Ionized Calcium Levels Research Articles

Sodium Selenite Modulates Global Activation of Proinflammatory M1-like Macrophages, Necroinflammation and M1-like/M2-like Dichotomy at the Onset of Human Type 1 Diabetes.

The study aims to show that sodium selenite (Ss) would have an immunomodulatory effect on the functional activity of proinflammatory macrophages (Mφs) during their extended extracellular activation at the onset of human type 1 diabetes (T1D). Exacerbated activation of proinflammatory "M1" macrophages (Mφs) can promote chronic local pancreatic islet inflammation and T1D development. We investigated the ex vivo effects of Ss on the immune modulation of global/extended activation of human proinflammatory M1-like Mφs. Experiments were carried out on primary monocytes-derived Mφs (MDMs). The levels of IL-1β, TNF-α, H2O2 and intracellular free calcium ions (ifCa2+), and the ratios of IL-1β-to-IL-10 and TNF-α-to-IL-10 were markedly increased in T1D Mφs than in healthy control Mφs. Conversely, both IL-10 production and arginase 1 (ARG1) activity were downregulated in T1D Mφs. Additionally, Ss treatment induced a marked downregulation of respiratory burst, ifCa2+ levels, M1-like Mφ-associated inducible nitric oxide (NO) synthase (iNOS) activity, cell necrosis and related necroinflammation biomarkers, including IL-1β and TNF-α, CD14 expression, and the ratios of iNOS-to-ARG1, IL-1β-to-IL-10, and TNF-α-to-IL-10. Moreover, Ss upregulated anti-inflammatory "M2-like" Mφ activity as demonstrated by ARG1 activity and IL-10 production, as well as phagocytosis capacity. Ss exerts a potent immunomodulatory role on functional activities of human proinflammatory T1D M1-like Mφs subjected to extended activation, as well as on the M1-like/M2-like dichotomy. Additionally, the current study provides a novel therapeutic approach using Ss to promote the anti-inflammatory function of Mφs at the onset of T1D.

Serial Estimation of Serum Calcium and Ionic Calcium Level for Early Detection of Hypocalcemia After Total/Completion Thyroidectomy.

Hypocalcemia is an important and common complication following thyroid surgery. The development of postoperative hypocalcemia is likely to be multifactorial in nature. Patients with acute hypocalcemia may present with numbness of the distal extremities, circumoral paresthesia, and/or carpopedal spasm, laryngospasm, seizure and arrhythmias. In most cases, post-thyroidectomy hypocalcemia is temporary, but small percentage (0-12%) are permanent. The present study was a 1-year prospective interventional study conducted at tertiary care center, Jaipur, India. Total 42 patients who underwent thyroidectomy were included in study. Evaluation of Serum and Ionic Calcium Level done Preoperatively and Postoperative at 6, 12, 24 and 48h and patients who develops hypocalcemia symptoms were recorded and data were analyzed. In our study hypocalcemia was seen in 13 (31%) out of 42 subjects. Ionic calcium in 'All patients' gradually decreased from pre operative 1.28 ± 0.04mmol/l to 1.14 ± 0.08mmol/l by 24h. Highest incidence of hypocalcemia was seen in patients who had Total thyroidectomy + neck dissection (83.3%) compared to other type of thyroid surgery. we concluded that post thyroidectomy transient hypocalcemia is a frequent complication. Serial monitoring of calcium levels preoperatively and postoperatively combined with careful monitoring of signs and symptoms of hypocalcemia is an efficient and cost-effective tool to detect early post thyroidectomy hypocalcemia.

The effect of serum calcium level on the success of diltiazem treatment: A retrospective cohort study

