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Vitamin D is a promising anticancer agent for the prevention and treatment of several cancers, including melanoma. Low 25-hydroxyvitamin D levels, a routinely used marker for vitamin D, have been suggested as one of the factors in the development and progression of melanoma. The parent vitamin D needs activation by cytochrome P450 (CYP) enzymes to exert its actions via the vitamin D receptor (VDR). This review discusses the role of vitamin D in melanoma and how CYP-mediated metabolism can potentially affect the actions of vitamin D. Through interacting with the retinoid X receptor, VDR signaling leads to anti-inflammatory, antioxidative, and anticancer actions. Calcitriol, the dihydroxylated form of vitamin D3, is the most active and potent ligand of VDR. CYP27A1, CYP27B1, and CYP2R1 are involved in the activation of vitamin D, whereas CYP24A1 and CYP3A4 are responsible for the degradation of the active vitamin D. CYP24A1, the primary catabolic enzyme of calcitriol, is overexpressed in melanoma tissues and cells. Several drug classes and natural health products can modulate vitamin D-related CYP enzymes and eventually cause lower levels of vitamin D and its active metabolites in tissues. Although the role of vitamin D in the development of melanoma is yet to be fully elucidated, it has been proposed that melanoma prevention may be significantly aided by increased vitamin D signaling. Furthermore, selective targeting of the catabolic enzymes responsible for vitamin D degradation could be a plausible strategy in melanoma therapy. Vitamin D signaling can be improved by utilizing dietary supplements or by modulating CYP metabolism. A positive association exists between the intake of vitamin D supplements and improved prognosis for melanoma patients. Further investigation is required to determine the function of vitamin D supplementation and specific enzyme targeting in the prevention of melanoma. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is an independent osteoporosis risk factor. Biologic and immunosuppressive treatment, and levels of homocysteine and 25-OH vitamin D may influence the trabecular bone score (TBS) in RA patients. We aimed to compare the effects of biological (b) and conventional synthetic (cs) disease-modifying anti-rheumatic drugs (DMARDs) on TBS in patients with RA and hyperhomocysteinemia (HHcy) or 25-OH vitamin D deficiency. Patients who had tests conducted for trabecular bone score, bone mineral density (BMD), homocysteine (Hcy) and 25-OH vitamin D at an interval of one year and met the inclusion criteria were enrolled in this retrospective study. Sixty-four patients with RA were enrolled and were divided into the following two groups: the first group (34 patients) had received treatment with bDMARDs and the second group (30 patients) had received csDMARDs. BDMARDs and csDMARDs had a positive influence on TBS and BMD. The best results were observed in the Adalimumab group (p = 0.033). Hyperhomocysteinemia and 25-OH vitamin D deficiency led to lower TBS values. Both bDMARDs and csDMARDs positively affected TBS and BMD in RA patients. High homocysteine serum levels or 25-OH vitamin D deficiency had a negative impact on TBS and BMD after 12 months. Our study aims to show the potential benefits of anti-TNF α drugs on TBS. This impact appears to be strongly associated with serum 25-OH vitamin D and homocysteine levels. Anti-TNF drugs may increase bone mineral density and microstructure. As a result, they may minimize the incidence of fractures in RA patients. [ABSTRACT FROM AUTHOR]

In the present work, an efficient isocratic HPLC method was developed for the precise and accurate estimation of vitamin D3 in tablet form. The chromatographic conditions comprised an L3 silica column (5 µm in particle size, 4.6 mm × 250 mm) with a mobile phase n-hexane/ethyl acetate (85:15 v/v) with a flow rate of 2.0 mL/min and a detection wavelength of 292 nm. The new methodology was validated for accuracy, precision, specificity, robustness, and quantification limits according to an official monograph of USP/BP and ICH guidelines. The peak areas of the six replicates of the homogeneous sample were recorded. The mean value obtained was 67,301, and the relative standard deviation (RSD) was 0.1741. The linearity and range were in the acceptable bounds, i.e., 0.999, which was calculated using regression line analysis. The results show that the method is truly acceptable as the RSD, as the flow rate was 0.81%, while for the mobile phase composition, it was 0.72%, which lies in the acceptable range. The limit of detection (LOD) and the limit of quantification (LOQ) values were 0.0539 µg/mL and 0.1633 µg/mL, respectively. The % RSD of the intra and inter-day precision of the method was deemed acceptable according to the international commission for harmonization guidelines. The developed method has potential to be used for the detection and quantification of vitamin D3 during routine analysis for tablets in dosage form. [ABSTRACT FROM AUTHOR]

Introduction: Breast cancer stands as the leading cause of mortality among women in developing nations. The potential role of Vitamin D in mitigating the incidence of breast cancer is thought to stem from its ability to impede cell proliferation by interacting with the Vitamin D Receptor (VDR). The VDR gene is responsible for encoding the VDR, which plays a pivotal role in mediating the effects of vitamin D. Aim: To analyse vitamin D levels and the association of VDR FokI, ApaI, and BsmI genotypic distribution frequency with the risk of breast cancer. Materials and Methods: The case-control study included 220 samples, including 110 breast cancer patients and 110 agematched control women aged 30-70 years. The Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) genotyping was performed using Deoxyribonucleic acid (DNA) extracted from blood, and the circulating levels of 25-hydroxyvitamin D by case/control were estimated by chemiluminescence immunoassay. Results: The 3' VDR polymorphism BsmI sequence showed minimal association with breast cancer risk. The bb genotype had a significantly lower odds ratio of 0.056 (p-value<0.05). Conversely, the BB and Bb genotypes exhibited no statistically significant associations with odds ratios of 1.76 (95% CI: 0.36-8.54; p-value>0.05) and 1.30 (95% CI: 0.27-6.25; p-value>0.05), respectively. Isolated analysis of the FokI variant revealed a significant association with increased breast cancer risk, with odds ratios of 5.49 (FF) and 6.00 (Ff), both demonstrating statistical significance (p-value<0.05), and a Chi-square value of 0.006. Additionally, the p-value for serum Vitamin D levels was found to be highly significant at p-value<0.001, indicating that the levels were significantly lower in individuals newly diagnosed with breast cancer compared to those in the healthy control group. Conclusion: The study found a significant link between breast cancer susceptibility and VDR (FokI) polymorphism FF and Ff genotypes, with minimal impact observed for (BsmI) polymorphism bb genotype. This implies that certain genetic variations, especially in the FokI polymorphism of the VDR gene, are associated with an elevated risk of breast cancer. [ABSTRACT FROM AUTHOR]

Melatonin is a multifunctional hormone regulator that maintains homeostasis through circadian rhythms, and desynchronization of these rhythms can lead to gastrointestinal disorders and increase the risk of cancer. Preliminary clinical studies have shown that exogenous melatonin alleviates the harmful effects of anticancer therapy and improves quality of life, but the results are still inconclusive due to the heterogeneity of the studies. A personalized approach to testing clinical parameters and response to integrative treatment with nontoxic and bioavailable melatonin in patient-centered N-of-1 studies deserves greater attention. This clinical case of colon cancer analyzes and discusses the tumor pathology, the adverse effects of chemotherapy, and the dynamics of markers of inflammation (NLR, LMR, and PLR ratios), tumors (CEA, CA 19-9, and PSA), and hemostasis (D-dimer and activated partial thromboplastin time). The patient took melatonin during and after chemotherapy, nutrients (zinc, selenium, vitamin D, green tea, and taxifolin), and aspirin after chemotherapy. The patient's PSA levels decreased during CT combined with melatonin (19 mg/day), and melatonin normalized inflammatory markers and alleviated symptoms of polyneuropathy but did not help with thrombocytopenia. The results are analyzed and discussed in the context of the literature on oncostatic and systemic effects, alleviating therapy-mediated adverse effects, association with survival, and N-of-1 studies. [ABSTRACT FROM AUTHOR]

