Individuals Diagnosed With Type 2 Diabetes Mellitus and the Status of Vitamin B12 Deficiency: A Review.

Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder with a multifactorial etiology and a significant global burden. In recent years, emerging evidence has suggested a potential link between T2DM and vitamin B12 deficiency, raising concerns about its impact on disease progression, management, and associated complications. This comprehensive review critically examines the current understanding of the prevalence, risk factors, clinical implications, and management strategies related to vitamin B12 deficiency in individuals diagnosed with T2DM. The review begins by providing an overview of the epidemiology of T2DM and its associated complications, underscoring the need for comprehensive management approaches. Subsequently, it delves into the physiology of vitamin B12, including its sources, absorption mechanisms, and biological functions, laying the groundwork for understanding the potential implications of deficiency in T2DM. A thorough analysis of the literature is conducted to elucidate the prevalence and risk factors of vitamin B12 deficiency in individuals with T2DM, considering factors such as age, duration of diabetes, medication use (e.g., metformin), dietary patterns, and comorbidities. Special attention is given to the role of metformin, the first-line therapy for T2DM, in precipitating or exacerbating vitamin B12 deficiency through mechanisms involving alterations in the gut microbiota and intestinal absorption. The review further explores the clinical manifestations and diagnostic challenges associated with vitamin B12 deficiency in the context of T2DM, emphasizing the importance of recognizing subtle symptoms and implementing appropriate screening protocols. It discusses the potential implications of vitamin B12 deficiency on glycemic control, diabetic neuropathy, cognitive function, cardiovascular health, and overall quality of life in individuals with T2DM. In addressing the management of vitamin B12 deficiency in T2DM, the review examines various therapeutic strategies, including oral and parenteral supplementation, dietary modifications, and lifestyle interventions. It critically evaluates the evidence supporting routine screening for vitamin B12 deficiency in individuals with T2DM and discusses controversies surrounding optimal supplementation protocols, dosing regimens, and monitoring strategies. Furthermore, the review highlights gaps in current knowledge and identifies areas for future research, such as the long-term effects of vitamin B12 supplementation on clinical outcomes in T2DM, the impact of genetic factors on vitamin B12 metabolism, and the potential role of personalized interventions. Overall, this review consolidates existing evidence and provides insights into the complex relationship between T2DM and vitamin B12 deficiency, aiming to inform clinical practice, enhance patient care, and guide future research endeavors in this important area of metabolic medicine.

Vitamin C Deficiency Masquerading as Vasculitis in a Patient With Crohn's Disease.

This case study features a 40-year-old male with Crohn's disease (CD) who was initially misdiagnosed with vasculitis but was later shown to have scurvy owing to vitamin C deficiency. The patient's diet was nearly exclusively made up of highly processed fast food, with no fresh fruits or vegetables. A mildly sensitive, violaceous rash on his lower legs, mild gingival hemorrhage and enlargement, and muscle soreness were among his symptoms. Anemia and undetectable vitamin C levels were discovered in laboratory studies. A skin sample revealed follicular hyperkeratosis, coiled hairs, and perifollicular bleeding, eliminating the possibility of vasculitis. Scurvy was confirmed by undetectable vitamin C levels and intramuscular bleeding discovered during a muscle biopsy. After one month of vitamin C administration, the patient's skin was entirely clear. This instance emphasizes the significance of taking vitamin C insufficiency into account in patients with CD and other disorders that can cause malabsorption. Misdiagnosis might result in unneeded treatments and medical expenses. Scurvy must be diagnosed as soon as possible because it might cause gastrointestinal/intracerebral hemorrhage and death.

Prenatal but not continued postpartum vitamin D supplementation reduces maternal bone resorption as measured by C-terminal telopeptide of type 1 collagen without effects on other biomarkers of bone metabolism.

