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Author(s): Vahid Ahmadi [1]; Nazli Karimi (corresponding author) [2]; Arsoy S. Evans [1]; Ayşen Karaduman [1] Introduction NF1, an autosomal dominantly inherited multisystem disorder, is characterized by distinctive skin lesions, [...], Aim: This article aims to examine the demographic and clinical traits of neurofibromatosis type 1 (NF1) patients, particularly focusing on the potential links between vitamin D levels, BMI, and dermatological features. Methods: A retrospective review of medical records involving 128 patients diagnosed with neurofibromatosis type 1 (NF1) over a 3-year-period was conducted. The analysis emphasized investigating the demographic and clinical characteristics of the patients while evaluating key parameters. Result: Nevus anemicus was present in 32.8 of NF1 patients, and a significant association was found between nevus anemicus and low vitamin D levels (P = 0.001). We also observed a notable correlation between low vitamin D levels and an increased likelihood of neurofibromas (P < 0.001). Additionally, there appears to be an inverse relationship between serum vitamin D levels and the number of neurofibromas. Conclusion: Our study suggests a correlation between lower vitamin D levels and key dermatological characteristics in neurofibromatosis type 1 (NF1) individuals. Specifically, we observed associations with nevus anemicus prevalence and increased neurofibromas. This observation enriches NF1's understanding, offering practical implications for patient management by emphasizing the importance of monitoring and addressing vitamin D levels. Keywords: Demographic features, neurofibroma, neurofibromatosis type 1, nevus anemicus, vitamin D, Neurofibromatosis Type 1, Clinical, Nevus Anemiscus, Neurofibromas, Vitamin D

1 | INTRODUCTION Men who have sex with men (MSM) make up the largest population receiving new HIV diagnoses in the United States (87%) [1], a trend also seen in [...], Introduction: Tenofovir disoproxil fumarate with emtricitabine (TDF/FTC) is used for HIV pre-exposure prophylaxis (PrEP). TDF may affect bone mineral density (BMD), particularly in youth who are at a stage of peak bone mass accrual. The objective of this study was to evaluate the effect of vitamin D and calcium supplementation on BMD among Thai youth receiving daily oral PrEP. Methods: This open-label randomized trial was conducted in male youth aged between 15 and 24 years. Participants were randomized to Arm A who received once-daily TDF/FTC plus vitamin D3 and calcium supplementation with meals twice daily (400 units of vitamin D3 and 1200 mg of elemental calcium/day) or Arm B who received once-daily TDF/FTC only. PrEP users were defined as taking at least two tablets/week (tenofovir-diphosphate level of >350 fmol/punch). Adherence to vitamin D/calcium supplementation was defined as self-reported adherence of >50%. Lumbar spine (L2-L4) BMD (LSBMD) was evaluated by dual-energy X-ray absorptiometry scan zero and six months after PrEP initiation. Results: From March 2019 to March 2020, 100 youth were enrolled. Baseline characteristics between the two arms were similar. Median (IQR) age was 18 (17 to 20) years. At entry median (IQR) LSBMD z-score was -0.8 (-1.5 to -0.3), 17% had low LSBMD (Z-score < -2). The median amount of calcium intake from nutritional three-day recall was 167 (IQR 94 to 272) mg/day 39% of participants had vitamin D deficiency defined as 25(OH)D levels 3% increase in LSBMD at month 6 compared to baseline (67.6% vs. 42.9% respectively; p = 0.03). There were significantly higher increases in LSBMD among youth with vitamin D deficiency who were supplemented; arm A + 0.05 (0 to 0.05) compared to arm B + 0.03 (-0.1 to 0.03), p = 0.04. Conclusions: Increases in LSBMD over six months among youth using PrEP who received vitamin D/calcium supplementation was greater than those not supplemented. Long-term follow-up should be considered to explore long-term outcomes. Keywords: HIV pre-exposure prophylaxis; young men who have sex with men; young transgender women; bone mineral density; vitamin D; calcium