IntroductionDiltiazem is an antiarrhythmic drug widely used in the treatment of atrial fibrillation (AFib) with rapid ventricular response (RVR). It reveals its effect by blocking L-type calcium channels. Thus, it inhibits the extracellular calcium influx into the cytosol. The relationship between serum calcium level and the efficacy of intravenous (IV) diltiazem used in the treatment of AFib with RVR has not been investigated in vivo. The aim of this study is to investigate the mentioned relationship. MethodsThis study was planned as a single-center retrospective study. The data of 349 patients who presented to the emergency department with AFib with RVR and treated with diltiazem were retrospectively analyzed. A patient was considered to have responded to diltiazem treatment if the existing heart rhythm returned to sinus rhythm, or the heart rate decreased below 100 beats/min, or the heart rate decreased >20% provided that it was below 120 beats/min. The ionized calcium levels were recorded. The relationship between serum calcium level and the success of diltiazem treatment was examined. ResultsFifty five percent of the patients were female. The median age was 75 years. The rate of response to diltiazem treatment was 67.3%. The median of ionized calcium levels in the group which responded to diltiazem treatment (n = 235) was 1.14 mmol/L (IQR: 0.12), and the group which did not respond to diltiazem treatment (n = 114) was 1.11 mmol/L (IQR: 0.12) (p = 0.322). The patients were divided into three groups as low, normal, and high calcium levels according to the calcium reference levels determined by the hospital laboratory. The rate of response to diltiazem treatment was 61.4% in patients with low ionized calcium levels, 76.1% in patients with normal ionized calcium levels, and 40.0% in patients with high ionized calcium levels. The rate of response to diltiazem treatment was higher in patients with normal ionized calcium levels compared to patients with low or high ionized calcium levels (p = 0.004, p = 0.003). ConclusionThe success rate of diltiazem used in the treatment of AFib with RVR was highest in physiological calcium levels. The current study may provide the clinician with awareness about the consideration of serum ionized calcium levels when choosing drugs in patients with AFib with RVR.

Ex Vivo Osteogenesis Induced by Calcium Silicate-Based Cement Extracts.

Calcium silicate-based cements are used in a variety of clinical conditions affecting the pulp tissue, relying on their inductive effect on tissue mineralization. This work aimed to evaluate the biological response of calcium silicate-based cements with distinct properties-the fast-setting Biodentine™ and TotalFill® BC RRM™ Fast Putty, and the classical slow-setting ProRoot® MTA, in an ex vivo model of bone development. Briefly, eleven-day-old embryonic chick femurs were cultured for 10 days in organotypic conditions, being exposed to the set cements' eluates and, at the end of the culture period, evaluated for osteogenesis/bone formation by combining microtomographic analysis and histological histomorphometric assessment. ProRoot® MTA and TotalFill® extracts presented similar levels of calcium ions, although significantly lower than those released from BiodentineTM. All extracts increased the osteogenesis/tissue mineralization, assayed by microtomographic (BV/TV) and histomorphometric (% of mineralized area; % of total collagen area, and % of mature collagen area) indexes, although displaying distinct dose-dependent patterns and quantitative values. The fast-setting cements displayed better performance than that of ProRoot® MTA, with BiodentineTM presenting the best performance, within the assayed experimental model.

The effects of non-functionalized polystyrene nanoparticles of different diameters on the induction of apoptosis and mTOR level in human peripheral blood mononuclear cells

Particles of various types of plastics, including polystyrene nanoparticles (PS-NPs), have been determined in human blood, placenta, and lungs. These findings suggest a potential detrimental effect of PS-NPs on bloodstream cells. The purpose of this study was to assess the mechanism underlying PS-NPs-induced apoptosis in human peripheral blood mononuclear cells (PBMCs). Non-functionalized PS-NPs of three diameters: 29 nm, 44 nm, and 72 nm were studied used in this research. PBMCs were isolated from human leukocyte–platelet buffy coat and treated with PS-NPs at concentrations ranging from 0.001 to 200 μg/mL for 24 h. Apoptotic mechanism of action was evaluated by determining the level of cytosolic calcium ions, as well as mitochondrial transmembrane potential, and ATP levels. Furthermore, detection of caspase-8, -9, and -3 activation, as well as mTOR level was conducted. The presence of apoptotic PBMCs was confirmed by the method of double staining of the cells with propidium iodide and FITC-conjugated Annexin V. We found that all tested NPs increased calcium ion and depleted mitochondrial transmembrane potential levels. The tested NPs also activated caspase-9 and caspase-3, and the smallest NPs of 29 nm of diameter also activated caspase-8. The results clearly showed that apoptotic changes and an increase of mTOR level depended on the size of the tested NPs, while the smallest particles caused the greatest alterations. PS-NPs of 26 nm of diameter activated the extrinsic pathway (increased caspase-8 activity), as well as intrinsic (mitochondrial) pathway (increased caspase-9 activity, raised calcium ion level, and decreased transmembrane mitochondrial potential) of apoptosis. All PS-NPs increased mTOR level at the concentrations smaller than those that induced apoptosis and its level returned to control value when the process of apoptosis escalated.

