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The vitamin D3 metabolite 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), its nuclear receptor VDR (vitamin D receptor) and hundreds of their target genes are not only key regulators of calcium homeostasis, but also important modulators of the immune system. Innate immune cells like monocytes use VDR for efficient differentiation and are very responsive to vitamin D. So far, most information on the gene regulatory function of vitamin D and its physiological impact had been obtained from in vitro studies using supraphysiological doses of 1,25(OH)2D3. Therefore, medical experiments like the study VitDHiD (NCT03537027), where 25 healthy individuals were supplemented once with a vitamin D3 bolus (80,000 IU), provide important insight into the response to vitamin D under in vivo conditions. In this study, we inspected 452 in vivo vitamin D target genes from peripheral blood mononuclear cells (PBMCs) detected in VitDHiD and found 61 of them involved in eight major KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways of innate immunity. Under in vivo conditions in healthy individuals vitamin D either silences five pathways of innate immunity, stabilizes two and increases one, so that acute inflammation is suppressed and the release of cytokines is kept under control. A ranking of the 61 target genes by inducibility, basal expression and multiple involvements in the pathways highlighted the genes NFKBIA (NFκB inhibitor alpha), NFKBIZ, FOSL2 (FOS like 2, AP1 transcription factor subunit), JDP2 (Jun dimerization protein 2), PIK3R1 (phosphoinositide-3-kinase regulatory subunit 1), CLEC7A (C-type lectin domain containing 7A), DUSP6 (dual specificity phosphatase 6), NCF2 (neutrophil cytosolic factor 2), PLCB1 (phospholipase C beta 1), PLCG2 and TNFAIP3 (TNF alpha induced protein 3). In conclusion, vitamin D's in vivo effect on innate immunity in healthy adults is mediated by the interconnection of the pathways of neutrophil extracellular trap formation, Toll-like receptor, chemokine and phagosome signaling, NOD-like receptor, C-type lectin receptor, apoptosis and interleukin 17 through a limited set of proteins encoded by key target genes. [ABSTRACT FROM AUTHOR]

Background: Numerous organs, including the thyroid gland, depend on vitamin D to function normally. Insufficient levels of serum 25-hydroxyvitamin D [25(OH)D] are seen as a potential factor contributing to the emergence of several thyroid disorders, however, the causal relationship remains unclear. Here we use a Mendelian randomization (MR) approach to investigate the causal effect of serum 25(OH)D concentration on the indicators of thyroid function. Methods: We conducted a two-sample MR analysis utilizing summary data from the most extensive genome-wide association studies (GWAS) of serum 25(OH)D concentration (n = 443,734 and 417,580), thyroid-stimulating hormone (TSH, n = 271,040), free thyroxine (fT4, n = 119,120), free triiodothyronine (fT3, n = 59,061), total triiodothyronine (TT3, n = 15,829), as well as thyroid peroxidase antibody levels and positivity (TPOAb, n = 12,353 and n = 18,297), low TSH (n = 153,241), high TSH (n = 141,549), autoimmune hypothyroidism (n = 287,247) and autoimmune hyperthyroidism (n = 257,552). The primary analysis was conducted using the multiplicative random-effects inverse variance weighted (IVW) method. The weighted mode, weighted median, MR-Egger, MR-PRESSO, and Causal Analysis Using Summary Effect estimates (CAUSE) were used in the sensitivity analysis. Results: The IVW, as well as MR Egger and CAUSE analysis, showed a suggestive causal effect of 25(OH)D concentration on high TSH. Each 1 SD increase in serum 25(OH)D concentration was associated with a 12% decrease in the risk of high TSH (p = 0.02). Additionally, in the MR Egger and CAUSE analysis, we found a suggestive causal effect of 25(OH)D concentration on autoimmune hypothyroidism. Specifically, each 1 SD increase in serum 25(OH)D concentration was associated with a 16.34% decrease in the risk of autoimmune hypothyroidism (p = 0.02). Conclusions: Our results support a suggestive causal effect which was negative in direction across all methods used, meaning that higher genetically predicted vitamin D concentration possibly lowers the odds of having high TSH or autoimmune hypothyroidism. Other thyroid parameters were not causally influenced by vitamin D serum concentration. [ABSTRACT FROM AUTHOR]

Inflammation-derived oxidative stress is postulated to contribute to neuronal damage leading to poor clinical outcomes in Acute Ischemic Stroke (AIS). We aimed to investigate the association between serum levels of selected cytokines (IL-1β, IFN-γ, IL-4), and vitamin D in ischemic stroke progression, and their accuracy in predicting AIS prognosis, among Sri Lankans. We compared 60 AIS patients admitted in 4 phases post-stroke onset (<6 h; 6–24 h; 24–48 h; 48–96 h; n = 15/phase), with 15 age- and sex-matched controls. The 30-day functional outcome (FO) was assessed using the modified Rankin Scale (mRS). Serum cytokine and vitamin D levels were quantified using sandwich ELISAs, and competitive ELISA, respectively. The CombiROC web tool established optimal prognostic biomarker combinations. Serum IL-1β and IFN-γ were elevated in all four phases following stroke onset while IL-4 was elevated exclusively in the recovery phase (48–96 h) (p<0.05). Th1 bias polarization of the Th1:Th2 cytokine (IFN-γ:IL-4) ratio occurred with AIS progression while a Th2 bias occurred during AIS recovery (p<0.05). Lower serum IL-1β and higher IL-4 levels were associated with a good FO (p<0.05), while lower Vitamin D levels were related to a poor FO (p = 0.001). The triple-biomarker panel, IL-4- IFN-γ -Vit D, accurately predicted AIS prognosis (sensitivity = 100%, specificity = 91.9%, area under the curve = 0.98). Serum immunologic mediators IFN-γ, IL-4, and vitamin D may be useful biomarkers of AIS prognosis and may serve as therapeutic targets in improving stroke outcomes. Vitamin D supplementation may improve the prognosis of AIS patients. Furthermore, binary logistic model fitted for FO indicated Th1:Th2 cytokine ratio (IFN-γ:IL-4), vitamin D status, history of stroke, and ischemic heart disease as significant predictors of AIS prognosis. [ABSTRACT FROM AUTHOR]

Background and aim: Preeclampsia (PE) is characterized by hypertension and proteinuria mostly after 20 weeks of gestation. It affects 2–8% of pregnancies worldwide, with detrimental consequences for both mother and foetus. Evidence, suggests that genetic factors, including vitamin D receptor (VDR) gene polymorphisms, could contribute to PE complexity. However, their role in the Ghanaian population remains underexplored. We assessed the interplay between Vitamin D, VDR gene variants and preeclampsia risk in Ghanaian women. Methods: This unmatched case-control study was conducted at Kumasi South Hospital, Ghana, from June to November 2022. A total of 162 participants consisting of 62 PE cases and 100 normotensive controls were enrolled. Clinical and obstetric data were collected. Blood samples were also collected for DNA extraction and vitamin D assay. Genotyping of VDR Fok1 and Bsm1 gene variants was performed using Polymerase Chain Reaction (PCR) and Polymerase Chain Reaction—Restriction Fragment Length Polymorphism (PCR-RFLP) analysis whereas Vitamin D levels were estimated using sandwich ELISA. Statistical analyses were computed with SPSS version 25 and GraphPad prism version 8.0. A p-value of < 0.05 was considered statistically significant. Results: Vitamin D concentration were significantly lower in the PE group (p < 0.0001). Vitamin D deficiency (aOR = 3.311, 95% CI: 1.584–6.921, p = 0.0010) was significantly associated with a three-fold increase in preeclampsia risk, whilst VDR gene variants, particularly the "bb" genotype (cOR = 0.227, 95% CI: 0.055–0.944, p = 0.0410) was associated with reduced risk of PE. There was no association between the distribution of Fok1 genotypes and PE. Conclusion: This study highlights a significant association between vitamin D deficiency and an increased risk of PE among Ghanaian women. However, the VDR gene variant, "bb", genotype, for Bsm1 reduces the risk of PE. [ABSTRACT FROM AUTHOR]

Background: Acute respiratory infections (ARIs) have a substantial impact on morbidity, healthcare utilization, and functional decline among older adults. Therefore, we systematically reviewed evidence from randomized controlled trials (RCTs) to evaluate the efficacy and safety of vitamin D supplementation in preventing ARIs in older adults. Methods: PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov were searched until 1 February 2024. RCTs evaluating the use of vitamin D supplements to protect older adults from ARIs were included. Two reviewers independently screened papers, extracted the data and assessed the risk of bias. Data were summarised as relative risks (RRs) or odds ratios (ORs) with corresponding 95% confidence intervals (CIs). Random effects meta-analyses were used to synthesise the results. GRADE was used to evaluate the quality of evidence. All the analysis were performed with Stata version 17. Results: Twelve trials (41552 participants) were included in the meta-analysis. It showed that vitamin D supplementation probably does not reduce the incidence of ARIs (RR, 0.99; 95% CI, 0.97–1.02, I2 = 0%; moderate certainty). No significant effect of vitamin D supplementation on the risk of ARI was observed for any of the subgroups defined by baseline 25(OH)D concentration, control treatments, dose frequency, study duration, and participants' condition. However, there was a possibility, although not statistically significant, that vitamin D may reduce the risk of ARI in patients with a baseline 25(OH)D concentration <50 nmol/L (OR, 0.90; 95% CI, 0.79–1.04, I2 = 14.7%). Additionally, vitamin D supplements might result in little to no difference in death due to any cause, any adverse event, hypercalcinemia, and kidney stones. Conclusions: Vitamin D supplementation among older adults probably results in little to no difference in the incidence of ARIs. However, further evidence is needed, particularly for individuals with vitamin D deficiency and populations residing in low and middle income countries. Trial registration: This study was registered on PROSPERO (CRD42023451265). [ABSTRACT FROM AUTHOR]

VDX-111 (also identified as AMPI-109) is a vitamin D derivative which has shown anticancer activity. To further assess the function of this compound against multiple cancer types, we examined the efficacy of VDX-111 against a panel of 30 well characterized canine cancer cell lines. Across a variety of cancer types, VDX-111 induced widely variable growth inhibition, cell death, and migration inhibition, at concentrations ranging from 10 nM to 1 μM. Growth inhibition sensitivity did not correlate strongly with tumor cell histotype; however, it was significantly correlated with the expression of genes in multiple cell signaling pathways, including the MAPK and PI3K-AKT pathways. We confirmed inhibition of these signaling pathways as likely participants in the effects of VDX-111. These results suggest that a subset of canine tumors may be sensitive to treatment with VDX-111, and suggests possible predictive markers of drug sensitivity and pharmacodynamic biomarkers of drug exposure that could be employed in future clinical trials. [ABSTRACT FROM AUTHOR]

Objective: Maternal vitamin D deficiency is a prevalent public health issue worldwide. While isolated reports from certain cities in China have highlighted the existence of maternal vitamin D deficiency, no nationwide investigation has been conducted on this topic. Therefore, we conducted a meta-analysis and systematic review to examine the prevalence and associated influencing factors of maternal vitamin D deficiency in mainland China. This study aims to provide a theoretical foundation for future prevention and supplementation strategies for maternal vitamin D. Methods: We retrieved relevant Chinese and English literature on the status of maternal vitamin D deficiency in mainland China from databases such as CNKI, Wanfang Data, VIP, CBM, Web of Science, Google Scholar, and PubMed. The literature search and database construction were conducted until September 8, 2023. Data were extracted and synthesized following PRISMA guidelines.After literature screening and quality assessment, we performed meta-analysis, sensitivity analysis, and identified publication bias using RevMan 5.3 software. Results: A total of 26 articles were reviewed, involving 128,820 pregnant women. Among them, 108,768 had vitamin D insufficiency or deficiency, resulting in a prevalence of 84% (95% CI: 81%~88%). Subgroup analysis revealed the highest prevalence of vitamin D deficiency or insufficiency among pregnant women in mainland China to be in the northwest region (94%, 95% CI: 94%~95%). Furthermore, the highest prevalence was observed during the winter and spring seasons (80%, 95% CI: 77%~83%) and in the early stages of pregnancy (93%, 95% CI: 90%~95%). Significant statistical differences (P<0.05) were found among these three subgroups. No publication bias was detected, and sensitivity analysis indicated the stability of the meta-analysis outcome. Conclusion: This study provides evidence of the prevalence of vitamin D deficiency or insufficiency among pregnant women in mainland China. To improve the overall health and well-being of the population, relevant health authorities should develop policies aimed at alleviating this phenomenon. [ABSTRACT FROM AUTHOR]

