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Introduction to the contents of the book 'Vitamin D: Mechanisms of Action and Clinical Applications'
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... common missense point mutations in exon 11 of singlenucleotide polymorphisms (SNPs) rs7041 (G/T single-nucleotide variation) and rs4588 (an A/C single-nucleotide variation) result in 3 common isoforms and different protein products at positions 416 and 420: Gc1F (Asp416, Thr420), Gc1S (Glu 416, Thr420), and Gc2 (Asp416, Lys420). 48 The SNPs are in complete linkage disequilibrium, and only 6 haplotypes are observed with any significant frequency ( Table 1). Gc2 is the least abundant, and Gc1f is the most abundant. ...Similar publications
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... Furthermore, vitamin D deficiency has been associated with increased mortality and worse postoperative outcomes, making it a critical aspect to consider in hip fracture management [3]. However, vitamin D has also been linked to muscle, cognitive, and balance health [4][5][6]. In fact, it has been observed that more active and independent patients have higher levels of vitamin D, leading to the hypothesis that vitamin D could be a key factor for functional status in patients with hip fractures [7]. ...
... In contrast, some studies have found a positive relationship between vitamin D and functional status, which may be due to the influence of vitamin D on cognitive status and the reduction in falls, as shown in previous studies [4]. It has also been linked to increased musculoskeletal pain in patients with vitamin D deficiency [32]. ...
Vitamin D deficiency is common in patients with hip fractures and may negatively affect functional recovery and quality of life (QOL).
This study aimed to conduct a meta-analysis to quantify the effects of vitamin D deficiency on physical function and quality of life after hip fractures.
The PubMed, EMBASE, Scopus, and Cochrane Library databases were searched for relevant studies. The inclusion criteria were hip fracture, comparison between vitamin D deficiency and normal vitamin D levels in patients with hip fracture, and functional outcome as the primary outcome. The exclusion criteria were case reports, reviews, duplicates, studies with a high risk of bias, and non-comparable or missing data. Two independent reviewers selected studies, extracted data, assessed bias, and performed meta-analyses using the Review Manager. Heterogeneity and publication bias were also assessed. Two independent reviewers selected the studies, extracted data, and assessed the risk of bias. We performed a meta-analysis using Review Manager and assessed heterogeneity and publication bias.
Seven studies with 1,972 patients were included. Vitamin D deficiency was defined as a 25(OH)D level < 20 ng/mL. There were no significant differences in the ability to walk (OR 0.68, 95% CI 0.31–1.53, I2 = 69%) or length of hospital stay (MD 2.27 days, 95% CI − 2.47 to 7.01, I2 = 93%) between patients with and without vitamin D deficiency. However, patients with vitamin D deficiency had significantly worse functional ability and quality of life (SMD − 1.50, 95% CI − 2.88 to − 0.12, I2 = 96%).
Despite the limitations of this study, such as small sample size, heterogeneous outcome assessments, and variable vitamin D measurement techniques, the results demonstrated that screening for vitamin D status and optimizing levels through supplementation could facilitate rehabilitation, promote lifestyle changes, aid in the recovery of independence, and help reduce long-term burdens.
... The regulatory role of calcitriol, the active form of vitamin D 3 , has been determined in various cellular processes including cell proliferation, differentiation, apoptosis, angiogenesis and cancer metastasis. Furthermore, many studies reported calcitriol-mediated anti-proliferative and pro-differentiation effects in various cancer tissues, including gliomas [5][6][7][8][9][10][11][12][13]. These wide effects of vitamin D on cellular processes occur by way of its specific receptor, vitamin D receptor (VDR), which also acts as a transcription factor [14,15]. ...
Glioma is the most prevalent and lethal type of primary tumor of central nervous system. The regulatory role of calcitriol, the active form of vitamin D3, has been determined in various cellular processes including cell survival and apoptosis. To study the impact of AKT-pathway inhibition with or without calcitriol combination on glioma cell viability, the effects of AT7867 (AKT-pathway inhibitor) and calcitriol on cell viability and apoptosis were investigated in glioma C6 cell-line. Optimal doses of calcitriol and AT7867 were determined by MTT- and xCELLigence-assays. Both agents (alone/in combination) effectively suppressed the proliferation of C6 cells. While AT7867 inhibited glioma cell viability more effectively than calcitriol, this inhibitory action of AT7867 was not significantly increased by calcitriol combination. The expression levels of vitamin D receptor(VDR)-triggered molecules, AKT-pathway components and apoptosis factors were compared between calcitriol-, AT7867- and calcitriol + AT7867-treated and non-treated cells. CYP24A1 gene was upregulated and DBP, CYP1A1, CYP27B1, EGFRvIII, AKT-pathway (AKT1, MTOR, CREB, PTEN), apoptosis (BAD, CYC-C, CASP3, APAF-1, BCL2) and MMP3 genes were downregulated by calcitriol treatment.AT7867 treatment induced CYP27B1 upregulation, reduced VDR and AKT-pathway (PI3K, MTOR, CREB, PTEN) gene expression levels but showed a relatively less pronounced effect on apoptosis-related gene levels. The combination of calcitriol and AT7867 treatment generated an effect that was similar to that induced by calcitriol alone. Our results demonstrate that calcitriol and AT7867 have differing actions on AKT- and apoptotic-pathways of C6 glioma cell-line. Calcitriol has a lesser viability reducing impact than AT7867 putatively due to its apoptosis inhibiting action.