Black carbon nanoparticles activate the crosstalk mechanism between necroptosis and macrophage extracellular traps to change macrophages fate

PM2.5 still poses a threat to public health even at very low levels. Black carbon (BC) is a key component of PM2.5. Macrophage extracellular traps (METs) are a means by which macrophages capture and destroy invading pathogens. Necroptosis is an inflammatory programmed cell death. However, there is no research on the crosstalk mechanism between necroptosis and METs after BC exposure. In our study, fluorescence labeling, fluorescent probes, qPCR, and immunofluorescence were applied. Our research found that under normal physiological conditions, when macrophages receive external stimuli (in our experiment, phorbol 12-myristate 13-acetate (PMA)), they will form METs, thus exhibiting innate immune function. However, exposure to BC can cause necroptosis in macrophages accompanied by increased levels of ROS and cytosolic calcium ions as well as altered expression of inflammatory factors and chemokines that prevent the formation of METs, and weakening innate immune function. Notably, inhibition of necroptosis restored the formation of METs, indicating that necroptosis inhibits the formation of METs. Our experiment will enrich the understanding of the mechanism of macrophage injury caused by BC exposure, provide a new direction for studying harmful atmospheric particle toxicity, and propose new therapeutic insights for diseases caused by atmospheric particulate matter. This study is the first to explore the crosstalk mechanism between necroptosis and METs after BC exposure.

HEALTH ASSESSMENT OF PAINTED TURTLES (CHRYSEMYS PICTA) IN A RESTORED WETLAND HABITAT IN NORTHWESTERN INDIANA, USA.

Freshwater turtles are sensitive to environmental changes and can serve as sentinel species for ecosystem health assessments. The Efroymson Restoration at Kankakee Sands in northwestern Indiana, USA has been restored in the past 25 yr from primarily agricultural land to a mosaic of prairie and wetland habitats. Health assessments of 40 free-ranging painted turtles (Chrysemys picta) at Kankakee Sands were performed in May 2021 to evaluate overall health status, screen for infectious diseases, and obtain baseline clinical pathology values in this population. Assessment of each turtle included a physical examination, complete blood count, plasma biochemistry panel, blood lactate level, venous blood gas analysis, serum trace mineral panel, serum vitamin D3 level, and plasma protein electrophoresis. Oral and cloacal swabs were tested for adenoviruses, herpesviruses, frog virus 3, and Mycoplasmopsis species by PCR in 39 painted turtles. Four turtles were positive for adenovirus, which shared 100% homology to Sulawesi tortoise adenovirus. Two turtles were herpesvirus-positive with 100% homology to emydid herpesvirus 1. No Mycoplasmopsis spp. or frog virus 3 was detected. Female turtles had significantly higher manganese, prealbumin, uric acid, triglycerides, and ionized calcium levels, while male turtles had significantly higher cholesterol, glutamate dehydrogenase, and CO2 levels. These baseline data can be used for future research into freshwater turtle health in restored wetland habitats.

Evaluating the Role of Inorganic Elements of Camelus Dromedarius Saliva in Protecting Enamel Against Tooth Surface Loss.

The aim of this study was to provide insight into the role of camel's saliva in protecting enamel against erosion and to evaluate the levels of salivary sodium, potassium, calcium, and phosphate ions among 2 groups of camels, those with low-grade tooth surface loss and those with high-grade tooth surface loss. Twenty-eight healthy camels, 5 males and 23 females, aged 20 months to 10 years, were divided into 2 groups. Group I comprise camels with "low-grade tooth surface loss" and Group 2 with "high-grade tooth surface loss." Unstimulated saliva was collected by a draining method. The samples were then analyzed for sodium, potassium, calcium, and phosphate concentrations using automated chemistry analysis. Data were then statistically analyzed using the unpaired Student's t-test and Pearson correlation coefficient test. The study found the salivary calcium and phosphate concentrations were significantly lower in the "high-grade" erosion group, in comparison with the other group (P < .0001 and P = .0257, respectively). The results also revealed that the more extensive the tooth surface loss, the more carious lesions the subject had (P = .023), and that caries are more common in the anterior teeth, particularly the incisors. The authors conclude that alterations in inorganic elements of saliva, particularly the calcium and phosphate ions, play a major role in the development of resistance to tooth surface loss. This work may represent a direction for future research to develop custom-made preventive supplements, which can protect camelid teeth against tooth surface loss.