Vitamin D is a key regulator of bone mineral homeostasis and may modulate maternal bone health during pregnancy and postpartum. Using previously-collected data from the Maternal Vitamin D for Infant Growth (MDIG) trial in Dhaka, Bangladesh, we aimed to investigate the effects of prenatal and postpartum vitamin D3 supplementation on circulating biomarkers of bone formation and resorption at delivery and 6 months postpartum. MDIG trial participants were randomized to receive a prenatal;postpartum regimen of placebo or vitamin D3 (IU/week) as either 0;0 (Group A), 4200;0 (B), 16,800;0 (C), 28,000;0 (D) or 28,000;28,000 (E) from 17 to 24 weeks' gestation to 6 months postpartum. As this sub-study was not pre-planned, the study sample included MDIG participants who had data for at least 1 biomarker of interest at delivery or 6 months postpartum, with a corresponding baseline measurement (n = 690; 53 % of 1300 enrolled trial participants). Biomarkers related to bone turnover were measured in maternal venous blood samples collected at enrolment, delivery, and 6 months postpartum: osteoprotegerin (OPG), osteocalcin (OC), receptor activator nuclear factor kappa-B ligand (RANKL), fibroblast growth factor 23 (FGF23), procollagen type 1 N-terminal propeptide, (P1NP) and carboxy terminal telopeptide of type 1 collagen (CTx). Supplementation effects were expressed as percent differences between each vitamin D group and placebo with 95 % confidence intervals (95 % CI). Of 690 participants, 64 % had 25-hydroxyvitamin D concentrations (25OHD) <30 nmol/L and 94 % had 25OHD < 50 nmol/L at trial enrolment. At delivery, mean CTx concentrations were 27 % lower in group E versus placebo (95 % CI: -38, -13; P < 0.001), adjusting for enrolment concentrations. However, at 6 months postpartum, CTx concentrations were not statistically different in group E versus placebo (14 %; 95 % CI: -5.3, 37; P = 0.168), adjusting for delivery CTx concentrations. Effects on other biomarkers at delivery or postpartum were not statistically significant. In conclusion, prenatal high-dose vitamin D supplementation reduced bone resorption during pregnancy, albeit by only one biomarker, and without evidence of a sustained effect in the postpartum period. However, further evidence is needed to substantiate potential maternal bone health benefits of vitamin D in the postpartum period.

CRISPR/Cpf1-FOKI-induced gene editing in Gluconobacter oxydans.

Gluconobacter oxydans is an important Gram-negative industrial microorganism that produces vitamin C and other products due to its efficient membrane-bound dehydrogenase system. Its incomplete oxidation system has many crucial industrial applications. However, it also leads to slow growth and low biomass, requiring further metabolic modification for balancing the cell growth and incomplete oxidation process. As a non-model strain, G. oxydans lacks efficient genome editing tools and cannot perform rapid multi-gene editing and complex metabolic network regulation. In the last 15 years, our laboratory attempted to deploy multiple CRISPR/Cas systems in different G. oxydans strains and found none of them as functional. In this study, Cpf1-based or dCpf1-based CRISPRi was constructed to explore the targeted binding ability of Cpf1, while Cpf1-FokI was deployed to study its nuclease activity. A study on Cpf1 found that the CRISPR/Cpf1 system could locate the target genes in G. oxydans but lacked the nuclease cleavage activity. Therefore, the CRISPR/Cpf1-FokI system based on FokI nuclease was constructed. Single-gene knockout with efficiency up to 100% and double-gene iterative editing were achieved in G. oxydans. Using this system, AcrVA6, the anti-CRISPR protein of G. oxydans was discovered for the first time, and efficient genome editing was realized.

Silent Infections are not So Silent: The Emerging Role of Combined Infections, Inflammation, and Vitamin Levels in OCD.