Supplemental data for this article is available online at https://doi.org/10.1080/13102818.2021.1912641 .
... Also of importance is that 1,25(OH) 2 D itself is responsible for reducing 1,25(OH) 2 D concentrations in cells primarily by stimulating its catabolism through the induction of 24-hydroxylase, 24CYP24A1. This enzyme hydroxylates both 25(OH) D and 1,25(OH) 2 D in the 24 position to form 24,25(OH) 2 D and 1,24,25(OH) 3 D [24]. As is discussed next, during pregnancy, there is increased 1,25(OH) 2 D concentration presumed to be due to decreased catabolism. ...
Vitamin D is an endocrine regulator of calcium and bone metabolism. Yet, its effects include other systems, such as innate and adaptive immunity. Unique to pregnancy, circulating 1,25-dihydroxyvitamin D (1,25[OH]2D) increases early on to concentrations that are 2–3 times prepregnant values. At no other time during the lifecycle is the conversion of 25-hydroxyvitamin D (25[OH]D) to 1,25(OH)2D directly related and optimized at ≥100 nmol/L. Vitamin D deficiency appears to affect pregnancy outcomes, yet randomized controlled trials of vitamin D supplementation achieve mixed results depending on when supplementation is initiated during pregnancy, the dose and dosing interval, and the degree of deficiency at the onset of pregnancy. Analysis of trials on an intention-to-treat basis as opposed to the use of 25(OH)D as the intermediary biomarker of vitamin D metabolism yields differing results, with treatment effects often noted only in the most deficient women. Immediately after delivery, maternal circulating 1,25(OH)2D concentrations return to prepregnancy baseline, at a time when a breastfeeding woman has increased demands of calcium, beyond what was needed during the last trimester of pregnancy, making one question why 1,25(OH)2D increases so significantly during pregnancy. Is it to serve as an immune modulator? The vitamin D content of mother’s milk is directly related to maternal vitamin D status, and if a woman was deficient during pregnancy, her milk will be deficient unless she is taking higher doses of vitamin D. Because of this relative “deficiency,” there is a recommendation that all breastfed infants receive 400 IU vitamin D3/day starting a few days after birth. The alternative – maternal supplementation with 6,400 IU vitamin D3/day, effective in safely raising maternal circulating vitamin D, that of her breast milk, and effective in achieving sufficiency in her recipient breastfeeding infant – remains a viable option. Additional research is needed to understand vitamin D’s influence on pregnancy health and the effect of maternal supplementation on breast milk’s immune signaling.
... IL-15 plays a pivotal role in macrophage differentiation-the cytokine itself can induce a cascade from alpha hydroxylase CYP27b1 activation necessary for [25(OH)D] conversion into bioactive [1,25(OH) 2 D], ending in VDR activation and the induction of cathelicidin, an antimicrobial peptide largely engaged in first-line host defense [80,81]. A competent VDR is unquestionably required to mount a suitable immune response to intracellular pathogens [82]; the addition of vitamin D during IL-15-induced differentiation of monocytes into macrophages dose-dependently increased cathelicidin [83,84]. Interestingly, as from studies performed in human placental trophoblasts, a sex-dependent dimorphism in vitamin D metabolism would explain the major immune vulnerability to perinatal infections found in male fetuses and neonates vs. female ones. ...
The concept that extra-skeletal functions of vitamin D impact on human health have taken place since quite ago. Among all, the beneficial effects of vitamin D on immune regulation, skeletal muscle function, and metabolism are undeniable. Adequate vitamin D levels maintain the immune system and skeletal muscle metabolism integrity, promoting whole-body homeostasis; hypovitaminosis D associates with the important decline of both tissues and promotes chronic inflammation, which is recognized to underlie several disease developments. Growing evidence shows that the immune system and skeletal muscle reciprocally dialogue, modulating each other’s function. Within this crosstalk, vitamin D seems able to integrate and converge some biomolecular signaling towards anti-inflammatory protective effects. Thus, vitamin D regulation appears even more critical at the immune system-muscle signaling intersection, rather than at the single tissue level, opening to wider/newer opportunities in clinical applications to improve health. This paper aims to focus on the immune system-skeletal muscle interplay as a multifaceted target for vitamin D in health and disease after recalling the main regulatory functions of vitamin D on those systems, separately. Some myokines, particularly relevant within the immune system/skeletal muscle/vitamin D networking, are discussed. Since vitamin D supplementation potentially offers the opportunity to maintain health, comments on this issue, still under debate, are included.