Changes in elastin structure and extensibility induced by hypercalcemia and hyperglycemia.

Elastin is a key elastomeric protein responsible for the elasticity of many organs, including heart, skin, and blood vessels. Due to its intrinsic long life and low turnover rate, damage in elastin induced by pathophysiological conditions, such as hypercalcemia and hyperglycemia, accumulates during biological aging and in aging-associated diseases, such as diabetes mellitus and atherosclerosis. Prior studies have shown that calcification induced by hypercalcemia deteriorates the function of aortic tissues. Glycation of elastin is triggered by hyperglycemia and associated with elastic tissue damage and loss of mechanical functions via the accumulation of advanced glycation end products. To evaluate the effects on elastin's structural conformations and elasticity by hypercalcemia and hyperglycemia at the molecular scale, we perform classical atomistic and steered molecular dynamics simulations on tropoelastin, the soluble precursor of elastin, under different conditions. We characterize the interaction sites of glucose and calcium and associated structural conformational changes. Additionally, we find that elevated levels of calcium ions and glucose hinder the extensibility of tropoelastin by rearranging structural domains and altering hydrogen bonding patterns, respectively. Overall, our investigation helps to reveal the behavior of tropoelastin and the biomechanics of elastin biomaterials in these physiological environments. STATEMENT OF SIGNIFICANCE: Elastin is a key component of elastic fibers which endow many important tissues and organs, from arteries and veins, to skin and heart, with strength and elasticity. During aging and aging-associated diseases, such as diabetes mellitus and atherosclerosis, physicochemical stressors, including hypercalcemia and hyperglycemia, induce accumulated irreversible damage in elastin, and consequently alter mechanical function. Yet, molecular mechanisms associated with these processes are still poorly understood. Here, we present the first study on how these changes in elastin structure and extensibility are induced by hypercalcemia and hyperglycemia at the molecular scale, revealing the essential roles that calcium and glucose play in triggering structural alterations and mechanical stiffness. Our findings yield critical insights into the first steps of hypercalcemia- and hyperglycemia-mediated aging.

Postoperative Serum Parathyroid Hormone Levels as a Predictor of Hypocalcemia in Patients Undergoing Total Thyroidectomy.

Postoperative hypocalcemia is a common complication of total thyroidectomy; the onset and severity of post-operative hypocalcemia is unpredictable. Various attempts have been made to identify predictors of hypocalcemia. There has been an increasing interest in serum levels of parathyroid hormone (PTH) as an early predictor of the development of hypocalcemia after total thyroidectomy. However, there is no consensus on the time intervals and cut-off levels of serum PTH to predict hypocalcemia. In this study, we intend to use serum PTH levels at 4th and 12th hour after total thyroidectomy to identify patients at risk of developing Postoperative hypocalcemia and to evaluate the role of PTH in predicting hypocalcemia. A Cross sectional analytical study conducted in 33 patients undergoing total/completion thyroidectomy from December 2018 to May 2020. Serum total calcium, Serum ionized calcium and Serum intact PTH levels were measured on three occasions (Preoperative and 4th and 12th hour Postoperative). Between both Postoperative levels of PTH, the one with better predictability of hypocalcemia was determined. Postoperative 4th hour PTH is a better predictor of transient hypocalcemia than Postoperative 12th hour PTH, as the association of the former with serum ionized calcium level was statistically highly significant with p value 0.005 and 0.021 respectively. Serum PTH determination after four hours of total thyroidectomy is a relatively better predictor of transient hypocalcemia, and can guide calcium supplementation for those at high risk in the Postoperative period. However, to determine the risk of hypocalcemia at the end of 1month of follow-up, both the Postoperative 4th and post-operative 12th hour PTH have similar diagnostic accuracy.

Effect of ionized calcium level on short-term prognosis in severe multiple trauma patients: a clinical study

BackgroundHypocalcemia has been reported as an independent predictor of trauma mortality. We investigated the relationship between temporal variations in blood ionized calcium concentration (iCa) and prognosis in severe trauma patients...