Author(s): Tingting Geng 1,2, Qi Lu 1, Zhenzhen Wan 1, Jingyu Guo 1, Liegang Liu 1, An Pan 2, Gang Liu 1,* Introduction Type 2 diabetes (T2D) is a serious [...], Background Several epidemiological studies have suggested that vitamin D status is associated with risk of dementia in general populations. However, due to the synergistic effect between diabetic pathology and neuroinflammation, and the prothrombotic profile in patients with diabetes, whether vitamin D is associated with risk of dementia among patients with diabetes is unclear. This study aimed to investigate the associations of circulating vitamin D levels with risks of all-cause dementia, Alzheimer disease (AD), and vascular dementia (VD) among adults with type 2 diabetes (T2D). Methods and findings This study included 13,486 individuals ([greater than or equal to]60 years) with T2D and free of dementia at recruitment (2006-2010) from the UK Biobank study. Serum 25-hydroxyvitamin D (25[OH]D) concentrations were measured using the chemiluminescent immunoassay method at recruitment. Serum 25(OH)D [greater than or equal to] 75 nmol/L was considered sufficient, according to the Endocrine Society Clinical Practice Guidelines. Incidence of all-cause dementia, AD, and VD cases was ascertained using electronic health records (EHRs). Each participant&apos;s person-years at risk were calculated from the date of recruitment to the date that dementia was reported, date of death, date of loss to follow-up, or 28 February 2018, whichever occurred first. Among the 13,486 individuals with T2D (mean age, 64.6 years; men, 64.3%), 38.3% had vitamin D [greater than or equal to] 50 nmol/L and only 9.1% had vitamin D [greater than or equal to] 75 nmol/L. During a mean follow-up of 8.5 years, we observed 283 cases of all-cause dementia, including 101 AD and 97 VD cases. Restricted cubic spline analysis demonstrated a nonlinear relationship between serum 25(OH)D and risk of all-cause dementia (P.sub.nonlinearity < 0.001) and VD (P.sub.nonlinearity = 0.007), and the nonlinear association reached borderline significance for AD (P.sub.nonlinearity = 0.06), with a threshold at around a serum 25(OH)D value of 50 nmol/L for all the outcomes. Higher serum levels of 25(OH)D were significantly associated with a lower risk of all-cause dementia, AD, and VD. The multivariate hazard ratios and 95% confidence intervals for participants who had serum 25(OH)D [greater than or equal to] 50 nmol/L, compared with those who were severely deficient (25[OH]D < 25 nmol/L), were 0.41 (0.29-0.60) for all-cause dementia (P.sub.trend < 0.001), 0.50 (0.27-0.92) for AD (P.sub.trend = 0.06), and 0.41 (0.22-0.77) for VD (P.sub.trend = 0.01). The main limitation of the current analysis was the potential underreporting of dementia cases, as the cases were identified via EHRs. Conclusions In this study, we observed that higher concentrations of serum 25(OH)D were significantly associated with a lower risk of all-cause dementia, AD, and VD among individuals with T2D. Our findings, if confirmed by replication, may have relevance for dementia prevention strategies that target improving or maintaining serum vitamin D concentrations among patients with T2D.

Author(s): C M R Gonçalves de Carvalho [sup.1] , S M L Ribeiro [sup.2] [sup.3] Author Affiliations: (1) Department of Nutrition, Federal University of Piauí, Health Sciences Center, Teresina, Piauí, [...], We conducted a mini-review of the literature, focusing on aging-related systemic inflammation and its association with vitamin D (VitD). As main findings, data indicate that inflammation in aging seems to have multiple origins, including immunosenescence, and from intestinal and adipose tissue, where VitD may modulate these three factors, through mechanisms not totally known. From the selected studies, three randomized clinical trials of VitD supplementation showed improvements in inflammatory status, whereas two studies did not. Ten epidemiological studies showed associations between VitD and inflammation, whereas two studies did not. One case study reinforced this association. As such, we can assume a reasonable association between VitD and inflammation in the elderly, and a promising role of supplementation in some situations. However, most studies did not take into account environmental and individual factors such as the season of the year, latitude, skin color or even the use of some medicines; in addition, the doses, time of intervention and the sample sizes differed between the studies. In conclusion, although more controlled VitD studies, both clinical and epidemiological, are necessary, it is important to remember the network of factors involved in systemic inflammation in the elderly; an understanding of the dietetic and non-dietetic factors is needed to offer a realistic approach.

