The Synergy Beteeen Diurnal Temperature Range and Calcium Concentration Help to Predict Hospital Mortality in Patients with Acute Myocardial Infarction

Epidemiological studies have suggested that cold is an important contributor to acute cardiovascular events and mortality. However, little is known about the Diurnal Temperature Range(DTR)impact on mortality of the patients with myocardial infarction.Calcium ions(Ca2+)play a vital role in the human body, such as cardiac electrophysiology and contraction.To investigate whether DTR on admission moderates the association between serum calcium and in-hospital mortality in patients with acute myocardial infarction(AMI). This retrospective study enrolled consecutive adult patients with AMI at a single center in China (2003–2012). Patients were divided into four groups (Ca-Q1–4) according to serum calcium concentration quartiles. Multivariate logistic regression modeling was used to assess whether DTR moderated the association between serum calcium and in-hospital mortality. The predictive value of serum calcium was evaluated by receiver operating characteristic (ROC) curve and net reclassification improvement (NRI) analyses.The study included 3780 patients.In-hospital mortality was 4.97%(188/3780).DTR moderated the association between serum calcium and in-hospital mortality(P-interaction=0.020).Patients with low serum calcium in the highest DTR quartile exhibited an increased risk of in-hospital mortality(odds ratio for Ca-Q4 vs.Ca-Q1, 0.03;95%confidence interval[95%CI], 0.01–0.20;P for trend<0.001).In the highest DTR quartile, adding serum calcium concentration to the risk factor model increased the area under the ROC curve(0.81 vs.0.76;P<0.001)and increased NRI by 20.2%(95%CI 7.5–32.9;P=0.001).Low serum calcium was an independent risk factor for in-hospital mortality in patients with AMI, and this association was moderated by DTR.Careful attention should be paid to patients with low serum calcium who experience a higher DTR on admission.

The role of biased calcium-sensing receptor signalling in urinary calcium excretion and kidney stone disease

Michelle Goldsworthy1,2, Asha Bayliss2, Anna Gluck2, Akira Wiberg3, Benjamin Turney1, DominicFurniss3, Rajesh Thakker2, Sarah Howles1,2 1Nuffield Department of Surgical Sciences, University of Oxford, United Kingdom.2Academic Endocrine Unit, Radcliffe Department of Medicine, University of Oxford, UnitedKingdom.3Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Universityof Oxford, United Kingdom. Nephrolithiasis is a major health burden with a poorly understood pathogenesis. We conducted a genome-wide association study in British and Japanese populations identifying twenty nephrolithiasis-associated loci. Mutations in the calcium-sensing receptor (CaSR) cause disorders of calcium homeostasis and five identified loci (DGKD, DGKH, WDR72, GPIC1 and BCR) were predicted to influence CaSR-signalling. In a validation population, we demonstrated that genotype at the DGKD-associated locus correlated with urinary calcium excretion but not serum calcium concentration. In vitro studies demonstrated that knockdown and overexpression of DGKD resulted in biased CaSR-signalling. Thus, treatment of CaSR-expressing HEK cells with DGKD-targeted siRNA (DGKD-KD), resulted in decreased MAPK responses to alterations in extracellular calcium concentration [Ca2+]e, as assessed by SRE-reporter and ERK-phosphorylation (pERK) assays, when compared to cells treated with scrambled siRNA (WT) but without alteration in intracellular calcium responses [Ca2+]i as assessed by NFAT-reporter and Fluo-4 calcium assays (SRE maximal response DGKD-KD =5.28 fold change vs. WT=7.20 p=0.0065, pERK maximal response DGKD-KD=24.77, vs. WT= 39.46 fold change, p=0.0056). Conversely, DGKD overexpression (DGKD-OE) increased MAPK responses but suppressed [Ca2+]i responses to alterations in [Ca2+]e (SRE maximal response DGKD-OE =14.13 fold change vs. WT=9.06 fold change, p=0.01; NFAT maximal response DGKD-OE=13.67 fold change vs WT=59.16 fold change, p=0.0001). Our results demonstrate that alterations in DGKD expression cause biased CaSR-signalling. This biased signalling may provide an explanation for the correlation of genotype at the DGKD-associated locus with urinary calcium excretion but not serum calcium concentration. Our findings suggest that biased CaSR-signalling may be a common cause of nephrolithiasis.

The role of biased calcium-sensing receptor signalling in urinary calcium excretion and kidney stone disease

