences of care in death, dying and post death care, and to explore how students can be better prepared to provide such care. METHODS: This is a qualitative descriptive study that is concerned with the subjective reality of participant's experiences. FINDINGS: Six themes were developed from the analysis: first encounters with death and dying; preparedness; mentoring and support received; the caring role; striving to cope; working with families and working through COVID-19. CONCLUSION: Students described their experience of placements in end-of-life care as challenging, yet were also able to adopt ways to develop as compassionate practitioners.

National Diet and Nutrition Survey data reveal a decline in folate status in the United Kingdom population between 2008 and 2019.

BACKGROUND: Folate is essential for healthy growth and development. Fortification of foods with folic acid can improve folate status and reduce risk of neural tube defects (NTD). Following concern around folate status in the United Kingdom, the United Kingdom government announced in 2021 the intention to introduce mandatory folic acid fortification. OBJECTIVE: This study aimed to describe folate status in the United Kingdom population prior to the implementation of mandatory folic acid fortification of non-whole wheat (non-wholemeal) flour and to assess trends in folate status, including in females of reproductive age (FRA). METHODS: Data were from the United Kingdom National Diet and Nutrition Survey Rolling Program (2008-2019), a cross-sectional, nationally representative survey of children and adults aged 1.5+ (n = 5792 with folate result). Serum folate concentration was measured by liquid chromatography tandem mass spectrometry (LC-MS/MS) and red blood cell (RBC) folate concentration by microbiological assay. Concentration data were compared against method-specific cut-offs and thresholds, and relationships were explored against demographic and lifestyle characteristics. RESULTS: RBC and serum folate concentration significantly decreased by ∼3 percentage points per year between 2008 and 2019 in all age/sex groups. Prevalence of deficiency (RBC folate < 305 nmol/L) was highest in children aged 11 to 18 y (17% in 2016-2019). The proportion of FRA below the cut-off for increased risk of NTD (RBC folate < 748 nmol/L) increased from 69% to 89% between 2008 and 2019. Ethnicity, smoking status, and income were significant determinants of RBC and serum folate concentrations. CONCLUSIONS: These data reveal a decline in population folate status in the United Kingdom between 2008 and 2019 and a high prevalence of folate deficiency. A high proportion of FRA had RBC folate concentrations below the cut-off for increased risk of NTD. These data provide information on folate status in a population not currently exposed to mandatory folic acid fortification and are essential to model and assess its impact.

A randomised study of nurse collected venous blood and self-collected dried blood spots for the assessment of cardiovascular risk factors in the Understanding Society Innovation Panel.

Dried blood spot (DBS) sample collection has been suggested as a less invasive, cheaper and more convenient alternative to venepuncture, which requires trained personnel, making it a potentially viable approach for self-collection of blood on a large scale. We examine whether participants in a longitudinal survey were willing to provide a DBS sample in different interview settings, and how resulting cardiovascular risk biomarkers compared with those from venous blood to calculate clinical risk. Participants of the Understanding Society Innovation Panel, a representative sample of UK households, were randomly assigned to three modes of interview. Most participants (84%) were interviewed in their allocated mode. Participants (n = 2162) were interviewed by a nurse who collected both a blood sample by venepuncture and a DBS card ('nurse collection') or participants were seen by an interviewer or took part in the survey online to self-collect a DBS card ('self-collection'). All DBS cards were returned in the post after the sample had dried. Lipids (total cholesterol, HDL-cholesterol, triglycerides), HbA1c and C-reactive protein were measured in venous and DBS samples and equivalence was calculated. The resultant values were used to confirm equivalent prevalence of risk of cardiovascular disease in each type of blood sample by mode of participation. Of participants interviewed by a nurse 69% consented to venous blood sample and 74% to a DBS sample, while in the self-collection modes, 35% consented to DBS collection. Demographic characteristics of participants in self-collection mode was not different to those in nurse collection mode. The percentage of participants with clinically raised biomarkers did not significantly differ between type of blood collection (for example, 62% had high cholesterol (> 5 mmol/l) measured by venepuncture and 67% had high cholesterol within the self-collected DBS sample (p = 0.13)). While self-collected DBS sampling had a lower response rate to DBS collected by a nurse, participation did not vary by key demographic characteristics. This study demonstrates that DBS collection is a feasible method of sample collection that can provide acceptable measures of clinically relevant biomarkers, enabling the calculation of population levels of cardiovascular disease risk.