Objective: Recent evidence highlights that different agents may trigger immune-mediated processes involved in the pathophysiology of different neuropsychiatric conditions. Given the limited information on obsessive-compulsive disorder (OCD), the present study aimed at assessing current/past infections and plasma levels of vitamin D, vitamin B12, folic acid, homocysteine and common peripheral inflammatory markers in a group of OCD outpatients. Method: The sample included 217 adult outpatients with an OCD diagnosis according to the DSM-5 criteria. The Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) was used to assess the clinical phenotype and symptom severity. Laboratory blood tests measured levels of vitamin D, vitamin B12, folic acid, homocysteine, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), blood count and antibodies titers for cytomegalovirus (CMV), Epstein Barr virus (EBV), Toxoplasma gondii and antistreptolysin titer. Results: Sixty-one patients had a previous EBV infection, 46 were seropositive for CMV IgG, 24 showed positive antistreptolysin titer, 14 were seropositive for Toxoplasma gondii IgG, and four for CMV IgM. More than a half of patients showed vitamin D insufficiency. Compared to seronegative patients, patients with a past EBV infection displayed significantly higher scores on the Y-BOCS total score and compulsion subscale, and other symptoms. Vitamin D was negatively correlated with both the Y-BOCS total score and the subscales scores. Folic acid was negatively correlated with the Y-BOCS total and obsessions subscale score. Conclusions: The findings of our study show an association between Epstein-Barr infection and hypovitaminosis D and the overall severity and specific symptom patterns of OCD. The laboratory measures used in this study are useful, cheap and easy parameters that should be routinely assessed in patients with OCD. Further studies are needed to clarify their role in OCD pathophysiology and outcomes, as well as the potential therapeutic impact of vitamins and antibiotics/immunomodulatory agents in OCD and other psychiatric conditions.

Patients' Perspectives on Type 2 Diabetes, Vitamin B12 Deficiency, and Supplementation in Buraidah, Saudi Arabia.

Objectives Long-term metformin is associated with vitamin B12 deficiency. There is a significant misunderstanding among both physicians and patients regarding vitamin B12 indications. This study aims to identify knowledge gaps and attitudes toward vitamin B12 among diabetic patients. Materials and methods A cross-sectional study was conducted among type 2 diabetic patients visiting four primary healthcare centers in Buraidah, Saudi Arabia. The data were collected using a structured self-administered questionnaire. Data were collected on diabetes and vitamin B12 knowledge and attitude toward vitamin B12 supplementation. Logistic regression analyses were used to assess the predictors of knowledge and attitude. Results Of the 388 participants, 192 (49.5%) were male. About 84.5% of the total diabetics were on metformin. Nearly three-fourths (72.7%) were taking vitamin B12. A large proportion, 160 (41.2%), believed that it is necessary to take vitamin B12 for every diabetic patient. Nearly half, 193 (49.7%), did not know the factors affecting vitamin B12 deficiency. Young (less than 39 years) diabetics were more likely to perceive that vitamin B12 is recommended for all diabetics, OR (95% CI) [6.26 (1.86-21.06)], as compared to participants aged more than 59. Similarly, younger patients were more likely to assume vitamin B12 necessary, OR (95% CI) [3.71 (1.26-10.89)]. Conclusion We found the knowledge and attitude of diabetic patients regarding vitamin B12 to be poor. It is, therefore, recommended that primary health care providers educate their patients about vitamin B12 supplementation to reduce the number of medications and financial burden. Further large-scale studies are also needed to generate stronger evidence of the problem.

Simple fabrication of electrochemical sensor based on integration of dual signal amplification by the supporting electrode and modified nanochannel array for direct and sensitive detection of vitamin B2.

Development of simple and reliable sensor for detecting vitamin content is of great significance for guiding human nutrition metabolism, overseeing the quality of food or drugs, and advancing the treatment of related diseases. In this work, a simple electrochemical sensor was conveniently fabricated by modification a carbon electrode with vertically-ordered mesoporous silica film (VMSF), enabling highly sensitive electrochemical detection of vitamin B2 (VB2) based on the dual enrichment of the analyte by the supporting electrode and nanochannels. The widely used glassy carbon electrode (GCE), was preactivated using simple electrochemical polarization, The resulting preactivated GCE (p-GCE) exhibited improved potential resolution ability and enhanced peak current of VB2. Stable modification of VMSF on p-GCE (VMSF/p-GCE) was achieved without introducing another binding layer. The dual enrichment effect of the supporting p-GCE and nanochannels facilitated sensitive detection of VB2, with a linear concentration ranged from 20 nM to 7 µM and from 7 µM to 20 µM. The limit of detection (LOD), determined based on a signal-to-noise ratio of three (S/N = 3), was found to be 11 nM. The modification of ultra-small nanochannels of VMSF endowed VMSF/p-GCE with excellent anti-interference and anti-fouling performance, along with high stability. The constructed sensor demonstrated the capability to achieve direct electrochemical detection of VB2 in turbid samples including milk and leachate of compound vitamin B tablet without the need for complex sample pretreatment. The fabricated electrochemical can be easily regenerated and has high reusability. The advantages of simple preparation, high detection performance, and good regeneration endow the constructed electrochemical sensor with great potential for direct detection of small molecule in complex samples.