Introduction In the early 1970s, 1,25-dihydroxyvitamin [D.sub.3] [1,25[(OH).sub.2][D.sub.3]] was identified as both the exclusive, metabolically active form of vitamin D and a key component of what proved to be an [...], The vitamin D receptor (VDR) is the single known regulatory mediator of hormonal 1,25-dihydroxyvitamin [D.sub.3] [1,25[(OH).sub.2][D.sub.3]] in higher vertebrates. It acts in the nucleus of vitamin D target cells to regulate the expression of genes whose products control diverse, cell type-specific biological functions that include mineral homeostasis. In this Review we describe progress that has been made in defining new cellular sites of action of this receptor, the mechanisms through which this mediator controls the expression of genes, the biology that ensues, and the translational impact of this receptor on human health and disease. We conclude with a brief discussion of what comes next in understanding vitamin D biology and the mechanisms that underlie its actions.

Author(s): N Sawada [sup.1] , M Inoue [sup.1] [sup.2] , M Iwasaki [sup.1] , T Yamaji [sup.1] , T Shimazu [sup.1] , S Sasazuki [sup.1] , S Tsugane [sup.1] , [...], Background/Objectives: Although vitamin D has been experimentally reported to inhibit tumorigenesis, cell growth and prostate cancer invasion, epidemiologic data regarding prostate cancer risk are inconsistent, and some studies have suggested positive but nonsignificant associations. Further, the impact of vitamin D on prostate cancer between Western and Japanese populations may differ due to different plasma vitamin D levels. Subjects/Methods: We performed a nested case-control study within the Japan Public Health Center-based Prospective (JPHC) Study in 14,203 men (40-69 years) who answered a self-administered questionnaire at baseline (1990-1994) and gave blood samples, and were followed until 2005. We identified 201 prostate cancers which are newly diagnosed during follow-up (mean 12.8 years). We selected two matched controls for each case from the cohort. We used a conditional logistic regression model to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for prostate cancer with respect to levels of 25-hydroxy vitamin D (25(OH)D) in plasma. Results: We did not observe statistically significant association between 25(OH)D level and total prostate cancer (multivariate OR=1.13 (95%CI=0.66-1.94, P.sub.trend=0.94) for the highest versus lowest tertile) However, 25(OH) levels were slightly positively associated with advanced cancer. The results remained substantially unchanged after stratification by intake of fish or calcium intake. Conclusions: 25(OH)D level showed no association with overall prostate cancer among Japanese men in this large cohort.

