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Prognostic value of coronary artery calcium score in symptomatic individuals: A meta-analysis of 34,000 subjects.
Lo-Kioeng-Shioe, MS, Rijlaarsdam-Hermsen, D, van Domburg, RT, Hadamitzky, M, Lima, JAC, Hoeks, SE, Deckers, JW
International journal of cardiology. 2020;:56-62
Abstract
BACKGROUND Coronary artery calcium (CAC) scanning has evolved into an important subclinical prediction method for cardiovascular diseases in asymptomatic subjects. However, the prognostic implication of CAC scanning in symptomatic individuals is less clear. OBJECTIVES To assess the prognostic utility of CAC in predicting risk of major adverse cardiac events (MACE) in stable patients with suspected CAD. METHODS We did a systematic electronic literature search for studies presenting original data in CAC score, and reporting cardiovascular events in stable, symptomatic patients as primary outcome. Primary outcome of the meta-analysis was the occurrence of MACE, a composite of late coronary revascularization, hospitalization for unstable angina or heart failure, nonfatal myocardial infarction, and cardiac death or all-cause mortality. Using random effects models, we pooled relative risk ratios of CAC for MACE, and adjusted hazard ratios (HR) of the associations between different CAC strata (CAC 0-100,100-400, and ≥ 400, versus CAC = 0) and incident MACE. RESULTS We included 19 observational studies (n = 34,041). In total, 1601 events were analyzed, of which 158 in patients with CAC = 0. The pooled relative risk ratio was 5.71 (95%-CI: 3.98;8.19) for subjects with CAC > 0. The pooled estimate of adjusted HRs demonstrated increasing, positive associations, with the strongest association for CAC > 400 (HR: 4.88; 95%-CI: 2.44;9.27). CONCLUSIONS This meta-analysis demonstrated that increased levels of CAC are strongly and independently associated with increased risk for MACE in stable, symptomatic patients with suspected CAD, showing increasing risk with greater CAC scores. Application of CAC scanning as a prediction method could be useful for a considerable number of such patients.
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Vitamin D, calcium or a combination of vitamin D and calcium for the treatment of nutritional rickets in children.
Chibuzor, MT, Graham-Kalio, D, Osaji, JO, Meremikwu, MM
The Cochrane database of systematic reviews. 2020;(4):CD012581
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Abstract
BACKGROUND Nutritional rickets is a disease which affects children, especially in low- and middle-income countries. It causes problems such as skeletal deformities and impaired growth. The most common cause of nutritional rickets is vitamin D deficiency. Vitamin D administered with or without calcium is commonly regarded as the mainstay of treatment. In some sunny countries, however, where children are believed to have adequate vitamin D production from exposure to ultraviolet light, but who are deficient in calcium due to low dietary intake, calcium alone has also been used in the treatment of nutritional rickets. Therefore, it is important to compare the effects of vitamin D, calcium or a combination of vitamin D and calcium for the treatment of nutritional rickets in children living in different settings. OBJECTIVES To assess the effects of vitamin D, calcium or a combination of vitamin D and calcium for the treatment of nutritional rickets in children. SEARCH METHODS We searched CENTRAL, MEDLINE, LILACS, WHO ICTRP Search Portal and ClinicalTrials.gov. The date of the last search of all databases was 25 July 2019. We applied no language restrictions. SELECTION CRITERIA We included randomised controlled trials (RCT) involving children aged 0 to 18 years with nutritional rickets which compared treatment with vitamin D, calcium or a combination of vitamin D and calcium. DATA COLLECTION AND ANALYSIS Two review authors independently screened the title and abstracts of all studies, extracted data and assessed the risk of bias of included studies. We resolved any disagreements by consensus or recourse to a