Explore the vast range of titles available.

To investigate the association between serum 25-hydroxyvitamin D levels and its effect on adverse clinical outcomes, and parameters of immune function and mortality due to a SARS-CoV-2 infection. The hospital data of 235 patients infected with COVID-19 were analyzed. Based on CDC criteria, among our study patients, 74% had severe COVID-19 infection and 32.8% were vitamin D sufficient. After adjusting for confounding factors, there was a significant association between vitamin D sufficiency and reduction in clinical severity, inpatient mortality serum levels of C-reactive protein (CRP) and an increase in lymphocyte percentage. Only 9.7% of patients older than 40 years who were vitamin D sufficient succumbed to the infection compared to 20% who had a circulating level of 25(OH)D< 30 ng/ml. The significant reduction in serum CRP, an inflammatory marker, along with increased lymphocytes percentage suggest that vitamin D sufficiency also may help modulate the immune response possibly by reducing risk for cytokine storm in response to this viral infection. Therefore, it is recommended that improving vitamin D status in the general population and in particular hospitalized patients has a potential benefit in reducing the severity of morbidities and mortality associated with acquiring COVID-19.

Background/Objectives: Hypermobile Ehlers–Danlos syndrome (hEDS) remains genetically unexplained despite decades of clinical investigation, with the molecular basis undefined for the vast majority of cases. This study employs integrated machine learning approaches with rigorous subject-level statistical methods to decode the genetic architecture underlying hEDS. Methods: We analyzed 35,923 rare genetic variants (gnomAD MAF < 0.2) across 116 subjects from 43 families (86 hEDS patients diagnosed per 2017 international criteria; 30 unaffected intrafamilial controls) using whole-exome sequencing. Machine learning analysis employed Random Forest feature selection, deep neural networks, and ensemble methods with subject-stratified cross-validation to prevent data leakage. Statistical association testing used subject-level Fisher’s exact tests with Bonferroni correction (α = 3.77 × 10−6 for 13,281 genes). Sensitivity analyses assessed robustness to family structure. Results: Subject-level analysis identified statistically significant enrichment in variants associated with three major biological systems: (1) collagen biosynthesis pathway variants (present in 63% of hEDS subjects vs. 17% of controls, Fisher’s p = 1.06 × 10−5, OR = 8.4), predominantly affecting COL5A1, COL18A1, COL17A1, and post-translational modification enzymes; (2) HLA/adaptive immune axis variants (74% of hEDS vs. 30% of controls, p = 2.23 × 10−5, OR = 6.8), involving HLA-B, HLA-A, HLA-C, and TAP transporters; (3) mitochondrial respiratory chain variants (34% of hEDS vs. 7% of controls, p = 2.29 × 10−3, OR = 7.1), with striking 4.2-fold enrichment in pediatric fracture cases (52% vs. 21%, p = 0.021, 95% CI: 1.2–14.6). These associations require independent validation and functional studies to determine their mechanistic relevance. Genome-wide analysis identified seven genes achieving Bonferroni significance (p < 3.77 × 10−6), all encoding structural/cytoskeletal proteins. Machine learning models with proper subject-stratified cross-validation achieved 80% accuracy (95% CI: 73–86%, sensitivity = 82%, specificity = 77%). Conclusions: Our findings suggest that hEDS may involve genetic variation across multiple biological systems beyond classical collagen pathways. These hypothesis-generating associations require validation in independent cohorts and functional studies before mechanistic or clinical conclusions can be drawn.

Intrauterine fractures are a rare clinical finding caused by abnormal early-life osteogenesis. In this case report, we reported a male infant with twenty-three intrauterine/fetal fractures resembling osteogenesis imperfecta and tested negative for COL1A1 and COL1A2 mutations. The infant’s mother had Ehlers–Danlos syndrome, hypermobility type. Whole-genome sequencing revealed that there were no pathologic mutations previously documented to be associated with intrauterine fracture. Genetic mutations reported to be associated with fragility fractures were identified. These include the pathogenic homozygous mutation in the CCDC134 gene. Other genetic variants that might be responsible for variable expressivity of the skeletal manifestation include the homozygous variants of the genes CCDC134, COL15A1 and ZFPM1, and the heterozygous variants of the genes MYH3, BCHE, AUTS2. This is the first reported case of in utero fractures, that was confirmed by X-ray after birth, in an infant who had no genetic evidence for osteogenesis imperfecta, had a homozygous pathogenic mutation of an osteogenesis gene and whose mother had Ehlers-Danlos syndrome hypermobility type. Therefore, we have identified a new genetic cause for in utero fractures. If after birth, this infant were found to have these fractures in various stages of healing with a negative genetic test for osteogenesis imperfecta he would have been misdiagnosed as due to nonaccidental trauma.