In addition to being a lipid-soluble vitamin, vitamin D is also a steroid hormone that the skin can produce on its own when exposed to sunlight. A lack of vitamin D is linked to a number of health problems, including impaired immune function, an increased risk of cancer, diabetes, cardiovascular disease, rheumatic disease, muscle weakness, chronic pain, and neuropsychiatric disorders. Vitamin D insufficiency is frequent during pregnancy, particularly in high-risk populations such as vegetarians, women who live in cold climes or northern latitudes, wear clothing that protects them from the sun, and ethnic minorities, particularly those with darker complexion. It is a significant risk factor for low foetal growth, neonatal development, and infantile rickets. Furthermore, vitamin Ddeficiency may put expectant mothers at risk for preeclampsia and gestational diabetes. The purpose of this study is to assess the incidence of vitamin D insufficiency in Jammu and Kashmir, a state in northern India. A total of 120 pregnant women had their levels of vitamin D (25-OH D) checked; of them, 52 (43.3%) had levels below 20 ngm/ml, 41 (34.1%) had levels between 20-30 ngm/ml, and 27 (22.5%) had levels over 30 ngm/ml. The study undercuts the need for more research in this field by demonstrating the startlingly high frequency of vitamin D insufficiency among pregnant women who were otherwise in good health. [ABSTRACT FROM AUTHOR]

This article discusses the use of vitamin D as a potential treatment for warts. Warts are difficult to treat, and current treatment options are not always effective. Vitamin D has been shown to have immune therapeutic properties and can inhibit keratinocyte proliferation, which is a therapeutic goal in managing warts. Studies have demonstrated the beneficial effects of intralesional and topical vitamin D in treating resistant warts. However, the efficacy of vitamin D treatment can vary depending on the specific subtype of HPV involved and other factors such as dose and duration of treatment. Further research is needed to fully understand the potential of vitamin D in wart management. [Extracted from the article]

Introduction: Sufficient levels of vitamin D have been associated with higher chances for both clinical pregnancy and live birth among women undergoing assisted reproductive techniques, whereas low levels of maternal vitamin D have been associated with preeclampsia and late miscarriage. In Denmark, subgroups at risk for low vitamin D levels, including neonates and toddlers, are recommended to use supplementation. The aim was to study the level of vitamin D3 among neonates born after in vitro fertilization compared with neonates from the general population. Material and methods: In this cohort study a random sample of 1326 neonates representing the general population and 1200 neonates conceived by in vitro fertilization born in Denmark from 1995 to 2002 were identified from registries covering the whole Danish population. Information on use of assisted reproduction was collected from the Danish In Vitro Fertilization register, ICD‐10 code: DZ358F. 25‐Hydroxyvitamin D was measured from dried blood spots routinely collected by heel prick 48–72 h after birth and corrected according to the hematocrit fraction for capillary blood of neonates. Linear regression analysis was performed, both crude and adjusted, for predefined putative confounders, identified through directed acyclic graphs. Results: Vitamin D3 analysis could be performed from a total of 1105 neonates from the general population and 1072 neonates conceived by in vitro fertilization that were subsequently included in the study. The median vitamin D3 was 24.0 nmol/L (interquartile range [IQR] 14.1–39.3) and 33.0 nmol/L (IQR 21.3–48.8) among neonates from the general population and neonates conceived by in vitro fertilization, respectively. The adjusted mean difference between neonates from the general population and those conceived by in vitro fertilization was 6.1 nmol/L (95% confidence interval 4.1–8.1). Conclusions: In this study, children born after in vitro fertilization have a higher vitamin D3 than a random sample of neonates in Denmark. [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]

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]

"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]

Background: Polycystic ovary syndrome (PCOS) is a serious health condition affecting women of reproductive age. High prevalence of PCOS and associated metabolic complications needs effective treatment and management. This study evaluated the efficacy of optimal nutraceutical combinations in improving PCOS characteristics using system biology-based mathematical modelling and simulation. Methods: A shortlisting of eight potent nutraceuticals was carried out with literature search. Menstrual cycle model was used to perform simulations on an in-silico population of 2000 individuals to test individual and combined effects of shortlisted nutraceuticals on five PCOS characteristics [oligomenorrhea, anovulation, hirsutism, infertility, and polycystic ovarian morphology (PCOM)] for a duration of 6 months. Efficacy was tested across lean and obese phenotypes and age groups. Results: Individual assessment of nutraceuticals revealed seven most potent compounds. Myo-inositol among them was observed to be the most effective in alleviating the PCOS characteristics. The in-silico population analysis showed that the combination of melatonin and ALA along with myo-inositol was efficacious in restoring the hormonal balance across age-groups and Body Mass Index (BMI) categories. Conclusion: Supplementation with the combination of myo-inositol, melatonin, and ALA demonstrated potential in managing PCOS symptoms in our in-silico analysis of a heterogeneous population, including lean and obese phenotypes across various severities and age groups, over a 6-month period. Future clinical studies are recommended to validate these 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]

Objective: Idiopathic infantile hypercalcemia (IIH) is a rare disorder of PTH-independent hypercalcemia. CYP24A1 and SLC34A1 gene mutations cause two forms of hereditary IIH. In this study, the clinical manifestations and molecular aspects of six new Chinese patients were investigated. Methods: The clinical manifestations and laboratory study of six patients with idiopathic infantile hypercalcemia were analyzed retrospectively. Results: Five of the patients were diagnosed with hypercalcemia, hypercalciuria, and bilateral medullary nephrocalcinosis. Their clinical symptoms and biochemical abnormalities improved after treatment. One patient presented at age 11 years old with arterial hypertension, hypercalciuria and nephrocalcinosis, but normal serum calcium. Gene analysis showed that two patients had compound heterozygous mutations of CYP24A1, one patient had a monoallelic CYP24A1 variant, and three patients had a monoallelic SLC34A1 variant. Four novel CYP24A1 variants (c.116G > C, c.287T > A, c.476G > A and c.1349T > C) and three novel SLC34A1 variants (c.1322 A > G, c.1697_1698insT and c.1726T > C) were found in these patients. Conclusions: A monoallelic variant of CYP24A1 or SLC34A1 gene contributes to symptomatic hypercalcemia, hypercalciuria and nephrocalcinosis. Manifestations of IIH vary with onset age. Hypercalcemia may not necessarily present after infancy and IIH should be considered in patients with nephrolithiasis either in older children or adults. [ABSTRACT FROM AUTHOR]

The mucosa of the respiratory system is an essential site for local vitamin D synthesis, degradation, and signaling. It modulates the inflammatory and immune response by saving the integrity of the mucosal barrier and killing the invading pathogen through the induction of antimicrobial peptides. The proper functioning of the immune system within the respiratory system is influenced by the complex interactions of numerous immune pathways, including the gut-lung axis. Recent research has indicated that the gut microbiota is vital in developing and progressing chronic inflammatory chest conditions, such as asthma and chronic obstructive pulmonary disease (COPD). Furthermore, the immune-modulating function of vitamin D operates through the gut mucosa; hence, the vitamin D receptor is expressed to regulate the antimicrobial peptide. The potential protective role of vitamin D and its correlation with COPD has garnered significant interest. It is currently under exploration as a possible adjuvant therapy to aid in managing frequent exacerbation of COPD. In this review, we explored the connection between vitamin D and the immune system, as well as its relationship with microbiota. We also summarized some novel mechanisms of action of vitamin D supplementation that can impact disease exacerbation. [ABSTRACT FROM AUTHOR]

Cutaneous T-cell lymphoma (CTCL) is characterized by the proliferation of malignant T cells in inflamed skin lesions. Mycosis fungoides (MF)—the most common variant of CTCL—often presents with skin lesions around the abdomen and buttocks ("bathing suit" distribution), i.e., in skin areas devoid of sun-induced vitamin D. For decades, sunlight and vitamin D have been connected to CTCL. Thus, vitamin D induces apoptosis and inhibits the expression of cytokines in malignant T cells. Furthermore, CTCL patients often display vitamin D deficiency, whereas phototherapy induces vitamin D and has beneficial effects in CTCL, suggesting that light and vitamin D have beneficial/protective effects in CTCL. Inversely, vitamin D promotes T helper 2 (Th2) cell specific cytokine production, regulatory T cells, tolerogenic dendritic cells, as well as the expression of immune checkpoint molecules, all of which may have disease-promoting effects by stimulating malignant T-cell proliferation and inhibiting anticancer immunity. Studies on vitamin D treatment in CTCL patients showed conflicting results. Some studies found positive effects, others negative effects, while the largest study showed no apparent clinical effect. Taken together, vitamin D may have both pro- and anticancer effects in CTCL. The balance between the opposing effects of vitamin D in CTCL is likely influenced by treatment and may change during the disease course. Therefore, it remains to be discovered whether and how the effect of vitamin D can be tilted toward an anticancer response in CTCL. [ABSTRACT FROM AUTHOR]