Michelle Goldsworthy1,2, Asha Bayliss2, Anna Gluck2, Akira Wiberg3, Benjamin Turney1, DominicFurniss3, Rajesh Thakker2, Sarah Howles1,2 1Nuffield Department of Surgical Sciences, University of Oxford, United Kingdom.2Academic Endocrine Unit, Radcliffe Department of Medicine, University of Oxford, UnitedKingdom.3Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Universityof Oxford, United Kingdom. Nephrolithiasis is a major health burden with a poorly understood pathogenesis. We conducteda genome-wide association study in British and Japanese populations identifying twentynephrolithiasis-associated loci. Mutations in the calcium-sensing receptor (CaSR) causedisorders of calcium homeostasis and five identified loci (DGKD, DGKH, WDR72, GPIC1 and BCR)were predicted to influence CaSR-signalling. In a validation population, we demonstrated that genotype at the DGKD-associated locuscorrelated with urinary calcium excretion but not serum calcium concentration. In vitro studiesdemonstrated that knockdown and overexpression of DGKD resulted in biased CaSR-signalling.Thus, treatment of CaSR-expressing HEK cells with DGKD-targeted siRNA (DGKD-KD), resulted indecreased MAPK responses to alterations in extracellular calcium concentration [Ca2+]e, asassessed by SRE-reporter and ERK-phosphorylation (pERK) assays, when compared to cellstreated with scrambled siRNA (WT) but without alteration in intracellular calcium responses[Ca2+]i as assessed by NFAT-reporter and Fluo-4 calcium assays (SRE maximal response DGKD-KD=5.28 fold change vs. WT=7.20 p=0.0065, pERK maximal response DGKD-KD=24.77, vs. WT=39.46 fold change, p=0.0056). Conversely, DGKD overexpression (DGKD-OE) increased MAPKresponses but suppressed [Ca2+]i responses to alterations in [Ca2+]e (SRE maximal responseDGKD-OE =14.13 fold change vs. WT=9.06 fold change, p=0.01; NFAT maximal response DGKDOE=13.67 fold change vs WT=59.16 fold change, p=0.0001). Our results demonstrate that alterations in DGKD expression cause biased CaSR-signalling. Thisbiased signalling may provide an explanation for the correlation of genotype at the DGKDassociatedlocus with urinary calcium excretion but not serum calcium concentration. Ourfindings suggest that biased CaSR-signalling may be a common cause of nephrolithiasis.

COVID-19-associated coagulopathy: thromboembolism prophylaxis and poor prognosis in ICU

Background Coronavirus disease 2019 (COVID-19) is associated with coagulation abnormalities which are indicators of higher mortality especially in severe cases. Methods We studied patients with proven COVID-19 disease in the intensive care unit of Jinyintan Hospital, Wuhan, China from 30 to 2019 to 31 March 2020. Results Of 180 patients, 89 (49.44 %) had died, 85 (47.22 %) had been discharged alive, and 6 (3.33 %) were still hospitalised by the end of data collection. A D-dimer concentration of > 0.5 mg/L on admission was significantly associated with 30 day mortality, and a D-dimer concentration of > 5 mg/L was found in a much higher proportion of non-survivors than survivors. Sepsis-induced coagulopathy (SIC) and disseminated intravascular coagulation (DIC) scoring systems were dichotomised as < 4 or ≥ 4 and < 5 or ≥ 5, respectively, and the mortality rate was significantly different between the two stratifications in both scoring systems. Enoxaparin was administered to 68 (37.78 %) patients for thromboembolic prophylaxis, and stratification by the D-dimer concentration and DIC score confirmed lower mortality in patients who received enoxaparin when the D-dimer concentration was > 2 than < 2 mg/L or DIC score was ≥ 5 than < 5. A low platelet count and low serum calcium concentration were also related to mortality. Conclusions A D-dimer concentration of > 0.5 mg/L on admission is a risk factor for severe disease. A SIC score of > 4 and DIC score of > 5 may be used to predict mortality. Thromboembolic prophylaxis can reduce mortality only in patients with a D-dimer concentration of > 2 mg/L or DIC score of ≥ 5.

Serum Calcium and Its Association with Preeclampsia

Background: The purpose of the study was to evaluate association of serum calcium concentration with preeclampsia. Method: This study was carried out in the Department of Obstetrics and Gynaecology of Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh from January 2016 to December 2016 including 120 antenatal patients in their second half of pregnancy. All the included patients were classified as 40 mild preeclampsia (Group A) 40 severe preeclampsia (Group B) and 40 normal pregnant women (Group C). Serum calcium was estimated in the Department of Biochemistry and correlated with preeclampsia. Result: In results the mean serum calcium concentration was found 8.2±0.2mg /dl in Group A, 7.6 ± 0.3 mg/dl in Group B and 9.0±0.5 mg/dl in Group C (p=0.001). Low serum calcium was found 53.7% and 12.5% in case and control respectively. The difference was statistically significant (p=<0.05) between case and control groups having OR=8.1 with 95% CI (2.7 - 26.5) %. Pearson’s correlation test revealed that both systolic and diastolic blood pressure had negative correlation with the serum calcium concentration (p=<0.05). Conclusion: In conclusion this study showed that low serum calcium is associated with preeclampsia and its concentration inversely proportional to the severity of preeclampsia and both systolic and diastolic blood pressure. Bangladesh Journal of Medical Science Vol.20(2) 2021 p.379-383