Background: The role of Vitamin D in immune function is well reported with a growing evidence base linking low levels to poorer outcomes from infectious disease. Vitamin D deficiency and insufficiency are prevalent worldwide with healthcare workers identified as a known at-risk group. Here we aim to investigate serum Vitamin D levels in a UK population of front line healthcare workers and to promote the occupational risk. Methods: A cross-sectional study of 639 volunteers was conducted to identify the prevalence of Vitamin D deficiency and insufficiency amongst a population of front-line health care workers in the UK. Participant demographics and co-morbid factors were collected at the time of serum sampling for multivariate analysis. Results: Only 18.8% of the population had a normal vitamin D level greater than or equal to 75nmol/L. This is compared to Public Health England's (PHE) stipulated normal levels of 60% during winter. 81.2% had a level less than 75nmol/L, with 51.2% less than 50nmol/L and 6.6% less than 25nmol/L. For serum levels less than 25nmol/L, Asian ethnicity was more likely to have a vitamin D deficiency than non-asian (OR (95%CI): 3.81 (1.73-8.39), p = 0.001), whereas white ethnicity was less likely to have a vitamin D deficiency compared to non-white (OR (95%CI: 0.43 (0.20-0.83), p = 0.03). Other factors that contributed to a higher likelihood of lower-than-normal levels within this population included male sex, decreased age and not taking supplementation. Conclusion: It is concluded that our population of healthcare workers have higher rates of abnormal vitamin D levels in comparison with the general UK population reported prevalence. Furthermore, Asian ethnicity and age 30 years and below are more at risk of vitamin D insufficiency and deficiency. This highlights an occupational risk factor for the healthcare community to consider. [ABSTRACT FROM AUTHOR]

Vitamin D plays an essential role in bone and mineral metabolism. There is increased interest in understanding prevalence of Vitamin D deficiency in pregnancy as many studies report association of low vitamin D levels with obstetric complications and neonatal sequelae. There is a paucity of studies in Singapore evaluating levels of vitamin D levels during the first trimester of pregnancies. We aim to study the prevalence of vitamin D insufficiency in this population. Our study assessed vitamin D levels in these women. Vitamin D (Plasma 25(OH)D concentration) levels in multiracial women during the first trimester were collected via venepuncture at their booking antenatal visit. They were stratified into sufficient ≥30ng/ml, insufficient ≥20ng/ml and <30ng/ml, moderately deficient ≥10ng/ml and <20ng/ml and severely deficient <10ng/ml. 93 women were included in this study. Only 2.2% of our study population had sufficient vitamin D levels. In women who had insufficient levels, the heavier the weight, the more likely to be vitamin D deficient. Interestingly, we also note that the older the patient, the less likely they are to be deficient. In women with periconceptual multivitamin supplementation, the average vitamin D level for those with supplementation was 2.10ng/ml higher than those without. Majority of patients were recruited from a single study member's patient pool who were mostly Chinese. Prevalence of Vitamin D deficiency in general obstetric patients with higher BMI and darker skinned patients may be even lower in Singapore. The high prevalence of Vitamin D insufficiency in our patients prove that it is a prominent problem in our population. We aim to implement screening of vitamin D levels as part of antenatal investigations in the first trimester and recommend supplementation as required. We also hope to evaluate the association of low vitamin D levels with obstetric or neonatal complications further understanding its implications. [ABSTRACT FROM AUTHOR]

Vitamin D deficiency is a worldwide health issue especially in women. Serum vitamin D concentrations vary depending on the weather. However, the ideal vitamin D supplementation strategy related to weather remains uncertain. We aimed to investigate the relationship between climate factors and serum 25-hydroxy vitamin D [25(OH)D] concentrations. This study included 11,272 women aged 20–79 who visited a health promotion center for annual checkups between January 2013 and December 2015. We reviewed medical records and collected daily meteorological data. We analyzed the association between serum 25(OH)D concentration and climate factors using simple and multiple regression models and then predicted serum 25(OH)D concentration using multiple fractional polynomial models. The median age of the participants was 51 years (20–79 years), and the mean serum 25(OH)D level was 17.4 ± 8.6 ng/mL. The serum 25(OH)D concentration was lower in young women than in older women. The proportions of women with adequate 25(OH)D levels were 14.9% and 47.0% in the age groups 20–29 and 70–79, respectively. The maximum level of predicted log 25(OH)D was found in September, and the minimum was found in January. In multiple regression analysis, age and monthly mean temperature were associated with 25(OH)D concentrations. Serum 25(OH)D level was predicted using the following formula: log (25(OH)D) = 2.144 + 0.009 × age + 0.018 × ((temperature + 12.4)/10)2 (P < 0.001, adjusted R2 = 0.091). Serum 25(OH)D concentrations changed according to air temperature. An adequate strategy for vitamin D supplementation, based on air temperature, is necessary to maintain healthy serum 25(OH)D levels. [ABSTRACT FROM AUTHOR]

Background: While several studies have investigated the association between vitamin D deficiency and biochemical parameters, the results are still inconsistent and mostly overlook seasonal variations. This study explored the relationships between 25-hydroxy-vitamin D (25(OH)D) concentrations, biochemical markers, and seasonal variation among young males and females. Methods: A cross-sectional study was conducted among 203 individuals aged 18–24 years of both sexes residing in Brasilia, Brazil (latitude: 15°S). Sociodemographic variables, season of blood collection, and serum levels of 25(OH)D, total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, glycated hemoglobin (HbA1c), glucose, insulin, hs-CRP, parathyroid hormone, ionized calcium, and alkaline phosphatase were included. Descriptive statistics and differences among groups, correlations, and linear regression tests were performed. Results: The mean age of the participants was 21.17±1.7 years, and the mean serum 25(OH)D level was 25.76±7.0 ng/mL. Of the participants, 50.7% had vitamin D insufficiency (20 to 29.9 ng/mL), and 23.2% were vitamin D deficient (≤20 ng/mL). Vitamin D deficiency was higher in the spring (53.2%) and among females (29.5%). In young men with vitamin D insufficiency/deficiency (≤29.9 ng/mL) (n = 49), 25(OH)D levels were inversely correlated with HOMA-β (r = -0.234, p = 0.032) and triglyceride (r = -0.415, p = 0.003) levels. However, there were no significant correlations between 25(OH)D concentrations and biochemical markers among women with insufficient and deficient vitamin D levels. Conclusion: This study found a high prevalence of vitamin D insufficiency/deficiency among young individuals living in Brasília, Brazil, particularly women and during the spring season. Our findings suggest that lower 25(OH)D levels (≤29.9 ng/mL) may be associated with insulin resistance and an increased risk of cardiovascular disease in young men studied. However, further studies with larger representative samples are needed to explore the mechanisms underlying the association between vitamin D and biochemical parameters. [ABSTRACT FROM AUTHOR]

"Persistent organic pollutants (POPs)" have a plethora of deleterious effects on humans and the environment due to their bioaccumulative, persistent, and mimicking properties. Individually, each of these chemicals has been tested and its effects measured, however they are rather found as parts of complex mixtures of which we do not fully grasp the extent of their potential consequences. Here we studied the effects of realistic, environmentally relevant mixtures of 29 POPs on cartilage and bone development using zebrafish as a model species. We observed developmental issues in cartilage, in the form of diverse malformations such as micrognathia, reduced size of the Meckel's and other structures. Also, mineralized bone formation was disrupted, hence impacting the overall development of the larvae at later life stages. Assessment of the transcriptome revealed disruption of nuclear receptor pathways, such as androgen, vitamin D, and retinoic acid, that may explain the mechanisms of action of the compounds within the tested mixtures. In addition, clustering of the compounds using their chemical signatures revealed structural similarities with the model chemicals vitamin D and retinoic acid that can explain the effects and/or enhancing the phenotypes we witnessed. Further mechanistic studies will be required to fully understand this kind of molecular interactions and their repercussions in organisms. Our results contribute to the already existing catalogue of deleterious effects caused by exposure to POPs and help to understand the potential consequences in at risk populations. [ABSTRACT FROM AUTHOR]

Objective: To systematically evaluate the safety and efficacy of antioxidant therapy in children and adolescents with attention deficit hyperactivity disorder (ADHD). Methods: Randomized controlled trials and prospective studies on antioxidant therapy in children and adolescents with ADHD were searched in PubMed, Embase, and Cochrane Library from the inception of databases to November 12, 2022. Two investigators independently screened the literature, extracted data, and evaluated the quality of the included studies. Network meta-analysis (PROSPERO registration number CRD 42023382824) was carried out by using R Studio 4.2.1. Results: 48 studies involving 12 antioxidant drugs (resveratrol, pycnogenol, omega-3, omega-6, quercetin, phosphatidylserine, almond, vitamin D, zinc, folic acid, ginkgo biloba, Acetyl-L-carnitine) were finally included, with 3,650 patients. Network meta-analysis showed that omega-6 (0.18), vitamin D (0.19), and quercetin (0.24) were the top three safest drugs according to SUCRA. The omega-3 (SUCRA 0.35), pycnogenol (SUCRA 0.36), and vitamin D (SUCRA 0.27) were the most effective in improving attention, hyperactivity, and total score of Conners' parent rating scale (CPRS), respectively. In terms of improving attention, hyperactivity, and total score of Conners' teacher rating scale (CTRS), pycnogenol (SUCRA 0.32), phosphatidylserine+omega-3 (SUCRA 0.26), and zinc (SUCRA 0.34) were the most effective, respectively. In terms of improving attention, hyperactivity and total score of ADHD Rating Scale-Parent, the optimal agents were phosphatidylserine (SUCRA 0.39), resveratrol+MPH (SUCRA 0.24), and phosphatidylserine (SUCRA 0.34), respectively. In terms of improving attention, hyperactivity and total score of ADHD Rating Scale-Teacher, pycnogenol (SUCRA 0.32), vitamin D (SUCRA 0.31) and vitamin D (SUCRA 0.18) were the optimal agents, respectively. The response rate of omega-3+6 was the highest in CGI (SUCRA 0.95) and CPT (SUCRA 0.42). Conclusion: The rankings of safety and efficacy of the 12 antioxidants vary. Due to the low methodological quality of the included studies, the probability ranking cannot fully explain the clinical efficacy, and the results need to be interpreted with caution. More high-quality studies are still needed to verify our findings. [ABSTRACT FROM AUTHOR]