third review author. We conducted meta-analyses for the outcomes reported by study authors. For dichotomous outcomes, we calculated the risk ratio (RR) and 95% confidence interval (CI) and, for continuous outcomes, we calculated mean differences (MD) with 95% CIs. We assessed the certainty of the evidence of the included studies using GRADE. MAIN RESULTS We identified 4562 studies; of these, we included four RCTs with 286 participants. The studies compared two or more of the following: vitamin D, calcium or vitamin D plus calcium. The number of participants randomised to receive vitamin D was 64, calcium was 102 and vitamin D plus calcium was 120. Two studies were conducted in India and two were conducted in Nigeria. None of the included studies had a low risk of bias in all domains. Three studies had a high risk of bias in at least one domain. The age of the participants ranged between six months and 14 years. The duration of follow-up ranged between 12 weeks and 24 weeks. Two studies compared vitamin D to calcium. There is low-certainty evidence that, at 24 weeks' follow-up, calcium alone improved the healing of rickets compared to vitamin D alone (RR 3.26, 95% CI 1.59 to 6.69; P = 0.001; 1 study, 71 participants). Comparing vitamin D to calcium showed no firm evidence of an advantage or disadvantage in reducing morbidity (fractures) (RR 0.27, 95% CI 0.03 to 2.32; P = 0.23; 1 study, 71 participants; very low-certainty evidence). Adverse events were not reported. Two studies compared vitamin D plus calcium to vitamin D at 12 or 24 weeks. Vitamin D plus calcium improved healing of rickets compared to vitamin D alone at 24 weeks' follow-up (RR 3.06, 95% CI 1.49 to 6.29; P = 0.002; 1 study, 75 participants; low-certainty evidence). There is no conclusive evidence in favour of either intervention for reducing morbidity (fractures) (RR 0.24, 95% CI 0.03 to 2.08; P = 0.20; 1 study, 71 participants; very low-certainty evidence) or adverse events (RR 4.76, 95% CI 0.24 to 93.19; P = 0.30; 1 study, 39 participants; very low-certainty evidence). All four included studies compared vitamin D plus calcium to calcium at different follow-up times. There is no conclusive evidence on whether vitamin D plus calcium in comparison to calcium alone improved healing of rickets at 24 weeks' follow-up (RR 1.17, 95% CI 0.72 to 1.90; P = 0.53; 2 studies, 140 participants; very low-certainty evidence). Evidence is also inconclusive for morbidity (fractures) (RR 0.89, 95% CI 0.06 to 13.76; P = 0.94; 1 study, 72 participants; very low-certainty evidence) and adverse events (RR 4.29, 0.22 to 83.57; P = 0.34; 1 study, 37 participants; very low-certainty evidence). Most of the evidence in the review is low or very low certainty due to risk of bias, imprecision or both. None of the included studies assessed all-cause mortality, health-related quality of life or socioeconomic effects. One study assessed growth pattern but this was not measured at the time-point stipulated in the protocol of our review (one or more years after commencement of therapy). AUTHORS' CONCLUSIONS This review provides low-certainty evidence that vitamin D plus calcium or calcium alone improve healing in children with nutritional rickets compared to vitamin D alone. We are unable to make conclusions on the effects of the interventions on adverse events or morbidity (fractures).
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Calcium, Bioenergetics, and Parkinson's Disease.
Zampese, E, Surmeier, DJ
Cells. 2020;(9)
Abstract
Degeneration of substantia nigra (SN) dopaminergic (DAergic) neurons is responsible for the core motor deficits of Parkinson's disease (PD). These neurons are autonomous pacemakers that have large cytosolic Ca2+ oscillations that have been linked to basal mitochondrial oxidant stress and turnover. This review explores the origin of Ca2+ oscillations and their role in the control of mitochondrial respiration, bioenergetics, and mitochondrial oxidant stress.
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Evaluation of an AI-based, automatic coronary artery calcium scoring software.