Disease modifiers, whether from cancer, sepsis, systemic inflammation, or microbial pathogens, all appear to induce epithelial barrier leak, with induced changes of the Tight Junctional (TJ) complex being pivotal to the process. This leak—and the ensuant breakdown of compartmentation—plays a central role in disease morbidity on many levels. Accumulation of lung water in the luminal compartment of airways was a major driver of morbidity and mortality in COVID-19 and is an excellent example of the phenomenon. Increasing awareness of the ability of micronutrients to improve basal barrier function and reduce barrier compromise in pathophysiology may prove to be a low-cost, safe, and easily administered prophylactic and/or therapeutic option amenable to large populations. The growing appreciation of the clinical utility of supplemental doses of Vitamin D in COVID-19 is but one example. This narrative review is intended to propose a general theory on how and why micronutrients—at levels above normal dietary intake—successfully remodel TJs and improve barrier function. It discusses the key difference between dietary/Recommended Daily Allowance (RDA) levels of micronutrients versus supplemental levels, and why the latter are needed in disease situations. It advances a hypothesis for why signal transduction regulation of barrier function may require these higher supplemental doses to achieve the TJ remodeling and other barrier element changes that are clinically beneficial. [ABSTRACT FROM AUTHOR]

In arterial hypertension, the dysregulation of several metabolic pathways is closely associated with chronic immune imbalance and inflammation progression. With time, these disturbances lead to the development of progressive disease and end-organ involvement. However, the influence of cholecalciferol on metabolic pathways as a possible mechanism of its immunomodulatory activity in obesity-related hypertension is not known. In a phase 2, randomized, single-center, 24-week trial, we evaluated, as a secondary outcome, the serum metabolome of 36 age- and gender-matched adults with obesity-related hypertension and vitamin D deficiency, before and after supplementation with cholecalciferol therapy along with routine medication. The defined endpoint was the assessment of circulating metabolites using a nuclear magnetic resonance-based metabolomics approach. Univariate and multivariate analyses were used to evaluate the systemic metabolic alterations caused by cholecalciferol. In comparison with normotensive controls, hypertensive patients presented overall decreased expression of several amino acids (p < 0.05), including amino acids with ketogenic and glucogenic properties as well as aromatic amino acids. Following cholecalciferol supplementation, increases were observed in glutamine (p < 0.001) and histidine levels (p < 0.05), with several other amino acids remaining unaffected. Glucose (p < 0.05) and acetate (p < 0.05) decreased after 24 weeks in the group taking the supplement, and changes in the saturation of fatty acids (p < 0.05) were also observed, suggesting a role of liposoluble vitamin D in lipid metabolism. Long-term cholecalciferol supplementation in chronically obese and overweight hypertensives induced changes in the blood serum metabolome, which reflected systemic metabolism and may have fostered a new microenvironment for cell proliferation and biology. Of note, the increased availability of glutamine may be relevant for the proliferation of different T-cell subsets. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease (NAFLD) exponentially affects the global healthcare burden, and it is currently gaining increasing interest in relation to its potential impact on central nervous system (CNS) diseases, especially concerning cognitive deterioration and dementias. Overall, scientific research nowadays extends to different levels, exploring NAFLD's putative proinflammatory mechanism of such dysmetabolic conditions, spreading out from the liver to a multisystemic involvement. The aim of this review is to analyze the most recent scientific literature on cognitive involvement in NAFLD, as well as understand its underlying potential background processes, i.e., neuroinflammation, the role of microbiota in the brain–liver–gut axis, hyperammonemia neurotoxicity, insulin resistance, free fatty acids, and vitamins. [ABSTRACT FROM AUTHOR]

Hashimoto's thyroiditis (HT) is marked by self-tissue destruction as a consequence of an alteration in the adaptive immune response that entails the evasion of immune regulation. Vitamin D carries out an immunomodulatory role that appears to promote immune tolerance. The aim of this study is to elaborate a narrative review of the relationship between vitamin D status and HT and the role of vitamin D supplementation in reducing HT risk by modulating the immune system. There is extensive literature confirming that vitamin D levels are significantly lower in HT patients compared to healthy people. On the other hand, after the supplementation with cholecalciferol in patients with HT and vitamin D deficiency, thyroid autoantibody titers decreased significantly. Further knowledge of the beneficial effects of vitamin D in the prevention and treatment of autoimmune thyroid diseases requires the execution of additional randomized, double-blind, placebo-controlled trials and longer follow-up periods. [ABSTRACT FROM AUTHOR]

Background and Objective. Diabetes contributes to considerable morbidity and mortality through vascular complications. Sonographic evaluation of carotid intima-media thickness (CIMT) is accepted as a surrogate marker for atherosclerosis. The aim of this study was to find out the difference in the CIMT between diabetes and nondiabetes and determine its correlation with serum vitamin D and some other modifiable and nonmodifiable cardiovascular risk factors. Methods. This multicenter cross-sectional study was performed on two groups of adults (nondiabetes and type 2 diabetes) of various ages, sexes, and body mass index (BMI). CIMT for each side was measured at three segments using high-resolution ultrasound, and the mean of both sides was determined. Comparison was made between each group, and the association of CIMT with each of age, sex, BMI, serum vitamin D status, smoking, and physical activity status was studied. The chi-square test was used to compare categorical data, and binary logistic regression was utilized to ascertain the relationship between CIMT and the study variables. Results. A significant difference was observed between the CIMT of the diabetes and nondiabetes group, average CIMT was 0.82 ± 0.23 mm vs. 1.12 ± 0.24 mm for the nondiabetes and diabetes group, respectively, with P value <0.005. No significant correlation was observed between serum vitamin D level and CIMT neither in the study group as a whole nor in either subgroup; however, a significant association was observed between CIMT with each of age, sex, BMI, smoking, and physical activity status. Conclusion. Ultrasound is a sensitive tool for CIMT evaluation. Diabetes has a 5.4-fold higher risk of having high CIMT. Serum vitamin D level showed no significant influence on CIMT. Smoking, BMI, and physical activity are among the modifiable risk factors with significant influence on CIMT. [ABSTRACT FROM AUTHOR]

Emerging evidence has demonstrated a strong correlation between vitamin D status and fatty liver disease. Aberrant hepatic fat infiltration contributes to oxidant overproduction, promoting metabolic dysfunction, and inflammatory responses. Vitamin D supplementation might be a good strategy for reducing hepatic lipid accumulation and inflammation in non-alcoholic fatty liver disease and its associated diseases. This study aimed to investigate the role of the most biologically active form of vitamin D, 1,25-dihydroxyvitamin D (1,25(OH)2D), in hepatic fat accumulation and inflammation in palmitic acid (PA)-treated AML-12 hepatocytes. The results indicated that treatment with 1,25(OH)2D significantly decreased triglyceride contents, lipid peroxidation, and cellular damage. In addition, mRNA levels of apoptosis-associated speck-like CARD-domain protein (ASC), thioredoxin-interacting protein (TXNIP), NOD-like receptor family pyrin domain-containing 3 (NLRP3), and interleukin-1β (IL-1β) involved in the NLRP3 inflammasome accompanied by caspase-1 activity and IL-1β expression were significantly suppressed by 1,25(OH)2D in PA-treated hepatocytes. Moreover, upon PA exposure, 1,25(OH)2D-incubated AML-12 hepatocytes showed higher sirtulin 1 (SIRT1) expression and adenosine monophosphate-activated protein kinase (AMPK) phosphorylation. A SIRT1 inhibitor alleviated the beneficial effects of 1,25(OH)2D on PA-induced hepatic fat deposition, IL-1β expression, and caspase-1 activity. These results suggest that the favorable effects of 1,25(OH)2D on hepatic fat accumulation and inflammation may be, at least in part, associated with the SIRT1. [ABSTRACT FROM AUTHOR]