Vitamin B12 status and folic acid supplementation influence mitochondrial heteroplasmy levels in mice.

One-carbon metabolism is a complex network of metabolic reactions that are essential for cellular function including DNA synthesis. Vitamin B12 and folate are micronutrients that are utilized in this pathway and their deficiency can result in the perturbation of one-carbon metabolism and subsequent perturbations in DNA replication and repair. This effect has been well characterized in nuclear DNA but to date, mitochondrial DNA (mtDNA) has not been investigated extensively. Mitochondrial variants have been associated with several inherited and age-related disease states; therefore, the study of factors that impact heteroplasmy are important for advancing our understanding of the mitochondrial genome's impact on human health. Heteroplasmy studies require robust and efficient mitochondrial DNA enrichment to carry out in-depth mtDNA sequencing. Many of the current methods for mtDNA enrichment can introduce biases and false-positive results. Here, we use a method that overcomes these limitations and have applied it to assess mitochondrial heteroplasmy in mouse models of altered one-carbon metabolism. Vitamin B12 deficiency was found to cause increased levels of mitochondrial DNA heteroplasmy across all tissues that were investigated. Folic acid supplementation also contributed to elevated mitochondrial DNA heteroplasmy across all mouse tissues investigated. Heteroplasmy analysis of human data from the Framingham Heart Study suggested a potential sex-specific effect of folate and vitamin B12 status on mitochondrial heteroplasmy. This is a novel relationship that may have broader consequences for our understanding of one-carbon metabolism, mitochondrial-related disease and the influence of nutrients on DNA mutation rates.

Preparation and characterization of vitamin A microcapsules nutrient fortified salt.

Vitamin A, also known as retinol, is a fat-soluble vitamin that plays crucial role in various physiological functions In vivo. However, factors such as light, oxygen, and others may impact the stability of VA. To enhance its stability. This study microencapsulated VA, Gelatin, carboxymethyl cellulose, and salt were mixed in a ratio of 5:1:0.1 as the shell material. Additionally, 12% TG and 3.5% sucrose ester were added with core-shell ratio of 1:8. The experimental results indicated that VA microcapsules exhibited an encapsulation efficiency of 81.12%, after 9 weeks of storage this rate decreased to 75.38%, and the encapsulated VA oil did not exhibit extravasation. The addition of an appropriate amount of salt to the shell material enhanced the mechanical properties of the shell material, compared to the shell material without added salt, the leakage of VA in the salt-added sample decreased by 5.8% for 30 min and 14.5% for 60 min. In vitro release experiments showed that after 3 h of incubation in simulated gastric fluid, the microcapsules had an 18.52% release rate. In simulated intestinal fluid, this increased to 66.58%, indicating strong enteric solubility. Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-024-05962-w.

Vitamin C and Thiamin Deficiencies in Patients Undergoing Laparoscopic and Robotic Gastric Band Removal.

Outcomes after adjustable gastric banding (AGB) were unsatisfactory and many devices need to be removed for dysphagia. Vitamin C and thiamin deficiency are rare conditions in industrialized countries. Patients undergoing AGB removal (90% for dysphagia) from 2021 to 2023 (laparoscopic 15 and robotic 5) were tested for vitamin C and thiamin levels. Twenty patients (8 m/12 f median aged 56 (range 33.6-79.4) were included. BMI at AGB removal was 39.7 (range 24.4-50.1) kg/m2. Only 20% of patients had normal thiamin levels, 30% had low levels, 20% were deficient, and 30% were critically low. Only 25% of patients had normal vitamin C levels, 40% had low levels, 25% were deficient, and 10% were critically low. One third of patients had HbA1c levels between 5.8 and 6.4 and 22% had levels >6.5; 60% of patients had hyperlipidemia. Adjustable gastric banding patients develop concerning rates of vitamin C and thiamin deficiency, and routine testing for levels is recommended.

