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Postpartum blood calcium (Ca) concentration is related to the reproduction and health of cattle. Oral calcium supplements were given to dairy cows after calving to increase blood Ca concentration and reduce the risk of hypocalcemia. However, studies have shown that oral Ca has different effects in preventing disease. The purposes of this study were (i) to conduct a meta-analysis to evaluate the expected effect of oral Ca on incidence of calving-related diseases, pregnancy risk and milk yield in dairy cows, and (ii) to make a quality assessment of these related studies. In total, 22 eligible studies were included in this review. Meta-analysis showed that oral Ca could significantly reduce the incidence of hypocalcemia (clinical hypocalcemia: relative risk (RR) = 0.67, 95% confidence interval (CI) = [0.52, 0.87]; subclinical hypocalcemia: RR = 0.81, CI = [0.72, 0.91]), and incidence of retained placenta (RR = 0.77, CI = [0.62, 0.95]), improved blood Ca concentrations: mean difference (MD) = 0.08; 95% CI = [0.04, 0.11]. For other results, the meta-analysis revealed a lack of evidence of the correlation between oral Ca and serum magnesium (Mg) / phosphorus (P) concentration (Mg: MD = -0.04; 95% CI = [-0.10, 0.02]; P: MD = 0.05; 95% CI = [-0.10, 0.21]) or incidence of other calving-related disorders (metritis: RR = 1.06, CI = [0.94, 1.19]; ketosis: RR = 1.04, CI = [0.91, 1.18]; mastitis: RR = 1.02, CI = [0.86, 1.21]; displacement of the abomasum: RR = 0.81, CI = [0.57, 1.16]) or pregnancy risk (pregnancy risk at first service: RR = 0.99, CI = [0.94, 1.05]; overall pregnancy rate: RR = 1.03, CI = [0.98, 1.08]) or milk yield (MD = 0.44; 95% CI = [-0.24, 1.13]). The distribution of the funnel plot formed by the included studies was symmetrical, and the Egger's test had a p > 0.05, indicating that there was no significant publication bias. Sensitivity analyses results suggested that the results of metaanalysis are robust. Quality assessment of the included studies revealed that the risk of bias was focused on selection bias, performance bias, detection bias and other sources of bias, and the future research should focus on these aspects. [ABSTRACT FROM AUTHOR]

Aim: To explore the risk factors of osteoporosis in postmenopausal women in China. Method: This study collected all patient data from January 2014 to December 2015. Basic information and questionnaires were collected from 524 postmenopausal women in Sanya and Hainan Province. The questionnaire was administered to the enrolled participants by endocrinologists. Biochemical parameters were measured using fasting blood samples, and bone density was measured by dual energy X-ray absorptiometry at the department of radiology of Hainan hospital, PLA General Hospital. Participants with an R-value of ≤-2.5 were diagnosed with osteoporosis. After deleting missing values for each factor, 334 participants were divided into the osteoporosis (n=35) and non-osteoporosis (n=299) groups according to the R-values. Results: The participants had a median age of 60.8 years (range: 44–94 years). Among the 334 postmenopausal women included in this study, 35 (10.5%) were diagnosed with osteoporosis. Univariate analysis showed statistically significant differences in age, BMI, type of work, alkaline phosphatase, years of smoking, blood calcium levels, kyphosis, fracture, and asthma between the two groups (P<0.05). In addition, multivariate logistic analysis showed that age (odds ratio [OR]: 1.185, 95% confidence interval [CI]: 1.085–1.293, P<0.001) and kyphosis times (OR:1.468, 95% CI: 1.076–2.001, P=0.015) were positively correlated with postmenopausal osteoporosis, whereas BMI (OR: 0.717, 95% CI: 0.617–0.832, P<0.001), blood calcium levels (OR: 0.920, 95% CI: 0.854-0.991, P=0.027), vitamin D levels (OR: 0.787, 95% CI: 0.674–0.918, P=0.002), and outdoor activity time (OR: 0.556, 95% CI: 0.338-0.915, P=0.021) were negatively correlated with postmenopausal osteoporosis. Conclusion: Low BMI, blood calcium and vitamin D levels, kyphosis time, and outdoor activity time are independent risk factors for osteoporosis in postmenopausal women. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether prior cholecystectomy is associated with incident osteoporosis. Background: Cholecystectomy may have consequences involving abnormal metabolism. Studies investigating the association between prior cholecystectomy and osteoporosis have yielded inconsistent results. Methods: In total, 17,603 UK Biobank participants underwent cholecystectomy, and 35,206 matched controls were included in this study. They were followed up for incident osteoporosis, which was determined using ICD-10 codes (M80-82). The association between cholecystectomy and osteoporosis was assessed using Cox proportional regression modeling. The association between osteoporosis risk and cholecystectomy was further analyzed across age, sex, serum vitamin D level, and body mass index (BMI) categories. Results: Within a median follow-up period of 13.56 years, 3,217 participants were diagnosed with osteoporosis. After adjustment for relevant confounders, prior cholecystectomy was associated with a 1.21 times higher risk of osteoporosis in women (hazard ratio (HR): 1.21 [95% CI, 1.12-1.31], p < 0.001) and a 1.45 times higher risk in men (HR: 1.45 [95% CI, 1.10-1.90], p = 0.007). In women, the association was stronger for patients who were aged 40-55 years, with BMI < 18.5 kg/m2, and vitamin D between 30 and 50 nmol/ml. No significant interactions between cholecystectomy and income level, education level, presence of hypertension, or diabetes were identified in either sex. Conclusions: Our findings indicated that people who underwent cholecystectomy had a higher risk of developing osteoporosis after adjustment for potential confounders. Our findings suggest that awareness of the risk of osteoporosis in patients with a history of cholecystectomy is merited. [ABSTRACT FROM AUTHOR]