Optimization of Rock Salt Washing Process to Remove Selected Chemical Impurities in Lake Katwe Rock Salt

Rich deposits of mineral salts, present in substantial economic quantities, characterize the geological bounty of Uganda. The primary location of this wealth is lake Katwe, a saline crater lake southwest of the country. However, all grades of rock salt extracted from Lake Katwe remain contaminated with chemical impurities such as calcium, magnesium, heavy metals and sulphate ions, even after solar evaporation process from the salt pans. There is a need to conduct research into possible contaminant removal methods which could increase the market value of the extracted salt, and add to the body of knowledge for future salt processing and chlor-alkali industries in Uganda. This study examined the effect of varying water volumes and temperature on the levels of Calcium, Magnesium and Sulphate ions in rock salt samples from Lake Katwe. The samples were methodically crushed and washed. The salt was then dissolved, crystallized, dried and meticulous analysis to determine the concentration of these impurities was carried out. The data was analysed and represented in Microsoft Excel and MATLAB. Results obtained revealed that a temperature of 40°C and salt-water ratio of 1:2 are the optimal parameters for maximum reduction of calcium, magnesium and sulphate impurities in rock salt. This analysis enhances the purity of salt harvested from Lake Katwe’s solar evaporation process and offers optimal washing parameters to reduce impurities in brine, thereby improving plant yield and reducing production costs across various salt grades. It also provides new information to the mining communities at Lake Katwe on how to affordably improve the percentage purity of their rock salt. The study will also contribute novel industry-tailored data for future prospective salt processing and chlor-alkali industrial plants near the Lake while also filling a knowledge gap for further research on rock salt purification.

Prevalence of hypocalcemia in term newborns requiring phototherapy

Background: Neonatal hyperbilirubinemia in the first week of life is one of the most prevalent clinical entity observed, affecting 60% of term-babies and 80% of preterm newborn babies, many requiring intervention in the form of phototherapy. The effect of phototherapy on serum calcium levels has not been studied much in Indian literature. The objectives of this study was to evaluate the prevalence of hypocalcemia in healthy, term newborn babies receiving phototherapy for unconjugated hyperbilirubinemia and to determine the association, if any between serum calcium and birth weight, postnatal age at start of phototherapy, weight at enrolment, gestational age at birth, maternal age and duration of phototherapy. Methods: This was a prospective observational study conducted over a period of 10 months among 80 term neonates admitted to the inpatient department at a tertiary care centre in Mumbai. Total serum calcium and ionised calcium levels were measured at the start of phototherapy and on stopping phototherapy/discharge. Data were analysed using statistical package for social sciences (SPSS) version 21 software. Results: Two (2.5%) out of the 80 neonates were found to have hypocalcemia after phototherapy with serum ionic calcium levels less than 1 mmol/l. Even though a larger proportion of neonates showed a decrease in the serum total calcium (56.25%) and serum ionic calcium (58.75%) levels after phototherapy, none of the neonates developed symptomatic hypocalcemia at those levels. A statistically significant association was found between maternal age in years with the serum total calcium levels after phototherapy and age at starting phototherapy (in hours) with the serum ionic calcium levels after phototherapy. Conclusions: The present study concludes that there is significant decrease in the levels of ionised calcium after phototherapy, however there was no significant decrease in the total serum calcium levels and none of the neonates were symptomatic. Hence, we do not recommend regular serum calcium monitoring in healthy term neonates receiving phototherapy and find no indication for the prophylactic use of calcium supplementation in these neonates.

3-Hydroxybutyrate ameliorates insulin resistance by inhibiting PPARγ Ser273 phosphorylation in type 2 diabetic mice

3-Hydroxybutyrate (3HB) is a small ketone body molecule produced endogenously by the body in the liver. Previous studies have shown that 3HB can reduce blood glucose level in type 2 diabetic (T2D) patients. However, there is no systematic study and clear mechanism to evaluate and explain the hypoglycemic effect of 3HB. Here we demonstrate that 3HB reduces fasting blood glucose level, improves glucose tolerance, and ameliorates insulin resistance in type 2 diabetic mice through hydroxycarboxylic acid receptor 2 (HCAR2). Mechanistically, 3HB increases intracellular calcium ion (Ca2+) levels by activating HCAR2, thereby stimulating adenylate cyclase (AC) to increase cyclic adenosine monophosphate (cAMP) concentration, and then activating protein kinase A (PKA). Activated PKA inhibits Raf1 proto-oncogene serine/threonine-protein kinase (Raf1) activity, resulting in a decrease in extracellular signal-regulated kinases 1/2 (ERK1/2) activity and ultimately inhibiting peroxisome proliferator-activated receptor γ (PPARγ) Ser273 phosphorylation in adipocytes. Inhibition of PPARγ Ser273 phosphorylation by 3HB altered the expression of PPARγ regulated genes and reduced insulin resistance. Collectively, 3HB ameliorates insulin resistance in type 2 diabetic mice through a pathway of HCAR2/Ca2+/cAMP/PKA/Raf1/ERK1/2/PPARγ.