Simple Summary: The primary focus of this review revolves around actinic keratoses (AKs), common skin conditions primarily induced by prolonged sun exposure. These lesions are of particular concern due to their potential progression into skin cancer, thereby warranting in-depth investigation for effective treatment and prevention strategies. There are different approaches to treat AK; some of them target the dysplastic cells, whereas others act on the immunological response of the host to fight against abnormal cells. This review summarizes all the therapies used for AK and field cancerization, whose mechanism of action include the participation of the immune system. Moreover, the research extends to immunosuppressed individuals, mainly organ transplant recipients, who require tailored approaches due to their immune profiles. In essence, this research tries to update the therapeutic approaches for AKs, ultimately lowering the risk of malignant transformation and contributing to improved clinical management. This comprehensive review delves into various immunotherapeutic approaches for the management of actinic keratoses (AKs), precancerous skin lesions associated with UV exposure. Although there are treatments whose main mechanism of action is immune modulation, such as imiquimod or diclofenac, other treatments, apart from their main effect on dysplastic cells, exert some immunological action, which in the end contributes to their efficacy. While treatments like 5-fluorouracil, imiquimod, photodynamic therapy, and nicotinamide are promising in the management of AKs, especially in immunocompetent individuals, their efficacy is somewhat reduced in solid organ transplant recipients due to immunosuppression. The analysis extends to optimal combination, focusing on cryoimmunotherapy as the most relevant. New immunotherapies include resimiquimod, ingenol disoxate, N-phosphonacetyl-L-aspartate (PALA), or anti-PD1 that have shown promising results, although more studies are needed in order to standardize their use. [ABSTRACT FROM AUTHOR]

Purpose: There is controversy concerning the relationship between Helicobacter pylori (H. pylori) infection and osteoporosis. This study is to examine the causal relationship between H. pylori infection and osteoporosis and to analyze the potential mechanism underlying the relationship. Methods: The clinical data of H. pylori infection and bone mineral density from patients or physical examiner with good general condition in our hospital between September 2019 and September 2020 were retrospectively collected. The relationship between H. pylori infection and osteoporosis was compared and analyzed, using logistic regression to examine the potential mechanism underlying the association. To investigate the causal effects of H. pylori infection and osteoporosis, we conducted a two-sample bidirectional Mendelian randomization (MR) analysis. Results: A total of 470 patients were positive for H. pylori, with a detection rate of 52.22%. It was found that age, SBP, FPG, DBP, ALB, LDL-C, hs-CRP, and OC were positively correlated with osteoporosis, while negative correlations were observed with BMI, LYM, ALB, TP, TG, HDL-C, SCr, UA, and VitD. After stratified analysis of sex and age, it was found that there was a significant correlation between H. pylori infection and osteoporosis. The levels of SBP, ALP, FPG, LDL-C, hs-CRP, and OC in both H. pylori-positive group and osteoporosis group were higher than those in the H. pylori-negative group while the levels of BMI, ALB, TP, HDL-C, SCr, UA, and VitD in the positive group were significantly lower than those in the negative group. Logistic regression analyses with gender and age showed that ALB, FPG, HDL-C, and VitD were common risk factors for osteoporosis and H. pylori infection. In the MR analysis, the IVW results found a positive effect of H. pylori infection on osteoporosis (OR = 1.0017, 95% CI: 1.0002–1.0033, P = 0.0217). Regarding the reverse direction analysis, there was insufficient evidence to prove the causal effects of osteoporosis on H. pylori infection. Conclusion: Our study provides evidence for causal effects of H. pylori infection on osteoporosis. H. pylori may affect osteoporosis through serum albumin, high-density lipoprotein, fasting blood glucose and vitamin D. [ABSTRACT FROM AUTHOR]

Background: Vitamin D may help to alleviate asthma exacerbation because of its anti-inflammation effect, but the evidence is inconsistent in childhood asthma. MiRNAs are important mediators in asthma pathogenesis and also excellent non-invasive biomarkers. We hypothesized that circulating miRNAs are associated with asthma exacerbation and modified by vitamin D levels. Methods: We sequenced baseline serum miRNAs from 461 participants in the Childhood Asthma Management Program (CAMP). Logistic regression was used to associate miRNA expression with asthma exacerbation through interaction analysis first and then stratified by vitamin D insufficient and sufficient groups. Microarray from lymphoblastoid B-cells (LCLs) treated by vitamin D or sham of 43 subjects in CAMP were used for validation in vitro. The function of miRNAs was associated with gene modules by weighted gene co-expression network analysis (WGCNA). Results: We identified eleven miRNAs associated with asthma exacerbation with vitamin D effect modification. Of which, five were significant in vitamin D insufficient group and nine were significant in vitamin D sufficient group. Six miRNAs, including hsa-miR-143-3p, hsa-miR-192-5p, hsa-miR-151a-5p, hsa-miR-24-3p, hsa-miR-22-3p and hsa-miR-451a were significantly associated with gene modules of immune-related functions, implying miRNAs may mediate vitamin D effect on asthma exacerbation through immune pathways. In addition, hsa-miR-143-3p and hsa-miR-451a are potential predictors of childhood asthma exacerbation at different vitamin D levels. Conclusions: miRNAs are potential mediators of asthma exacerbation and their effects are directly impacted by vitamin D levels. [ABSTRACT FROM AUTHOR]

Background: The relationship between vitamin D status and mortality among adults with hypertension remains unclear. Methods: This prospective cohort study involved a sample of 19,500 adults with hypertension who participated in the National Health and Nutrition Examination Survey (NHANES) from 2001 to 2018. We utilized a weighted COX proportional hazard model to assess the association between vitamin D status and mortality. This statistical model calculates hazard ratios (HR) and their corresponding 95% confidence intervals (95% CI). Results: The study indicated that lower serum 25(OH)D concentration was associated with an increased risk of all-cause mortality among individuals with hypertension. Specially. Those with concentrations between 25.0 and 49.9 nmol/L (HR = 1.71, 95%CI = 1.22–2.40) and less than 25.0 nmol/L (HR = 1.97, 95%CI = 1.15–3.39) had higher hazard ratios for all-cause mortality. Individuals with hypertension who took vitamin D supplements had a lower risk of all-cause mortality, but not the risk of CVD mortality (HR 0.75, 95%CI 0.54–1.03), compared to those who did not supplement (HR = 0.76, 95%CI = 0.61–0.94). Subgroup analysis further revealed that vitamin D supplementation was associated with a reduced risk of all-cause mortality among individuals without diabetes (HR = 0.65, 95%CI = 0.52–0.81) and individuals without CVD (HR = 0.75, 95%CI = 0.58–0.97), and a decreased risk of CVD mortality among individuals without diabetes (HR = 0.63, 95%CI = 0.45–0.88) and without CVD (HR = 0.61, 95%CI = 0.40–0.92). Furthermore, higher-dose vitamin D supplementation was also associated with a greater reduction in all-cause mortality among hypertensive individuals, and there was the potential synergistic effect of combining normal-dose calcium and vitamin D supplementation, showing a superior effect on mortality compared to low-dose supplementation in adults with hypertension. Conclusions: This prospective cohort study demonstrated a significant association between lower serum 25 (OH)D concentration and increased all-cause mortality among adults with hypertension. Furthermore, the study found that vitamin D supplementation had a strong and significantly positive correlation with reduced all-cause and CVD mortality among hypertensive individuals without diabetes or CVD. This positive correlation suggests that vitamin D supplementation could potentially be an effective strategy to reduce the risk of mortality in this specific group of people. [ABSTRACT FROM AUTHOR]

Quantitative analysis of the biologically-active metabolites of vitamin D (VitD), which are crucial in regulating various physiological and pathological processes, is important for clinical investigations. Liquid chromatography-tandem mass spectrometry (LC-MS) has been widely used for this purpose but existing LC-MS methods face challenges in achieving highly sensitive and accurate quantification of low-abundance VitD metabolites while maintaining high throughput and robustness. Here we developed a novel pipeline that combines a trapping-micro-LC-(T-µLC) with narrow-window-isolation selected-reaction monitoring MS(NWI-SRM) for ultra-sensitive, robust and high-throughput quantification of VitD metabolites in serum samples after derivatization. The selective-trapping and delivery approach efficiently removes matrix components, enabling high-capacity sample loading and enhancing sensitivity, throughput, and robustness. The NWI-SRM further improves the sensitivity by providing high selectivity. The lower limits of quantification (LOQs) achieved were markedly lower than any existing LC-MS methods: 1.0 pg/mL for 1,25(OH)2D3, 5.0 pg/mL for 24,25(OH)2D3, 30 pg/mL for both 25(OH)D2 and 25(OH)D3, all within a 9-min cycle. The method is applied to quantify VitD metabolites from 218 patients with multiple sclerosis. This study revealed negative correlations(r=− 0.44 to − 0.51) between the levels of 25(OH)D2 and all the three D3 metabolites in multiple sclerosis patients. [ABSTRACT FROM AUTHOR]