Background: Bisphosphonates have been reported to increase the risk of atrial fibrillation. Therefore, it is conceivable that they may increase the risk of cardioembolic ischemic stroke (IS). However, most epidemiological studies carried out thus far have not shown an increased risk of IS, though none separated by the main pathophysiologic IS subtype (cardioembolic and noncardioembolic) which may be crucial. In this study, we tested the hypothesis that the use of oral bisphosphonates increases specifically the risk of cardioembolic IS, and explored the effect of treatment duration, as well as the potential interaction between oral bisphosphonates and calcium supplements and anticoagulants. Methods: We performed a case-control study nested in a cohort of patients aged 40-99 years, using the Spanish primary healthcare database BIFAP, over the period 2002-2015. Incident cases of IS were identified and classified as cardioembolic or non-cardioembolic. Five controls per case were randomly selected, matched for age, sex, and index date (first recording of IS) using an incidence-density sampling. The association of IS (overall and by subtype) with the use of oral bisphosphonates within the last year before index date was assessed by computing the adjusted odds ratios (AOR) and their 95% CI using a conditional logistic regression. Only initiators of oral bisphosphonates were considered. Results: A total of 13,781 incident cases of IS and 65,909 controls were included. The mean age was 74.5 (SD ± 12.4) years and 51.6% were male. Among cases, 3.15% were current users of oral bisphosphonates, while among controls they were 2.62%, yielding an AOR of 1.15 (95% CI:1.01-1.30). Of all cases, 4,568 (33.1%) were classified as cardioembolic IS (matched with 21,697 controls) and 9,213 (66.9%) as non-cardioembolic IS (matched with 44,212 controls) yielding an AOR of 1.35 (95% CI:1.10-1.66) and 1.03 (95% CI: 0.88-1.21), respectively. The association with cardioembolic IS was clearly duration-dependent (AOR≤1 year = 1.10; 95% CI:0.82-1.49; AOR>1-3 years = 1.41; 95% CI: 1.01-1.97; AOR>3 years = 1.81; 95% CI:1.25-2.62; p for trend = 0.001) and completely blunted by anticoagulants, even in long-term users (AOR>1 year = 0.59; 0.30-1.16). An interaction between oral bisphosphonates and calcium supplements was suggested. Conclusion: The use of oral bisphosphonates increases specifically the odds of cardioembolic IS, in a duration-dependent manner, while leaves materially unaffected the odds of non-cardioembolic IS. [ABSTRACT FROM AUTHOR]

Osteoporosis is an age-related disease of bone metabolism marked by reduced bone mineral density and impaired bone strength. The disease causes the bones to weaken and break more easily. Osteoclasts participate in bone resorption more than osteoblasts participate in bone formation, disrupting bone homeostasis and leading to osteoporosis. Currently, drug therapy for osteoporosis includes calcium supplements, vitamin D, parathyroid hormone, estrogen, calcitonin, bisphosphates, and other medications. These medications are effective in treating osteoporosis but have side effects. Copper is a necessary trace element in the human body, and studies have shown that it links to the development of osteoporosis. Cuproptosis is a recently proposed new type of cell death. Copper-induced cell death regulates by lipoylated components mediated via mitochondrial ferredoxin 1; that is, copper binds directly to the lipoylated components of the tricarboxylic acid cycle, resulting in lipoylated protein accumulation and subsequent loss of iron-sulfur cluster proteins, leading to proteotoxic stress and eventually cell death. Therapeutic options for tumor disorders include targeting the intracellular toxicity of copper and cuproptosis. The hypoxic environment in bone and the metabolic pathway of glycolysis to provide energy in cells can inhibit cuproptosis, which may promote the survival and proliferation of various cells, including osteoblasts, osteoclasts, effector T cells, and macrophages, thereby mediating the osteoporosis process. As a result, our group tried to explain the relationship between the role of cuproptosis and its essential regulatory genes, as well as the pathological mechanism of osteoporosis and its effects on various cells. This study intends to investigate a new treatment approach for the clinical treatment of osteoporosis that is beneficial to the treatment of osteoporosis. [ABSTRACT FROM AUTHOR]

IntroductionBioavailability of calcium is an important consideration when designing supplements for achieving adequate calcium intake, mainly in high-risk, and aged populations. Alternative supplementation strategies may be able to circumvent absorption issues commonly seen with calcium supplements. The objective of this study was to assess the bioavailability of a single serving of two calcium formulations vs. comparator product in healthy postmenopausal women.MethodsA total of 24 participants between 45 and 65 years were enrolled in a randomized, double-blind, three-phase, crossover study, with a 7-day washout period between phases. The bioavailability of calcium from calcium-carrying Saccharomyces cerevisiae (Ca-SC) or calcium-carrying Lactobacillus (Ca-LAB) in the form of postbiotic products versus calcium citrate, a conventional salt-based calcium supplement, was determined. Each product provided 630 mg of calcium and 400 IU of vitamin D3. After a 14-h (overnight) fast followed by a single dose of product with a standard low-calcium breakfast, both serum and urine calcium concentrations were assessed for up to 8 and 24 h, respectively.ResultsCa-LAB resulted in greater calcium bioavailability, demonstrated by significantly higher area under the curve and peak concentration both in blood and urine, and total calcium mass excreted in urine. The bioavailability of calcium was similar for Ca-SC and calcium citrate except for the peak concentration value that was significantly higher for calcium citrate. Both Ca-LAB and Ca-SC were well tolerated with no significant difference in adverse events between the products during the study.DiscussionThese findings suggest that calcium enriched in a Lactobacillus-based postbiotic system is associated with higher levels of bioavailability as compared to calcium citrate, while a calcium-enriched yeast-based postbiotic does not influence calcium absorption.