Protocol and application of basal erythrocyte transketolase activity to improve assessment of thiamine status.

Thiamine (vitamin B1) is an essential micronutrient required as a cofactor in many metabolic processes. Clinical symptoms of thiamine deficiency are poorly defined, hence biomarkers of thiamine status are important. The erythrocyte transketolase activity coefficient (ETKac) is a sensitive measure of thiamine status, but its interpretation may be confounded where the availability of the transketolase enzyme is limited. Basal ETK activity per gram of hemoglobin provides a complementary biomarker of thiamine status; however, its measurement and calculation are poorly described. Here, we describe in detail the assessment of basal ETK activity, including the calculation of path length in microplates and the molar absorption coefficient of NADH specific to the assay, and the measurement of hemoglobin in sample hemolysates. To illustrate the application of the methods, we present ETKac and basal ETK activity from women in The Gambia and UK. In conclusion, we present a clear protocol for the measurement of basal ETK activity that will permit the harmonization of methods to improve replication between laboratories.

The association between plasma zinc concentrations and markers of glucose metabolism in adults in Cameroon.

An abnormal Zn status has been suggested to play a role in the pathogenesis of type 2 diabetes. However, epidemiological studies of the relationship between plasma Zn concentrations and diabetes are sparse and inconclusive. We aimed to investigate the association between plasma Zn concentrations and glycaemic markers (fasting glucose, 2-h glucose and homeostatic model assessment of insulin resistance) in rural and urban Cameroon. We studied 596 healthy adults (63·3 % women) aged 25-55 years in a population-based cross-sectional study. The mean plasma Zn concentration was 13·7 ± 2·7 µmol/L overall, with higher levels in men (14·4 ± 2·9 µmol/l) than in women (13·2 ± 2·6 µmol/l), P-value < 0·0001. There was an inverse relationship between tertiles of plasma Zn and 2-h glucose concentrations (P-value for linear trend = 0·002). The difference in 2-h glucose between those in the highest tertile of plasma Zn compared to the lowest was -0·63 (95 % CI - 1·02, -0·23) mmol/l. This remained significant after adjusting for age, sex, smoking status, alcohol intake, education level, area of residence, adiposity and objectively measured physical activity -0·43(-0·82, -0·04). Similar inverse associations were observed between plasma Zn concentrations and fasting glucose and homeostatic model assessment of insulin resistance when adjusted for socio-demographic and health-related behavioural characteristics. The current findings of an inverse association between plasma Zn concentrations and several markers of glucose homeostasis, together with growing evidence from intervention studies, suggest a role for Zn in glucose metabolism. If supported by further evidence, strategies to improve Zn status in populations may provide a cheap public health prevention approach for diabetes.

Does registered nurse involvement in improving healthcare services, influence registered nurse retention?

Background: Registered nurses are 'critical' to population health, international responses to emergencies, epidemics and disasters. Retention of registered nurses (RNs) is an international nursing priority. In England, RNs are encouraged to be involved in improving healthcare services. This benefits quality of care, operational and financial performance. However, RN involvement in improvement may reduce RN retention. It is important to understand this relationship when developing effective RN retention strategies. Aim: The purpose of this research is to describe possible relationships between RN involvement in improving healthcare services and RN retention, using published 2018 data for National Health Service (NHS) Trusts in England. Methods: The relationship between RN involvement in improving healthcare services and RN retention was explored using a correlational design, involving secondary data from the annual NHS Staff Survey and Model Hospital. Results: In mental health NHS Trusts in England, a statistically significant, positive correlation of 0.24 was found between RN 'ab(ility) to make suggestions for improvement' and RN retention. In mental health NHS Trusts, a statistically significant correlation of 0.278 was found between RNs 'making improvements happen' and RN retention. In acute NHS Trusts in England, a statistically significant, negative correlation of -0.15 was identified between RNs 'mak(ing) improvements happen' and RN retention. Conclusions: The findings suggest that RN retention factors in mental health and acute NHS Trusts differ from community and specialist NHS Trusts in England. This is an important consideration for national RN retention programmes as a single approach to RN retention may not be effective across all healthcare settings.