Sarcopenia frequently and progressively occurs in patients with chronic liver disease. This study aimed to clarify the relationship between vitamin D levels and muscle mass loss. A total of 166 patients with chronic liver disease were enrolled in this study. Skeletal muscle mass index (SMI) was measured by bioelectrical impedance analysis at baseline and after 1 year. The rate of change in SMI from baseline after 1 year was calculated: ΔSMI (%) = [(1-year SMI − baseline SMI) / baseline SMI] × 100. Muscle mass loss was defined as ΔSMI ≤ −2%. The median 25-hydroxyvitamin D was 15.2 (11.2–19.3) ng/mL. The median SMI were 6.8 (5.9–7.8) kg/m2 at baseline and 6.7 (5.9–7.6) kg/m2 after 1 year. The median ΔSMI was −1.23% (−2.21% to 1.61%). Multivariate analysis identified low 25-hydroxyvitamin D as an independent factor associated with muscle mass loss. The optimal cut-off value of 25-hydroxyvitamin D to predict muscle mass loss was 12.7 ng/mL. Muscle mass loss was found in 56.4% v.s. 18.0% of patients with 25-hydroxyvitamin D < 12.7 vs. ≥ 12.7 ng/mL, respectively (p = 9.01 × 10−7); with the highest incidence in patients with non-alcoholic fatty liver disease (NAFLD). Specifically, patients with NAFLD and 25-hydroxyvitamin D < 12.7 ng/mL had a significantly higher incidence of muscle mass loss than those with ≥ 12.7 ng/mL (p = 1.23 × 10−3). Low vitamin D levels are associated with muscle mass loss after 1 year in patients with chronic liver disease, especially NAFLD. [ABSTRACT FROM AUTHOR]

Background: Prenatal vitamin D deficiency is a common health concern among immigrants. No previous studies have examined the associations between prenatal vitamin D levels and developmental disorders of language, scholastic skills, and coordination in an immigrant sample. Methods: The sample included 542 immigrant mothers of cases with language, scholastic, coordination or mixed developmental disorders, 443 immigrant mothers of controls without these disorders and 542 Finnish mothers of controls. Maternal vitamin D was measured in serum samples collected during early pregnancy and stored in a national biobank. Results: The mean vitamin D levels during pregnancy were 25.0 (SD 14.4) nmol/L for immigrant mothers of cases, 25.4 (SD 15.5) for immigrant mothers of controls and 42.3 (SD 19.1) for Finnish mothers of controls. Low maternal vitamin D levels during pregnancy were not associated with the selected developmental disorders in offspring when immigrant mothers of cases were compared to immigrant mothers of controls (adjusted OR for continuous log-transformed vitamin D: 1.01, 95% CI 0.75–1.36, p = 0.96). When immigrant mothers of cases were compared to Finnish mothers of controls, the adjusted OR for continuous vitamin D was 18.94 (95% CI 11.47–31.25), p <0.001). The results were similar when vitamin D was examined as a categorical variable or divided into quintiles. Conclusions: Prenatal vitamin D levels were low, and similar, among immigrant mothers of cases with selected developmental disorders and unaffected controls. This indicates that vitamin D unlikely mediates previously observed associations between maternal immigrant status and the selected developmental disorders in offspring. The proportion of immigrant mothers with severe vitamin D deficiency was very high, which underlines the importance of prenatal counselling and overall public health efforts to improve immigrant health. [ABSTRACT FROM AUTHOR]

Objectives: The post-medieval period in Europe saw a dramatic increase in metabolic bone disease related to vitamin D deficiency (VDD). Recent paleopathological work has utilized interglobular dentin (IGD) as a proxy for poor vitamin D status during development, while enamel peptide analysis allows the identification of chromosomal sex in non-adult remains. Here we explore the relationship between sex, the presence of IGD, and macroscopic markers of VDD in an industrial era assemblage from Northeast England. Materials and methods: 25 individuals (9 females, 9 males, 9 unknown sex) from the cemetery site at Coach Lane, North Shields (1711–1857) were selected for paleopathological analysis, histological assessment of IGD, and enamel peptide determination of chromosomal sex. Results: Ground tooth sections from 21 individuals were of suitable quality for detection of IGD, and enamel peptide analysis confirmed the chromosomal sex of ten individuals. Sixteen individuals (76.1%) exhibited ≥1 episode of IGD. Nine of these (42.8%) exhibited >1 episode and four (19%) exhibited ≥4 episodes in regular intervals. Male sex was significantly associated with the presence of IGD (p = 0.0351; 100% males vs. 54.5% females). Females were more likely to exhibit macroscopic evidence of VDD (45.5% females vs 30% males) but this was not statistically significant. Discussion and conclusions: Periods of poor mineral metabolism during childhood appear much more prevalent at Coach Lane than macroscopic evidence suggests. Evidence of seasonal IGD episodes indicates that northern latitude played a major role in poor VD status in the Northeast of England. The significant association of IGD with male sex may be due to sex-related differences in dentinal mineralization or a higher risk of poor VD status in males aged <5 years. More work is needed to establish an evidence-based threshold for pathological levels of IGD before the presence of this feature can confidently be used as a biomarker for poor VD status. [ABSTRACT FROM AUTHOR]

Early in the pandemic, the spread of the emerging virus SARS-CoV-2 was causing mild illness lasting less than two weeks for most people, with a small proportion of people developing serious illness or death. However, as the pandemic progressed, many people reported suffering from symptoms for weeks or months after their initial infection. Persistence of COVID-19 symptoms beyond one month, or what is known as long COVID-19, is recognized as a risk of acute infection. Up to date, information on long COVID-19 among Jordanian patients has not been reported. Therefore, we sought to conduct this cross-sectional study utilizing a self-administered survey. The survey asks a series of questions regarding participant demographics, long COVID-19 symptoms, information about pre-existing medical history, supplements, vaccination history, and symptoms recorded after vaccination. Chi square analysis was conducted on 990 responders, and the results showed a significant correlation (P<0.05) between long COVID-19 syndrome and age, obesity, chronic illness, vitamin D intake, number of times infected by COVID-19, number of COVID-19 symptoms and whether the infection was pre or post vaccination. The long-term symptoms most enriched in those with long COVID-19 were tinnitus (73.4%), concentration problems (68.6%) and muscle and joint ache (68.3%).A binomial logistic regression analysis was done to explore the predictors of long COVID-19 and found that age 18–45, marital status, vitamin D, number of COVID-19 symptoms and signs after vaccination are positive predictors of long COVID-19, while zinc intake is a negative predictor. Although further studies on long-term persistence of symptoms are needed, the present study provides a baseline that allows us to understand the frequency and nature of long COVID-19 among Jordanians [ABSTRACT FROM AUTHOR]

Endometriosis is a multifactorial disease associated with inflammation. Vitamin D has anti-inflammatory, antiproliferative, anti-oxidative, and immunomodulatory effects. Whether vitamin D levels are correlated with endometriosis is a subject of ongoing debate. This study aimed to examine the association between endometriosis and serum vitamin D levels. From the National Health and Nutrition Examination Survey, this study examined the cross-sectional data of American women aged 20–54 years from 2001 to 2006. After adjusting for covariates, multivariable logistic regression analysis was used to assess correlations. A total of 3,232 women were included in this study. The multiple linear regression model demonstrated a negative correlation between the serum 25-hydroxyvitamin D3 (cholecalciferol) concentration and the risk of endometriosis after controlling for all confounding variables. The odds ratio was 0.73 with a 95% confidence interval of 0.54–0.97 in the adequate vitamin D level group compared with the insufficient vitamin D level group. Our results showed that endometriosis was inversely correlated with serum 25-hydroxyvitamin D3 levels. Further research is needed to establish a causal relationship and determine the potential benefits of maintaining sufficient vitamin D levels for endometriosis prevention. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a chronic degenerative joint disorder primarily affecting the elderly, characterized by a prominent inflammatory component. The long-term side effects associated with current therapeutic approaches necessitate the development of safer and more efficacious alternatives. Nutraceuticals, such as Vitamin D and curcumin, present promising therapeutic potentials due to their safety, efficacy, and cost-effectiveness. In this study, we utilized a proinflammatory human chondrocyte model of OA to assess the anti-inflammatory properties of Vitamin D and curcumin, with a particular focus on the Protease-Activated Receptor-2 (PAR-2) mediated inflammatory pathway. Employing a robust siRNA approach, we effectively modulated the expression of PAR-2 to understand its role in the inflammatory process. Our results reveal that both Vitamin D and curcumin attenuate the expression of PAR-2, leading to a reduction in the downstream proinflammatory cytokines, such as Tumor Necrosis Factor-alpha (TNF-α), Interleukin 6 (IL-6), and Interleukin 8 (IL-8), implicated in the OA pathogenesis. Concurrently, these compounds suppressed the expression of Receptor Activator of Nuclear Factor kappa-Β Ligand (RANKL) and its receptor RANK, which are associated with PAR-2 mediated TNF-α stimulation. Additionally, Vitamin D and curcumin downregulated the expression of Interferon gamma (IFN-γ), known to elevate RANKL levels, underscoring their potential therapeutic implications in OA. This study, for the first time, provides evidence of the mitigating effect of Vitamin D and curcumin on PAR-2 mediated inflammation, employing an siRNA approach in OA. Thus, our findings pave the way for future research and the development of novel, safer, and more effective therapeutic strategies for managing OA. [ABSTRACT FROM AUTHOR]

Introduction: Persons living with obesity treated with bariatric surgery are at a high risk of developing nutritional deficiencies. The primary aim of this observational cohort study was to compare vitamin D levels in patients two years after bariatric surgery (Roux-en-Y gastric bypass/RYGB and sleeve gastrectomy/SG) with a very low-energy diet (VLED). The same subjects were also compared with a population sample from the same region at baseline. The primary hypothesis was that surgery, especially RYGB, would lead to an increased prevalence of vitamin D deficiency compared to subjects treated with VLED. 971 individuals eligible for surgical, RYGB (n = 388), SG (n = 201), and medical treatment (n = 382), in routine care, were included consecutively between 2015 and 2017. A random population sample from the WHO-MONICA project was used as a reference, (n = 414). S-calcium, S-25(OH)D (vitamin D), and S-PTH (parathyroid hormone) were measured in all persons with obesity at baseline and two years after treatment (n = 713). Self-reported use of vitamin D and calcium supplementation was registered. Results: Vitamin D deficiency (S-25(OH)D <25mmol/l) was found in 5.2% of the persons with obesity at baseline versus 1.7% of the general population (SMD>0.1). S-25(OH)D increased for all treatment groups but was higher in RYGB and SG (SMD>0.1, standardized mean difference). Thirteen subjects (1.8%) had vitamin D deficiency after obesity treatment. Conclusion: Surgical intervention for obesity followed by vitamin D supplementation was not associated with a higher risk for vitamin D deficiency, irrespective of surgery type, compared to individuals on medical treatment. However, persons living with obesity seeking weight loss treatment are more likely to have deficient vitamin D levels compared to the general population. [ABSTRACT FROM AUTHOR]

Vitamin D (VD) exerts a wide variety of biological functions including calcemic activity. VD nutritional status is closely associated with the onset and development of chronic diseases. To develop a VD analog with the desired VD activity but without calcemic activity, we screened synthetic VDR antagonists. We identified 1α,25-dihydroxyvitamin D3-26-23-lactams (DLAM)-2a-d (DLAM-2s) as nuclear vitamin D receptor (VDR) ligands in a competitive VDR binding assay for 1α,25(OH)2 vitamin D3 (1α,25(OH)2D3), and DLAM-2s showed an antagonistic effect on 1α,25(OH)2 D3-induced cell differentiation in HL60 cells. In a luciferase reporter assay in which human VDR was exogenously expressed in cultured COS-1 cells, DLAM-2s acted as transcriptional antagonists. Consistently, DLAM-2s had an antagonistic effect on the 1α,25(OH)2D3-induced expression of a known VD target gene [Cytochrome P450 24A1 (CYP24A1)], and VDR bound DLAM-2s was recruited to an endogenous VD response element in chromatin in human keratinocytes (HaCaT cells) endogenously expressing VDR. In an ATAC-seq assay, the effects of 1α,25(OH)2 D3 and DLAM-2b on chromatin reorganization were undetectable in HaCaT cells, while the effect of an androgen receptor (AR) antagonist (bicalutamide) was confirmed in prostate cancer cells (LNCaP) expressing endogenous AR. However, whole genome analysis using RNA-seq and ATAC (Assay for Transposase Accessible Chromatin)-seq revealed differential gene expression profiles regulated by DLAM-2b versus 1α,25(OH)2D3. The upregulated and downregulated genes only partially overlapped between cells treated with 1α,25(OH)2D3 and those treated with DLAM-2b. Thus, the present findings illustrate a novel VDR ligand with gene regulatory activity differing from that of 1α,25(OH)2D3. [ABSTRACT FROM AUTHOR]