... Vitamin D 3 (cholecalciferol) is hydroxylated to 25hydroxyvitamin D [25(OH)D] in the liver, and low concentrations of serum 25(OH)D (<20 ng/mL) are considered a risk factor for fracture (8) and are associated with worse outcomes (9,10). Maintaining normal concentrations of vitamin D can positively affect a diverse array of body functions, such as muscle health and cognitive domains that could affect mobility and risk of falls (11)(12)(13). In addition, elevated circulatory parathyroid hormone (PTH) may contribute to poor outcomes (14). ...
Background:
Hip fractures are associated with a high rate of morbidity and mortality, and successful ambulation after surgery is an important outcome in this patient population.
Objective:
This study aims to determine whether 25-hydroxyvitamin D [25(OH)D] concentration or the Geriatric Nutritional Risk Index (GNRI) is associated with mortality or rates of walking in a patient cohort after hip fracture surgery.
Methods:
Patients undergoing hip fracture repair from a multisite study in North America were included. Mortality and mobility were assessed at 30 and 60 d after surgery. Serum albumin, 25(OH)D, and intact parathyroid hormone were measured. Patients were characterized according to 25(OH)D <12 ng/mL, 12 to <20 ng/mL, 20 to <30 ng/mL, or ≥30 ng/mL. GNRI was categorized into major/moderate nutritional risk (<92), some risk (92 to <98), or in good nutritional status (≥98).
Results:
Of the 290 patients [aged 82 ± 7 y, BMI (kg/m2): 25 ± 5], 73% were women. Compared with patients with <12 ng/mL, those with higher 25(OH)D concentrations had higher rates of walking at 30 d (P = 0.031): 12 to <20 ng/mL (adjusted OR: 2.61; 95% CI: 1.13, 5.99); 20 to <30 ng/mL (3.48; 1.53, 7.95); ≥30 ng/mL (2.84; 1.12, 7.20). In addition, there was also greater mobility at 60 d (P = 0.028) in patients with higher 25(OH)D compared with the reference group (<12 ng/mL). Poor nutritional status (GNRI <92) showed an overall trend to reduce mobility (unadjusted P = 0.044 and adjusted P = 0.056) at 30 but not at 60 d. There was no association of vitamin D or GNRI with mortality at either time.
Conclusions:
Vitamin D deficiency (<12 ng/mL) is associated with reduced ambulation after hip fracture surgery, whereas GNRI also contributes to immobility but is a less reliable predictor. Mechanisms that can explain why vitamin D deficiency is associated with mobility should be addressed in future studies.
... After the induction, the clinician offers a variety of hypnotic suggestions directed at changing or eliminating the patient's painful sensations or altering how these sensations are perceived. Hypnotic analgesia suggestions can include the following [24]: Reduction of pain intensitydhaving the patient imagine that the intensity of the sensory component of his or her pain is decreasing Decreased unpleasantnessdsuggesting that the affective component of pain is separate from the sensory component of pain and that painful sensations do not have to be interpreted as unpleasant or bothersome Sensory substitutiondasking the patient to imagine that a painful or uncomfortable sensation is replaced by a sensation that is more tolerable and less distressing (eg, replacing a hot burning sensation with a sensation of cold) Displacement of paindsuggesting that a localized painful sensation move from an area of the body where the patient perceives the pain as intolerable to a location in the body where the individual can better tolerate feelings of pain (eg, from the central part of the body to an extremity) Posthypnotic suggestions can also be given with the intent of extending any changes or reductions in pain sensations (eg, suggestions for pain relief to continue for longer and longer periods of time or that it will become easier and easier for the patient to use hypnotic analgesia strategies). The final component of hypnotic analgesia treatment involves assisting the patient to transition back into a normal waking state. ...
As a biopsychosocial understanding of chronic pain has become more sophisticated during recent decades, a variety of psychologically based treatment approaches have been developed and empirically validated for helping people better manage their pain. These approaches to pain management have much to offer persons with chronic pain in terms of enhancing quality of life and pain-related coping, as well as reducing disability and pain-related interference with functioning. Although some treatments, like hypnotic analgesia, may require referral to a specialized provider, several of the principles of other psychologically based treatment approaches for pain management (eg, operant behavioral therapy, cognitive-behavioral therapy, motivational interviewing) can easily be integrated into work with persons with pain in a rehabilitation setting. Rehabilitation providers who are interested in incorporating these treatment strategies into their clinical work who do not have prior exposure to these approaches are encouraged to review the suggested references and to seek out related training opportunities.