Microbial communities play critical roles in mobilizing soil nutrition and, consequentially, shaping plant growth and stress responses. Soluble calcium in the pegging zone is essential for peanut yield. Calcium starvation may lead to seed abortion and increased incidence of disease, such as pod rot. Currently, gypsum or lime are often used to supplement calcium in the pegging zone. Calcite Dissolving Bacteria (CDB) can dissolve poorly soluble calcite into Ca2+ thus making it available to plants. Here, we report the isolation and characterization of CDB from a peanut field in Tifton, Georgia. We identified 65 CDB isolates, representing 15 unique strains belonging to 10 different genera. When applied to field soil, most of these CDB survived only several days. However, a synthetic community of CDB strains increased soluble calcium levels when applied to field soil. We also found that CDB abundancy was negatively associated with a soluble calcium level in soil. In summary, we conclude that CDB has the capacity to influence calcium availability in soil, and the abundance of CDB in a bacterial community dynamically respond to soil calcium levels. [ABSTRACT FROM AUTHOR]

Background: Sea buckthorn (SBT) is a traditional Chinese medicine (TCM), rich in calcium, phosphorus, and vitamins, which can potentially prevent and treat osteoporosis. However, no research has been conducted to confirm these hypotheses. QiangGuYin (QGY) is a TCM compound used to treat osteoporosis. There is a need to investigate whether SBT enhances QGY efficacy. Objectives: The aim of this study was to explore whether SBT enhances QGY efficacy by inhibiting CKIP-1 and Notum expression through the Wnt/β-catenin pathway. The study also aimed to explore the active components of SBT. Methods: Experimental animals were divided into control, model, QGY, SBT, SBT + Eucommia ulmoides (EU), and SBT + QGY groups. After treatment, bone morphometric parameters, such as estrogen, PINP, and S-CTX levels, and Notum, CKIP-1, and β-catenin expression were examined. Screening of SBT active components was conducted by molecular docking to obtain small molecules that bind Notum and CKIP-1. Results: The results showed that all the drug groups could elevate the estrogen, PINP, and S-CTX levels, improve femoral bone morphometric parameters, inhibit Notum and CKIP-1 expression, and promote β-catenin expression. The effect of SBT + EU and SBT + QGY was superior to the others. Molecular docking identified that SBT contains seven small molecules (folic acid, rhein, quercetin, kaempferol, mandenol, isorhamnetin, and entepicatechin) with potential effects on CKIP-1 and Notum. Conclusion: SBT improves bone morphometric performance in PMOP rats by inhibiting CKIP-1 and Notum expression, increasing estrogen levels, and activating the Wnt/β-catenin signaling pathway. Furthermore, SBT enhances the properties of QGY. Folic acid, rhein, quercetin, kaempferol, mandenol, isorhamnetin, and ent-epicatechin are the most likely active ingredients of SBT. These results provide insight into the pharmacological mechanisms of SBT in treating osteoporosis. [ABSTRACT FROM AUTHOR]

Denosumab is a pivotal treatment for postmenopausal women with osteoporosis. Although its clinical use is generally well tolerated by patients, denosumab in patients with renal insufficiency may increase the risk of hypocalcemia. Thus, we have to consider the population of denosumab in the treatment of osteoporosis and preventive measures for related complications. In a patient with cardiorenal insufficiency, we reported a case of denosumab-induced hypocalcemia complicated by acute left heart failure due to delayed administration of active vitamin D and calcium supplements. The patient's symptoms did not improve after anti-heart failure treatment. However, after adequate calcium and vitamin D supplementation subsequently, the patient's symptoms of heart failure were rapidly relieved, and the serum calcium level returned to normal within three weeks. Therefore, our case showed that the application of denosumab in patients requires assessment of cardiac and renal function, timely calcium and vitamin D supplementation, and enhanced monitoring of serum calcium levels to prevent acute left heart failure induced by denosumab-related hypocalcemia. [ABSTRACT FROM AUTHOR]

Background: Hypocalcemia is the most common complication that challenges surgeons performing total thyroidectomy. Conventional postoperative calcium and calcitriol supplement has been reportedly effective; however, a time lag has been reported before taking effect. Therefore, the role of preoperative strategy is yet to be determined. Study design: In this prospective, randomized, open-label, parallel-controlled phase II clinical study (registration number: ChiCTR2200059815), a short-term preoperative administration of calcitriol and calcium was proposed in 210 patients undergoing total thyroidectomy and bilateral central compartment neck dissection. Patients were recruited and randomized (1:1:1) into three groups: (A) combined (preoperative calcitriol and calcium), (B) calcium only (preoperative calcium only), and (C) control (no preoperative intervention). Finally, a total of 172 patients were qualified for final analysis. Results: Our data showed that 16 of 63 patients (25.4%) in the combined group had symptomatic hypocalcemia, whereas more patients from the control group (25 of 57 patients, 43.9%, P = 0.033) had symptomatic hypocalcemia. Further, the postoperative calcium level in the combined group is higher than in the control group (2.15 ± 0.15 vs. 2.09 ± 0.15 mmol/L, P = 0.031). Moreover, patients from the combined group showed lower calcium rates of <2.00 mmol/L (12.7% vs. 28.1%, P = 0.036). Remarkably, compared with the control group, patients with transient hypoparathyroidism in the combined group showed fewer rates for both symptomatic and biochemical hypocalcemia (28.6% vs. 61.1% for symptomatic hypocalcemia; 47.6% vs. 75% for biochemical hypocalcemia). Patients without transient hypoparathyroidism in all three groups showed no significant difference in rates for either symptomatic or biochemical hypocalcemia, indicating that this preoperative strategy is only effective for patients with transient hypoparathyroidism. We did not observe such beneficial effects in patients from the calcium group. Conclusions: Preoperative administration of calcitriol and calcium could reduce symptomatic and biochemical hypocalcemia, especially for those with transient hypoparathyroidism. Moreover, this maneuver could be recommended as a clinical routine in patients undergoing total thyroidectomy and bilateral central compartment neck dissection. [ABSTRACT FROM AUTHOR]