Efficacy and safety of oral factor Xa inhibitors versus vitamin-K antagonists in the early phase after acute ischemic stroke or TIA in the real-world setting: The PRODAST study.

INTRODUCTION: Factor Xa (FXa) inhibitors are superior to vitamin K antagonists (VKAs) in terms of avoiding hemorrhagic complications. However, no robust data are available to date as to whether this also applies to the early phase after stroke. In this prospective registry study, we aimed to investigate whether anticoagulation with FXa inhibitors in the early phase after acute ischemic stroke or transient ischemic attack (TIA) is associated with a lower risk of major bleeding events compared with VKAs. MATERIALS AND METHODS: The Prospective Record of the Use of Dabigatran in Patients with Acute Stroke or TIA (PRODAST) study is a prospective, multicenter, observational, post-authorization safety study at 86 German stroke units between July 2015 and November 2020. Primary outcome was a major bleeding event during hospital stay. Secondary endpoints were recurrent strokes, recurrent ischemic strokes, TIA, systemic/pulmonary embolism, myocardial infarction, death and the composite endpoint of stroke, systemic embolism, life-threatening bleeding and death. RESULTS: In total, 10,039 patients have been recruited. 5,874 patients were treated with FXa inhibitors and 1,050 patients received VKAs and were eligible for this analysis. Overall, event rates were low. We observed 49 major bleeding complications during 33,297 treatment days with FXa-inhibitors (rate of 14.7 cases per 10,000 treatment days) and 16 cases during 7,714 treatment days with VKAs (rate of 20.7 events per 10,000 treatment days), translating into an adjusted hazard ratio (aHR) of 0.70 (95% confidence interval (95% CI): 0.37-1.32) in favor of FXa inhibitors. Hazards for ischemic endpoints (63 vs 17 strokes, aHR: 0.96 (95% CI: 0.53-1.74), mortality (33 vs 6 deaths, aHR: 0.87 (95% CI: 0.33-2.34)) and the combined endpoint (154 vs 39 events, aHR: 0.99 (95% CI: 0.65-1.41) were not substantially different. DISCUSSION AND CONCLUSION: This large real-world study shows that FXa inhibitors appear to be similarly effective in terms of bleeding events and ischemic endpoints compared to VKAs in the early post-stroke phase of hospitalization. However, the results need to be interpreted with caution due to the low precision of the estimates.

Vitamin D inhibits ferroptosis and mitigates the kidney injury of prediabetic mice by activating the Klotho/p53 signaling pathway.

Diabetic nephropathy (DN) is a serious public health problem worldwide, and ferroptosis is deeply involved in the pathogenesis of DN. Prediabetes is a critical period in the prevention and control of diabetes and its complications, in which kidney injury occurs. This study aimed to explore whether ferroptosis would induce kidney injury in prediabetic mice, and whether vitamin D (VD) supplementation is capable of preventing kidney injury by inhibiting ferroptosis, while discussing the potential mechanisms. High-fat diet (HFD) fed KKAy mice and high glucose (HG) treated HK-2 cells were used as experimental subjects in the current study. Our results revealed that serious injury and ferroptosis take place in the kidney tissue of prediabetic mice; furthermore, VD intervention significantly improved the kidney structure and function in prediabetic mice and inhibited ferroptosis, showing ameliorated iron deposition, enhanced antioxidant capability, reduced reactive oxygen species (ROS) and lipid peroxidation accumulation. Meanwhile, VD up-regulated Klotho, solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) expression, and down-regulated p53, transferrin receptor 1 (TFR1) and Acyl-Coenzyme A synthetase long-chain family member 4 (ACSL4) expression. Moreover, we demonstrated that HG-induced ferroptosis is antagonized by treatment of VD and knockdown of Klotho attenuates the protective effect of VD on ferroptosis in vitro. In conclusion, ferroptosis occurs in the kidney of prediabetic mice and VD owns a protective effect on prediabetic kidney injury, possibly by via the Klotho/p53 pathway, thus inhibiting hyperglycemia-induced ferroptosis.

Outcomes after newborn screening for propionic and methylmalonic acidemia and homocystinurias.