Background: Maternal vitamin status preconception and during pregnancy has important consequences for pregnancy outcome and offspring development. Changes in vitamin status from preconception through early and late pregnancy and postpartum have been inferred from cross-sectional data, but longitudinal data on vitamin status from preconception throughout pregnancy and postdelivery are sparse. As such, the influence of vitamin supplementation on vitamin status during pregnancy remains uncertain. This study presents one prespecified outcome from the randomized controlled NiPPeR trial, aiming to identify longitudinal patterns of maternal vitamin status from preconception, through early and late pregnancy, to 6 months postdelivery, and determine the influence of vitamin supplementation. Methods and findings: In the NiPPeR trial, 1,729 women (from the United Kingdom, Singapore, and New Zealand) aged 18 to 38 years and planning conception were randomized to receive a standard vitamin supplement (control; n = 859) or an enhanced vitamin supplement (intervention; n = 870) starting in preconception and continued throughout pregnancy, with blinding of participants and research staff. Supplement components common to both treatment groups included folic acid, β-carotene, iron, calcium, and iodine; components additionally included in the intervention group were riboflavin, vitamins B6, B12, and D (in amounts available in over-the-counter supplements), myo-inositol, probiotics, and zinc. The primary outcome of the study was glucose tolerance at 28 weeks' gestation, measured by oral glucose tolerance test. The secondary outcome reported in this study was the reduction in maternal micronutrient insufficiency in riboflavin, vitamin B6, vitamin B12, and vitamin D, before and during pregnancy. We measured maternal plasma concentrations of B-vitamins, vitamin D, and markers of insufficiency/deficiency (homocysteine, hydroxykynurenine-ratio, methylmalonic acid) at recruitment, 1 month after commencing intervention preconception, in early pregnancy (7 to 11 weeks' gestation) and late pregnancy (around 28 weeks' gestation), and postdelivery (6 months after supplement discontinuation). We derived standard deviation scores (SDS) to characterize longitudinal changes among participants in the control group and measured differences between the 2 groups. At recruitment, the proportion of patients with marginal or low plasma status was 29.2% for folate (<13.6 nmol/L), 7.5% and 82.0% for riboflavin (<5 nmol/L and ≤26.5 nmol/L, respectively), 9.1% for vitamin B12 (<221 pmol/L), and 48.7% for vitamin D (<50 nmol/L); these proportions were balanced between the groups. Over 90% of all participants had low or marginal status for one or more of these vitamins at recruitment. Among participants in the control group, plasma concentrations of riboflavin declined through early and late pregnancy, whereas concentrations of 25-hydroxyvitamin D were unchanged in early pregnancy, and concentrations of vitamin B6 and B12 declined throughout pregnancy, becoming >1 SDS lower than baseline by 28 weeks gestation. In the control group, 54.2% of participants developed low late-pregnancy vitamin B6 concentrations (pyridoxal 5-phosphate <20 nmol/L). After 1 month of supplementation, plasma concentrations of supplement components were substantially higher among participants in the intervention group than those in the control group: riboflavin by 0.77 SDS (95% CI 0.68 to 0.87, p < 0.0001), vitamin B6 by 1.07 SDS (0.99 to 1.14, p < 0.0001), vitamin B12 by 0.55 SDS (0.46 to 0.64, p < 0.0001), and vitamin D by 0.51 SDS (0.43 to 0.60, p < 0.0001), with higher levels in the intervention group maintained during pregnancy. Markers of vitamin insufficiency/deficiency were reduced in the intervention group, and the proportion of participants with vitamin D insufficiency (<50 nmol/L) during late pregnancy was lower in the intervention group (35.1% versus 8.5%; p < 0.0001). Plasma vitamin B12 remained higher in the intervention group than in the control group 6 months postdelivery (by 0.30 SDS (0.14, 0.46), p = 0.0003). The main limitation is that generalizability to the global population is limited by the high-resource settings and the lack of African and Amerindian women in particular. Conclusions: Over 90% of the trial participants had marginal or low concentrations of one or more of folate, riboflavin, vitamin B12, or vitamin D during preconception, and many developed markers of vitamin B6 deficiency in late pregnancy. Preconception/pregnancy supplementation in amounts available in over-the-counter supplements substantially reduces the prevalence of vitamin deficiency and depletion markers before and during pregnancy, with higher maternal plasma vitamin B12 maintained during the recommended lactational period. Trial registration: ClinicalTrials.govNCT02509988; U1111-1171-8056. In this pre-specified secondary analysis of the NiPPeR double-blind randomized controlled trial, Keith M Godfrey and colleagues investigate maternal B-vitamin and vitamin D status before, during and after pregnancy, and the influence of supplementation preconception and during pregnancy Author summary: Why was this study done?: A mother's vitamin status preconception and during pregnancy are important for healthy pregnancy outcomes and offspring development. Truly longitudinal data on changes in vitamin status from preconception to early and late pregnancy and postpartum are sparse, with changes generally inferred from cross-sectional data and lower pregnancy concentrations often ascribed to plasma volume expansion. Few studies have evaluated the influence of vitamin supplementation preconception and during pregnancy. What did the researchers do and find?: As prespecified secondary outcomes of a randomized trial, this study characterized longitudinal patterns of maternal vitamin status from preconception, through early and late pregnancy, to 6 months postdelivery, and determined the influence of supplementation. Significant proportions of preconception women living in high-income countries had marginal or low status of folate, riboflavin, vitamin B12, and vitamin D, and many developed markers of vitamin B6 deficiency in late pregnancy. In the absence of intervention supplementation, maternal plasma concentrations of different vitamins showed differing longitudinal patterns from preconception to early and late pregnancy, and markers of functional B6 and B12 insufficiency increased during pregnancy. Our trial indicates that preconception and pregnancy supplementation in amounts available in over-the-counter supplements substantially reduced the prevalence of deficiency/depletion markers before and during pregnancy, with a higher maternal plasma vitamin B12 maintained during the recommended lactational period. What do these findings mean?: The study findings are inconsistent with plasma volume expansion wholly accounting for lower gestational vitamin concentrations. In the setting of advocacy for more sustainable diets that are likely to be less nutrient dense, the findings suggest a need to reappraise dietary recommendations for preconception and pregnancy and to consider further the role of multiple micronutrient supplements in women living in higher-income countries. [ABSTRACT FROM AUTHOR]

Vitamin D status–a complex trait influenced by environmental and genetic factors–is tightly associated with skin colour and ancestry. Yet very few studies have investigated the genetic underpinnings of vitamin D levels across diverse ancestries, and the ones that have, relied on small sample sizes, resulting in inconclusive results. Here, we conduct genome-wide association studies (GWAS) of 25 hydroxyvitamin D (25OHD)–the main circulating form of vitamin D–in 442,435 individuals from four broad genetically-determined ancestry groups represented in the UK Biobank: European (N = 421,867), South Asian (N = 9,983), African (N = 8,306) and East Asian (N = 2,279). We identify a new genetic determinant of 25OHD (rs146759773) in individuals of African ancestry, which was not detected in previous analysis of much larger European cohorts due to low minor allele frequency. We show genome-wide significant evidence of dominance effects in 25OHD that protect against vitamin D deficiency. Given that key events in the synthesis of 25OHD occur in the skin and are affected by pigmentation levels, we conduct GWAS of 25OHD stratified by skin colour and identify new associations. Lastly, we test the interaction between skin colour and variants associated with variance in 25OHD levels and identify two loci (rs10832254 and rs1352846) whose association with 25OHD differs in individuals of distinct complexions. Collectively, our results provide new insights into the complex relationship between 25OHD and skin colour and highlight the importance of diversity in genomic studies. Despite the much larger rates of vitamin D deficiency that we and others report for ancestry groups with dark skin (e.g., South Asian), our study highlights the importance of considering ancestral background and/or skin colour when assessing the implications of low vitamin D. Author summary: Vitamin D synthesis in the skin is inversely related to the level of skin pigmentation. This is reflected in lower vitamin D levels in dark-skin populations. Asides from environmental determinants, like sun exposure, there are also genetic factors that influence vitamin D levels. Yet, despite the intertwined relationship with skin colour, genetic studies of vitamin D have largely focused on white individuals of European ancestry. Here, we study the genetic determinants of vitamin D across four ancestry groups represented in the UK Biobank (European, African, South Asian, and East Asian). We show that genetic effects on the main circulating form of vitamin D are correlated in genetically-distant groups, suggesting that the biological mechanisms underlying its synthesis and metabolism are largely shared. Nevertheless, we identify a new association with a genetic variant only seen in African-ancestry individuals. We find new associations with genetic variants that influence both skin colour and vitamin D levels, and we report variants with different effects in individuals with different complexions. Our study highlights the importance of considering ancestral background and/or skin complexion when assessing vitamin D status and its implications. This is relevant given the large numbers of ongoing clinical trials using vitamin D as intervention. [ABSTRACT FROM AUTHOR]

Allogeneic hematopoietic stem cell transplant (aHSCT) patients are well known to be at high risk of vitamin D (vit D) deficiency. This study assessed whether a loading dose (100,000 IU) of vitamin D3 pre-aHSCT could effectively achieve and maintain sufficient post-transplant vit D levels (serum total 25 hydroxy vitamin D (25(OH)D) ≥ 75nmol/L). Dual-energy X-ray absorptiometry (DXA) was also conducted for bone health evaluation. 74 patients were enrolled and randomly assigned, in a 1:1 ratio, either to the high vit D group (single loading dose (100,000 IU) plus 2,000 IU vit D3 daily) or the control group (2,000 IU vit D3 daily). Vit D levels were measured at three time points (baseline, day 30 and day 100 post-aHSCT). At baseline, fewer than 50% patients had a sufficient 25(OH)D (control: 42.9%; high vit D: 43.6%). The proportion of patients with sufficient 25(OH)D (nmol/L) was increased at day 30 and day 100, with a trend of higher proportion in the high vit D group at day 30 (high vit D vs. control: 89.7% vs. 74.3%, p = 0.08). The increased 25(OH)D was significantly higher in the high vit D group at day 30 (high vit D vs. control: 29±25.2 vs. 14 ±21.9, p = 0.01). Insufficient vit D level before transplant (baseline) was an independent risk factor for vit D insufficiency (serum 25(OH)D < 75nmol/L) post-aHSCT (OR = 4.16, p = 0.03). DXA suggested significant bone loss for total hip in both groups, and in the femoral neck for the control group only. In conclusion, single loading dose vitamin D3 significantly increased total 25(OH)D levels at day 30 post-transplant, and the intervention was especially beneficial for patients with baseline vit D insufficiency. We acknowledge that the primary outcome at day 100 post-aHSCT indicating superiority of loading dose versus daily dose supplementation was not met. [ABSTRACT FROM AUTHOR]