Estimation of serum calcium levels in apheresis platelet donors.

Apheresis is practiced widely to collect single donor platelets (SDPs). This procedure utilizes an anticoagulant acid citrate dextrose to prevent clotting of blood in the extracorporeal circuit which chelates divalent ions like calcium. This alters the calcium homeostasis resulting in hypocalcemia causing acute adverse events. The study aimed to know the calcium homeostasis in apheresis platelet donors. This cross-sectional study was conducted from January 2020 to December 2020 in the department of transfusion medicine. The sample size was 50. Donors who walk in for voluntary SDP donation were selected. Total and ionized calcium, pH, and serum albumin for all the donors at baseline and ionic calcium at the end of the procedure and 30 min after the procedure were measured. According to statistical analysis of the ionic calcium level at pre procedure, immediate post procedure and 30 minutes post procedure, there was decrease in the value immediate post procedure and values returned to baseline within 30 minutes. The levels of pH change were analyzed. On comparing the preprocedure and immediate postprocedure values, there was a significant lowering of pH value from the baseline (P = 0.5), indicating acute lowering of pH immediate postprocedure. Hence, most of the citrate metabolism can be achieved within 30 min after completion of the apheresis procedure. SDP collection is essentially a safe procedure with minimal adverse effects. Toxicity of citrate is not much pronounced. Recovery of calcium levels is within 30 min of completion of plateletpheresis.

Hypocalcemia in Trauma is Determined by the Number of Units Transfused, Not Whole Blood Versus Component Therapy

IntroductionBlood component resuscitation is associated with hypocalcemia (HC) (iCal <0.9 mmol/L) that contributes to coagulopathy and death in trauma patients. It is unknown whether or not whole blood (WB) resuscitation helps mitigate the risk of HC in trauma patients. We hypothesized that calcium homeostasis is maintained and mortality improved in patients who only receive WB. Materials and methodsThis is a retrospective review of all adult trauma patients who received WB from July 2018 to December 2020. Variables included transfusions, ionized calcium levels, and calcium replacement. Patients were characterized as follows based on blood products received: WB or WB with other blood components. Groups were compared with respect to HC, correction of HC, 24 h, and inpatient mortality. ResultsTwo hundred twenty-three patients received WB and met the inclusion criteria. 107 (48%) received WB only. HC occurred in 13% of patients who received more than one WB unit compared to 29% of WB and other blood component patients (P = 0.02). WB patients received less calcium replacement (median 250 mg versus 2000 mg, P < 0.01). HC and total units transfused within 4 h were associated with mortality in the adjusted model. HC significantly increased after 5 units of blood products were transfused, regardless of product type. WB was not protective against HC. ConclusionsHC and failure to correct HC are significant risk factors for mortality in trauma. Resuscitations with WB only and WB in combination with other blood components are associated with HC especially when more than 5 units of any blood product are transfused. Calcium supplementation should be prioritized in any large volume transfusion, regardless of blood product type.

Ozone-oxidized black carbon particles change macrophage fate: Crosstalk between necroptosis and macrophage extracellular traps