Background: Trichohepatoenteric syndrome (THES) is a rare Mendelian autosomal recessive genetic disease characterized by intractable diarrhea, woolly hair, facial abnormality, immune dysfunction, and intrauterine growth restriction. THES mutations are found in the TTC37 and SKIV2L genes, which encode two components of the human superkiller (SKI) complex. Methods and results: We report one case of a 32-year-old woman of Chinese descent with THES, who was born with a low weight (2000 g). She had intractable diarrhea during the neonatal period and was allergic to cow's milk and condensed milk, but did not require total parenteral nutrition. She experienced menarche at age 12 and amenorrhea at age 28. In May 2019, the patient presented with a left fibular head fracture and was diagnosed with osteoporosis. Genetic testing showed a novel mutation in exon1 [p.E5Afs∗37 (c.12_13del)] of SKIV2L , which is composed of 28 exons. After the diagnosis, hormone replacement therapy was prescribed, in addition to the routine calcium and vitamin D supplements. Conclusion: This case expands the clinical characteristic and phenotype spectrum of THES, providing further understanding of SKIV2L and its autoimmune influence. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is a common, multifactorial disease. While observational studies have identified an association between lower vitamin D and higher CRC risk, supplementation trials have been inconclusive and the mechanisms by which vitamin D may modulate CRC risk are not well understood. We sought to perform a weighted gene co-expression network analysis (WGCNA) to identify modules present after vitamin D supplementation (when plasma vitamin D level was sufficient) which were absent before supplementation, and then to identify influential genes in those modules. The transcriptome from normal rectal mucosa biopsies of 49 individuals free from CRC were assessed before and after 12 weeks of 3200IU/day vitamin D (Fultium-D3) supplementation using paired-end total RNAseq. While the effects on expression patterns following vitamin D supplementation were subtle, WGCNA identified highly correlated genes forming gene modules. Four of the 17 modules identified in the post-vitamin D network were not preserved in the pre-vitamin D network, shedding new light on the biochemical impact of supplementation. These modules were enriched for GO terms related to the immune system, hormone metabolism, cell growth and RNA metabolism. Across the four treatment-associated modules, 51 hub genes were identified, with enrichment of 40 different transcription factor motifs in promoter regions of those genes, including VDR:RXR. Six of the hub genes were nominally differentially expressed in studies of vitamin D effects on adult normal mucosa organoids: LCN2, HLA-C, AIF1L, PTPRU, PDE4B and IFI6. By taking a gene-correlation network approach, we have described vitamin D induced changes to gene modules in normal human rectal epithelium in vivo , the target tissue from which CRC develops. [ABSTRACT FROM AUTHOR]

It has been a long time that the relationship between serum calcium levels and Alzheimer's disease (AD) remains unclear. Until recently, observational studies have evaluated the association between serum calcium levels and the risk of AD, however, reported inconsistent findings. Meanwhile, a Mendelian randomization (MR) study had been conducted to test the causal association between serum calcium levels and AD risk, however, only selected 6 serum calcium SNPs as the instrumental variables. Hence, these findings should be further verified using additional more genetic variants and large-scale genome-wide association study (GWAS) dataset to increase the statistical power. Here, we conduct an updated MR analysis of the causal association between serum calcium levels and the risk of AD using a two-stage design. In discovery stage, we conducted a MR analysis using 14 SNPs from serum calcium GWAS dataset (N = 61,079), and AD GWAS dataset (N = 63,926, 21,982 cases, 41,944 cognitively normal controls). All four MR methods including IVW, weighted median, MR-Egger, and MR-PRESSO showed a reduced trend of AD risk with the increased serum calcium levels. In the replication stage, we performed a MR analysis using 166 SNPs from serum calcium GWAS dataset (N = 305,349), and AD GWAS dataset (N = 63,926, 21,982 cases, 41,944 cognitively normal controls). Only the weighted median indicated that genetically increased serum calcium level was associated with the reduced risk of AD. Hence, additional studies are required to investigate these findings. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to investigate parathyroid hormone (PTH), serum calcium, phosphorus, and 25-hydroxyvitamin D (25-OH-VD) changes before and after radioactive iodine (RAI) in differentiated thyroid carcinoma (DTC) patients at different time points. Methods: A total of 259 DTC patients who received RAI were prospectively enrolled. We evaluated PTH, serum calcium, phosphorus, and 25-OH-VD levels at baseline pre-RAI, five days, six weeks, and six months post-RAI, respectively. We analyzed the risk factors of hypocalcemia at five days post-RAI. Results: The mean PTH, serum calcium and phosphorus values decreased five days post-RAI compared with pre-RAI (PTH 4.18 ± 1.23 pmol/L vs. 3.95 ± 1.41 pmol/L; calcium 2.27 ± 0.09 mmol/L vs. 2.20 ± 0.11 mmol/L; phosphorus 1.25 ± 0.17 vs. 0.98 ± 0.20 mmol/L, P < 0.05), and the differences were statistically significant. The mean 25-OH-VD levels did not significantly decrease at five days post-RAI. 21.2% (55/259) of patients had hypocalcemia at five days post-RAI, and all of them were given oral calcium supplements. At six weeks post-RAI, all of the above parameters were higher than those at five days post-RAI. Multivariate regression analysis showed that baseline pre-RAI serum calcium < 2.27 mmol/L, PTH < 4.18 pmol/L and negative 99mTcO4- thyroid imaging were risk factors for hypocalcemia at five days post-RAI. Conclusion: For DTC patients with normal PTH and serum calcium levels at pre-RAI, their PTH, serum calcium, and phosphorus levels decreased at five days post-RAI. About one-fifth of patients could have hypocalcemia at five days post-RAI. Lower baseline pre-RAI serum calcium and PTH levels and negative 99mTcO4- thyroid imaging were risk factors for hypocalcemia five days post-RAI. [ABSTRACT FROM AUTHOR]