Background: Reduced bone mineral density (BMD) and osteoporosis are common in chronic liver diseases. However, the causal effect of alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) on BMD remains uncertain. Objectives: This study uses a two-sample Mendelian randomization (MR) design to evaluate the genetically predicted effect of ALD and NAFLD on BMDs using summary data from publically available genome-wide association studies (GWASs). Methods: The GWAS summary statistics of ALD (1416 cases and 213,592 controls) and NAFLD (894 cases and 217,898 controls) were obtained from the FinnGen consortium. BMDs of four sites (total body, n = 56,284; femoral neck, n = 32,735; lumbar spine, n = 28,498; forearm, n = 8143) were from the GEnetic Factors for OSteoporosis Consortium. Data for alcohol consumption (n = 112,117) and smoking (n = 33,299) and serum 25-Hydroxyvitamin D (25-OHD) level (n = 417,580) were from UK-biobank. We first performed univariate MR analysis with the Inverse Variance Weighted (IVW) method as the primary analysis to investigate the genetically predicted effect of ALD or NAFLD on BMD. Then, multivariate MR and mediation analysis were performed to identify whether the effect was mediated by alcohol consumption, smoking, or serum 25-OHD level. Results: The MR results suggested a robust genetically predicted effect of ALD on reduced BMD in the femoral neck (FN-BMD) (IVW beta = -0.0288; 95% CI: -0.0488, -0.00871; P = 0.00494) but not the other three sites. Serum 25-OHD level exhibited a significant mediating effect on the association between ALD and reduced FN-BMD albeit the proportion of mediation was mild (2.21%). No significant effects of NAFLD, alcohol consumption, or smoking on BMD in four sites, or reverse effect of BMD on ALD or NAFLD were detected. Conclusion: Our findings confirm the genetically predicted effect of ALD on reduced FN-BMD, and highlight the importance of periodic BMD and serum 25-OHD monitoring and vitamin D supplementation as needed in patients with ALD. Future research is required to validate our results and investigate the probable underlying mechanisms. [ABSTRACT FROM AUTHOR]

Oral calcium and calcium plus vitamin D supplements are commonly prescribed to several groups of patients, e.g., osteoporosis, fracture, and calcium deficiency. Adequate and steady extracellular calcium levels are essential for neuronal activity, whereas certain forms of calcium supplement (e.g., CaCO3) probably interfere with memory function. However, it was unclear whether a long-term use of ionized calcium (calcium chloride in drinking water ad libitum), vitamin D supplement (oral gavage) or the combination of both affected anxiety and memory, the latter of which was probably dependent on the hippocampal neurogenesis. Here, we aimed to determine the effects of calcium and/or vitamin D supplement on the anxiety- and memory-related behaviors and the expression of doublecortin (DCX), an indirect proxy indicator of hippocampal neurogenesis. Eight-week-old male Wistar rats were divided into 4 groups, i.e., control, calcium chloride-, 400 UI/kg vitamin D3-, and calcium chloride plus vitamin D-treated groups. After 4 weeks of treatment, anxiety-, exploration- and recognition memory-related behaviors were evaluated by elevated pulse-maze (EPM), open field test (OFT), and novel object recognition (NOR), respectively. The hippocampi were investigated for the expression of DCX protein by Western blot analysis. We found that oral calcium supplement increased exploratory behavior as evaluated by OFT and the recognition index in NOR test without any effect on anxiety behavior in EPM. On the other hand, vitamin D supplement was found to reduce anxiety-like behaviors. Significant upregulation of DCX protein expression was observed in the hippocampus of both calcium- and vitamin D-treated rats, suggesting their positive effects on neurogenesis. In conclusion, oral calcium and vitamin D supplements positively affected exploratory, anxiety-like behaviors and/or memory in male rats. Thus, they potentially benefit on mood and memory in osteoporotic patients beyond bone metabolism. [ABSTRACT FROM AUTHOR]

The prognostic value of vitamin D receptor (VDR) in a variety of digestive system tumours remains controversial. In view of this, we conducted a meta-analysis. Published studies (as of Mar 30, 2023) assessing the prognostic role of VDR in digestive system tumours were retrieved. Pooled analyses were conducted based on the hazard ratios (HRs) of high VDR expression extracted from the included studies. If heterogeneity was detected, the random-effects model was used; otherwise, the fixed-effects model was used. Subgroup analysis, sensitivity analysis and meta-regression were performed to explore the sources of heterogeneity. Eight studies with 3,109 patients were included. The pooled results indicated that patients with high VDR expression generally had better overall survival (OS) (pooled HR = 0.67; 95% CI = 0.53–0.85; P = 0.001). Subgroup analyses showed that tumour type was the variable affecting the association between VDR expression and OS. VDR expression in colorectal cancer was not associated with OS (pooled HR = 0.84; 95% CI = 0.68–1.03; P = 0.086). We eliminated publication bias using the "trim and fill" method and found that high VDR expression remained an indicator of good OS (P = 0.001). Only a few studies explored the relationship between VDR expression and cancer-specific survival (CSS) or progression-free survival (PFS), and the pooled results indicated no association between them (P>0.05). VDR expression is a prognostic indicator in digestive system tumours and may also be used as a reference for vitamin D supplementation. Detection of VDR expression not only helps to evaluate prognosis but also to formulate more precise treatment plans for patients with digestive system tumours. [ABSTRACT FROM AUTHOR]

Objective: Assess knowledge, attitudes, and practices (KAPs) of a diverse population. Identify barriers and facilitators that inform routine vitamin D supplementation and self-care in the community setting. Design: Cross-sectional online voluntary survey. Electronic survey link published on college Qualtrics platform and advertised widely. Study information provided with Participant Information Sheet. Setting and participants: 556 community dwelling adults across the UK. Methods: The overarching study included two phases, incorporating quantitative and qualitative methodologies. This paper reports findings from the first phase of the FABCOM-D (Facilitators and Barriers to Community (Healthy) Vitamin D status) study. Online survey questions were iteratively developed after background literature searches and piloted to ensure clarity and ease of understanding. Survey responses summarised using frequencies and percentages, and univariable and multivariable logistic regression models explored for any association. A p-value less than 0.05 was considered statistically significant. The Checklist for Reporting Results of Internet E-Surveys guided reporting. Statistical analysis performed using IBM SPSS software. Main outcome measures: Awareness of vitamin D information sources, health benefits and testing. Attitudes to supplementation, sun exposure and fortification. Results: Three quarters of the community had some awareness of vitamin D and around half were taking supplements. The two most trusted sources of information included health professionals and the NHS website. Participants were willing to pay for supplements, supporting a self-care agenda. With increasing age, there was significant reduced intake of vitamin D supplements. This aspect needs to be explored further as this could be a concern in deficiency status in the elderly. There was acceptance of food fortification but uncertainty on how to balance food intake with supplementation. Conclusion: We were successful in eliciting views on KAPs around vitamin D from a community population including a large proportion of Black and Minority Ethnic individuals. The community wanted information and guidance to help manage individual vitamin D status, especially for high-risk groups, and on balancing supplementation, food fortification and sun exposure. [ABSTRACT FROM AUTHOR]

Background: Deficiency of silent information regulator 1 (SIRT1) can trigger inflammation, mitochondrial malfunctioning, and apoptosis through the hypothalamic-pituitary-ovarian axis, producing poor quality oocytes, leading to infertility. Normal vitamin D (VD) levels promote SIRT1 activity required for optimal fertility, and low levels of either may result in fertility problems owing to cell-membrane de-stabilization, increased autophagy, DNA damage leading to increased reactive oxygen species and mitochondrial dysfunction. Therefore, in this study, we want to estimate the levels of VD, SIRT1 and antioxidants (MnSOD; manganese superoxide dismutase, GR; glutathione reductase, visfatin) and oxidants (adrenaline & cortisol) in individuals living with infertility and explore the association of VD with SIRT1 expression (levels), antioxidants, and oxidants contributing to infertility in women. The significance of this study is that it highlights the importance of maintaining optimal levels of VD for reproductive health in females. Methods: This cross-sectional study included 342 (135 infertile and 207 fertile) female subjects. Serum levels of MnSOD, SIRT1, visfatin, GR, VD, adrenaline, and cortisol were analyzed by ELISA and were compared in fertile and infertile samples using the Mann Whitney U test. Results: There were significantly high levels of VD, SIRT1, GR, MnSOD and visfatin in fertile female participants. However, mean adrenaline and cortisol levels were higher in infertile samples with a significant negative correlation with VD. A significant negative correlation of VD with MnSOD, SIRT1, visfatin and GR was observed (p <0.01). In VD subset groups, MnSOD levels were significantly high in VD sufficient groups however, adrenaline and cortisol levels were significantly high in groups suffering from VD deficiency. Conclusions: Deficiency of VD is associated with a decrease in SIRT1 and other antioxidants, which may deter natural reproductive functions leading to infertility. Further studies are required to determine the cause-effect relationship of VD deficiency on conception and interpretation of the involved mechanism. [ABSTRACT FROM AUTHOR]

Research studies have observed associations of vitamin D with inflammation but data in representative older adult studies is lacking. We aimed to investigate the association of C-reactive protein (CRP) with vitamin D status in a representative sample of the older Irish population. The concentrations of 25-hydroxyvitamin D (25(OH)D) and CRP was measured in 5,381 community dwelling Irish adults aged ≥50 years from the Irish Longitudinal Study on Ageing (TILDA). Demographic, health and lifestyle variables were assessed by questionnaire and categorical proportions of CRP were generated by vitamin D status and age. Multi-nominal logistic regression was used to investigate the association of 25(OH)D and CRP status. The prevalence (mean; 95% confidence interval (95% CI)) of normal CRP status (0–5 mg/dL) was 83.9% (82.6–85.0%), elevated status (5–10 mg/dL) 11.0% (9.9–12.0%) and high status (>10 mg/dL) was 5.1% (4.5–5.8%). Mean (95% CI) CRP concentrations were lower in those with normal vs. deficient 25(OH)D status (2.02 mg/dL (1.95–2.08) vs. 2.60 mg/dL (2.41–2.82); p<0.0001). In a logistic regression analysis, those with insufficient or sufficient 25(OH)D status were less likely to have a high CRP status compared to those with deficient 25(OH)D status (insufficient: coefficient (CE) -0.732, 95% CI -1.12–0.33, p<0.0001; sufficient: CE -0.599, 95% CI -0.95–0.24, p = 0.001). In conclusion older adults with deficient vitamin D status had higher levels of inflammation as measured by CRP. Given that inflammation is an important pathological driver of chronic diseases of ageing, and that emerging evidence suggests that vitamin D therapy can reduce inflammation in some disease settings, optimising vitamin D status could represent an effective low risk/low-cost pathway to modulate inflammation in community dwelling older adults. [ABSTRACT FROM AUTHOR]