Towards harmonization of directly measured free 25-hydroxyvitamin D using an enzyme-linked immunosorbent assay.

The majority of circulating 25-hydroxyvitamin D (25(OH)D) is protein bound and perhaps less available than the free fraction of 25(OH)D; therefore, researchers have proposed that the measurement of free 25(OH)D in human serum may be a better indicator of vitamin D health status than total 25(OH)D. The availability of a new enzyme-linked immunosorbent assay (ELISA) for the determination of free 25(OH)D provides a method for direct measurement of the low levels of non-protein bound 25(OH)D. As an initial step towards harmonization of measurements of free 25(OH)D, the ELISA was used to measure free 25(OH)D in three existing Standard Reference Materials (SRMs): SRM 972a Vitamin D Metabolites in Frozen Human Serum, SRM 2973 Vitamin D Metabolites in Frozen Human Serum (High Level), and SRM 1949 Frozen Prenatal Human Serum. Target values for free 25(OH)D in the nine SRM serum pools, obtained by combining the results from two laboratories, ranged from 3.76 ± 0.36 to 10.0 ± 0.58 pg/mL. Of particular significance is the assignment of free 25(OH)D target values to SRM 1949, which consists of four serum pools from non-pregnant female donors of reproductive age and pregnant women in each of the three trimesters and which also has values assigned for vitamin D binding protein, which increases during pregnancy. The availability of target values for free 25(OH)D in these SRMs will allow researchers to validate new analytical methods and to compare their results with other researchers as an initial step towards harmonization of measurements among different studies and laboratories.

The implications of COVID-19 on health and social care personnel in long-term care facilities for older people: An international scoping review.

This scoping review mapped out the existing literature pertaining to health and social care personnel experiences during the coronavirus disease-2019 (COVID-19) pandemic and their work in a long-term care setting for older people. This review identified the gaps in the implications of health and social care personnel's own health and well-being during the pandemic as well as the ethical dilemmas inherent in providing care during the COVID-19 pandemic. The authors utilised the PRISMA checklist for undertaking scoping reviews. The Databases Medline, PsychINFO, CINAHL, SCOPUS, Web of Science and Google Scholar were searched for relevant articles in English that were published between March 28, 2020 and June 1, 2022. This time period was selected to focus specifically on the COVID-19 pandemic. In the context of this review, long-term care facilities were defined to include institutions such as nursing homes, skilled nursing facilities, retirement homes and residential care homes. The gaps identified were a paucity of research on the experiences of health and social care personnel in long-term care facilities, the impact on their mental health, and the wider challenges experienced during the COVID-19 pandemic is discussed. The findings of this scoping review indicate a need for adequate preparedness during a pandemic within the health and social care sector to protect health and social care personnel and the individuals they care for.

Association between circulating 25-hydroxyvitamin D and cardiometabolic risk factors in adults in rural and urban settings.

BACKGROUND: An inverse association between vitamin D status and cardiometabolic risk has been reported but this relationship may have been affected by residual confounding from adiposity and physical activity due to imprecise measures of these variables. We aimed to investigate the relationship between serum 25-hydroxyvitamin D (25(OH)D) and cardiometabolic risk factors, with adjustment for objectively-measured physical activity and adiposity. METHODS: This was a population-based cross-sectional study in 586 adults in Cameroon (63.5% women). We assessed markers of glucose homoeostasis (fasting blood glucose (BG), 2 h post glucose load BG, HOMA-IR)) and computed a metabolic syndrome score by summing the sex-specific z-scores of five risk components measuring central adiposity, blood pressure, glucose, HDL cholesterol and triglycerides. RESULTS: Mean±SD age was 38.3 ± 8.6 years, and serum 25(OH)D was 51.7 ± 12.5 nmol/L. Mean 25(OH)D was higher in rural (53.4 ± 12.8 nmol/L) than urban residents (50.2 ± 12.1 nmol/L), p = 0.002. The prevalence of vitamin D insufficiency (<50 nmol/L) was 45.7%. There was an inverse association between 25(OH)D and the metabolic syndrome score in unadjusted analyses (ß = -0.30, 95% CI -0.55 to -0.05), which became non-significant after adjusting for age, sex, smoking status, alcohol intake and education level. Serum 25(OH)D was inversely associated with fasting BG (-0.21, -0.34 to -0.08)), which remained significant after adjustment for age, sex, education, smoking, alcohol intake, the season of data collection, BMI and physical activity (-0.17, -0.29 to -0.06). There was an inverse association of 25(OH)D with 2-h BG (-0.20, -0.34 to -0.05) and HOMA-IR (-0.12, -0.19 to -0.04) in unadjusted analysis, but these associations became non-significant after adjustment for potential confounders. CONCLUSION: Vitamin D insufficiency was common in this population. This study showed an inverse association between vitamin D status and fasting glucose that was independent of potential confounders, including objectively measured physical activity and adiposity, suggesting a possible mechanism through insulin secretion.