Moraxella bovoculi is the bacterium most often cultured from ocular lesions of cattle with infectious bovine keratoconjunctivitis, also known as bovine pinkeye. Some strains of M. bovoculi contain operons encoding for a repeats-in-toxin (RTX) toxin, which is a known virulence factor of multiple veterinary pathogens. We explored the utility of MALDI-TOF MS and biomarker detection models to classify the presence or absence of an RTX phenotype in M. bovoculi. Ninety strains that had undergone whole genome sequencing were classified by the presence or absence of complete RTX operons and confirmed with a visual assessment of hemolysis on blood agar. Strains were grown on Tryptic Soy Agar (TSA) with 5% sheep blood, TSA with 5% bovine blood that was supplemented with 10% fetal bovine serum, 10 mmol/LCaCl2, or both. The formulations were designed to determine the influence of growth media on toxin production or activity, as calcium ions are required for toxin secretion and activity. Mass spectra were obtained for strains grown on each agar formulation and biomarker models were developed using ClinProTools 3.0 software. The most accurate model was developed using spectra from strains grown on TSA with 5% bovine blood and supplemented with CaCl2, which had a sensitivity and specificity of 93.3% and 73.3%, respectively, regarding RTX phenotype classification. The same biomarker model algorithm developed from strains grown on TSA with 5% sheep blood had a substantially lower sensitivity and specificity of 68.0% and 52.0%, respectively. Our results indicate that MALDI-TOF MS biomarker models can accurately classify strains of M. bovoculi regarding the presence or absence of RTX toxin operons and that agar media modifications improve the accuracy of these models. [ABSTRACT FROM AUTHOR]

Administration of the optimal dose of levothyroxine (LT4) is crucial to restore euthyroidism after total thyroidectomy. An insufficient or excessive dosage may result in hypothyroidism or thyrotoxicosis, either one associated with a number of symptoms/complications. Most literature regarding the LT4 dosage deals with the treatment of primary hypothyroidism, whereas a limited number of studies handle the issue of thyroxin replacement after total thyroidectomy. A literature review was performed focusing on all papers dealing with this topic within the last 15 years. Papers that reported a scheme to calculate the proper LT4 dose were collected and compared to set up a review exploring limits and drawbacks of LT4 replacement therapy in the wide population of patients who had undergone thyroidectomy. Most of the methods for monitoring and adjusting thyroid hormone replacement after thyroidectomy for benign disease use LT4 at an empirical dose of approximately 1.6 μg/kg, with subsequent changes according to thyroid function test results and assessments of the patient's symptoms. Approximately 75% of patients require a dose adjustment, suggesting that factors other than body weight play a role in the determination of the proper LT4 dose. Hence, several schemes are reported in the literature for the proper initial dose of LT4. An inadequate level of thyroid hormone levels in these patients can be due to several factors. The most common ones that lead to the necessity of LT4 dose adjustments include lack of compliance, changes in LT4 formulation, dosage errors, increased serum levels of T4-binding globulin, body mass changes, and dietary habits. Moreover, concomitant ingestion of calcium supplements, ferrous sulfate, proton-pump inhibitors, bile acid sequestrants, and sucralfate might influence LT4 absorption and/or metabolism. Furthermore, some gastrointestinal conditions and their treatments can contribute to suboptimal LT4 performance by altering gastric acidity and thereby reducing its bioavailability, particularly in the solid form. Beyond the classic tablet form, new formulations of LT4, such as a soft gel capsule and an oral solution, recently became available. The liquid formulation is supposed to overcome the food and beverages interference with absorption of LT4 tablets. [ABSTRACT FROM AUTHOR]