Background: CL endemicity was reported worldwide including in Saudi Arabia, imposing a major challenge on the health authorities. Vitamin D and its receptor (VDR) are key modulators of the immune response where the VDR is expressed. A remarkable lack of data exists in humans about the contribution of vitamin D and polymorphisms of the VDR gene in protozoan infections, especially cutaneous leishmaniasis (CL). Objective: This is the first work conducted to assess the relationship between vitamin D status, polymorphisms of the VDR gene (BsmI, ApaI, TaqI, and FokI), and VDR haplotype with parasite tissue load and susceptibility to CL. Methods: Fifty-two patients with confirmed CL (21 patients receiving vitamin D medication and 31 patients not receiving it) and 46 control subjects participated in this cross-sectional investigation. VDR genotyping was determined by restriction fragment length polymorphism analysis. Serum levels of 25-OH vitamin D were assessed using the ELISA method in all participants. The skin biopsy quantified the parasite load based on the Ridley parasitic index. Results: The mean serum level of 25-OH vitamin D in CL patients who were not receiving vitamin D therapy was significantly lower compared to CL patients on vitamin D therapy and controls (p <0.001 for both) and CL patients with no history of vitamin D therapy had a significantly higher frequency of vitamin D deficiency compared to CL patients on vitamin D therapy and controls (p < 0.05). Compared to CL patients with no history of vitamin D therapy, CL patients receiving vitamin D therapy had a significantly lower mean size of the lesion and RPI (p = 0.02,.03 respectively). The frequency of genotype "aa" and its "a" allele in ApaI SNP of VDR was significantly lower in CL patients compared to controls (p = 0.006 and 0.03 respectively). However, patients with CL had a considerably greater frequency of the "A" allele than the controls (p = 0.03), suggesting its role in CL susceptibility. There was no statistically significant difference between the two groups in the genotype and allele frequency distributions of BsmI, TaqI, and FokI (p > 0.05). When compared to controls, CL cases had a considerably greater frequency of the "B-A-T-F" haplotype (p = 0.04), and a significantly lower frequency of the "B-a-T-F" haplotype (p = 0.01) suggesting that these haplotypes may have the potential susceptibility or protection against CL respectively. The "Aa" genotype in ApaI SNP of VDR had considerably lower levels of vitamin D with higher parasite load compared to the "AA" and: aa" genotypes (p = 0.02,0.02 respectively). A significant negative correlation was found between the parasite load and 25-OH vitamin D levels (r2 = -0.53, p< 0.001). Conclusions: According to these findings, vitamin D levels and "ApaI" VDR gene polymorphisms could affect the parasite load and susceptibility to infection, whereas BsmI, FokI, and TaqI polymorphisms did not. Correction of vitamin D levels may aid in CL management. Author summary: Cutaneous leishmaniasis (CL) is the most prevalent type of leishmaniasis with varied clinical presentations. It is caused by a group of protozoan intracellular parasites belonging to the genus Leishmania and transmitted through the bite of blood-sucking female sandfly species. few studies have examined the relationship between vitamin D and the VDR gene polymorphism and protozoal infection including leishmaniasis. Therefore, in this study, we aimed to investigate for the first time the possible association of VDR gene polymorphisms (BsmI, ApaI, TaqI, and FokI genotypes) with parasite load and susceptibility to CL and attempted to ascertain such an a ociation with serum levels of 25(OH) vitamin D in a trial to improve treatment strategies for CL.the results revealed that 25-OH vitamin D level was significantly lower among patients with CL compared to controls. The frequency of genotype "aa" and its "a" allele in ApaI SNP of VDR was significantly lower in CL patients compared to controls. However, the "A" allele frequency was significantly higher in patients with CL compared to controls, suggesting its role in CL susceptibility. The distribution of genotype and allele frequencies of BsmI, TaqI, and FokI were non-significantly different 86 between both groups. The parasite load was significantly negatively correlated with 25-OH vitamin D levels. Correction of vitamin D levels may aid in CL management. [ABSTRACT FROM AUTHOR]

Background: Studies have revealed the association of vitamin D with specific types of cancer development, however, its correlation with colorectal polyps (CRPs) remains unverified. Our study aimed to investigate the relationship between vitamin D levels, metabolic factors, and CRPs. Methods: A cross-sectional study from 2017 to 2019 involving 1306 participants was conducted to investigate the association among vitamin D levels, metabolic factors, uric acid and CRPs in Taiwan. CRPs diagnoses were determined via colonoscopies conducted by experienced gastrointestinal physicians, and biopsied polyps were inspected under a microscope by experienced pathologists. We employed both simple and multiple logistic regression analyses to identify significant factors associated with CRPs and adenomatous polyps, respectively. Results: Our result showed that the prevalence of 25(OH)-vitamin D deficiency (≦ 20 ng/mL) and CRPs was 21.21% and 40.89%, respectively. Multiple logistic regression revealed that the risk of CRPs increased with old age, male sex, hyperglycemia, high triglyceride levels, and low 25(OH)D levels after adjustment for other factors. Besides, low 25(OH)D levels were significantly associated with CRPs risk in women, whereas elevated blood pressure was associated with CRPs risk in men. 25(OH)D Deficiency was revealed to be significantly associated with risk of CRPs in adults over 50 years old. Compared to nonadenomatous polyps, older age, higher 25(OH) vitamin D and higher uric acid levels were at increased risk for adenomatous polyps. Conclusions: Our study revealed that vitamin D deficiency was significantly associated with the risk of CRPs, especially in adults over 50 years old and women. We should therefore be concerned about the CRP risk of vitamin D deficiency and metabolic syndrome (especially hyperglycemia, elevated blood pressure in men, and high triglyceride levels) in this population. [ABSTRACT FROM AUTHOR]

The pathogenesis of testicular germ cell tumours (GCTs) is still incompletely understood. Any progress in its understanding must derive from observational studies. Recently, it has been suggested that the incidence of GCTs may follow a seasonal pattern based on circannual changes in the Vitamin D serum levels, with maximum incidence rates in winter months. To examine this promising hypothesis, we studied monthly incidence rates of testicular GCTs in Germany by analysing 30,988 GCT cases aged 15–69 years, diagnosed during 2009–2019. Monthly incident case numbers with data regarding histology and patient age were obtained from the Robert Koch Institut, Berlin, along with annual male population counts. We used precision weighting for deriving pooled monthly incidence rates for GCTs of the period 2009–2019. We stratified pooled rates by histology (seminoma and nonseminoma) and age (15–39 and 40–69 years). By assuming a cyclical effect, we used an estimator of the intensity of seasonal occurrence and report seasonal relative risks (RR). The mean monthly incidence rate was 11.93/105 person-months. The seasonal RR for testicular cancer over-all is 1.022 (95% CI 1.000–1.054). The highest seasonal RR was found in the subgroup of nonseminoma aged 15–39 years, with a RR 1.044 (95% CI 1.000–1.112). The comparison of the pooled monthly rates of the winter months (October—March) with the summer months (April-September) revealed a maximum relative difference of 5% (95% CI 1–10%) for nonseminoma, aged 15–39 years. We conclude that there is no evidence of a seasonal variation of incidence rates of testicular cancer. Our results are at odds with an Austrian study, but the present data appear sound because the results were obtained with precision weighted monthly incidence rates in a large population of GCT cases. [ABSTRACT FROM AUTHOR]

Introduction: Previous studies have found mixed associations between body mass index (BMI) and adolescent idiopathic scoliosis (AIS) incidence and progression. The aim of this study was to examine the association between BMI and the incidence of posterior spine fusion (PSF) among pediatric patients with AIS. Methods: This was a retrospective cohort study of patients diagnosed with AIS at a single large tertiary care center between January 1, 2014 and December 31, 2020. BMI-for-age percentiles were used to categorize BMI into four categories: underweight (<5th percentile), healthy weight (≥5th to <85th percentile), overweight (≥85th to <95th percentile), and obese (≥95th percentile). Chi-square and t-tests were used to compare distributions of baseline characteristics by incident PSF outcome status. Multivariable logistic regression assessed the association between BMI category at baseline and incident PSF adjusting for sex, age at diagnosis, race/ethnicity, health insurance type, vitamin D supplementation, and low vitamin D levels. Results: A total of 2,258 patients met the inclusion criteria with 2,113 patients (93.6%) who did not undergo PSF during the study period and 145 patients (6.4%) who did undergo PSF. At baseline, 7.3% of patients were categorized as underweight, 73.2% were healthy weight, 10.2% were overweight, and 9.3% were obese. Compared to those in the healthy weight group, there was no significant association between PSF and being underweight (adjusted odds ratio [AOR] 1.64, 95% CI 0.90–2.99, p = 0.107), being overweight (AOR 1.25, 95% CI 0.71–2.20, p = 0.436), or being obese (AOR 1.19, 95% CI 0.63–2.27, p = 0.594). Conclusions: This study did not find a statistically significant association between underweight, overweight, or obese BMI category and incident PSF among patients with AIS. These findings add to the current mixed evidence on the relationship between BMI and surgical risk and may support the recommendation of conservative treatment to patients regardless of BMI. [ABSTRACT FROM AUTHOR]

Objective: This study examined whether daily safe, low-dose ultraviolet-B (UVB) exposure using a home-based lighting solution could maintain healthy serum 25(OH)D during winter. Methods: Twenty-eight (12 male, 16 female) daytime (~9:00 to 17:00) indoor workers (mean age = 42.46; SD = 14.23) participated in this study and were allocated to one of the two study conditions. During an 8-week period, fourteen participants received extra UVB exposure (max 0.3 standard erythema dose (SED) daily), while fourteen participants in the control group did not receive extra UVB exposure. Daily questionnaires were used to measure UVB exposure time, exposed body surface area (BSA), and time spent outside in daylight. Serum 25(OH)D, vitamin D related food intake, and secondary parameters (i.e., subjective fatigue, sleep timing and quality) were investigated at baseline, Week 4, and Week 8. Results: Serum 25(OH)D significantly declined over the 8-week study period in both groups. The combination of using a low-dose UVB exposure, a small BSA, and a lower-than-expected amount of exposure hours likely resulted in an insufficient UVB dose to significantly improve serum 25(OH)D. Changes in serum 25(OH)D over time did not significantly correlate with changes in secondary parameters of sleep and fatigue. Conclusion: The received low-dose UVB exposure in this study did not significantly change serum 25(OH)D during the winter period. Future research could explore whether a longer lasting exposure period and/or using different exposure positions of the device (maximizing exposed skin surface) yields more promising results for improving serum 25(OH)D. Trial registration: Trial registration: https://www.isrctn.com/ISRCTN47902923. [ABSTRACT FROM AUTHOR]

Background and aim: Vitamin D deficiency is widespread worldwide and associated with negative effects on maternal and neonatal health. This study aimed to evaluate the relationship between vitamin D and thyroid and parathyroid hormone levels in the first trimester of pregnancy. Material and methods: This case control study included 200 participants aged (18–40) years divided into two groups; 100 pregnant females at the first trimester as case group, attending the main general clinical centers in Gaza strip, Palestine and 100 apparently healthy non-pregnant females as control group. Vitamin D, free thyroxine, free triiodothyronine, thyroid stimulating hormone, parathyroid, and the autoantibodies specific for thyroglobulin and thyroid peroxidase in serum were measured in all mothers and statistically analyzed using SPSS version 21 software. Results: Serum vitamin D, TSH, anti-TPO, and anti-TG levels were significantly decrease while, parathyroid levels were non-significantly decreased in the first trimester of pregnancy compered to control group. The levels of fT4 were significantly increased and level of fT3 were non significantly increased among pregnant mothers compered to control group. Analyses using Pearson correlation coefficients showed positive correlations between vitamin D with fT4, fT3, Anti-TPO with P -value < 0.05 and negative correlations with mother age, TSH, PTH with P-value < 0.05 in early pregnancy. Conclusions: Vitamin D deficiency among pregnant women in the first-trimester can be associated with thyroid, parathyroid parameters and thyroid autoantibodies with potential adverse consequences for overall health, emphasizing a routine monitoring and vitamin D supplementation prevention strategies to optimize maternal and fetal outcomes. [ABSTRACT FROM AUTHOR]