Background: The interplay between vitamin D status and inflammatory cytokines in a supposedly sufficient sunshine environment has not well been evaluated. The study sought to determine their association. Methods: This cross-sectional study involved 500 healthy adult blood donors from some selected hospitals in Ghana enrolled from June to November 2016. Venous blood samples were obtained from participants, 25(OH)D, TNF-alpha, IFN-gamma, and IL 10 were measured using enzyme linked immunosorbent assay (ELISA) technique. Serum levels of 25(OH)D < 20ng/ml were classified as being deficient or low. Results: The average age of the participants was 27.97 years. No statistically significant association was established between 25(OH) D status, mean age (p = 0.1693), and gender (p = 0.5461) of study participants. Similarly, the median 25(OH) D (p = 0.8392), IL-10 (p = 0.5355), TNF-alpha (p = 0.9740), and IFN-gamma (p = 0.6908) were not significantly different across gender. There was a significantly increased levels of TNF-alpha (p < 0.0001) and IFN-gamma (p < 0.0001) among participants with 25(OH) D deficiency compared to those without deficiency. Concurrently, participants with 25(OH)D deficiency had a significantly reduced levels of IL-10 (p < 0.0001) compared to those without 25 (OH) D deficiency. The most accurate biochemical markers for identifying 25 (OH) D deficiency were IFN-gamma (AUC = 0.879; p < 0.0001) followed by TNF-gamma (AUC = 0.849; p < 0.0001) and IL-10 (AUC = 0.707; p < 0.0001). Conclusion: There was a significant association between vitamin D levels and pro-inflammatory cytokines (TNF-alpha, IFN-gamma) and anti-inflammatory cytokine (IL 10) among healthy Ghanaian populace. [ABSTRACT FROM AUTHOR]

Objective: Circulating endothelial progenitor cells (EPCs) play an essential role in endothelial repair and neovascularization. Vitamin D deficiency may contribute to EPC depletion and endothelial dysfunction in patients with type 2 diabetes. In addition, iron overload is closely related to the development of diabetes and its various chronic complications. This study was designed to determine the relationship between EPC markers (CD34, CD133), vitamin D, and iron in patients with diabetic nephropathy. Materials and Methods: This case-control study was conducted on 67 diabetic patients with or without nephropathy. Blood pressure and all biochemical parameters were measured and compared. Serum concentrations of insulin, vitamin D, CD34, and CD133 were measured using ELISA. Serum iron concentration was measured using atomic absorption spectrometry. Results: Body mass index (P= 0.006), diastolic pressure (P= 0.018), insulin level (P= 0.028), Creatinine (P= 0.013), duration of diabetes, uric acid, and glomerular filtration rate (GFR) were significantly different between the two groups (each P= 0.0001). The vitamin D (P= 0.034), CD34 (P= 0.0001), and CD133 (P= 0.025) levels decreased, and Iron (P= 0.0001) increased in the case group. Also, CD34 has a significant direct relationship with insulin, insulin resistance, and CD133. The results showed that vitamin D, iron, CD34, and CD133 had a significant relationship with the severity of nephropathy (P= 0.0001, each). Conclusion: Increased iron levels and decreased vitamin D, CD34, and CD133 levels are associated with the severity of nephropathy. This result indicates that diabetic nephropathy may directly reduce CD34 and CD133 levels in the body, increasing the incidence of secondary complications in these patients. [ABSTRACT FROM AUTHOR]

Skin cancer is a significant health burden being the fourth most common cancer globally and accounts for 6.2% of the total combined cancer cases. However, mortality rates due to skin cancer are less when compared with other cancers, but it is significantly high in the Asian population (43%). DNA mutations and environmental and genetic factors are linked with skin cancer prognosis; however, long-term exposure to ultraviolet (UV) radiation remains one of the leading factors worldwide. Sun exposure is a major environmental risk factor for skin cancers but is also an essential source of vitamin D. On the other hand, studies exploring the relationship between skin cancer risk and vitamin D show mixed, somewhat conflicting results. This study investigates the role of vitamin D and skin carcinogenesis to clarify the associations. Moreover, in addition to suppressing cancer stem cells, it has been observed that vitamin D also regulates tumour initiation and metastasis. In conclusion, the incorporation of well-designed studies on the metabolism of vitamin D from a genotypic and phenotypic perspective is required to understand the intricate mechanisms linking the role of vitamin D in skin carcinogenesis. These new findings will open up new pathways in targeting the disease and lead to novel opportunities for its treatment and cure. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to investigate the effect of vitamin D supplementation therapy on disease activity and fatigue in rheumatoid arthritis (RA) patients. Material and methods: A prospective randomized clinical trial was conducted at rheumatology clinics in Tripoli Central Hospital, Libya. The eligible patients received disease-modifying antirheumatic drugs (DMARDs) and were divided into two groups: group A received 50,000 IU of vitamin D once a week; while group B received conventional DMARDs without vitamin D supplementation. The groups were monitored for 12 weeks. Results: The study included 68 RA patients, with the majority being female (75%). There were no significant differences in parameters such as age, sex, duration of illness, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), calcium, and vitamin D levels, as well as DAS28 (Disease Activity Score with 28-joint count) and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) levels between these two groups at baseline. After 12 weeks, group A showed a significant improvement in mean vitamin D levels and FACIT-F scores compared to group B. The increase in vitamin D levels in group A (24.21 ±4.81 nmol/l) was higher than that in group B (5.76 ±3.36 nmol/l). Furthermore, the FACIT-F score in group A was in the normal range (mean: 39.36 ±6.15), whereas group B still exhibited "abnormal" FACIT-F < 27.75 ±4.41. Correlation analysis indicated a positive correlation between FACIT-F and vitamin D levels, suggesting that higher vitamin D levels were associated with improved fatigue. Additionally, a weak inverse correlation was observed between DAS28 and vitamin D levels though the difference was not statistically significant (p > 0.05). Finally, the correlation between DAS28 and FACIT-F was positive (R = 0.557, p = 0.000). Conclusions: The results of the recent study indicated that vitamin D3 (50,000 IU of cholecalciferol) supplementation had a positive impact in RA patients compared to conventional DMARDs drugs, as was clear from the significant FACIT-F. [ABSTRACT FROM AUTHOR]

The efficacy of administering high doses of vitamin D to patients diagnosed with COVID‐19 remains uncertain. We conducted a comprehensive search across multiple databases (PubMed, EMBASE, Cochrane Library, and ISI Web of Science) from inception until August 2022, with no limitations on language, to locate randomized controlled trials (RCTs) that investigated the impact of high‐dose vitamin D supplementation (defined as a single dose of ≥100,000 IU or daily dose of ≥10,000 IU reaching a total dose of ≥100,000 IU) on COVID‐19 patients. Risk ratios (RR) with 95% confidence intervals (CI) and weighted mean differences (WMD) with 95% CI were calculated. Our meta‐analysis included 5 RCTs with a total of 834 patients. High‐dose vitamin D supplementation did not show any significant benefits for mortality (I2 = 0.0%, p =.670; RR 1.092, 95% CI 0.685–1.742, p =.711) or intensive care unit (ICU) admission (I2 = 0.0%, p =.519; RR 0.707, 95% CI 0.454–1.102, p =.126) in COVID‐19 patients compared to the control group. However, it was found to be safe and well‐tolerated (I2 = 0.0%, p =.887; RR 1.218, 95% CI 0.930–1.594, p =.151). Subgroup analysis also showed no benefits in overall mortality, including for patients with vitamin D deficiency (I2 = 0.0%, p =.452; RR 2.441, 95% CI 0.448–13.312, p =.303) or compared to the placebo (I2 = 0.0%, p =.673; RR 1.666, 95% CI 0.711–3.902, p =.240). Our research indicates that there is no evidence to support the efficacy of high‐dose vitamin D supplementation in improving clinical outcomes among individuals with COVID‐19, in line with previous studies focused on contexts including rickets. Considering the limitations of the study, additional research may be required. [ABSTRACT FROM AUTHOR]