Korelasi Konsentrasi Kalsium Serum dengan Fungsi Paru pada Remaja di Makassar

Abstrak. Penelitian ini bertujuan untuk mngetahui korelasi antara konsentrasi kalsium serum dengan fungsi paru pada remaja di SMA Sanur Makassar. Desain penelitian yang digunakan adalah cross sectional study. Populasi dan sampel dalam penelitian ini adalah remaja di SMA Sanur Makassar. Pengumpulan data menggunakan data primer dan data sekunder. Data dianalisis menggunakan analisis univariat dan bivariat. Hasil penelitian menunjukkan bahwa responden paling banyak adalah dengan konsentrasi kalsium serum > 9 mg/dl yaitu 66,67%, dan memiliki fungsi paru (KV) normal yaitu 73,68%, demikian dengan fungsi paru (KVP) normal yaitu 75,44%. Hasil uji statistik diperoleh nilai signifikansi 0,423 > 0,05, dan nilai F hitung 0,651 < F tabel 2,55, maka disimpulkan bahwa ada korelasi secara signifikan antara konsentrasi kalsium serum dengan fungsi paru (KV). Kata kunci: Korelasi, kalsium serum, fungsi paru. Correlation of Serum Calcium Concentration with Lung Function Adolescents in Makassar Abstract. This study aims to determine the correlation between serum calcium concentration and lung function in adolescents at Sanur Makassar High School. The research design used was cross sectional study. The population and sample in this study were teenagers at Sanur Makassar High School. Data collection uses primary data and secondary data. Data were analyzed using univariate and bivariate analysis. The results showed that the most respondents were with serum calcium concentrations> 9 mg / dl that is 66.67%, and had normal lung function (KV) which was 73.68%, so with normal lung function (KVP) which was 75.44%. Statistical test results obtained a significance value of 0.423> 0.05, and a calculated F value of 0.651 <F table 2.55, it was concluded that there was a significant correlation between serum calcium concentration and pulmonary function (CV). Keywords: Correlation, serum calcium, pulmonary function.

The effectivity of Difructose Anhydride III to increase absorption of calcium in the femur bone of calcium deficient rats

Background: Dried yogurt enriched by Difructose Anhydride III when used as a functional food has been observed to increase calcium absorption, making it useful in osteoporosis prevention. The objective of this study was to analyze the effectiveness of Difructose Anhydride III in increasing the absorption of calcium in female rat models, strain Sprague Dawley, in the pre-menopausal age during which they’re calcium deficient.Methods: The effectiveness test of Difructose Anhydride III to increase absorption of calcium in pre-menopausal Sprague Dawley rats was performed in calcium-deficient conditions. A completely randomized experimental design was used with 4 treatments for 6 weeks and 4 replications: normal rats fed with purified diet (C), calcium-deficient rats fed with calcium-deficient diet (CD), calcium-deficient rats fed with calcium-deficient diet and DFA III (dahlia tubers) fortified in dry yogurt (CD+DFA III dahlia), and calcium-deficient rats fed with a calcium-deficient diet and DFA III (chicory roots) fortified in dry yogurt (CD+DFA III chicory). The parameters measured were serum calcium concentration, femur bone calcium concentration, femur bone matrix condition, and femur bone strength.Results: DFA III (dahlia tubers and chicory roots) fortified in dry yogurt contained 0.334% and 0.322% of calcium concentration. The provision of a calcium-deficient diet for 12 weeks was shown to reduce the serum calcium concentration of the deficient calcium rat to 7.72±1.08 mg dL-1 and the control rat to 11.60±0.85 mg dL-1. CD+DFA III chicory treatments also showed a high calcium concentration in the femur bone (34.94±3.21%), a relatively higher bone strength (9.34±3.61 kg cm-2), and a denser femur bone matrix condition than the control. The femur bone calcium level of rats treated with CD+DFA III dahlia and chicory tubers was 28.95±1.95% and 34.94±3.21%, respectively. These results were significantly different than the CD treatment (17.49±4.38%).Conclusion: The evidence from this study suggests that sufficient calcium intake could provide high calcium deposits in the bones. Diets containing 3.60% w/w DFA III fortified in dry yogurt have been shown to enhance calcium absorption in calcium-deficient rats. Additionally, the effectiveness of dried yogurt enriched by DFA III from chicory tubers was higher than that of the dried yogurt enriched by DFA III from dahlia tubers.Preclinical Trial Registration: Animal Ethics Committee at IPB University No. 12-2013Keywords: Bone femur; calcium deficiency; effectivity of Difructose Anhydride III

Clinical and Molecular Genetics of Primary Hyperparathyroidism

Calcium homeostasis is maintained by the actions of the parathyroid glands, which release parathyroid hormone into the systemic circulation as necessary to maintain the serum calcium concentration within a tight physiologic range. Excessive secretion of parathyroid hormone from one or more neoplastic parathyroid glands, however, causes the metabolic disease primary hyperparathyroidism (HPT) typically associated with hypercalcemia. Although the majority of cases of HPT are sporadic, it can present in the context of a familial syndrome. Mutations in the tumor suppressor genes discovered by the study of such families are now recognized to be pathogenic for many sporadic parathyroid tumors. Inherited and somatic mutations of proto-oncogenes causing parathyroid neoplasia are also known. Future investigation of somatic changes in parathyroid tumor DNA and the study of kindreds with HPT yet lacking germline mutation in the set of genes known to predispose to HPT represent two avenues likely to unmask additional novel genes relevant to parathyroid neoplasia.