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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

BACKGROUND: Benfotiamine provides an important novel therapeutic direction in Alzheimers 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.

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 Peoples Democratic Republic and explores possible nutritional causes and risk factors for anaemia. Hospitalised children (ages 21 days to

Reported here are substrate-dictated rearrangements of chrysanthenol derivatives prepared from verbenone to access complex bicyclic frameworks. These rearrangements set the stage for a 10-step formal synthesis of the natural product xishacorene B. Key steps include an anionic allenol oxy-Cope rearrangement and a Suárez directed C-H functionalization. The success of this work was guided by extensive computational calculations which provided invaluable insight into the reactivity of the chrysanthenol-derived systems, especially in the key oxy-Cope rearrangement.

School psychology journals yield hundreds of articles each year. As these journals are often evaluated based on the impact factors they produce, the aim of this study was to provide a historically complete record of the five impact factor values for the generalist school psychology journals that yield them. This study identified impact factors beginning in 1977, 20 years earlier than previously reported, and ending in 2019. Across all years and journals, the average Journal Impact Factor (JIF) was about 1.0, the average Immediacy Index was less than 0.4, the average 5-year Impact Factor was about 2.3, the average original CiteScore was 1.8, and the average new CiteScore was about 3.0. Increases in values were evident across time, and the highest recorded values across journals are held by the "Journal of School Psychology" (for the JIF, 5-year Impact Factor, and both CiteScore metrics) and "School Psychology Review" (for the Immediacy Index). Most impact factors, with the exception of the Immediacy Index, were moderately to highly correlated. The new CiteScore values were always the highest, and Immediacy Index values were always the lowest. School psychology has added journals to the list of those indexed by major databases, and these journals have increased their impact over time.

Micronutrient (MN) deficiencies can produce a broad array of adverse health and functional outcomes. Young, preschool children and women of reproductive age in low- and middle-income countries are most affected by these deficiencies, but the true magnitude of the problems and their related disease burdens remain uncertain because of the dearth of reliable biomarker information on population MN status. The reasons for this lack of information include a limited understanding by policy makers of the importance of MNs for human health and the usefulness of information on MN status for program planning and management; insufficient professional capacity to advocate for this information and design and implement related MN status surveys; high costs and logistical constraints involved in specimen collection, transport, storage, and laboratory analyses; poor access to adequately equipped and staffed laboratories to complete the analyses reliably; and inadequate capacity to interpret and apply this information for public health program design and evaluation. This report describes the current situation with regard to data availability, the reasons for the lack of relevant information, and the steps needed to correct this situation, including implementation of a multi-component MN Data Generation Initiative to advocate for critical data collection and provide related technical assistance, laboratory services, professional training, and financial support.

BackgroundInfantile beriberi-related mortality is still common in South and Southeast Asia. Interventions to increase maternal thiamine intakes, and thus human milk thiamine, are warranted; however, the required dose remains unknown.ObjectivesWe sought to estimate the dose at which additional maternal intake of oral thiamine no longer meaningfully increased milk thiamine concentrations in infants at 24 wk postpartum, and to investigate the impact of 4 thiamine supplementation doses on milk and blood thiamine status biomarkers.MethodsIn this double-blind, 4-parallel arm randomized controlled dose-response trial, healthy mothers were recruited in Kampong Thom, Cambodia. At 2 wk postpartum, women were randomly assigned to consume 1 capsule, containing 0, 1.2 (estimated average requirement), 2.4, or 10 mg of thiamine daily from 2 through 24 weeks postpartum. Human milk total thiamine concentrations were measured using HPLC. An Emax curve was plotted, which was estimated using a nonlinear least squares model in an intention-to-treat analysis. Linear mixed-effects models were used to test for differences between treatment groups. Maternal and infant blood thiamine biomarkers were also assessed.ResultsIn total, each of 335 women was randomly assigned to1 of the following thiamine-dose groups: placebo (n = 83), 1.2 mg (n = 86), 2.4 mg (n = 81), and 10 mg (n = 85). The estimated dose required to reach 90% of the maximum average total thiamine concentration in human milk (191 µg/L) is 2.35 (95% CI: 0.58, 7.01) mg/d. The mean ± SD milk thiamine concentrations were significantly higher in all intervention groups (183 ± 91, 190 ± 105, and 206 ± 89 µg/L for 1.2, 2.4, and 10 mg, respectively) compared with the placebo group (153 ± 85 µg/L; P

Service-learning programs provide students with opportunities to gain discipline-specific skills, while providing community organizations with a steady pool of volunteers. However, because students may lack the skills needed to effectively serve the community, skills-based training may need to be incorporated into service-learning courses. Students in a community nutrition service-learning course engaged in 7 weeks of training before teaching a 6-week-long nutrition education course to community members. The training included three layers of activities: (1) basic activities, which introduced the students to material necessary to build skills for their service-learning experience; (2) directed activities, which allowed them to refine a targeted skillset; (3) and collective activities, which allowed for the application of multiple skills. Through qualitative interviews with 12 of the 19 students who had been enrolled in the course, we determined the impact of a pre-service-learning training program on the development of the skills necessary to successfully teach a nutrition education course. Thematic analysis of the data revealed two major themes: (1) "layered learning" activities facilitate skill building and (2) a stressful, yet supportive, environment facilitates growth. Together, these aspects of course design allow students to develop skills and their self-efficacy in those skills. Therefore, instructors who plan to incorporate servicelearning into their nutrition courses may benefit from designing a pre-servicelearning training to improve student learning outcomes.