The current German newborn screening (NBS) panel includes 13 inherited metabolic diseases (IMDs). In addition, a NBS pilot study in Southwest Germany identifies individuals with propionic acidemia (PA), methylmalonic acidemia (MMA), combined and isolated remethylation disorders (e.g., cobalamin [cbl] C and methylenetetrahydrofolate reductase [MTHFR] deficiency), cystathionine ß-synthase (CBS) deficiency, and neonatal cbl deficiency through one multiple-tier algorithm. The long-term health benefits of screened individuals are evaluated in a multicenter observational study. Twenty seven screened individuals with IMDs (PA [N = 13], MMA [N = 6], cblC deficiency [N = 5], MTHFR deficiency [N = 2] and CBS deficiency [N = 1]), and 42 with neonatal cbl deficiency were followed for a median of 3.6 years. Seventeen screened IMD patients (63%) experienced at least one metabolic decompensation, 14 of them neonatally and six even before the NBS report (PA, cbl-nonresponsive MMA). Three PA patients died despite NBS and immediate treatment. Fifteen individuals (79%) with PA or MMA and all with cblC deficiency developed permanent, mostly neurological symptoms, while individuals with MTHFR, CBS, and neonatal cbl deficiency had a favorable clinical outcome. Utilizing a combined multiple-tier algorithm, we demonstrate that NBS and specialized metabolic care result in substantial benefits for individuals with MTHFR deficiency, CBS deficiency, neonatal cbl deficiency, and to some extent, cbl-responsive MMA and cblC deficiency. However, its advantage is less evident for individuals with PA and cbl-nonresponsive MMA. SYNOPSIS: Early detection through newborn screening and subsequent specialized metabolic care improve clinical outcomes and survival in individuals with MTHFR deficiency and cystathionine-ß-synthase deficiency, and to some extent in cobalamin-responsive methylmalonic acidemia (MMA) and cblC deficiency while the benefit for individuals with propionic acidemia and cobalamin-nonresponsive MMA is less evident due to the high (neonatal) decompensation rate, mortality, and long-term complications.

Exploration of vitamin D metabolic activity-related biological effects and corresponding therapeutic targets in prostate cancer.

BACKGROUND: Previous studies have unequivocally demonstrated that the vitamin D (VD) metabolism pathway significantly influences prognosis and sensitivity to hormone therapy in prostate cancer (PCa). However, the precise underlying mechanism remains unclear. METHODS: We performed molecular profiling of 1045 PCa patients, leveraging genes linked to VD synthesis and VD receptors. We then identified highly variable gene modules with substantial associations with patient stratification. Subsequently, we intersected these modules with differentially expressed genes between PCa and adjacent paracancerous tissues. Following a meticulous process involving single-factor regression and LASSO regression to eliminate extraneous variables and construct a prognostic model. Within the high-risk subgroup defined by the calculated risk score, we analyzed their differences in cell infiltration, immune status, mutation landscape, and drug sensitivity. Finally, we selected Apolipoprotein E (APOE), which featured prominently in this model for further experimental exploration to evaluate its potential as a therapeutic target. RESULTS: The prognostic model established in this study had commendable predictive efficacy. We observed diminished infiltration of various T-cell subtypes and reduced expression of co-stimulatory signals from antigen-presenting cells. Mutation analysis revealed that the high-risk cohort harbored a higher frequency of mutations in the TP53 and FOXA genes. Notably, drug sensitivity analysis suggested the heightened responsiveness of high-risk patients to molecular inhibitors targeting the Bcl-2 and MAPK pathways. Finally, our investigation also confirmed that APOE upregulates the proliferative and invasive capacity of PCa cells and concurrently enhances resistance to androgen receptor antagonist therapy. CONCLUSION: This comprehensive study elucidated the potential mechanisms through which this metabolic pathway orchestrates the biological behavior of PCa and findings hold promise in advancing the development of combination therapies in PCa.

Vitamin D metabolism in critically ill patients with acute kidney injury: a prospective observational study.