Vitamin D has long been known to be essential for calcium-phosphorus homeostasis and bone health. The recognition that vitamin D metabolites influence other physiologic processes has prompted the examination of [...], OBJECTIVES: Evidence suggests a beneficial effect of vitamin D on perinatal health; however, low vitamin D status is prevalent in pregnant women and neonates. The objective was to determine factors that are associated with vitamin D status of mothers in early pregnancy and neonates. METHODS: The study comprised 1,635 pregnant women from Quebec City and Halifax, Canada, 2002-2010. Vitamin D status was based on the concentration of 25-hydroxy-vitamin D [25(OH)D] determined with a chemiluminescence immunoassay in maternal sera collected at a median of 15 weeks&apos; gestation and in neonatal cord sera at delivery. A questionnaire with information on potential determinants was completed midpregnancy. RESULTS: A total of 44.8% of mothers and 24.4% of neonates had 25(OH)D concentrations CONCLUSION: This study suggests that vitamin D status of pregnant women and/or neonates might be improved through supplementation, adequate dairy intake, a move towards a healthy pre-pregnancy body weight, and participation in physical activity. Controlled studies are needed to determine the effectiveness of interventions aimed at these factors. KEY WORDS: Pregnancy; newborn; vitamin D; lifestyle; epidemiology; Canada OBJECTIFS : Les donnees semblent indiquer que la vitamine D a un effet benefique sur la sante perinatale, mais un faible statut en vitamine D prevaut chez les femmes enceintes et les nouveau-nes. Nous avons voulu determiner les facteurs associes au statut en vitamine D de meres en debut de grossesse et de nouveau-nes. METHODE : L&apos;etude a compris 1 635 femmes enceintes de Quebec et de Halifax, au Canada, de 2002 a 2010. Le statut en vitamine D etait fonde sur la concentration de 25-hydroxyvitamine D [25(OH)D], determinee grace a un immunoessai par chimiluminescence dans le serum maternel preleve a la duree mediane de 15 semaines de grossesse et dans le serum du cordon ombilical des nouveau-nes a l&apos;accouchement. Au milieu de leur grossesse, les femmes ont rempli un questionnaire donnant de l&apos;information sur les determinants potentiels. RESULTATS : En tout, 44,8 % des meres et 24,4 % des nouveau-nes avaient des concentrations de 25(OH)D CONCLUSION : Notre etude indique que le statut en vitamine D des femmes enceintes et/ou des nouveau-nes pourrait etre ameliore par la supplementation, par un apport suffisant en produits laitiers, par un effort pour atteindre un poids-sante avant la grossesse et par la participation a l&apos;activite physique. Il faudrait mener des etudes controlees pour determiner l&apos;efficacite des interventions ciblant ces facteurs. MOTS CLES : grossesse; nouveau-ne; vitamine D; style de vie; epidemiologie; Canada La traduction du resume se trouve a la fin de l&apos;article. Can J Public Health 2016;107(4-5):e410-e416 doi: 10.17269/CJPH.107.5629

INTRODUCTION Known for its classical role in calcium/bone homeostasis, vitamin D has been receiving renewed attention for its extraskeletal/ pleiotropic effects. Vitamin D acts as a transcription factor, through the [...], BACKGROUND/OBJECTIVES: To determine the interrelationships between body composition, glycemic control and vitamin D status in an ambulatory population with diabetes (DM) and chronic kidney disease (CKD). SUBJECTS/METHODS: Adult (18-80 years) patients (n = 60) with DM and stage 1-4 CKD were recruited from the Northern Alberta Renal Program. Outcome variables included body composition (absolute/regional fat (FM)/lean soft tissue/total mass, percent fat/ lean/fat-free (FFM) mass), glycemic control (glycated hemoglobin (HbA1c)), vitamin D intake (dietary/supplemental) and vitamin D status (25-hydroxyvitamin D (25(OH)D) and 1,25-dihydroxyvitamin D (1,25[(OH).sub.2]D)) measured by validated methodologies. Sarcopenia was determined as an appendicular skeletal mass/[height.sup.2] less than 7.26 kg/[m.sup.2] (males) and 5.45 kg/[m.sup.2] (females). RESULTS: Suboptimal HbA1c (>7%), 25(OH)D (< 50 nmol/l) and 1,25[(OH).sub.2]D (< 43 pmol/l) concentrations were present in 57, 8 and 11% of participants. Ten percent of subjects had sarcopenia. Gender/age/DM type, not CKD, significantly influenced regional/ whole body composition. Females, older participants and those with type 2 DM had higher %FM. No significant interrelationships between vitamin D status and glycemic control were observed (P>0.05). Serum 25(OH)D concentrations were inversely associated with arm lean soft tissue/FFM/total mass, weight, appendicular skeletal mass, lean soft tissue/[height.sup.2], FFM/[height.sup.2], appendicular skeletal mass/[height.sup.2] and body mass index (P < 0.05). Sarcopenia occurred more frequently in patients with 25(OH)D concentrations [greater than or equal to] 100 nmol/l. Regional/whole body %FM was inversely related to 1,25[(OH).sub.2]D, not 25(OH)D. CONCLUSIONS: Body composition, not glycemic control, is associated with vitamin D status in an ambulatory population of adults with DM and CKD. European Journal of Clinical Nutrition (2016) 70, 743-749; doi:10.1038/ejcn.2015.185; published online 4 November 2015