The impacts of environmental PM 2.5 on public health have become a major concern all over the world. Many studies have shown that PM 2.5 still poses a threat to public health even at very low levels. Physical or chemical reactions occur between primary particles and other components in the environment, which changes the properties of primary particles. Such newly formed particles with changed properties are called secondary particles. Ozone-oxidized black carbon (oBC) is a key part of PM 2.5 and a representative secondary particle. Macrophages extracellular traps (METs) is a means for macrophages to capture and destroy invading pathogens, thereby exercising innate immunity. Necroptosis is a kind of programmed cell death, which is accompanied by the destruction of membrane integrity, thus inducing inflammatory reaction. However, there is no research on the crosstalk mechanism between necroptosis and MET after oBC exposure. In our study, AO/EB staining, SYTOX Green staining, fluorescent probe, qPCR, Western blot, and immunofluorescence were applied. This experiment found that under normal physiological conditions, when macrophages receive external stimuli (such as pathogens; in our experiment: phorbol 12-myristate 13-acetate (PMA)), they will form METs, capture and kill pathogens, thus exerting innate immune function. However, exposure to oBC can cause necroptosis in macrophages, accompanied by increased levels of reactive oxygen species (ROS) and cytosolic calcium ions, as well as the expression disorder of inflammatory factors and chemokines, and prevent the formation of METs, lose the function of capturing and killing pathogens, and weaken the innate immune function. Notably, inhibition of necroptosis restored the formation of METs, indicating that necroptosis inhibited the formation of METs. This study was the first to explore the crosstalk mechanism between necroptosis and METs after oBC exposure.

1,4-Naphthoquinone-Coated Black Carbon, a Kind of Atmospheric Fine Particulate Matter, Affects Macrophage Fate: New Insights into Crosstalk between Necroptosis and Macrophage Extracellular Traps

1,4-Naphthoquinone-coated BC (1,4 NQ-BC) is an important component of PM2.5 and a representative secondary particle. However, there is no research on the crosstalk mechanism between necroptosis and macrophage extracellular traps (METs) after 1,4 NQ-BC exposure. In this study, we treated RAW264.7 cells with 50, 100, and 200 mg/L 1,4 NQ-BC for 24 h, with 10 μM necrostatin-1 for 24 h, and with 2.5 μM phorbol 12-myristate 13-acetate (PMA) for 3 h. Our experiment revealed that under normal physiological conditions, when macrophages receive external stimuli (such as pathogens; in this experiment, PMA), they will form METs and capture and kill pathogens, thus exerting innate immune function. However, exposure to 1,4 NQ-BC can cause necroptosis in macrophages, accompanied by increased levels of reactive oxygen species (ROS) and cytosolic calcium ions, as well as the expression disorder of inflammatory factors and chemokines, prevent the formation of METs, lead to loss of the function of capturing and killing pathogens, and weaken the innate immune function. Notably, inhibition of necroptosis restored the formation of METs, indicating that necroptosis inhibited the formation of METs. Our study was the first to explore the crosstalk mechanism between necroptosis and METs. This experiment will enrich the mechanism of macrophage injury caused by 1,4 NQ-BC exposure.

Оценка обеспеченности витамином D, кальцием и фосфором лиц, проходящих службу в условиях Арктики

Inadequate ultraviolet insolation is one of the the key prerequisites for the pathogenesis of body's vitamin D insufficiency in the North. The study was aimed to assess the body's vitamin D, calcium and phosphorus sufficiency in the contract servicemen deployed in Arctic. The contract servicemen deployed on the Cape Chelyuskin and Dixon Island were surveyed (n = 51). The serum levels of 25(OH)D, the intermediate of the vitamin D conversion, along with the ionized calcium, total calcium, and inorganic phosphorus levels, were determined in June. Three degrees of the vitamin D sufficiency were revealed in the military, who had been deployed in Arctic for 5.9 ± 0.4 years: deficiency (in 29.4%), insufficiency (in 52.9%), and optimal levels (in 17.7%). However, the optimal levels revealed were close to the lower limit of normal range. Low ionized calcium levels were found in 29.4% of blood samples (15.5 ± 0.6 ng/mL). A total of 70.6% of samples that were within normal range were close to the lower limit of normal range based on Q25 (1.16 mmol/L) and were within the lower half of normal range (1.15–1.35 ng/mL) based on Q75 (1.22 mmol/L). The measured total calcium and inorganic phosphorus levels were close to the lower limits of reference ranges (2.29 ± 0.009 and 0.83 ± 0.006 mmol/L, respectively). In general, the reduced ionized calcium levels associated with vitamin D insufficiency were revealed, which were indicative of impaired calcium metabolism. The vitamin D deficiency results from the total calcium and inorganic phosphorus concentrations that are close to lower limits of reference ranges. Further negative changes in the body's vitamin D, phosphorus and calcium sufficiency should be expected during polar night. The study actualizes the year-round replenishement of the vitamin D and mineral deficiency in the military.