ARHGAP21 is a RhoGAP protein implicated in the modulation of insulin secretion and energy metabolism. ARHGAP21 transient-inhibition increase glucose-stimulated insulin secretion (GSIS) in neonatal islets; however, ARHGAP21 heterozygote mice have a reduced insulin secretion. These discrepancies are not totally understood, and it might be related to functional maturation of beta cells and peripheral sensitivity. Here, we investigated the real ARHGAP21 role in the insulin secretion process using an adult mouse model of acute ARHGAP21 inhibition, induced by antisense. After ARHGAP21 knockdown induction by antisense injection in 60-day old male mice, we investigated glucose and insulin tolerance test, glucose-induced insulin secretion, glucose-induced intracellular calcium dynamics, and gene expression. Our results showed that ARHGAP21 acts negatively in the GSIS of adult islet. This effect seems to be due to the modulation of important points of insulin secretion process, such as the energy metabolism (PGC1α), Ca2+ signalization (SYTVII), granule-extrusion (SNAP25), and cell-cell interaction (CX36). Therefore, based on these finds, ARHGAP21 may be an important target in Diabetes Mellitus (DM) treatment. [ABSTRACT FROM AUTHOR]

We previously showed that extracellular ATP and hydrogen sulfide (H2S), a recently discovered gasotransmitter, are both triggering the nociceptive firing in trigeminal nociceptors implicated in migraine pain. ATP contributes to meningeal nociception by activating the P2X3 subunit-containing receptors whereas H2S operates mainly via TRP receptors. However, H2S was also proposed as a neuroprotective and anti-nociceptive agent. This study aimed to test the effect of H2S on ATP-mediated nociceptive responses in rat meningeal afferents and trigeminal neurons and on ATP-induced degranulation of dural mast cells. Electrophysiological recording of trigeminal nerve activity in meninges was supplemented by patch-clamp and calcium imaging studies of isolated trigeminal neurons. The H2S donor NaHS induced a mild activation of afferents and fully suppressed the subsequent ATP-induced firing of meningeal trigeminal nerve fibers. This anti-nociceptive effect of H2S was specific as an even stronger effect of capsaicin did not abolish the action of ATP. In isolated trigeminal neurons, NaHS decreased the inward currents and calcium transients evoked by activation of ATP-gated P2X3 receptors. Moreover, NaHS prevented ATP-induced P2X7 receptor-mediated degranulation of meningeal mast cells which emerged as triggers of migraine pain. Finally, NaHS decreased the concentration of extracellular ATP in the meningeal preparation. Thus, H2S exerted the multiple protective actions against the nociceptive effects of ATP. These data highlight the novel pathways to reduce purinergic mechanisms of migraine with pharmacological donors or by stimulation production of endogenous H2S. [ABSTRACT FROM AUTHOR]

Background: Though increasing epidemiological studies have evaluated the correlation between serum calcium contents and Parkinson's disease (PD), the results are inconsistent. At present, whether there is a causal association between serum calcium content and PD remains undetermined. Objective and Methods: This study was designed to explore the relationship between increased serum calcium contents and PD risk. In this present study, a Mendelian randomization trial was carried out using a large-scale serum calcium genome-wide association study (GWAS) dataset (N = 61,079, Europeans) and a large-scale PD GWAS dataset (N = 8,477, Europeans including 4,238 PD patients and 4,239 controls). Here, a total of four Mendelian randomization methods comprising weighted median, inverse-variance weighted meta-analysis (IVW), MR-Egger, and MR-PRESSO were used. Results: Our data concluded that genetically higher serum calcium contents were not significantly related to PD. Conclusion: In conclusion, we provided genetic evidence that there was no direct causal relationship between serum calcium contents and PD. Hence, calcium supplementation may not result in reduced PD risk. [ABSTRACT FROM AUTHOR]

Keywords: SARS-Cov-2; COVID-19; vitamin D; antiviral; anti-inflammatory EN SARS-Cov-2 COVID-19 vitamin D antiviral anti-inflammatory 1 4 4 06/26/20 20200623 NES 200623 The ongoing pandemic: Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 has become one of the most important epidemiological events within the last 100 years, causing devastating consequences for the public health systems and the socioeconomical tissue around the world ([1]-[3]). In line with findings from other reports ([10]), our observations that vitamin D-derived antiviral mechanisms can restrict viral infection and attenuate the pro-inflammatory response ([22]) have been corroborated I ex vivo i in two different vitamin D supplementation exploratory studies. Indeed, outbreaks and higher incidence of respiratory viruses such as influenza and coronavirus are common beyond subtropical areas with low sunlight exposure levels and prevalence of vitamin D deficiency/insufficiency such as Europe and Northern United States, which have been highly affected by COVID-19 ([10], [11], [58]). In summary, we postulate that conventional oral vitamin D supplementation can be a readily strategy to aim: (i) restriction of SARS-CoV-2 infection via downregulation of ACE2 receptor, and (ii) attenuation of disease severity by down-tuning the pulmonary pro-inflammatory response or cytokine storm that fuels COVID-19 severity. [Extracted from the article]

Background and Purpose: Rabeprazole, a proton pump inhibitor (PPIs) is much endorsed to patients with increased gastric acidity. PPIs were accused to have osteoporotic effects on patients who chronically use them. The point of the current investigation was to decide the impact of rabeprazole on osteoporosis and to explore the modulatory effects of dietary calcium or alendronate on this side effect. Methods: 80 female mice were alienated into four groups maintained for 18 weeks: [1] Vehicle group: given distilled water in 12 ml/kg, P.O. [2] Rabeprazole control group: given rabeprazole in a dose equals 10 mg/kg every 48 h, P.O. [3] Rabeprazole + calcium: given rabeprazole (10 mg/kg every 48 h) along with calcium supplement. [4] Rabeprazole + alendronate: given rabeprazole (10 mg/kg every 48 h) and alendronate (1 mg/kg per week, i.p.). Serum calcium, phosphorus and parathyroid hormone were measured. Both femurs were kept in paraformaldehyde, and then the right one was used for X-ray examination with analysis by Digora software and the left one for histopathological examination (H&E) and immunohistochemical stains for osteopontin and tartrate resistant acid phosphatase (TRAP). Results: Calcium supplementation or administration of alendronate along with rabeprazole significantly restored the mean bone density as shown by X-ray analysis. Femurs from mice received rabeprazole showed widely separated, thin-walled bone trabeculae and increased number of osteoclasts. Calcium or alendronate with rabeprazole showed thick bone trabeculae without full recovery from rabeprazole induced damage. Adding calcium supplementation to rabeprazole did not affect the histological abnormalities related to osteoclasts meanwhile alendronate produced inactivation of osteoclasts. Both calcium and alendronate decreased the rabeprazole-induced increment in the femur osteopontin level. Conclusion: Calcium or alendronate can be recommended for female patients on PPI therapy who are at risk of osteopenia. [ABSTRACT FROM AUTHOR]