Wound healing is a highly coordinated biological event as a response to injured skin. It commonly takes 14 days for a wound to be completely healed. However, the duration of wound healing may vary between individuals due to certain factors. One major factor that delays the wound-healing process is Diabetes Mellitus. Delayed wound healing with poor prognosis commonly occurs in diabetic patients. Chronic hyperglycemia may affect macrophage polarisation, which is essential in the wound healing mechanism. The macrophage polarisation enables the pro-inflammatory M1 phenotype to switch to the anti-inflammatory M2 phenotype. Thus, pro-inflammatory M1 phenotype prevails persistently in diabetic wounds, while the anti-inflammatory M2 phenotype remains deficient. It results in significantly elevated levels of pro-inflammatory cytokines triggered by the M1 phenotype. Prolonged wound healing times increase the risk of infection, which can lead to more severe complications. Vitamin D is widely recognized for its essential role in regulating calcium levels and supporting bone health, as well as its positive effects on the immune system. This vitamin has the potential to skew macrophages towards the M2 phenotype and promote a regenerative and anti-inflammatory environment. [ABSTRACT FROM AUTHOR]

Background: Arthritis is a term often used to mean any disorder that affects joints. Symptoms generally include joint pain and stiffness. Other symptoms may include redness, warmth, swelling, and decreased range of motion of the affected joints. In some types of arthritis, other organs are also affected. Aim: This study aimed to identify the impact of vitamin D therapy on serum level of vitamin D-binding protein and procalcitonin in Patients with arthritis. Methods: This cross-sectional study, was conducted in Kirkuk city between January 1st and March 1st, 2024. A total of 180 subjects were included, categorized into three groups: arthritis patients not receiving vitamin D (Group 1), arthritis patients receiving vitamin D for at least 2 months (Group 2), and a control group comprising 40 healthy subjects. Blood samples were collected from participants, processed, and stored for subsequent analysis. Various biomarkers, including vitamin D-binding protein and procalcitonin, were determined using ELISA kits. Results: The study revealed a higher prevalence of females among arthritis patients (54.29%), with most affected individuals aged above 60 years. Urban residency was predominant among arthritis patients (75.71%). The majority of RA patients had been affected for 6-10 years (40%). Comparative analysis demonstrated significantly higher procalcitonin levels in RA patients without vitamin D supplementation (112.4±24.3 ng/ml) compared to those with supplementation (48.33±10.73 ng/ml) and healthy controls (9.68±5.49 ng/ml). Furthermore, vitamin D binding protein levels were significantly lower in arthritis patients without supplementation (1.26±0.12 ng/ml) compared to those with supplementation (0.75±0.15 ng/ml) and healthy controls (0.23±0.14 ng/ml). Conclusion: These findings underscore the potential role of vitamin D supplementation in modulating inflammatory markers and enhancing vitamin D binding protein levels in arthritis patients, suggesting its therapeutic implications in disease management. [ABSTRACT FROM AUTHOR]

Background: Arthritis is an inflammatory condition affecting the diarthrodial joints. A joint's bone, cartilage, and structural design all preserve its integrity, and arthritis alters that integrity, resulting in joint activity loss and discomfort. The primary symptom of arthritis is joint pain, although other symptoms include stiffness, inflammation, and impaired joint motor function. Methods: The cross-sectional study comprised 90 subjects: 70 arthritis sufferers and 20 controls, ages 25-60, both sexes. From September 2023 to March 2024, patients were referred to Kirkuk city in Azadi hospital and Kirkuk general hospital. The research participants were placed into three groups: Group 1 for arthritic patients without Vit D (35). Patients with arthritis who received vitamin D for at least two months (G2), n (35), were the second group. The third group comprised healthy individuals without arthritis n (20). Result: Significant (P<0.05) increase in ETA protein levels in G1 and G2 compared to G3. G1 had ETA protein levels of 28.05±5.34 ng/L, G2 had 24.10±3.67 ng/L, and G3 had 8.92±2.80 ng/L. Sclerostin levels peaked in G1 (0.4273±0.3023 pg/mL) and declined in G2 (P<0.05) compared to G3. Calcitonin levels were higher in G1 (34.72±4.72 pg/mL) and G2 (27.06±5.85 pg/mL) than G3 (14.71±3.71 pg/mL) at (P<0.05). Conclusion: The study found a rise in ETA protein and calcitonin levels in arthritic patients before and after therapy with vitamin D, which was not influenced by vitamin supplementation. Sclerostin levels increase in arthritic patients and decrease following therapy with vitamin D. [ABSTRACT FROM AUTHOR]

Objective: Vitamin D is a potent immune modulator and is associated with autoimmune diseases, including type 1 diabetes (T1D). The vitamin D levels and its receptor gene polymorphisms together in T1D are not yet investigated in the South Indian population. The present study focused on exploring the significance of vitamin D levels and vitamin D receptor (VDR) gene polymorphisms with the risk of developing T1D in the South Indian population. Methods: Patients with T1D and unaffected first-degree relatives (FDRs) were included in this study. Genotyping of VDR polymorphisms at four different loci (FokI-F/f, BsmI-B/b, TaqI-T/t, and ApaI-A/a) was assessed through the amplification refractive mutation systempolymerase chain reaction method. Serum vitamin D levels were measured in 98 T1D patients and 75 age- and sex-matched siblings. Results: A total of 120 patients with T1D and 214 FDRs were included. Vitamin D deficiency (VDD) was observed in a higher proportion of T1D patients than in controls (52% vs. 32%; p<0.03). The frequency of the FokI-FF genotype was significantly higher [odds ratio (OR)=1.66; p<0.03] in T1D patients conferring a susceptible association with the disease. Nevertheless, the increased frequency of heterozygous Ff genotype (OR=0.57; p<0.02) among controls may confer a protective association with T1D. Furthermore, the transmission disequilibrium test revealed over-transmission of ApaI-A (T: U=15/5; p<0.006) and BsmI-B alleles (T: U=17/5; p<0.01) and under-transmission of BsmI-b/ApaI-a/TaqI-T haplotype (T: U=5.4/14.4; p=0.04) from parents to T1D patients. Conclusion: The present study concludes that VDD is the major contributing risk factor to T1D development in the South Indian population. Furthermore, the FokI-FF genotype, BsmI-B, and ApaI-A alleles were positively associated with T1D. In contrast, the FokI-Ff genotype and BsmI-b/ApaI-a/TaqI-T haplotype were negatively associated with T1D. [ABSTRACT FROM AUTHOR]

Background and Objectives: To assess the vitamin D nutritional status (VDN) of pregnant women in early pregnancy and investigate the effects of periconceptional supplementation with multiple micronutrients (MMs) on this status. Methods and Study Design: Data were taken from the Pregnancy Health Care System and Hospital Information System in 2018 in Beijing. Vitamin D nutritional status in early pregnancy was evaluated among 4,978 pregnant women, and 4,540 women who took folic acid only (FA) or multiple micronutrients supplements (MM) during the periconceptional period, were included to estimate the associations between periconceptional supplementation with MM and prevalence of vitamin D deficiency or insufficiency with logistic regression model. Results: The mean early-pregnancy vitamin D concentration was 18.6 (±7.5) ng/mL, and the rates of deficiency and insufficiency were 31.6% and 60.5%, respectively. Compared to the FA group, the adjusted odds ratio (aOR, 95%confidence interval, CI) for insufficiency or deficiency of the MM group were 0.25(0.18–0.34), and the aOR (95%CI) for deficiency of the MM group were 0.17 (0.12–0.23). Women who took MMs for a longer period of time, at higher frequencies, and with higher compliance scores had lower rates of deficiency and insufficiency. In winter, spring, and autumn, taking MMs could reduce deficiency by about 70%; in summer, there was little effect. Conclusions: Among women in Beijing, serum concentrations of vitamin D in early pregnancy are relatively low, and the rates of deficiency and insufficiency are high. Taking MMs during the periconceptional period could improve this situation. [ABSTRACT FROM AUTHOR]

Background and Objectives: Recent controversy over the bone benefits of calcium and vitamin D supplementation, and the potential detrimental effects of excess calcium supplementation, has confused clinicians. To systematically evaluate the effectiveness and safety of vitamin D combined with calcium in preventing and treating osteoporotic symptoms in the elderly. Methods and Study Design: Databases were searched to collect randomized controlled trials (RCTs) on vitamin D combined with calcium in the prevention and treatment of osteoporotic fractures in the elderly. After screening the literature, extracting data, and assessing the risk of bias in the included studies, the Meta-analysis was performed. Results: 19 RCTs were included, including 69,234 patients. Meta-analysis results showed that the mortality rate of the vitamin D combined with calcium group was not statistically significant compared with the control group; the calcium combined with vitamin D significantly reduced the incidence of fractures compared with the control group, Density and serum 25-hydroxyl concentration, adverse reactions of calcium combined with vitamin D were higher than those in the control group. Conclusions: The combination of vitamin D and calcium has no difference in mortality rate, and it can prevent fractures in the elderly, and enhance bone density and serum 25-hydroxyvitamin D concentration, but still need to pay attention to adverse reactions in the gastrointestinal tract. [ABSTRACT FROM AUTHOR]