Sandstedt, M, Henriksson, L, Janzon, M, Nyberg, G, Engvall, J, De Geer, J, Alfredsson, J, Persson, A
European radiology. 2020;(3):1671-1678
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OBJECTIVES To evaluate an artificial intelligence (AI)-based, automatic coronary artery calcium (CAC) scoring software, using a semi-automatic software as a reference. METHODS This observational study included 315 consecutive, non-contrast-enhanced calcium scoring computed tomography (CSCT) scans. A semi-automatic and an automatic software obtained the Agatston score (AS), the volume score (VS), the mass score (MS), and the number of calcified coronary lesions. Semi-automatic and automatic analysis time were registered, including a manual double-check of the automatic results. Statistical analyses were Spearman's rank correlation coefficient (⍴), intra-class correlation (ICC), Bland Altman plots, weighted kappa analysis (κ), and Wilcoxon signed-rank test. RESULTS The correlation and agreement for the AS, VS, and MS were ⍴ = 0.935, 0.932, 0.934 (p < 0.001), and ICC = 0.996, 0.996, 0.991, respectively (p < 0.001). The correlation and agreement for the number of calcified lesions were ⍴ = 0.903 and ICC = 0.977 (p < 0.001), respectively. The Bland Altman mean difference and 1.96 SD upper and lower limits of agreements for the AS, VS, and MS were - 8.2 (- 115.1 to 98.2), - 7.4 (- 93.9 to 79.1), and - 3.8 (- 33.6 to 25.9), respectively. Agreement in risk category assignment was 89.5% and κ = 0.919 (p < 0.001). The median time for the semi-automatic and automatic method was 59 s (IQR 35-100) and 36 s (IQR 29-49), respectively (p < 0.001). CONCLUSIONS There was an excellent correlation and agreement between the automatic software and the semi-automatic software for three CAC scores and the number of calcified lesions. Risk category classification was accurate but showing an overestimation bias tendency. Also, the automatic method was less time-demanding. KEY POINTS • Coronary artery calcium (CAC) scoring is an excellent candidate for artificial intelligence (AI) development in a clinical setting. • An AI-based, automatic software obtained CAC scores with excellent correlation and agreement compared with a conventional method but was less time-consuming.
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Phosphate Binders and Nonphosphate Effects in the Gastrointestinal Tract.
Biruete, A, Hill Gallant, KM, Lindemann, SR, Wiese, GN, Chen, NX, Moe, SM
Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation. 2020;(1):4-10
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Phosphate binders are commonly prescribed in patients with end-stage kidney disease to prevent and treat hyperphosphatemia. These binders are usually associated with gastrointestinal distress, may bind molecules other than phosphate, and may alter the gut microbiota, altogether having systemic effects unrelated to phosphate control. Sevelamer is the most studied of the available binders for nonphosphate-related effects including binding to bile acids, endotoxins, gut microbiota-derived metabolites, and advanced glycation end products. Other binders (calcium- and noncalcium-based binders) may bind vitamins, such as vitamin K and folic acid. Moreover, the relatively new iron-based phosphate binders may alter the gut microbiota, as some of the iron or organic ligands may be used by the gastrointestinal bacteria. The objective of this narrative review is to provide the current evidence for the nonphosphate effects of phosphate binders on gastrointestinal function, nutrient and molecule binding, and the gut microbiome.
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Calcium supplementation for improving bone density in lactating women: a systematic review and meta-analysis of randomized controlled trials.