Background/Objectives: Hypermobile Ehlers–Danlos Syndrome (hEDS) is a complex connective tissue disorder with multi-systemic manifestations that significantly impact quality of life. This case report investigates the clinical course and molecular mechanisms of advanced hEDS through an in-depth case study and post-mortem findings. Methods: The clinical history of a 24-year-old patient with advanced hEDS was analyzed, focusing on progressive complications across multiple systems. Post-mortem examination and genetic analysis were performed to elucidate the underlying pathophysiology. Results: The patient’s clinical course was marked by gastrointestinal, neurological, and immune complications requiring numerous surgical interventions. Post-mortem findings revealed severe gastrointestinal dysmotility and Alzheimer’s Type II astrocytes. Genetic analysis identified variants in mtDNA genes ATP6, CYB, and ND, suggesting a potential role of impaired mitochondrial function in hEDS pathogenesis but requiring further validation through functional studies. Conclusions: This case report provides valuable insights into the potential role of mitochondrial dysfunction in advanced hEDS and highlights the need for further research in this area. Future studies should include comprehensive functional assays, longitudinal tissue sampling, family genetic analyses, and muscle biopsies to better understand the complex interplay between genetic factors, mitochondrial function, and clinical manifestations in hEDS. Establishing genetic bases and developing targeted therapies addressing both structural and metabolic aspects are crucial. The patient’s legacy offers invaluable information that could significantly contribute to enhancing diagnostic accuracy and developing personalized treatment strategies for this challenging disorder, potentially leading to better care for individuals living with hEDS.

Aim: A commercially available light emitting diode (LED) that transmitted narrow band ultraviolet B (UVB) radiation was evaluated for its efficacy and efficiency to produce vitamin D3 in human skin. Materials and Methods: Human skin samples were obtained from surgical procedures. The LED had peak emission wavelength of 295 nm. Skin samples were exposed to the UVB-LED for varying times and then were analyzed by high-pressure liquid chromatography (HPLC) to determine the vitamin D3 content. Results: There was a statistically significant time- and dose-dependent increase in the percent of 7-dehydrocholesterol that was converted to vitamin D3 in the skin type II samples; 1.3%±0.5, 2.3%±0.6 and 4.5%±1.67 after exposure to 0.75 (11.7 mJ/cm2), 1.5 (23.4 mJ/cm2) and 3 (46.8 mJ/cm2) minimal erythemal doses (MEDs), respectively. Conclusion: The UVB-LED was effective and efficient in generating vitamin D3 in human skin, in vitro. The amount of vitamin D3 production increased in a dose-dependent fashion with increased UVB energy. UVB-LEDs can be developed for devices that can efficiently produce vitamin D3 in human skin.

Cardiovascular disease (CVD) is the leading cause of mortality all over the globe. Inflammation is believed to play a pivotal role in the pathophysiology of CVD. While there are studies on the interrelationship of telomerase and vitamin D and their involvement in CVD, their independent contributions to long-term outcomes in patients with CVD are not well-defined. This study aimed to investigate the association of both telomerase and vitamin D concentrations with 10-year survival among candidates of coronary artery bypass grafting (CABG) surgery. The mean serum telomerase enzyme level was 24.92 ±21.4 nmol/L and the mean serum 25(OH)D was 27.27±10.3 ng/mL. 10-year mortality was reported in 64 (15.8%) patients. 25(OH)D was categorized into three groups (30) and the cut-point for telomerase was set at 25.0 nmol/L. In Cox regression analysis, higher levels of telomerase (>25 nmol/L) were significantly associated with longer survival (p = 0.041), whereas 25(OH)D concentrations were not associated with survival time. Further analysis showed that telomerase concentrations significantly predicted survival only in the presence of insufficient levels of 25(OH)D (20-30 ng/mL) (p = 0.037). Telomerase can be regarded as a potential predictor of long-term outcomes in patients who underwent CABG. However, the association of telomerase with the mortality may be modified by vitamin D concentrations.

Aims This study aimed to investigate the association between circulating levels of vitamin D binding protein (VDBP) and its genotypes and diabetic retinopathy risk. Methods This case–control study recruited 154 patients with type 2 diabetes mellitus; 62 with diabetic retinopathy (DR) and 92 without DR and diabetic nephropathy (DN). Circulating levels of 25-hydroxyvitamin D3 and VDBP levels were measured in the patients. The genotype and phenotype of VDBP were evaluated based on two common VDBP variations; rs7041 and rs4588. Results Serum levels of VDBP were significantly lower in patients with DR than in patients without DR and/or DN (Ln-VDBP (μg/ml): 6.14 ± 0.92 vs. 6.73 ± 1.45, p  = 0.001) even after adjustment for age, sex, body mass index, disease duration, estimated glomerular filtration rate (eGFR), HbA1C, insulin therapy profile, and serum levels of 25(OH)D. The distribution of VDBP phenotypes and genotypes in the two studied groups were nearly the same, and the distribution was similar to that of the general population. Conclusions In this study, we found the association between lower circulating levels of VDBP and risk of DR. However, the precise mechanism linking these two remains unknown. Further and more in-depth research is needed to find out the underlying causes of the relationship.