BACKGROUND: Vitamin D deficiency in critically ill patients is associated with poor outcomes, and vitamin D supplementation is recommended for patients with chronic kidney disease. Whether acute kidney injury (AKI) is associated with altered Vitamin D metabolism is unknown. We aimed to compare the longitudinal profiles of serum 25(OH)D and 1,25(OH)2D concentrations in critically ill patients with and without moderate to severe AKI and explore the impact of renal recovery and parathyroid hormone (PTH). METHODS: In this prospective, observational study in two centres in the UK, critically ill patients with and without AKI underwent serial measurement of serum 25(OH)D and 1,25(OH)2D and plasma PTH concentrations for 5 days. Linear mixed model analysis and sensitivity analyses were performed. RESULTS: Serial data of 137 patients were analysed. Seventy-one patients had AKI stage II/III of whom 23 recovered kidney function during the 5-day study period; 66 patients did not have AKI at enrolment of whom 14 developed new AKI. On day of enrolment, patients' serum 25(OH)D concentrations were low (median 18 nmol/L) but there was no significant difference between patients with and without AKI. Median serum 1,25(OH)2D levels were significantly lower in patients with AKI II/III (41 pmol/L [IQR 26, 58]) compared to similarly unwell patients without AKI (54 pmol/L [IQR 33, 69]) during the 5-day period. Recovery of kidney function in patients with AKI was associated with a rise in 1,25(OH)2D concentrations. Plasma PTH results were impacted by serum calcium and magnesium levels but not associated with 1,25(OH)2D levels. CONCLUSIONS: Critically ill patients with moderate-to-severe AKI have significantly lower serum 1,25(OH)2D concentrations than similarly sick patients without AKI but there was no difference in serum 25(OH)D concentrations. Recovery of AKI was associated with a rise in serum 1,25(OH)2D concentrations. More research is needed to investigate the health benefits and safety of supplementation with active vitamin D in critically ill patients with moderate-to-severe AKI. Trial registration Clinicaltrials.gov (NCT02869919), registered on 16 May 2016.

Vitamin D deficiency in Scheuermann's disease is associated with increased adverse outcomes.

INTRODUCTION: Scheuermann's disease is a diagnosis of hyperkyphosis commonly encountered in pediatric patients. Studies in animal models suggest an association with vitamin D deficiency, however, extensive studies have not been performed in humans. This study analyzes the role of vitamin D deficiency on unfavorable results in patients with Scheuermann's disease. METHODS: The TriNetX database was utilized to perform a retrospective analysis. Patients in the United States aged 0-18 years with Scheuermann's disease were identified using International Classification of Diseases, Tenth Revision (ICD-10) codes and categorized into those with and without a diagnosis of vitamin D deficiency. Comparison of patient groups depending on age, sex, ethnic origin, prior diagnosis of fibromyalgia, anxiety disorder, myositis, and major depressive disorder. Statistical analysis was conducted to identify the association between vitamin D levels and unfavorable results including pain, depression, suicide attempt, emergency department (ED) consult, hospitalization, and procedures on the spine or spinal cord. RESULTS: In total, 11,277 patients were identified, 39% of whom had a concurrent diagnosis of scoliosis. A total of 1,024 (9.08%) were deficient in vitamin D. Patients with vitamin D deficiency had greater odds of pain (P < 0.0001), depression (P < 0.0001), suicide attempt (P = 0.0021), ED visits (P = 0.0246), and hospital admission (P < 0.0015). Conversely, patients with vitamin D deficiency had decreased odds of surgery on the spine or spinal cord (P = 0.0009). CONCLUSION: Vitamin D deficiency is associated with an elevated risk of pain, depression, suicide attempts, ED visits, and hospitalization. Our analysis highlights the need for more research to study the effect of vitamin D on Scheuermann's disease. LEVEL OF EVIDENCE: Level III, Prognostic.

Engineering and finetuning expression of SerC for balanced metabolic flux in vitamin B6 production.