Little is known about the most important factors that inform a nephrologist's decision to treat (DTT) pre-dialysis chronic kidney disease (CKD) patients with vitamin D insufficiency (VDI) and secondary hyperparathyroidism (SHPT). The objective of this study was to identify such factors and their relative importance in the DTT with a vitamin D therapy. A web-based, adaptive design conjoint analysis discrete-choice survey was developed to study factors that informed the DTT among a sample of 200 nephrologists located throughout the United States. Based on literature review and clinician input, eight attributes were selected that could influence a provider's DTT: age, race, CKD stage, serum 25-hydroxyvitamin D (25D), parathyroid hormone (PTH), serum calcium (Ca), serum phosphorus (P), and history of comorbidities. Respondents were asked to select one patient profile most suitable for treatment from three profiles with varying attribute levels. Each attribute's relative importance score was computed using hierarchical-Bayesian statistics to measure the influence of each factor where higher scores represented greater DTT consideration. The pooled analysis revealed the four most important factors: serum 25D (31.4%), serum Ca (22.7%), plasma PTH (11.5%) levels, and history of comorbidities (8.5%). Age (8.2%), serum P (7.7%), CKD stage (5.7%), and race (4.4%) were relatively less important. Patients' 25D and Ca levels contributed to more than half of nephrologists' DTT, with the consideration of PTH levels being less of a factor. Further understanding of the driving forces behind the factors that inform the DTT may help to standardize the management of CKD patients with SHPT and VDI and improve outcomes. [ABSTRACT FROM AUTHOR]

A cyclin-dependent kinase (CDK) inhibitor, p57Kip2, is an important molecule involved in bone development; p57Kip2-deficient (p57-/-) mice display neonatal lethality resulting from abnormal bone formation and cleft palate. The modulator 1α,25-dihydroxyvitamin D3 (l,25-(OH)2VD3) has shown the potential to suppress the proliferation and induce the differentiation of normal and tumor cells. The current study assessed the role of p57Kip2 in the 1,25-(OH)2VD3-regulated differentiation of osteoblasts because p57Kip2 is associated with the vitamin D receptor (VDR). Additionally, 1,25-(OH)2VD3 treatment increased p57KIP2 expression and induced the colocalization of p57KIP2 with VDR in the osteoblast nucleus. Primary p57-/- osteoblasts exhibited higher proliferation rates with Cdk activation than p57+/+ cells. A lower level of nodule mineralization was observed in p57-/- osteoblasts than in p57+/+ cells. In p57+/+ osteoblasts, 1,25-(OH)2VD3 upregulated the p57Kip2 and opn mRNA expression levels, while the opn expression levels were significantly decreased in p57-/- cells. The osteoclastogenesis assay performed using bone marrow cocultured with 1,25-(OH)2VD3-treated osteoblasts revealed a decreased efficiency of 1,25-(OH)2VD3-stimulated osteoclastogenesis in p57-/- cells. Based on these results, p57Kip2 might function as a mediator of 1,25-(OH)2VD3 signaling, thereby enabling sufficient VDR activation for osteoblast maturation. [ABSTRACT FROM AUTHOR]

Melioidosis is an infectious disease with high mortality rates in human, caused by the bacterium Burkholderia pseudomallei. As an intracellular pathogen, B. pseudomallei can escape from the phagosome and induce multinucleated giant cells (MNGCs) formation resulting in antibiotic resistance and immune evasion. A novel strategy to modulate host response against B. pseudomallei pathogenesis is required. In this study, an active metabolite of vitamin D3 (1α,25-dihydroxyvitamin D3 or 1α,25(OH)2D3) was selected to interrupt pathogenesis of B. pseudomallei in a human lung epithelium cell line, A549. The results demonstrated that pretreatment with 10−6 M 1α,25(OH)2D3 could reduce B. pseudomallei internalization to A549 cells at 4 h post infection (P < 0.05). Interestingly, the presence of 1α,25(OH)2D3 gradually reduced MNGC formation at 8, 10 and 12 h compared to that of the untreated cells (P < 0.05). Furthermore, pretreatment with 10−6 M 1α,25(OH)2D3 considerably increased hCAP-18/LL-37 mRNA expression (P < 0.001). Additionally, pro-inflammatory cytokines, including MIF, PAI-1, IL-18, CXCL1, CXCL12 and IL-8, were statistically decreased (P < 0.05) in 10−6 M 1α,25(OH)2D3-pretreated A549 cells by 12 h post-infection. Taken together, this study indicates that pretreatment with 10−6 M 1α,25(OH)2D3 has the potential to reduce the internalization of B. pseudomallei into host cells, decrease MNGC formation and modulate host response during B. pseudomallei infection by minimizing the excessive inflammatory response. Therefore, 1α,25(OH)2D3 supplement may provide an effective supportive treatment for melioidosis patients to combat B. pseudomallei infection and reduce inflammation in these patients. [ABSTRACT FROM AUTHOR]

Background: Now the occurrence of delirium is more concerning to clinicians and psychiatrists. It has been reported that vitamin D deficiency may be a relevant factor in the development of delirium in hospitalized patients. Study objective: To investigate the association between vitamin D concentration and delirium in hospitalized patients. Design: Meta-analysis. Methods: A systematic literature search was conducted using PubMed, EMBASE, and the Cochrane Library. The primary outcome was the occurrence of delirium in the inpatient setting. Odds ratios (OR) were calculated with random or fixed effects models. Results: In this article, we define the normal range of vitamin D concentrations as greater than 75 nmol / L, 50–75 nmol / L as vitamin D insufficiency, 25–50 nmol / L as vitamin D deficiency, and less than 25 nmol / L as vitamin D severe deficiency. The Results showed that severe vitamin D deficiency (OR: 1.98 [1.41–2.79], P<0.001) and vitamin D deficiency (OR: 1.50 [1.12–2.00], P = 0.006) were more likely to develop delirium than normal vitamin D levels. Subgroup analysis also revealed that low vitamin D concentrations were associated with a higher incidence of delirium, whether the cutoff point was 25 nmol/L (OR: 1.52 [1.40–1.64], P<0.001), 50 nmol/L (OR: 1.47 [1.19–1.82], P<0.001), or 75 nmol/L (OR: 1.54 [1.21–1.96], P<0.001). The included studies scored medium and high on the Newcastle-Ottawa quality assessment scale. Conclusion: Compared with normal vitamin D levels, severe vitamin D deficiency and vitamin D deficiency, but not vitamin D insufficiency, are associated with a higher incidence of delirium in hospitalized patients. Trial registration: This review was registered in the PROSPERO database under identifier CRD42021271347. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021271347. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to examine the sex lives of male cirrhotic patients organic factors affect them. Method: We did an observational study of 220 cirrhotic men's satisfaction with their sexual lives. Assessment of sex satisfaction was carried out using the New Sexual Satisfaction Scale. The frequency of intercourse and masturbation was estimated. Then, the levels of albumin, total bilirubin, vitamin D, and sex steroids were examined. Ascites and sarcopenia subgroups of our patients were stratified. Results: Along with sex steroids, albumin, total bilirubin, and vitamin D all had an impact on how satisfying sex was (r = 0.22), (r = 0.24), and (r = −0.17) affected sex satisfaction. There were strong positive correlations between vitamin D (r = 0.33), albumin (r = 0.59), and free testosterone, along with a negative correlation between total bilirubin (r = −0.63) and free testosterone. An imbalance in sex steroid levels was observed, leading to decreased frequency of intercourse(p < 0.0001), weakened erections(p < 0.0001), and reduced quality of orgasm (p < 0.0001). Significant new sex behavior changes were found, such as an increase in masturbation. Physical limitations such as ascites and sarcopenia also impacted the decreasing sex life. Conclusion: The sex life of cirrhotic men is affected. The decrease in the frequency of intercourse and sexual satisfaction is noticeable in male patients and leads to increased masturbation. Free Testosterone, vitamin D, albumin, and bilirubin play role in their sex life. In addition, ascites and sarcopenia not only affect their sex life but also hamper the quality of their well-being. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this study is to determine the associations between Vitamin D supplementation, 25(OH) blood serum levels, suicide attempts, and intentional self-harm in a population of veterans in the Department of Veterans Affairs (VA). Methods: A retrospective cohort study of US Veterans supplemented with Vitamin D. Veterans with any Vitamin D3 (cholecalciferol) or Vitamin D2 (ergocalciferol) fill between 2010 and 2018 were matched 1:1 to untreated control veterans having similar demographics and medical histories. Cox proportional hazards regression was used to estimate the time from the first Vitamin D3 (cholecalciferol) or Vitamin D2 (ergocalciferol) prescription fill to the first suicide attempt or intentional self-harm. Analyses were repeated in stratified samples to measure associations by race (Black or White), gender (male or female), blood levels (0–19 ng/ml, 20–39 ng/ml, and 40+ ng/ml), and average daily dosage. Results: Vitamin D3 and D2 supplementation were associated with a 45% and 48% lower risk of suicide attempt and self-harm ((D2 Hazard Ratio (HR) = 0.512, [95% CI, 0.457, 0.574]; D3 HR = 0.552, [95% CI, 0.511, 0.597])). Supplemented black veterans and veterans with 0–19 ng/ml vitamin D serum levels were at ~64% lower risk relative to controls (Black Veteran HR: 0.362 [95% CI: 0.298,0.440]; 0–19 ng/ml HR: 0.359 [95% CI: 0.215,0.598]). Supplementation with higher vitamin D dosages was associated with greater risk reductions than lower dosages (Log Average Dosage HR: 0.837 [95% CI: 0.779,0.900]). Conclusions: Vitamin D supplementation was associated with a reduced risk of suicide attempt and self-harm in Veterans, especially in veterans with low blood serum levels and Black veterans. [ABSTRACT FROM AUTHOR]

Background: Growing evidence suggests an association between the vitamin D levels and respiratory outcomes of preterm infants. The objective of this systematic review and meta-analysis was to explore whether premature neonates with a vitamin D deficiency have an increased risk of respiratory distress syndrome (RDS). Methods: We searched PubMed, EMBASE, and the Cochrane Library up through July 20, 2021. The search terms were 'premature infant', 'vitamin D', and 'respiratory distress syndrome'. We retrieved randomized controlled trials and cohort and case-control studies. For statistical analysis, we employed the random-effects model in Comprehensive Meta-Analysis Software ver. 3.3. We employed the Newcastle-Ottawa Scales for quality assessment of the included studies. Results: A total of 121 potentially relevant studies were found, of which 15 (12 cohort studies and 3 case-control studies) met the inclusion criteria; the studies included 2,051 preterm infants. We found significant associations between RDS development in such infants and vitamin D deficiency within 24 h of birth based on various criteria, thus vitamin D levels < 30 ng/mL (OR 3.478; 95% CI 1.817–6.659; p < 0.001), < 20 ng/mL (OR 4.549; 95% CI 3.007–6.881; p < 0.001), < 15 ng/mL (OR 17.267; 95% CI 1.084–275.112; p = 0.044), and < 10 ng/ml (OR 1.732; 95% CI 1.031–2.910; p = 0.038), and an even lower level of vitamin D (SMD = –0.656; 95% CI –1.029 to –0.283; p = 0.001). Conclusion: Although the vitamin D deficiency definitions varied and different methods were used to measure vitamin D levels, vitamin D deficiency or lower levels of vitamin D within 24 h of birth were always associated with RDS development. Monitoring of neonatal vitamin D levels or the maintenance of adequate levels may reduce the risk of RDS. [ABSTRACT FROM AUTHOR]