Silicone/mineral oil‐induced granulomas have been described as an inflammatory granulomatous response when silicone/mineral oil is injected for cosmetic purposes. These sclerosing granulomas can lead to hypercalcemia. Here we present a 33‐year‐old man with hypercalcemia, hypophosphatemia, progressively worsening fatigue, severe proximal muscle weakness, and depression. He had an athletic build with increased muscle bulk and several areas of indurated, nontender, firm, well‐circumscribed lesions in the subcutaneous tissue of his anterior pectoralis, triceps, and biceps bilaterally because of injecting himself with silicone/mineral oil‐based product into his muscles. Sclerosing granulomas were diagnosed on the MRI. He had extremely low or undetectable serum levels of 25‐hydroxyvitamin D [25(OH)D], and persistently elevated serum levels of 1,25‐dihydroxyvitamin D [1,25(OH)2D] and calcium. He developed hypophosphatemia associated with elevated levels of fibroblast growth factor 23 (FGF‐23) and severe proximal muscle weakness. Treatment with systemic steroids, furosemide, calcitonin, ketoconazole, and denosumab resulted in a significant decrease in his serum calcium, but with minimal impact on his hypophosphatemia and fatigue.Correcting his severe vitamin D deficiency with small doses of vitamin D and raising his blood level of 25(OH)D from undetectable to 10 ng/mL without significantly affecting his serum calcium or phosphate was effective in reversing his severe proximal muscle weakness, permitting him to lift his head and to be free of his wheelchair. Although measurement of the 1,25(OH)2D level is not mandatory in all cases of hypercalcemia, it is indicated in a patient who has low serum PTH levels. Clinicians need to be aware that vitamin D deficiency can cause severe proximal muscle weakness such that the patient is unable to lift his head from his chest or ambulate. This may lead to a psychiatric disorder misdiagnosis. © 2019 The Authors. JBMR Plus is published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.

With on-going climate change, coral susceptibility to thermal stress constitutes a central concern in reefconservation. In the Persian Gulf, coral reefs are confronted with a high seasonal variability in water temperature, and both hot and cold extremes have been associated with episodes of coral bleaching and mortality. Using physiological performance as a measure of coral health, we investigated the thermal susceptibility of the common acroporid, Acropora downingi, near Hengam Island where the temperature oscillates seasonally in the range 20.2-34.2 °C. In a series of two short-term experiments comparing coral response in summer versus winter conditions, we exposed corals during each season (1) to the corresponding seasonal average and extreme temperature levels in a static thermal environment, and (2) to a progressive temperature deviation from the annual mean toward the corresponding extreme seasonal value and beyond in a dynamic thermal environment. We monitored four indictors of coral physiological performance: net photosynthesis (Pn), dark respiration (R), autotrophic capability (Pn/R), and survival. Corals exposed to warming during summer showed a decrease in net photosynthesis and ultimately died, while corals exposed to cooling during winter were not affected in their photosynthetic performance and survival. Coral autotrophic capability Pn/R was lower at the warmer thermal level within eachseason, and during summer compared to winter. Corals exposed to the maximum temperature of summer displayed Pn/R < 1, inferring that photosynthetic performance could not support basal metabolic needs under this environment. Our results suggest that the autotrophic performance of the Persian Gulf A. downingi is sensitive to the extreme temperatures endured in summer, and therefore its populations may be impacted by future increases in water temperature.

The aims of this randomized controlled double-blind clinical trial were to assess the impact of vitamin D supplementation on calcium metabolism and non-calcemic broad gene expression by relating them to the individual’s responsiveness to varying doses of vitamin D 3 . Thirty healthy adults were randomized to receive 600, 4,000 or 10,000 IU/d of vitamin D 3 for 6 months. Circulating parathyroid hormone (PTH), 25(OH)D, calcium and peripheral white blood cells broad gene expression were evaluated. We observed a dose-dependent increase in 25(OH)D concentrations, decreased PTH and no change in serum calcium. A plateau in PTH levels was achieved at 16 weeks in the 4000 and 10,000 IU/d groups. There was a dose-dependent 25(OH)D alteration in broad gene expression with 162, 320 and 1289 genes up- or down-regulated in their white blood cells, respectively. Our results clearly indicated that there is an individual’s responsiveness on broad gene expression to varying doses of vitamin D 3 . Vitamin D 3 supplementation at 10,000 IU/d produced genomic alterations several fold higher than 4,000 IU/d even without further changes in PTH levels. Our findings may help explain why there are some inconsistency in the results of different vitamin D’s clinical trials.