INTRODUCTION Lower serum 25-hydroxy vitamin D (25(OH)D) levels (hereafter referred to as 25D) are well known to be associated with obesity, but the direction of causality remains unclear as summarized [...], BACKGROUND/OBJECTIVES: The long-term chronology of the association between low serum concentrations of 25-hydroxy vitamin D (25(OH)D) and weight status is unclear. We examined whether lower 25(OH)D in middle-aged women drives upwards the weight, body mass index (BMI) and waist-hip ratio (WHR) over the next 32 years, and whether higher 25(OH)D might predict less decline in the mid- to late-life height trajectory. SUBJECTS/METHODS: The Population Study of Women in Gothenburg started in 1968-1969 (the baseline) in 38-60-year-old women residing in Gothenburg, Sweden. Anthropometric measures were taken at baseline and 4 re-examinations until 2000- 2003. Levels of 25(OH)D were analyzed in serum stored since baseline in 1227 (84%) women. Repeated measures analyses were used to model associations between 25(OH)D (dichotomized, cut point 51.45 nmol/l) at baseline and anthropometric trajectories, adjusting for fixed and time-dependent covariates. RESULTS: At baseline, mean BMI was 25.2 kg/[m.sup.2] in women with low 25(OH)D and 23.8 kg/[m.sup.2] in the remaining women (P < 0.001), but this difference did not increase over 32 years and longitudinal differences were explained by the baseline BMI. Similar results were observed for weight and WHR. In contrast, no association was seen for height at baseline or longitudinally. CONCLUSIONS: No relationship was observed between 25(OH)D height trajectory, but lower 25(OH)D was associated with higher BMI, weight and WHR differences that were maintained over three decades. This provides no evidence for the direction of causality, but for a life-long difference in adiposity-related measures according to the 25D level in middle-aged women. European Journal of Clinical Nutrition (2016) 70, 709-714; doi:10.1038/ejcn.2016.11; published online 24 February 2016

INTRODUCTION Vitamin D deficiency is related to various adverse health outcomes in early and later life. (1-4) An accumulating body of evidence suggests that vitamin D status during pregnancy may [...], BACKGROUND/OBJECTIVES: Maternal vitamin D deficiency during pregnancy may influence offspring kidney health. We aimed to examine the associations of 25-hydroxyvitamin D (25(OH)D) blood levels during fetal life with kidney outcomes at school age. SUBJECTS/METHODS: This study was embedded in a population-based prospective cohort study among 4212 mother-child pairs. We measured maternal second trimester (18-25 weeks) and fetal cord blood (at birth) 25(OH)D levels. At a median age of 6.0 years, we measured children's combined kidney volume, glomerular filtration rate (eGFR) from creatinine and cystatin C serum levels, and microalbuminuria from albumin and creatinine urine levels. RESULTS: Of all mothers, 21.9% had severely deficient levels (25(OH)D < 25.0 nmol/l), 25.7% had deficient levels (25.0-49.9 nmol/l), 25% had sufficient levels (50.0-74.9 nmol/l) and 27.4% had optimal levels (≥ 75.0 nmol/l). Maternal 25(OH)D levels were not consistently associated with childhood combined kidney volume. Higher maternal 25(OH)D levels were associated with lower childhood eGFR (difference -0.94 ml/min per 1.73 [m.sup.2] (95% confidence interval, -1.73;-0.15) per 1 standard deviation (s.d.) increase in 25(OH)D). Maternal 25(OH)D levels were not associated with microalbuminuria. Cord blood 25(OH)D levels were not associated with childhood kidney outcomes. The associations of maternal 25(OH)D levels with childhood eGFR were partly explained by childhood vitamin D status. CONCLUSIONS: Our findings suggest that maternal 25(OH)D levels during pregnancy may influence childhood kidney outcomes. These results should be considered hypothesis generating. Further studies are needed to replicate the observations, to examine the underlying mechanisms and to identify the long-term clinical consequences. European Journal of Clinical Nutrition (2016) 70, 629-634; doi: 10.1038/ejcn.2015.216; published online 23 December 2015