Cai, G, Tian, J, Winzenberg, T, Wu, F
The American journal of clinical nutrition. 2020;(1):48-56
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BACKGROUND Clinical trials evaluating the effect of calcium supplementation on bone loss in lactating women have been small, with inconsistent results. OBJECTIVES We aimed to determine the effect of calcium supplementation on bone mineral density (BMD) in lactating women. METHODS An electronic search of databases was conducted from inception to January 2020. Two authors screened studies, extracted data, and assessed the risk of bias of eligible studies. Percentage change in BMD was pooled using random-effects models and reported as weighted mean differences (WMDs) with 95% CIs. Risk of bias was assessed using the Cochrane risk of bias tool. RESULTS Five randomized controlled trials including 567 lactating women were included. All had a high risk of bias. Mean baseline calcium intake ranged from 562 to 1333 mg/d. Compared with control groups (placebo/no intervention), calcium supplementation (600/1000 mg/d) had no significant effect on BMD at the lumbar spine (WMD: 0.74%; 95% CI: -0.10%, 1.59%; I2 = 47%; 95% CI: 0%, 81%; n = 527 from 5 trials) or the forearm (WMD: 0.53%; 95% CI: -0.35%, 1.42%; I2 = 55%; 95% CI: 0%, 85%; n = 415 from 4 trials). BMD at other sites was assessed in single trials: calcium supplementation had a small to moderate effect on total-hip BMD (WMD: 3.3%; 95% CI: 1.5%, 5.1%) but no effect on total body or femoral neck BMD. CONCLUSIONS Overall, the meta-analysis indicates that calcium supplementation does not provide clinically important benefits for BMD in lactating women. However, there was adequate dietary intake before supplementation in some studies, and others did not measure baseline calcium intake. Advising lactating women to meet the current recommended calcium intakes (with supplementation if dietary intake is low) is warranted unless new high-certainty evidence to the contrary from robust clinical trials becomes available. More research needs to be done in larger samples of women from diverse ethnic and racial groups.This systematic review was registered at www.crd.york.ac.uk/prospero as CRD42015022092.
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Coupling Ion Specificity of the Flagellar Stator Proteins MotA1/MotB1 of Paenibacillus sp. TCA20.
Onoe, S, Yoshida, M, Terahara, N, Sowa, Y
Biomolecules. 2020;(7)
Abstract
The bacterial flagellar motor is a reversible rotary molecular nanomachine, which couples ion flux across the cytoplasmic membrane to torque generation. It comprises a rotor and multiple stator complexes, and each stator complex functions as an ion channel and determines the ion specificity of the motor. Although coupling ions for the motor rotation were presumed to be only monovalent cations, such as H+ and Na+, the stator complex MotA1/MotB1 of Paenibacillus sp. TCA20 (MotA1TCA/MotB1TCA) was reported to use divalent cations as coupling ions, such as Ca2+ and Mg2+. In this study, we initially aimed to measure the motor torque generated by MotA1TCA/MotB1TCA under the control of divalent cation motive force; however, we identified that the coupling ion of MotA1TCAMotB1TCA is very likely to be a monovalent ion. We engineered a series of functional chimeric stator proteins between MotB1TCA and Escherichia coli MotB. E. coli ΔmotAB cells expressing MotA1TCA and the chimeric MotB presented significant motility in the absence of divalent cations. Moreover, we confirmed that MotA1TCA/MotB1TCA in Bacillus subtilis ΔmotABΔmotPS cells generates torque without divalent cations. Based on two independent experimental results, we conclude that the MotA1TCA/MotB1TCA complex directly converts the energy released from monovalent cation flux to motor rotation.
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Is It Time to Remove Total Calcium from the Basic and Comprehensive Metabolic Panels? Assessing the Effects of American Medical Association-Approved Chemical Test Panels on Laboratory Utilization.
Katzman, BM, Bryant, SC, Karon, BS
Clinical chemistry. 2020;(11):1444-1449
Abstract
BACKGROUND The necessity of individual tests within the most commonly used disease-oriented test panels has not been well established. We evaluated test-ordering practices for total calcium, both before and after implementation of American Medical Association (AMA)-approved panels (basic metabolic panel [BMP] and comprehensive metabolic panel [CMP]) in our electronic ordering system. METHODS We performed a retrospective review of all total calcium orders placed during April and June 2018, before and after implementation of the panels. Orders from inpatient, outpatient, and emergency department (ED) care units were totaled, and the percentage of abnormal test results was calculated. We then queried institutional databases to determine the number of unique patients with calcium-related diagnoses and compared the rates from a 5-month period both before and after implementation of the panels. RESULTS Total test volumes and tests per unique patient increased by more than 3-fold after implementation of calcium-containing AMA-approved panels, with the majority of those orders coming from BMPs and CMPs. The rate of low calcium values increased because of the shift toward more inpatient testing; however, the percentage of abnormal results within each patient population (inpatient, outpatient, ED) decreased. The prevalence of hypo- and hypercalcemia-related diagnoses among patients in the 5 months after implementation did not change significantly (1.29% before implementation vs 1.27% after implementation). CONCLUSIONS Implementation of BMPs and CMPs dramatically increased total calcium testing volumes without changing the rate of calcium-related diagnoses. The results suggest that the increase in total calcium orders associated with panel-based testing largely constitutes excess or unnecessary testing.