Background: Vitamin D deficiency is an emerging public health problem globally, with devastating health consequences. Pregnant women are most susceptible for Vitamin D deficiency, and black women particularly are under double burden of the problem. Therefore, this study aimed to determine the prevalence of Vitamin D deficiency and identify associated factors among antenatal care attending pregnant women. Methods: A facility-based cross-sectional study involving 331 pregnant women was conducted from March to April in 2021. Systematic random sampling technique was used to select the study participants from antenatal care service providing facilities. Data were collected by using interviewer-administered questionnaire and 5ml of blood sample was collected using aseptic techniques. Data were entered into Epi Data software version 3.1 and exported to SPSS version 20 for analysis. Binary logistic regression analysis was used to identify the associated factors. Results: In this study, about 39% of the women were Vitamin D deficient; of which 8.8% were severely deficient. The mean serum Vitamin D level was 24.43ng/ml. Women with Body Mass Index (BMI) ≥30 (AOR = 47.31; 95% CI: 3.94, 567.70) and who never ate egg had a higher chance of being Vitamin D deficient (AOR = 7.48; 95% CI: 1.02, 55.05). On the other hand, women who were exposed to mid-day time sunlight (AOR = 0.30; 95% CI: 0.11, 0.77) were less likely to become Vitamin D deficient. Conclusions: Vitamin D deficiency is higher among obese women and women who did not consume egg. Being exposed to mid-day sunlight is protective against Vitamin D deficiency. Having optimal body weight, mid-day sun light exposure and consumption of Vitamin D rich diet might contribute to reduce the risk of Vitamin D deficiency. [ABSTRACT FROM AUTHOR]

Background: Type-II diabetes mellitus (T2DM) is a major risk factor for cognitive impairment. Protecting the brain environment against inflammation, and neurodegeneration, as well as preservation of the BBB veracity through modulating the crosstalk between insulin/AKT/GSK-3β and Wnt/β-catenin signaling, might introduce novel therapeutic targets. Purpose: This study aimed at exploring the possible neuroprotective potential of vitamin D3 (VitD) and/or rosuvastatin (RSV) in T2DM-induced cognitive deficits. Methods: T2DM was induced by a high-fat sucrose diet and a single streptozotocin (STZ) dose. Diabetic rats were allocated into a diabetic control and three groups treated with RSV (15 mg/kg/day, PO), VitD (500 IU/kg/day, PO), or their combination. Results: Administration of VitD and/or RSV mitigated T2DM-induced metabolic abnormalities and restored the balance between the anti-inflammatory, IL 27 and the proinflammatory, IL 23 levels in the hippocampus. In addition, they markedly activated both the canonical and noncanonical Wnt/β-catenin cassettes with stimulation of their downstream molecular targets. VitD and/or RSV upregulated insulin and α7 nicotinic acetylcholine (α7nACh) receptors gene expression, as well as blood-brain barrier integrity markers including Annexin A1, claudin 3, and VE-cadherin. Also, they obliterated hippocampal ApoE-4 content, Tau hyperphosphorylation, and Aβ deposition. These biochemical changes were reflected as improved behavioral performance in Morris water maze and novel object recognition tests and restored hippocampal histological profile. Conclusion: The current findings have accentuated the neuroprotective potential of VitD and RSV and provide new incentives to expand their use in T2DM-induced cognitive and memory decline. This study also suggests a superior benefit of combining both treatments over either drug alone. [ABSTRACT FROM AUTHOR]

Background: Vitamin D deficiency affects 7–86% of infants globally and results in recurrent infections, impaired growth and nutritional rickets. Low-birth-weight infants in Uganda are at risk of vitamin D deficiency due to limited sunlight exposure and dependence on breastmilk. We aimed to determine the prevalence and factors associated with vitamin D deficiency among low-birth-weight infants aged 6 weeks to 6 months at Mulago national referral hospital in Uganda. Methods: We conducted a cross-sectional study at Mulago Hospital between September 2016 and March 2017. We enrolled infants born with low birth weight between six weeks and six months whose mothers were available and willing to provide informed consent. Upon obtaining informed consent, we administered a structured questionnaire and performed a physical examination on the participants. Blood was drawn for calcium, phosphorus and vitamin D estimation. We measured serum 25 hydroxy vitamin D (25(OH)D) using the electrochemiluminescence method. Vitamin D deficiency and insufficiency were defined as (25(OH)D) < 20ng/ml and from 20ng/ml to <30 ng/ml respectively. To determine factors associated with vitamin D deficiency, we fit multivariable logistic regression models with exposure factors determined a priori. Data were analysed using Stata version 14. Results: We enrolled 297 participants, 49.2% (167/297) of whom were males. The median infant age was nine weeks (interquartile range 7–13). All infants had less than one hour of sunlight exposure and over 90.6% (269/297) had received multivitamin supplements containing vitamin D. The prevalence of vitamin D deficiency was 12.1% (36/297): 95% CI (8.9%-16.4%). The prevalence of vitamin D insufficiency was 19.9% (59/297): 95% CI (15.7%-24.8%). Boys had higher odds of vitamin D deficiency compared to girls [adjusted odds ratio 2.8: 95% CI 1.3–6.1]. Conclusion: Vitamin D deficiency was 12.1% among low-birth-weight infants in Uganda although almost all of them had received multivitamin supplements containing vitamin D. We recommend that more studies are done in low-birth-weight infants to assess the risk factors for vitamin D in these population in Uganda. [ABSTRACT FROM AUTHOR]

Irritable bowel syndrome (IBS) is one of the most common gastrointestinal disorders and affects approximately 4% of the global population. The diagnosis of IBS can be made based on symptoms using the validated Rome criteria and ruling out commonly occurring organic diseases. Although biomarkers exist for "IBS mimickers" such as celiac disease and inflammatory bowel disease (IBD), no such test exists for IBS. DNA microarrays of colonic tissue have been used to identify disease-associated variants in other gastrointestinal (GI) disorders. In this study, our objective was to identify biomarkers and unique gene expression patterns that may define the pathological state of IBS. Mucosal tissue samples were collected from the sigmoid colon of 29 participants (11 IBS and 18 healthy controls). DNA microarray analysis was used to assess gene expression profiling. Extraction and purification of RNA were then performed and used to synthesize cDNA. Reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) was employed to identify differentially expressed genes in patients diagnosed with IBS compared to healthy, non-IBS patient-derived cDNA. Additional testing probed vitamin D-mediated regulation of select genes associated with serotonergic metabolism. DNA microarray analyses led to the identification of 858 differentially expressed genes that may characterize the IBS pathological state. After screening a series of genes using a combination of gene ontological analysis and RT-qPCR, this spectrum of potential IBS biomarkers was narrowed to 23 genes, some of which are regulated by vitamin D. Seven putative IBS biomarkers, including genes involved in serotonin metabolism, were identified. This work further supports the hypothesis that IBS pathophysiology is evident within the human transcriptome and that vitamin D modulates differential expression of genes in IBS patients. This suggests that IBS pathophysiology may also involve vitamin D deficiency and/or an irregularity in serotonin metabolism. [ABSTRACT FROM AUTHOR]

Background: Whether vitamin D supplementation during pregnancy is beneficial to bone health and offspring growth remains controversial. Moreover, there is no universal agreement regarding the appropriate dose and the time of commencement of vitamin D supplementation during pregnancy. Objective: We aimed to systematically review the effects of vitamin D supplementation during pregnancy on bone development and offspring growth. Methods: A literature search for randomized controlled trials (RCTs) was performed in 7 electronic databases to identify relevant studies about the effects of vitamin D supplementation during pregnancy on bone development and offspring growth from inception to May 22, 2022. A Cochrane Risk Assessment Tool was used for quality assessment. Vitamin D supplementation was compared with placebo or standard supplements. The effects are presented as the mean differences (MDs) with 95% CIs. The outcomes include bone mineral content (BMC), bone mineral density (BMD), bone area (BA), femur length (FL) and humeral length (HL); measurement indicators of growth, including length, weight and head circumference; and secondary outcome measures, including biochemical indicators of bone health, such as the serum 25(OH)D concentration. Additionally, subgroup analyses were carried out to evaluate the impact of different doses and different initiation times of supplementation with vitamin D. Results: Twenty-three studies with 5390 participants met our inclusion criteria. Vitamin D supplementation during pregnancy was associated with increased humeral length (HL) (MD 0.13, 95% CI 0.06, 0.21, I2 = 0, P = 0.0007) during the fetal period (third trimester). Vitamin D supplementation during pregnancy was associated with a significantly increased length at birth (MD 0.14, 95% CI 0.04, 0.24, I2 = 24%, P = 0.005) and was associated with a higher cord blood 25(OH)D concentration (MD 48.74, 95% CI 8.47, 89.01, I2 = 100%, P = 0.02). Additionally, subgroup analysis revealed that birth length was significantly higher in the vitamin D intervention groups of ≤1000 IU/day and ≥4001 IU/day compared with the control group. Prenatal (third trimester) vitamin D supplementation was associated with a significant increase in birth length, while prenatal (second trimester) vitamin D supplementation was associated with a significant increase in birth weight. Conclusion: Vitamin D supplementation during pregnancy may be associated with increased humeral length (HL) in the uterus, increased body length at birth and higher cord blood 25(OH)D concentration. Evidence of its effect on long-term growth in children is lacking. Additional rigorous high-quality, long-term and larger randomized trials are required to more fully investigate the effects of vitamin D supplementation during pregnancy. [ABSTRACT FROM AUTHOR]

Objectives: The impact of antiretroviral treatment (ART) on the occurrence of oral diseases among children and adolescents living with HIV (CALHIV) is poorly understood. The aim of this study was to determine the effect of ART timing on vitamin D levels and the prevalence of four oral diseases (dry mouth, dental caries, enamel hypoplasia, and non-herpes oral ulcer) among Kenyan CALHIV from two pediatric HIV cohorts. Methods: This nested cross-sectional study was conducted at the Kenyatta National Hospital, Nairobi, Kenya. CALHIV, 51 with early-ART initiated at <12 months of age and 27 with late-ART initiated between 18 months-12 years of age, were included. Demographics, HIV diagnosis, baseline CD4 and HIV RNA viral load data were extracted from the primary study databases. Community Oral Health Officers performed oral health examinations following standardized training. Results: Among 78 CALHIV in the study, median age at the time of the oral examination was 11.4 years old and median ART duration at the time of oral examination was 11 years (IQR: 10.1, 13.4). Mean serum vitamin D level was significantly higher among the early-ART group than the late-ART group (29.5 versus 22.4 ng/mL, p = 0.0002). Children who received early-ART had a 70% reduction in risk of inadequate vitamin D level (<20 ng/mL), compared to those who received late-ART (p = 0.02). Although both groups had similar prevalence of oral diseases overall (early-ART 82.4%; late-ART 85.2%; p = 0.2), there was a trend for higher prevalence of dry mouth (p = 0.1) and dental caries (p = 0.1) in the early versus late ART groups. The prevalence of the four oral diseases was not associated with vitamin D levels (p = 0.583). Conclusions: After >10 years of ART, CALHIV with early-ART initiation had higher serum vitamin D levels compared to the late-ART group. The four oral diseases were not significantly associated with timing of ART initiation or serum vitamin D concentrations in this cohort. There was a trend for higher prevalence of dry mouth and dental caries in the early-ART group, probably as side-effects of ART. [ABSTRACT FROM AUTHOR]

The selection of dialysate calcium concentration (D-Ca) is still controversial among chronic hemodialysis (HD) regimens. We examined the trajectories of CKD MBD parameters among the J-DAVID trial participants to see the effect of D-Ca and alfacalcidol. The trial was an open-label randomized clinical trial including 976 HD patients with intact PTH of 180 pg/mL or lower which compared the users of vitamin D receptor activator (oral alfacalcidol) and non-users over a median of 4 years. The main D-Ca used at baseline were 3.0 mEq/L in 70% and 2.5 mEq/L in 25%, respectively. The primary endpoint was the composite of fatal and non-fatal cardiovascular events and the secondary endpoint was all-cause mortality. Multivariable Cox proportional hazard regression analyses in which D-Ca was included as a possible effect modifier and serum laboratory data as time-varying covariates showed no significant effect modification for composite cardiovascular events or all-cause mortality. This post hoc analysis showed that the effects of alfacalcidol on cardiovascular outcomes were not significantly modified by D-Ca. [ABSTRACT FROM AUTHOR]