INTRODUCTION In countries located increasingly distant from the Earth's equator, the population concentration of 25-hydroxyvitamin D (25OHD) tends to follow changes in the ultraviolet B radiation from the sun. (1-6) [...], BACKGROUND/OBJECTIVES: Seasonal variation may reduce the validity of 25-hydroxyvltamln D (25OHD) as a blomarker of vitamin D status. Here we aimed to identify potential determinants of seasonal variation in 25OHD concentrations and to evaluate cosinor modelling as a method to adjust single 25OHD measurements for seasonal variation. SUBJECTS/METHODS: In Caucasian cardiovascular patients (1999-2004), we measured 25OHD by liquid chromatography tandem mass spectrometry in 4116 baseline and 528 follow-up samples. To baseline values, we fitted a cosinor model for monthly concentrations of 25OHD. Using the model, we estimated each patient's adjusted annual 25OHD value. Further, we studied how covariates affected the annual mean 25OHD concentration and seasonal variation of the study cohort. To evaluate the model, we predicted follow-up measurements with and without covariates and compared accuracy with carrying forward baseline values and linear regression adjusting for season, common approaches in research and clinical practice, respectively. RESULTS: The annual mean (59.6 nmol/l) was associated with participants' age, gender, smoking status, body mass, physical activity level, diabetes diagnosis, vitamin D supplement use and study site (adjusted models, P < 0.05). Seasonal 25OHD variation was 15.8 nmol/l, and older age (>62 years) was associated with less variation (adjusted model, P = 0.025). Prediction of follow-up measurements was more accurate with the cosinor model compared with the other approaches (P < 0.05). Adding covariates to cosinor models did not improve prediction (P>0.05). CONCLUSIONS: We find cosinor models suitable and flexible for analysing and adjusting for seasonal variation in 25OHD concentrations, which is influenced by age. European Journal of Clinical Nutrition (2016) 70, 517-522; doi: 10.1038/ejcn.2015.200; published online 25 November 2015

INTRODUCTION Vitamin D in the body is derived from dietary intake or supplementation and from endogenous production of vitamin D in the skin following sun exposure. (1) The primary physiological [...], BACKGROUND/OBJECTIVES: Previous studies have suggested that serum 25-hydroxyvitamin D (25(OH)D) is associated with hypertension. However, the effects of age and sex on the relation between serum 25(OH)D and hypertension has not been examined. The present study examined the relationship between serum 25(OH)D and hypertension by age and sex in the general Korean population, considering potential confounders for hypertension. SUBJECTS/METHODS: We conducted a population-based, cross-sectional study. Twenty thousand four hundred and forty adults aged 19 years or older, who participated in the 2009-2012 Korean National Health and Nutrition Examination Surveys, were selected for the present study. Hypertension was defined as a systolic blood pressure [greater than or equal to] 140mmHg, diastolic blood pressure [greater than or equal to] 90 mm Hg or current use of antihypertensive medication. RESULTS: We found that serum 25(OH)D levels are inversely associated with hypertension in young and middle-aged adults, but not in the elderly population. In young and middle-aged adults, the adjusted odds ratios (ORs) for hypertension tended to decrease according to the quartiles of serum 25(OH)D after adjustment for potential confounders, although it was only significant in women (OR = 0.73, 95% confidence interval (CI) = 0.58-0.91, P for trend =0.0349). There was no association between serum 25(OH)D concentration and hypertension in elderly subjects of either sex. CONCLUSIONS: A higher serum 25(OH)D level was strongly associated with a lower prevalence of hypertension in young and middle-aged Korean women, but not in elderly adults. European Journal of Clinical Nutrition (2016) 70, 326-332; doi: 10.1038/ejcn.2015.115; published online 15 July 2015