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Novel inter-domain Ca2+-binding site in the gelsolin superfamily protein fragmin.
Takeda, S, Fujiwara, I, Sugimoto, Y, Oda, T, Narita, A, Maéda, Y
Journal of muscle research and cell motility. 2020;(1):153-162
Abstract
Gelsolin superfamily proteins, consisting of multiple domains (usually six), sever actin filaments and cap the barbed ends in a Ca2+-dependent manner. Two types of evolutionally conserved Ca2+-binding sites have been identified in this family; type-1 (between gelsolin and actin) and type-2 (within the gelsolin domain). Fragmin, a member in the slime mold Physarum polycephalum, consists of three domains (F1-F3) that are highly similar to the N-terminal half of mammalian gelsolin (G1-G3). Despite their similarities, the two proteins exhibit a significant difference in the Ca2+ dependency; F1-F3 absolutely requires Ca2+ for the filament severing whereas G1-G3 does not. In this study, we examined the strong dependency of fragmin on Ca2+ using biochemical and structural approaches. Our co-sedimentation assay demonstrated that Ca2+ significantly enhanced the binding of F2-F3 to actin. We determined the crystal structure of F2-F3 in the presence of Ca2+. F2-F3 binds a total of three calcium ions; while two are located in type-2 sites within F2 or F3, the remaining one resides between the F2 long helix and the F3 short helix. The inter-domain Ca2+-coordination appears to stabilize F2-F3 in a closely packed configuration. Notably, the F3 long helix exhibits a bent conformation which is different from the straight G3 long helix in the presence of Ca2+. Our results provide the first structural evidence for the existence of an unconventional Ca2+-binding site in the gelsolin superfamily proteins.
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Inactivation of GAP-43 due to the depletion of cellular calcium by the Pb and amyloid peptide induced toxicity: An in vitro approach.
Ayyalasomayajula, N, Bandaru, M, Dixit, PK, Ajumeera, R, Chetty, CS, Challa, S
Chemico-biological interactions. 2020;:108927
Abstract
Environmental pollutant, Lead (Pb) is known to induce neurotoxicity in human. The central nervous system is the most vulnerable to the minute levels of Pb induced toxicity. Pb has been linked to Alzheimer's disease (AD) as a probable risk factor, as it shows epigenetic and developmental link associated with Alzheimer's disease-like pathology. Beta amyloid peptides were considered as the crucial factors in the beta amyloid plaque formation in Alzheimer's disease brain. In this context, we investigated the molecular mechanism involved in the development of Pb induced Alzheimer's disease in in vitro. Previous data from our studies have reported that Pb in the presence of beta Amyloid peptide (1-40) and (25-35) induces more apoptosis than individual exposures. Here, to further evaluate the molecular mechanism underlying Pb induced Alzheimer's disease; we focussed on the involvement of calcium signalling in inducing cell death. Our experimental observations suggesting that Pb in the presence of beta amyloid peptide alters intracellular calcium levels, which leads to the increased beta-secretase activity, which further promotes the generation of beta amyloid peptides. It also showed depression in the levels of GAP-43 expression, inhibition of PKC activity and altering synaptic activity further leads to cell death.