Background: The impact of non‐pharmacological interventions (NPIs) on asthma prevention and management is insufficiently examined. We aim to comprehensively evaluate and synthesize existing evidence regarding the effectiveness of various NPIs throughout the life course. Methods: We conducted a systematic search and screening of reviews that examined the effectiveness of various NPIs on asthma prevention and control in the Cochrane Library, PubMed, Embase, and Ovid databases. Data extraction was performed by considering the type of NPIs and the life course stages of the target population. Recommendations were provided by considering the quality of review assessed using the AMSTAR2 tool and the consistency of findings across reviews. Results: We identified 145 reviews and mapped the evidence on the impact of 25 subtypes of NPIs on asthma prevention and control based on five stages of life course. Reviews indicated a shift of focus and various impacts of major NPIs on asthma prevention and control across life courses, while a few types of NPIs, such as physical exercise, appeared to be beneficial in children, adolescents and adults. Consistent and high‐level evidence was observed only for psychological intervention on asthma control and quality of life among adults and older adults. Potential benefit with high‐level evidence was reported on certain NPIs, such as vitamin D in reducing risk of developing asthma in offsprings in the prenatal stage, digital health interventions in improving asthma control from childhood to older adulthood, and breathing exercise in improving quality of life, asthma‐related symptoms and lung function in adulthood and older adulthood. Conclusion: This study emphasizes the significance of delivering NPIs to improve asthma prevention and management and highlights the heterogeneity regarding the impact of NPIs across life courses. High‐quality research is urgently needed to further strengthen the evidence base of NPIs and tailored interventions should be considered in guideline development. [ABSTRACT FROM AUTHOR]

Background: Vitamin D is a fat-soluble vitamin that prevents cardiovascular diseases and diabetes mellitus (DM). The present research aimed to study the impact of 25-hydroxyvitamin D (25(OH)D) level on the health status of patients with type 2 DM (T2DM) hospitalized in the "Pius Brînzeu" Emergency Clinical County University Hospital in Timisoara, Romania. Methods: The study retrospectively included 160 patients with T2DM who were clinically and biologically evaluated during hospitalization. Results: 13.1% of patients had optimal, 23.1% insufficient, and 63.8% deficient 25(OH)D values. Patients with 25(OH)D deficiency presented poorer glycemic control and were older, with higher weight, but had altered renal function, anemia, and lower iron values. Also, patients with associated neoplasia, diabetic neuropathy, cardiovascular disease (CVD), dementia, and grade 3 arterial hypertension (HTN) had lower values of 25(OH)D. An age > 55 years (sensitivity 69.9, specificity 82.5, AUROC 0.786, p < 0.001) and an HbA1c > 7.7% (sensitivity 89.3, specificity 92.9, AUROC 0.938, p < 0.001) predict 25(OH)D deficiency in T2DM patients. Conclusions: Vitamin D influences almost every system and organ in the body, so it should be a routine test for all patients with DM to correct the deficiency and prevent other diseases and complications. [ABSTRACT FROM AUTHOR]

Background: Rapidly destructive osteoarthritis (RDO) of the hip joint is characterised by the rapid destruction of the femoral head with or without acetabular involvement. There has been increasing interest in this disease over the past years; however, the entity is still poorly understood, and its pathophysiology remains unknown. Yet, there is ample evidence today that increased bone metabolism might play a role in the onset and progression of the disease. Vitamin D is of utmost importance to maintain a balanced bone metabolism. However, whether vitamin D deficiency is involved in disease development remains to be elucidated. Further, the vitamin D status of patients with RDO has not yet been analysed. For this reason, the objective of this study was to assess the vitamin D status of patients with RDO. Moreover, the aim was to clarify whether there is a difference in the vitamin D status of patients with RDO compared with patients with primary osteoarthritis (OA). Methods: In this single-centre analysis, the 25(OH)D, PTH, and calcium levels of 29 patients who presented with RDO between 2020 and 2022 were assessed. Results: Altogether, 97% of patients (28/29) were vitamin D deficient, a further 3% (1/29) were vitamin D insufficient, and not a single patient presented with a sufficient vitamin D status. Notably, the vitamin D levels of RDO patients (mean = 11.04 ng/mL) were significantly lower than the vitamin D levels of patients with OA (mean = 22.16 ng/mL, p = 0.001). Conclusion: In conclusion, we found a widespread and high rate of vitamin D deficiency in patients with RDO. Hence, we believe that 25(OH)D status should routinely be analysed in these patients. [ABSTRACT FROM AUTHOR]

Purpose: To investigate whether serum hormone (testosterone, prolactin, gonadotropins, and thyroid hormones) and vitamin (vitamin B12, folic acid, and vitamin D) levels are associated with premature ejaculation (PE). Materials and Methods: This prospective case-control study included 126 patients with PE (lifelong PE [LPE] in 94 and acquired PE [APE] in 32) who presented to the urology outpatient clinic between April 2016 and January 2023 and 92 healthy men as a control group. The diagnosis of PE was based on the criteria defined by the International Society for Sexual Medicine. Serum total testosterone (TT), free and bioavailable testosterone, follicle-stimulating hormone, luteinizing hormone, prolactin, thyroid-stimulating hormone, free triiodothyronine, thyroxine (fT4), vitamin B12, folic acid, and vitamin D levels were measured. Results: Serum TT, fT4, and vitamin D levels were significantly higher in patients with PE than in the control group (p=0.022, p=0.002, and p=0.044, respectively). However, the serum vitamin B12 level was significantly lower in the PE group (p=0.021). In the multivariate logistic regression analysis, only vitamin B12 was found to be an independent risk factor for PE, with an estimated odds ratio of 0.997 (95% confidence interval 0.994-0.999, p=0.036). Conclusions: This study demonstrated that lower vitamin B12 levels are associated with the presence of PE. Therefore, we believe that it would be beneficial to consider vitamin B12 levels in the evaluation of patients with PE. [ABSTRACT FROM AUTHOR]

To investigate the effect of vitamin D deficiency on metabolic diseases induced by high-fat diet in young male rats and its possible mechanism. Twenty four 4 w old male mice were randomly divided into three groups; control group (group A), model group (group B) and experimental group (group C). The mice in the group A were given normal diet, the mice in the group B were given high-fat diet, and the mice in the group C were given high-fat diet plus vitamin D deficiency. The changes of body length, body weight and liver mass of mice in each group were observed; fasting blood samples were collected to measure the changes of blood glucose and blood lipids; hepatic steatosis and lipid droplet content were observed by hematoxylin and eosin staining; serum interleukin-1 beta and interleukin-8 levels were compared by enzyme-linked immunosorbent assay; nucleotide oligomerization domain-like receptor protein 3, ASC, pro-caspase-1, interleukin-1 beta and gasdermin D protein levels in three groups were detected by Western blot. Compared with the group A, the body weight, liver weight, blood glucose and blood lipid increased in the group B, while these in the group C decreased compared with the group B. The liver tissue of the group B and the group C showed steatosis and the content of lipid droplets increased under microscope. Vitamin D deficiency aggravates metabolic diseases in young male rats induced by high-fat diet, which is mainly related to inflammatory response and activation of cell pyrogenesis pathway. Through the supplement of vitamin D deficiency, it can effectively reduce the occurrence of metabolic diseases such as weight, blood glucose, blood lipids and liver steatosis caused by highfat diet. [ABSTRACT FROM AUTHOR]