Calcium (Ca2+) is an essential signaling molecule that controls a wide range of biological functions. In the immune system, calcium signals play a central role in a variety of cellular functions such as proliferation, differentiation, apoptosis, and numerous gene transcriptions. During an immune response, the engagement of T-cell and B-cell antigen receptors induces a decrease in the intracellular Ca2+ store and then activates store-operated Ca2+ entry (SOCE) to raise the intracellular Ca2+ concentration, which is mediated by the Ca2+ release-activated Ca2+ (CRAC) channels. Recently, identification of the two critical regulators of the CRAC channel, stromal interaction molecule (STIM) and Orai1, has broadened our understanding of the regulatory mechanisms of Ca2+ signaling in lymphocytes. Repetitive or prolonged increase in intracellular Ca2+ is required for the calcineurin-mediated dephosphorylation of the nuclear factor of an activated T cell (NFAT). Recent data indicate that Ca2+-calcineurin-NFAT1 to 4 pathways are dysregulated in autoimmune diseases. Therefore, calcineurin inhibitors, cyclosporine and tacrolimus, have been used for the treatment of such autoimmune diseases as systemic lupus erythematosus and rheumatoid arthritis. Here, we review the role of the Ca2+-calcineurin–NFAT signaling pathway in health and diseases, focusing on the STIM and Orai1, and discuss the deregulated calcium-mediated calcineurin-NFAT pathway in autoimmune diseases. [ABSTRACT FROM AUTHOR]

Calcium supplements are broadly prescribed to treat osteoporosis either as monotherapy or together with vitamin D to enhance calcium absorption. It is still unclear whether calcium supplementation significantly contributes to the reduction of bone fragility and fracture risk. Data suggest that supplementing post-menopausal women with high doses of calcium has a detrimental impact on cardiovascular morbidity and mortality. Chronic kidney disease (CKD) patients are prone to vascular calcification in part due to impaired phosphate excretion. Calcium-based phosphate binders further increase risk of vascular calcification progression. In both bone and vascular tissue, vitamin K-dependent processes play an important role in calcium homeostasis and it is tempting to speculate that vitamin K supplementation might protect from the potentially untoward effects of calcium supplementation. This review provides an update on current literature on calcium supplementation among post-menopausal women and CKD patients and discusses underlying molecular mechanisms of vascular calcification. We propose therapeutic strategies with vitamin K2 treatment to prevent or hold progression of vascular calcification as a consequence of excessive calcium intake.

The recent worldwide rise in idiopathic immune and inflammatory diseases such as multiple sclerosis (MS) and inflammatory bowel diseases (IBD) has been linked to Western society-based changes in lifestyle and environment. These include decreased exposure to sunlight/UVB light and subsequent impairment in the production of vitamin D, as well as dysbiotic changes in the makeup of the gut microbiome. Despite their association, it is unclear if there are any direct links between UVB light and the gut microbiome. In this study we investigated whether exposing the skin to Narrow Band Ultraviolet B (NB-UVB) light to increase serum vitamin D levels would also modulate the makeup of the human intestinal microbiota. The effects of NB-UVB light were studied in a clinical pilot study using a healthy human female cohort (n = 21). Participants were divided into those that took vitamin D supplements throughout the winter prior to the start of the study (VDS+) and those who did not (VDS−). After three NB-UVB light exposures within the same week, the serum 25(OH)D levels of participants increased on average 7.3 nmol/L. The serum response was negatively correlated to the starting 25-hydroxy vitamin D [25(OH)D] serum concentration. Fecal microbiota composition analysis using 16S rRNA sequencing showed that exposure to NB-UVB significantly increased alpha and beta diversity in the VDS− group whereas there were no changes in the VDS+ group. Bacteria from several families were enriched in the VDS− group after the UVB exposures according to a Linear Discriminant Analysis (LDA) prediction, including Lachnospiracheae, Rikenellaceae, Desulfobacteraceae, Clostridiales vadinBB60 group, Clostridia Family XIII, Coriobacteriaceae, Marinifilaceae , and Ruminococcus. The serum 25(OH)D concentrations showed a correlation with the relative abundance of the Lachnospiraceae , specifically members of the Lachnopsira and Fusicatenibacter genera. This is the first study to show that humans with low 25(OH)D serum levels display overt changes in their intestinal microbiome in response to NB-UVB skin exposure and increases in 25(OH)D levels, suggesting the existence of a novel skin-gut axis that could be used to promote intestinal homeostasis and health. Clinical Trial Registration: clinicaltrials.gov, NCT03962673. Registered 23 May 2019 – Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03962673?term=NCT03962673&rank=1. [ABSTRACT FROM AUTHOR]