Background
Vitamin D regulates calcium and phosphorus homeostasis. Vitamin D deficiency (VDD) commonly occurs in people living with human immunodeficiency virus (HIV) (PLWHIV) and is linked to bone disorders and metabolic and infectious diseases. HIV seropositivity and VDD may worsen the consequences on the individual.
Methods
A cross-sectional analytical study was conducted using 90 serum samples from 42 HIV-positive and 48 HIV-negative patients attending the Nnamdi Azikiwe University Teaching Hospital (NAUTH). This study was approved by the NAUTH Ethics Committee. Serum Vitamin D levels were analyzed using enzyme-linked immunosorbent assay. Sociodemographic data were obtained using a questionnaire. Data analysis was performed using IBM SPSS Windows version 27, and P < 0.05 was considered statistically significant.
Results
Overall, 13.3% of the population had suboptimal Vitamin D levels, with 2.2% having VDD and 11.1% having Vitamin D insufficiency. VDD was found in 2.2% and 2.1% of the HIV-positive group and HIV-negative groups, respectively. No significant difference was observed in mean serum Vitamin D levels between the two groups ( P > 0.05). Within the HIV-positive group, education, place of living, and skin coloration were associated with suboptimal Vitamin D levels, and only skin coloration was associated with HIV-negative subjects.
Conclusion
VDD is relatively low in the region; however, it may contribute to poor bone health in PLWHIV. Interventions should target individuals with poor educational attainment, living in rural domains, or dark skin coloration. Studies with large sample size are needed to determine the effects of Vitamin D supplementation or exposure to sunlight on HIV infection.
Background
Vitamin D deficiency has been linked to numerous health issues, including an increased risk of hip fractures. This meta‐analysis aimed to investigate the relationship between vitamin D deficiency and mortality in patients with hip fracture. To assess the impact of different levels of vitamin D deficiency on mortality in patients with hip fractures and examine the influence of potential confounding factors.
Methods
A systematic search of PubMed, EMBASE, Scopus, and Cochrane Collaboration Library was conducted, resulting in nine eligible cohort studies ( n = 4409). Patients with hip fractures were categorized based on their vitamin D levels as severe, moderate, or insufficient. Mortality was the primary outcome measure in this study. Subgroup analyses were performed according to the follow‐up time. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using a random‐effects model in Review Manager 5.4.
Results
Nine studies, with a pool of 4409 patients, were included. Vitamin D insufficiency was significantly associated with increased mortality (OR 1.24, 95% CI 1.05–1.46; I ² = 4%). Severe deficiency also led to a significant increase in mortality (OR 2.08, 95% CI 1.09–3.97; I ² = 42%), whereas moderate deficiency did not show a significant effect (OR 1.06, 95% CI 0.79–1.44; I ² = 0%). Subgroup analysis revealed significant associations between vitamin D insufficiency and increased mortality at 1‐year (OR 1.37, 95% CI 1.06–1.77) and 2‐year follow‐ups (OR 1.78, 95% CI 1.01–3.15). After adjusting for potential confounders, no significant increase in the mortality rate was observed.
Conclusions
This meta‐analysis suggests that vitamin D insufficiency and severe deficiency are associated with increased mortality in patients with hip fracture. However, after adjusting for confounding factors, this association was not statistically significant. Further research is necessary to understand the role of vitamin D deficiency in this population.
AIM
There are no reports regarding the influence of vitamin D on thymosin ß4 and the cluster of differentiation CD4 levels which are important for maintaining a healthy immune system. Consequently, we aimed to explore this relationship through a study.
MATERIAL AND METHODS
The study was carried out on 35 subjects, screened for 25-hydroxy vitamin D[25 (OH) D] using ELISA method and they were divided into two groups: Group 1 consists of 10 healthy subjects with sufficient vit. D level > 24.8 ng/ml. Group 2 consists of 25 subjects suffering, severely, from vitamin D deficiency at level < 11.325 ng/ml. Also, Thymosin ß4, CD4 and zinc levels were performed.
RESULTS
There were significant differences between the two groups in the concentration levels of thymosin β4, as the group 1 has shown higher levels (P = 0.005). Whereas, CD4 and zinc levels didn’t show any significant difference between the two groups. At the same time, a significant positive correlation has been observed between vitamin D, thymosin β4, and CD4 at (r = 0.719; P = 0.001), and (r = 0.559, P = 0.001) respectively.
CONCLUSION
We concluded that vitamin D may be an essential factor that influence or determine the level of thymosin β4. This study is the first that focused on demonstrating that sufficient level of vitamin D may have the ability to influence the thymic hormone thymosin β4 levels. Further studies on large scale of subjects are needed to explore the positive correlation we had found between vitamin D and thymosin β4 and CD4.