The involvement of central and peripheral inflammation in the pathogenesis and prognosis of major depressive disorder (MDD) has been demonstrated. The increase of pro-inflammatory cytokines (interleukin (IL)-1β, IL-6, IL-18, and TNF-α) in individuals with depression may elicit neuroinflammatory processes and peripheral inflammation, mechanisms that, in turn, can contribute to gut microbiota dysbiosis. Together, neuroinflammation and gut dysbiosis induce alterations in tryptophan metabolism, culminating in decreased serotonin synthesis, impairments in neuroplasticity-related mechanisms, and glutamate-mediated excitotoxicity. This review aims to highlight the inflammatory mechanisms (neuroinflammation, peripheral inflammation, and gut dysbiosis) involved in the pathophysiology of MDD and to explore novel anti-inflammatory therapeutic approaches for this psychiatric disturbance. Several lines of evidence have indicated that in addition to antidepressants, physical exercise, probiotics, and nutraceuticals (agmatine, ascorbic acid, and vitamin D) possess anti-inflammatory effects that may contribute to their antidepressant properties. Further studies are necessary to explore the therapeutic benefits of these alternative therapies for MDD. [ABSTRACT FROM AUTHOR]

Background: Vitamin D, a key nutrient in the body, has been linked to a decrease in prostate cancer (PCa) morbidity and mortality rates. The study concluded that any compensation mechanism may no longer be adequate for patients with PCa, and further research is needed to understand the mechanisms underlying the relationship between serum Vitamin D and parathyroid hormone (PTH) homeostasis. The findings will help determine cancer prevalence and trends in India and support public health initiatives to control cancer. Aims and Objectives: The aim is to assess the mean values of Vitamin D and PTH in patients with PCa and also to compare these levels with that of healthy controls (non-PCa). Materials and Methods: One hundred participants in the outpatient department of the Department of Biochemistry were assigned as control subjects, and another 100 participants were participants with PCa. 5 mL of fasting venous blood were drawn into red top vials using a disposable syringe and needle in an aseptic manner. PTH and serum Vitamin D were estimated. Results: When comparing PCa patients to healthy controls, the observed Vitamin D level was significantly lower in the former group. Furthermore, a notable distinction in Vitamin D levels was noted between the two groups. Furthermore, we found that PCa patients had higher PTH values than healthy controls. When we compared the PTH values of the two groups, we found a substantial difference. Conclusion: The authors conclude from the study that with alterations in the study parameters in patients with PCa, any compensation mechanism may become insufficient. [ABSTRACT FROM AUTHOR]

Background: Vitamin D deficiency is widely prevalent among the elderly, posing significant health risks. This study aims to determine the global prevalence of vitamin D deficiency in the elderly. Methods: A systematic review and meta-analysis was conducted, examining databases including Scientific Information Database (SID), Medline (PubMed), ScienceDirect, Scopus, Embase, and Google Scholar until January 2023. The publication bias of the studies was assessed using the I2 test of heterogeneity and the Egger test. Results: The prevalence of vitamin D deficiency, defined as levels below 20 ng or 50 nmol was found to be 59.7% (95% CI 45.9–72.1). Furthermore, a review of six studies involving 6748 elderly individuals showed a prevalence of 27.5% (95% CI 21.8–34.1) for deficiency defined between 20 and 30 ng or 50–75 nmol. Additionally, a meta-analysis of seven studies with a sample size of 6918 elderly individuals reported a prevalence of 16% (95% CI 10.2–24.1) for deficiency defined above 30 nmol or 75 nmol. Conclusion: The results of the present study reveal that the prevalence of vitamin D deficiency among the elderly is high and requires the attention of health policymakers at the World Health Organization to prioritize extensive information dissemination and screening to mitigate the adverse effects on their quality of life. [ABSTRACT FROM AUTHOR]

Background: The incidence of type 1 diabetes (T1D) is showing a rising trend all over the world, and these patients are living longer than before. With increasing longevity, they are at increased risk of chronic complications including fractures. However, the bone mineral density (BMD) data in T1D patients are conflicting and variable across the studies. Here, we aimed to study the BMD in adult patients with T1D and delineate its predictors. Material and methods: We recruited 40 T1D patients and equal number of age- and sex-matched control subjects. Clinical, biochemical, hormonal, and densitometric assessments were performed for each of the participants and compared between the two groups. Results: The median age of T1D and control subjects was 23.5 (21–27.75) years and 24 (22–26) years, respectively. The median duration of diabetes in T1D patients was 12.5 (9–15.75) years with a mean HbA1C of 8.7 ± 1.9%. The serum corrected calcium, phosphorous, alkaline phosphatase, creatinine, and plasma 25-hydroxyvitamin D and iPTH levels were comparable between the groups. In T1D subjects, the mean lumbar spine and left hip BMD were 0.876 ± 0.154 gm/cm2 and 0.780 ± 0.112 gm/cm2, respectively, which corresponded to mean Z-scores of -1.5 ± 1.4 and -1.4 ± 0.9, respectively, which were significantly lower compared to control group. Multiple linear regression analyses showed that BMI and serum albumin were significant determinant of lumbar spine and hip BMD, respectively, in patients with T1D. Conclusion: Patients of T1D have apparently reduced BMD, which is being influenced by BMI and serum albumin level. [ABSTRACT FROM AUTHOR]

Regardless of the unprecedented progress in malignant melanoma treatment strategies and clinical outcomes of patients during the last twelve years, this skin cancer remains the most lethal one. We have previously documented that vitamin D and its low-calcaemic analogues enhance the anticancer activity of drugs including a classic chemotherapeutic—dacarbazine—and an antiangiogenic VEGFRs inhibitor—cediranib. In this study, we explored the response of A375 and RPMI7951 melanoma lines to CPL304110 (CPL110), a novel selective inhibitor of fibroblast growth factor receptors (FGFRs), and compared its efficacy with that of AZD4547, the first-generation FGFRs selective inhibitor. We also tested whether 1,25(OH)2D3, the active form of vitamin D, modulates the response of the cells to these drugs. CPL304110 efficiently decreased the viability of melanoma cells in both A375 and RPMI7951 cell lines, with the IC50 value below 1 µM. However, the metastatic RPMI7951 melanoma cells were less sensitive to the tested drug than A375 cells, isolated from primary tumour site. Both tested FGFR inhibitors triggered G0/G1 cell cycle arrest in A375 melanoma cells and increased apoptotic/necrotic SubG1 fraction in RPMI7951 melanoma cells. 1,25(OH)2D3 modulated the efficacy of CPL304110, by decreasing the IC50 value by more than 4-fold in A375 cell line, but not in RPMI7951 cells. Further analysis revealed that both inhibitors impact vitamin D signalling to some extent, and this effect is cell line-specific. On the other hand, 1,25(OH)2D3, have an impact on the expression of FGFR receptors and phosphorylation (FGFR-Tyr653/654). Interestingly, 1,25(OH)2D3 and CPL304110 co-treatment resulted in activation of the ERK1/2 pathway in A375 cells. Our results strongly suggested possible crosstalk between vitamin D-activated pathways and activity of FGFR inhibitors, which should be considered in further clinical studies. [ABSTRACT FROM AUTHOR]

Primary antiphospholipid syndrome (PAPS) is a systemic autoimmune disorder, characterised by consistently high levels of antiphospholipid antibodies, thrombosis, and/or pregnancy morbidity. Due to various suspected causes, deficient or insufficient levels of vitamin D in the serum have been reported in patients with PAPS; however, the reports have been sporadic and inconclusive. This systematic review and meta-analysis aimed to comprehensively evaluate the serum vitamin D levels in patients with PAPS compared to controls. A protocol was registered in PROSPERO (Registration No. CRD42019132128) and a systematic literature search was conducted through Google Scholar, PubMed, Web of Science, Scopus, and ScienceDirect databases without restricting language and year. Pooled prevalence, mean difference (MD), and odds ratio (OR) along with 95% confidence intervals (CI) were determined by using a random effects model. Study quality was assessed by the Joana Brigg's Institute (JBI) protocol and publication bias was evaluated by a trim and fill funnel plot, Begg's, and Egger's tests. The pooled prevalence of vitamin D deficiency and insufficiency was found to be 32.2% [95% CI: 16.3–48.2] and 61.5% [95% CI: 40.2–82.8], respectively. Serum levels of vitamin D were considerably lower in the PAPS patients compared to controls (MD: −5.75, 95% CI: −9.73 to −1.77; p = 0.005). Multiple sensitivity analyses showed that the results remained statistically significant, demonstrating the robustness of this meta-analysis. No significant publication bias was detected in determining the MD of serum vitamin D levels in PAPS and controls. In conclusion, PAPS patients had greater rates of vitamin D deficiency or insufficiency, higher frequency of thrombosis, and lower serum vitamin D levels than healthy individuals. [ABSTRACT FROM AUTHOR]