The present study investigates the regulatory role of exogenous calcium (Ca) in developing salt stress tolerance in rice seedlings. Hydroponically grown 13-day-old rice (Oryza sativa L. cv. BRRI dhan47) seedlings were exposed to 200 mM NaCl alone and combined with 2 mM CaCl2 and 2 mM ethylene glycol tetraacetic acid (EGTA, a Ca scavenger) for 3 days. The salt stress caused growth inhibition, chlorosis and water shortage in the rice seedlings. The salt-induced stress disrupted ion homeostasis through NaC influx and KC efflux, and decreased other mineral nutrient uptake. Salt stress caused oxidative stress in seedlings through lipid peroxidation, loss of plasma membrane integrity, higher reactive oxygen species (ROS) production and methylglyoxal (MG) formation. The salt-stressed seedlings supplemented with exogenous Ca recovered from water loss, chlorosis and growth inhibition. Calcium supplementation in the salt-stressed rice seedlings improved ion homeostasis by inhibition of NaC influx and KC leakage. Exogenous Ca also improved ROS and MG detoxification by improving the antioxidant defense and glyoxalase systems, respectively. On the other hand, applying EGTA along with salt and Ca again negatively affected the seedlings as EGTA negated Ca activity. It confirms that, the positive responses in salt-stressed rice seedlings to exogenous Ca were for Ca mediated improvement of ion homeostasis, antioxidant defense and glyoxalase system. [ABSTRACT FROM AUTHOR]

This work examined the role of exogenously applied calcium (Ca; 50 mM) and potassium (K; 10 mM) (alone and in combination) in alleviating the negative effects of cadmium (Cd; 200 µM) on growth, biochemical attributes, secondary metabolites and yield of chickpea (Cicer arietinum L.). Cd stress significantly decreased the length and weight (fresh and dry) of shoot and root and yield attributes in terms of number of pods and seed yield (vs. control). Exhibition of decreases in chlorophyll (Chl) a, Chl b, and total Chl was also observed with Cd-exposure when compared to control. However, Cd-exposure led to an increase in the content of carotenoids. In contrast, the exogenous application of Ca and K individually as well as in combination minimized the extent of Cd-impact on previous traits. C. arietinum seedlings subjected to Cd treatment exhibited increased contents of organic solute (proline, Pro) and total protein; whereas, Ca and K-supplementation further enhanced the Pro and total protein content. Additionally, compared to control, Cd-exposure also caused elevation in the contents of oxidative stress markers (hydrogen peroxidase, H2O2; malondialdehyde, MDA) and in the activity of antioxidant defense enzymes (superoxide dismutase, SOD; catalase, CAT; ascorbate peroxidase, APX; glutathione reductase, GR). Ca, K, and Ca + K supplementation caused further enhancements in the activity of these enzymes but significantly decreased contents of H2O2 and MDA, also that of Cd accumulation in shoot and root. The contents of total phenol, flavonoid and mineral elements (S, Mn, Mg, Ca and K) that were also suppressed in Cd stressed plants in both shoot and root were restored to appreciable levels with Ca- and K-supplementation. However, the combination of Ca + K supplementation was more effective in bringing the positive response as compared to individual effect of Ca and K on Cd-exposed C. arietinum. Overall, this investigation suggests that application of Ca and/or K can efficiently minimize Cd-toxicity and eventually improve health and yield in C. arietinum by the cumulative outcome of the enhanced contents of organic solute, secondary metabolites, mineral elements, and activity of antioxidant defense enzymes. [ABSTRACT FROM AUTHOR]

Background: In postthyroidectomy patients, hypocalcemia is the most common complication to prolong hospital stay and decrease patients' satisfaction. Based on current evidence, it is recommended to supply vitamin D to patients with high risk of developing hypocalcemia. However, how to stratify the risk of patients remains challenging. Aim: We conducted a prospective study to evaluate the effect of vitamin D supplement (calcitriol) on high-risk hypocalcemia patients based on relative decline of parathyroid hormone (RDP). Method: RDP was calculated by the difference between preoperative and postoperative first-day PTH divided by preoperative PTH and presented as percentage. Patients who underwent total thyroidectomy in addition to bilateral central compartment dissection were enrolled prospectively and were divided into two cohorts: Cohort I: patients with RDP ≤70% and Cohort II: patients with RDP >70%. Patients in Cohort I were then randomly assigned to Group A or B, and patients in Cohort II were randomly assigned to Group C or D. All groups received oral calcium, and patients in Groups B and D also received calcitriol. All patients were followed for one year. In the study, standard procedure dictates that only oral calcium is given to patients whose RDP ≤70% and that oral calcium and calcitriol are given to patients whose RDP >70%. Therefore, Cohort I Group A and Cohort II Group D are controls in this study. Results: The incidence of clinical hypocalcemia in Groups A and D (the controls) was 11.0% (10/91), and 17.6% (16/91) required additional intravenous calcium. Of note, no patients developed permanent hypocalcemia. Furthermore, calcitriol supplement did not have significant impact on clinical outcomes between Group A and B in Cohort I. By contrast, calcitriol supplement distinctly improved clinical outcome by comparing Groups C and D (Cohort II), as marked by clinical hypocalcemia, need of requiring intravenous calcium, and long-termed decreased levels of PTH. Conclusion: Supplying calcitriol based on RDP cutoff of 70% may be a wise practice in thyroidectomy patients, and RDP 70% may be a useful predictor to stratify high-risk patients. [ABSTRACT FROM AUTHOR]