Young People's Experiences of Death Anxiety and Responses to the Covid-19 Pandemic.

Capacity for death awareness and death anxiety in young people has been previously documented but the impact of Covid-19 is not currently known. Therefore, the aim of this study of this study was to explore young people's experiences and responses to the Covid-19 pandemic. Qualitative data was collected from young people via a two-stage process across the United Kingdom: Stage One consisted of an online questionnaire; Stage Two comprised online semi-structured interviews. Responses for Stage One of the study totalled 120 young people; 9 of these were interviewed for Stage Two of the study. Thematic analysis of data identified four themes relating to young people's experiences of the Covid-19 pandemic: death anxiety; mental health; normalising death; and identified support needs. Young people experienced heightened death anxiety due to the pandemic but death also became normalized for them and their mental health was negatively affected.

Placental uptake and metabolism of 25(OH)vitamin D determine its activity within the fetoplacental unit.

Pregnancy 25-hydroxyvitamin D [25(OH)D] concentrations are associated with maternal and fetal health outcomes. Using physiological human placental perfusion and villous explants, we investigate the role of the placenta in regulating the relationships between maternal 25(OH)D and fetal physiology. We demonstrate active placental uptake of 25(OH)D3 by endocytosis, placental metabolism of 25(OH)D3 into 24,25-dihydroxyvitamin D3 and active 1,25-dihydroxyvitamin D [1,25(OH)2D3], with subsequent release of these metabolites into both the maternal and fetal circulations. Active placental transport of 25(OH)D3 and synthesis of 1,25(OH)2D3 demonstrate that fetal supply is dependent on placental function rather than simply the availability of maternal 25(OH)D3. We demonstrate that 25(OH)D3 exposure induces rapid effects on the placental transcriptome and proteome. These map to multiple pathways central to placental function and thereby fetal development, independent of vitamin D transfer. Our data suggest that the underlying epigenetic landscape helps dictate the transcriptional response to vitamin D treatment. This is the first quantitative study demonstrating vitamin D transfer and metabolism by the human placenta, with widespread effects on the placenta itself. These data demonstrate a complex interplay between vitamin D and the placenta and will inform future interventions using vitamin D to support fetal development and maternal adaptations to pregnancy.

Thiamine deficiency in Gambian women of reproductive age.

Thiamine deficiency disorders are associated with a variety of clinical symptoms affecting the nervous and cardiovascular systems. There is growing recognition that thiamine deficiency can occur in populations well beyond the classical region of South Asia, and at-risk populations include those who receive a large proportion of their energy from polished white rice (or other low-thiamine staple foods) and with low dietary diversity. Reports of thiamine deficiency in West Africa over the last century have suggested that this has historically been an issue in this population, but in more recent decades, these reports have been limited to prison populations. To understand if thiamine deficiency might be an unrecognized problem in the communities of this region, erythrocyte samples collected during the wet and dry seasons from 226 women of reproductive age (mean age = 28 years old) were assessed for thiamine status by measuring the erythrocyte transketolase activity coefficient (ETKac). Overall, 35.8% of the sample was at high risk of thiamine deficiency (ETKac ≥ 1.25). Risk of thiamine deficiency was significantly higher in the wet (47.9%) compared with the dry season (22.9%) (P < 0.001). To our knowledge, this is the first report of biochemical thiamine deficiency in a free-living population in West Africa in the 21st century and suggests that further investigation is warranted.