Vitamin B6 plays a crucial role in cellular metabolism and stress response, making it an essential component for growth in all known organisms. However, achieving efficient biosynthesis of vitamin B6 faces the challenge of maintaining a balanced distribution of metabolic flux between growth and production. In this study, our focus is on addressing this challenge through the engineering of phosphoserine aminotransferase (SerC) to resolve its redundancy and promiscuity. The enzyme SerC was semi-designed and screened based on sequences and predicted kcat values, respectively. Mutants and heterologous proteins showing potential were then fine-tuned to optimize the production of vitamin B6. The resulting strain enhances the production of vitamin B6, indicating that different fluxes are distributed to the biosynthesis pathway of serine and vitamin B6. This study presents a promising strategy to address the challenge posed by multifunctional enzymes, with significant implications for enhancing biochemical production through engineering processes.

Vitamins for the Management of Nail Disease: A Literature Review.

Background: Vitamins have gained popularity among physicians and patients for purported benefits to hair, skin, and nail health. Safe and efficacious therapies for nail disorders, many of which are chronic conditions, are needed. Summary: We conducted a literature review of studies assessing the efficacy of oral, topical, and intralesional vitamin/vitamin derivatives for the treatment of nail disorders, including yellow nail syndrome, brittle nail syndrome, onychomycosis, habit-tic nail deformity, periungual/subungual verruca, and nail psoriasis. Forty-nine articles were reviewed. There is good evidence to support the use of topical tazarotene and vitamin D analogs for nail psoriasis treatment. We found overall limited evidence for treatment of other nail disorders with vitamin/vitamin derivatives, and further research is needed to support their use. Key Messages: Besides topical tazarotene and vitamin D analogs for nail psoriasis treatment, there is limited evidence for treatment of nail disorders with topical, oral, and intralesional vitamin/vitamin derivatives.

Review: Aspects of digestibility and requirements for minerals and vitamin D by growing pigs and sows.

Some of the biggest changes in mineral nutrition for pigs that have occurred due to recent research were caused by the understanding that there is a loss of endogenous Ca and P into the intestinal tract of pigs. This resulted in development of the concept of formulating diets based on standardized total tract digestibility (STTD) rather than apparent total tract digestibility because the values for STTD of these minerals are additive in mixed diets. There are, however, no recent summaries of research on digestibility and requirements of macro- and microminerals and vitamin D for pigs. Therefore, the objective of this review was to summarize selected results of research conducted over the last few decades to determine the digestibility and requirements of some minerals and vitamin D fed to sows and growing pigs. Benefits of microbial phytase in terms of increasing the digestibility of most minerals have been demonstrated. Negative effects on the growth performance of pigs of over-feeding Ca have also been demonstrated, and frequent analysis of Ca in complete diets and raw materials is, therefore, recommended. There is no evidence that current requirements for vitamin D for weanling or growing-finishing pigs are not accurate, but it is possible that gestating and lactating sows need more vitamin D than currently recommended. Vitamin D analogs and metabolites such as 1(OH)D3 and 25(OH)D3 have beneficial effects when added to diets for sows in combination with vitamin D3. Recent research on requirements for macrominerals other than Ca and P is scarce, but it is possible that Mg in diets containing low levels of soybean meal is marginal. Some of the chelated microminerals have increased digestibility compared with sulfate forms, and hydroxylated forms of Cu and Zn appear to be superior to sulfate or oxide forms. Likewise, dicopper oxide and Cu methionine hydroxy analog have a greater positive effect on the growth performance of growing pigs than copper sulfate. The requirement for Mn may need to be increased whereas there appears to be no benefits of providing Fe above current requirements. In conclusion, diets for pigs should be formulated based on values for STTD of Ca and P and there are negative effects of providing excess Ca in diets. It is possible vitamin D analogs and metabolites offer benefits over vitamin D3 in diets for sows. Likewise, chelated forms of microminerals or chemical forms of minerals other than sulfates or oxides may result in improved pig performance.

Evaluation of the Function of Vitamin D in Treating Oral Lichen Planus.

Objectives: The objective of the current research was to evaluate the role of vitamin D in the management of oral lichen planus. Materials and Method: Based on their vitamin D levels, 90 individuals with oral lichen planus were equally divided into three groups. Deficient subjects received oral vitamin D supplementation. Result: The majority of improvements were observed in patients who were taking vitamin D supplements. It was discovered that the data comparison was statistically considerable. Conclusion: It was determined that vitamin D was crucial for the management of oral lichen planus.