Herein, we describe an enantiospecific route to one enantiomer of a common decalin core that is present in numerous highly oxygenated terpenoids. This intermediate is accessed in eight steps from (R)-carvone, an inexpensive, enantioenriched building block, which can be elaborated to the desired bicycle through sequential Fe(III)-catalyzed reductive olefin coupling and Dieckmann condensation. The same synthetic route may be applied to (S)-carvone to afford the enantiomer of this common intermediate for other applications.

This paper addresses the role of 'emotional labour' in conducting sensitive research. As such it begins to unpick the emotional and embodied consequences of working with data which covers sensitive subjects, in this case perinatal death, and considers how such responses are likely to impact on the analysis of data. We draw upon two doctoral studies which explored parental experiences of perinatal bereavement. We argue that researchers need to understand and consider carefully how emotions experienced during the research may impact upon the findings. By exposing the authors' own positionality in this research based on their own experience of perinatal loss, we acknowledge that we are actors in research which has an impact on the process and final product of the studies.

The effect of acute exercise on circulating concentrations of vitamin D metabolites is unclear. To address this knowledge gap, we examined the effect of a bout of treadmill‐based exercise versus rest on circulating concentrations of 25(OH)D3, 25(OH)D2, 3‐epi‐25(OH)D3, 24,25(OH)2D3, 1,25(OH)2D3, and vitamin D2 and D3 in healthy men and women. Thirty‐three healthy adults (14 females, 41 (15) years, body mass index 26.2 (3.7) kg/m2, V̇O2max${{\dot{V}}_{{{{\mathrm{O}}}_{\mathrm{2}}}{\mathrm{max}}}}$ 36.2 (9.2) ml/kg/min; mean (SD)) completed two laboratory visits involving 60 min of moderate‐intensity treadmill exercise (60% V̇O2max${{\dot{V}}_{{{{\mathrm{O}}}_{\mathrm{2}}}{\mathrm{max}}}}$) versus 60 min of seated rest, both in an overnight fasted‐state, as part of a randomised crossover design. Venous blood samples were drawn at baseline, immediately (0 h), 1 h and 24 h after the exercise or rest‐period. There was a significant time × trial interaction effect for total circulating 25(OH)D (P = 0.0148), 25(OH)D3 (P = 0.0127) and 1,25(OH)2D3 (P = 0.0226). Immediately post‐exercise, 25(OH)D, 25(OH)D3 and 1,25(OH)2D3 concentrations were significantly elevated compared to the control resting condition, and 1,25(OH) 2D3 remained significantly elevated 1 h later. Circulating albumin, vitamin D binding protein, calcium and parathyroid hormone were elevated immediately post‐exercise. Thus, an acute bout of moderate intensity exercise transiently increases concentrations of circulating 25(OH)D and 1,25(OH)2D3 compared to resting conditions. Key points: Observational studies suggest that acute exercise might change circulating concentrations of vitamin D metabolites, but this has not been investigated using randomised crossover studies and using robust analytical procedures.In this study, we used a randomised crossover design to examine the effect of a bout of treadmill‐based exercise (vs. rest) on circulating concentrations of a wide range of vitamin D metabolites in healthy humans.We show that an acute bout of moderate intensity exercise transiently increases concentrations of circulating 25(OH)D and 1,25(OH)2D3 compared to resting conditions.These findings indicate that regular exercise could lead to transient but regular windows of enhanced vitamin D biological action. [ABSTRACT FROM AUTHOR]

ContextThe optimal measure of vitamin D status is unknown.ObjectiveTo directly measure circulating free 25-hydroxyvitamin D [25(OH)D] concentrations and relationships to total 25(OH)D in a clinically diverse sample of humans.DesignCross-sectional analysis.SettingSeven academic sites.PatientsA total of 1661 adults: healthy (n = 279), prediabetic (n = 479), outpatients (n = 714), cirrhotic (n = 90), pregnant (n = 20), nursing home resident (n = 79).InterventionsMerge research data on circulating free 25(OH)D (directly-measured immunoassay), total 25(OH)D (liquid chromatography/tandem mass spectrometry), D-binding protein [DBP; by radial (polyclonal) immunodiffusion assay], albumin, creatinine, intact parathyroid hormone, and DBP haplotype.Main outcome measuresDistribution of free 25(OH)D (ANOVA with Bonferroni correction for post hoc comparisons) and relationships between free and total 25(OH)D (mixed-effects modeling incorporating clinical condition, DBP haplotype with sex, race, estimated glomerular filtration rate (eGFR), body mass index (BMI), and other covariates).ResultsFree 25(OH)D was 4.7 ± 1.8 pg/mL (mean ± SD) in healthy persons and 4.3 ± 1.9 pg/mL in outpatients, with levels of 0.5 to 8.1 pg/mL and 0.9 to 8.1 pg/mL encompassing 95% of healthy persons and outpatients, respectively. Free 25(OH)D was higher in patients with cirrhosis (7.1 ± 3.0 pg/mL; P < 0.0033) and nursing home residents (7.9 ± 2.1 pg/mL; P < 0.0033) than in other groups and differed between whites and blacks (P < 0.0033) and between DBP haplotypes (P < 0.0001). Mixed-effects modeling of relationships between free and total 25(OH)D identified clinical conditions (patients with cirrhosis > nursing home residents > patients with prediabetes > outpatients > pregnant women) and BMI (lesser effect) as covariates affecting relationships but not eGFR, sex, race, or DBP haplotype.ConclusionsTotal 25(OH)D, health condition, race, and DBP haplotype affected free 25(OH)D, but only health conditions and BMI affected relationships between total and free 25(OH)D. Clinical importance of free 25(OH)D needs to be established in studies assessing outcomes.

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]