Some aspects of surgical strategies in patients with thyroid cancer with metastatic lesions of the neck lymph nodes

Objective — to improve the surgical treatment of patients with thyroid cancer with metastatic lesions of the neck lymph nodes by means of an individual approach to diagnostics, intraoperative imaging, and choice of optimal surgical technique.&#x0D; Materials and methods. The analysis involved results of examinations and treatment of 749 patients. The following was taken into account: complaints, thyroid and lymph nodes ultrasound, thyroid hormones level, results of general clinical examinations. Levels of parathyroid hormone, vitamin D, magnesium, total and ionic calcium were determined at the preoperative stage. In some cases, computer tomography results were included. A fine‑needle aspiration (FNA) biopsy was performed to all patients. Women prevailed: 607 from 749 (81.0%; 95% CI 78.0—83.8). The mean age of the patients was 51.3% (45.6—59.1) years. The causes of disease included: colloid nodular goiter 566 (75.6%; 95% CI 72.3—78.6), nodular (adenomatous) goiter with follicular neoplasm 72 (9.6%; 95% CI 7.6—12.0), papillary carcinoma 54 (7.2%; 95% CI 5.5—9.3), suspicious for papillary thyroid carcinoma (according to the cytology results) 17 (2.3%; 95% CI 1.3—3.6), medullary carcinoma 12 (1.6%; 95% CI 0.8—2.8), anaplastic thyroid cancer 6 (0.8%; 95% CI 0.3—1.7), other tumors 22 (2.9%; 95% CI 1.8—4.4). Statistical processing of the obtained results was carried out by using the standard program package «Statistica 6.0 for Windows» (StatSoft, USA).&#x0D; Results. Surgical interventions were performed in 89 of 749 (11.9%; 95% CI 9.7—14.4) patients with malignant tumors of the thyroid gland. The variety of surgical procedures performed on the thyroid gland: thyroidectomy performed in 81 of 89 patients (91%; 95% CI 83.1—96.0), hemithyroidectomy in 8 of 89 patients (9.0%; 95% CI 4.0—16.9). The reasons for the hemithyroidectomy: in 2 of 89 patients (2.2%; 95% CI 0.3—7.9) the diagnosis was not confirmed by express histological examination with suspicion for papillary thyroid carcinoma. In 6 other cases, single micro adenocarcinomas that ranged in size from 0.4 to 0.8 mm were found, without invasion into the tumor capsule, which was confirmed during a planned pathological examination. Lymphodisection of the central tissue, as an addition to thyroidectomy, was performed by us in 76 of 89 cases (85.4%; 95% CI 76.3—92.0). Metastatic lesions of the central tissue during pathological examination were found in 29 (32.6%; 95% CI 23.0—43.3) patients with papillary carcinoma, in 5 with medullary cancer (5.6%; 95% CI 1.8—12.6), in 6 cases with anaplastic thyroid cancer (6.7%; 95% CI 2.5—14.1). In 11 patients (12.4%; 95% CI 6.3—21.0) due to the metastatic spread to the platysma of the lateral triangle of the neck, its excision was performed. In 9 (10%; 95% CI 4.7—18.3) patients were performed thyroidectomy with sheath‑fascial excision (removal) of the neck tissue. The precession method was used to visualize the upper laryngeal nerve in order to prevent traumatization. The upper parathyroid glands served as the first anatomical landmark of the recurrent nerve, which were identified in 72 (80.9%; 95% CI 71.2—88.5) patients. Temporary unilateral vocal fold paresis was observed in 3 (3.4%; 95% CI 0.7—9.5) patients. Wound drainage was carried out separately by leaving micro‑drainage, for active aspiration, which was evacuated in 2 days.&#x0D; Соnclusions. One of the main prerequisites for the high‑quality performance surgery of thyroid gland is the precise nature of surgical manipulations with careful observance of tactical and technical requirements for a surgeon: timely identify and precisely mobilize. The choice of the final surgical intervention on lymphatic collectors in thyroid cancer is directly dependent on the preoperative and intraoperative pathological examination. However, given the substantial proportion of metastatic lesions of the central zone lymph nodes (level VI), the technical complexity of repeated operative interventions in this area, it is recommended to perform a preventive removal of the central fiber.