Calcium Measurements Research Articles

Coronary artery calcium measurement on attenuation correction computed tomography using artificial intelligence: correlation with coronary flow capacity and prognosis.

This study aimed to test whether the coronary artery calcium (CAC) burden on attenuation correction computed tomography (CTac), measured using artificial intelligence (AI-CACac), correlates with coronary flow capacity (CFC) and prognosis. We retrospectively enrolled patients who underwent [13N]ammonia positron emission tomography (PET) between September 2021 and May 2023. CTac data were obtained from all the patients. Patients with (history of) acute coronary syndrome, previous coronary stent insertion or bypass surgery, or left ventricular ejection fraction < 40% were excluded. The total Agatston score measured using a dedicated AI-CAC quantification software on CTac was defined as AI-CACac. The correlations between AI-CACac and PET-measured myocardial blood flow (MBF) and CFC and significant ischaemia (summed difference score ≥ 7) were analysed. Their prognostic values for major cardiovascular events (MACE), including death, nonfatal myocardial infarction, hospitalisation due to angina pectoris or heart failure, and late (> 90 days) revascularisation, were also evaluated. In total, 289 patients were included in this study. Significant negative correlations were found between AI-CACac and stress MBF (ρ = -0.363, p < 0.001) and MFR (ρ = -0.305, p < 0.001). AI-CACac > 10 was associated with a significantly higher prevalence of impaired CFC (31% vs. 7%, p < 0.001) and significant ischaemia (20% vs. 7%), which remained significant after adjusting for other risk factors. MACE occurred in 49 (17%) patients (median follow-up, 284 days), and those who experienced MACE had significantly higher AI-CACac (median, 166 vs. 56; p = 0.039). However, multivariable analysis revealed an independent prognostic association among impaired CFC, diabetes, smoking, but not for AI-CACac. AI-measured CACac correlates well with PET-measured MBF and CFC, but its prognostic significance requires further validation.

Monitoring Calcium-Sensing Receptor (CaSR)-Induced Intracellular Calcium Flux Using an Indo-1 Flow Cytometry Assay.

The calcium-sensing receptor (CaSR) has a critical role in maintaining serum calcium concentrations within the normal physiological range, and mutations in the receptor, or components of its signaling and trafficking pathway, cause disorders of calcium homeostasis. Inactivating mutations cause neonatal severe hyperparathyroidism or familial hypocalciuric hypercalcemia (FHH), while gain-of-function mutations cause autosomal dominant hypocalcemia (ADH). Characterizing the functional impact of mutations of the CaSR, and components of the CaSR-signaling pathway, is clinically important to enable correct diagnoses of FHH and ADH, optimize management, and prevent inappropriate parathyroidectomy or vitamin D supplementation. CaSR signals predominantly by activating the G-alpha subunit-11 to mobilize calcium release from intracellular stores. Thus, measurement of CaSR-induced intracellular calcium (Ca2+i) signaling is the gold standard method to investigate the pathogenicity of CaSR genetic variants. This protocol describes a method to assess CaSR-induced Ca2+I signaling using the Indo-1 calcium indicator dye and flow cytometry. This method has been used to assess multiple genetic variants in CaSR and components of its signaling and trafficking pathway in HEK293 cells.

Single-cell transcriptomic atlas of enteroendocrine cells along the murine gastrointestinal tract.

Enteroendocrine cells (EECs) produce over 20 gut hormones which contribute to intestinal physiology, nutrient metabolism and the regulation of food intake. The objective of this study was to generate a comprehensive transcriptomic map of mouse EECs from the stomach to the rectum. EECs were purified by flow-cytometry from the stomach, upper small intestine, lower small intestine, caecum and large intestine of NeuroD1-Cre mice, and analysed by single cell RNA sequencing. Regional datasets were analysed bioinformatically and combined into a large cluster map. Findings were validated by L-cell calcium imaging and measurements of CCK secretion in vitro. 20,006 EECs across the full gastrointestinal tract could be subdivided based on their full transcriptome into 10 major clusters, each exhibiting a different pattern of gut hormone expression. EECs from the stomach were largely distinct from those found more distally, even when expressing the same hormone. Cell clustering was also observed when performed only using genes related to GPCR cell signalling, revealing GPCRs predominating in different EEC populations. Mc4r was expressed in 55% of Cck-expressing cells in the upper small intestine, where MC4R agonism was found to stimulate CCK release in primary cultures. Many individual EECs expressed more than one hormone as well as machinery for activation by multiple nutrients, which was supported by the finding that the majority of L-cells exhibited calcium responses to multiple stimuli. This comprehensive transcriptomic map of mouse EECs reveals patterns of GPCR and hormone co-expression that should be helpful in predicting the effects of nutritional and pharmacological stimuli on EECs from different regions of the gut. The finding that MC4R agonism stimulates CCK secretion adds to our understanding of the melanocortin system.

6990 Vitamin D Supplementation in Primary Hyperparathyroidism: Effects on 1,25(OH)Vitamin D and FGF23 Levels

Abstract Disclosure: S.G. Pallone: None. M. Ohe: None. L.D. Santos: None. I.O. Nakaguma: None. I.S. Kunii: None. R.E. Silva: None. S.S. Maeda: None. C.M. Brandao: None. J.G. Vieira: None. M. Lazaretti-Castro: None. Background: Primary hyperparathyroidism (PHPT) is a condition characterized by high levels of PTH in the presence of hypercalcemia. Vitamin D deficiency has been associated with more severe presentations. Our aim was to evaluate the effects of Vitamin D supplementation on mineral homeostasis and related hormones in individuals with PHPT compared to controls without PHPT. Materials and methods: Individuals with and without PHPT received 14,000 IU/week of oral vitamin D3 for 12 weeks. At baseline and endpoint, blood samples were collected to measure 1,25(OH)2 vitamin D (1,25(OH)2D), intact Fibroblast Growth Factor 23 (FGF23), 25-hydroxyvitamin D (25OHD), Parathormon (PTH), total calcium (tCa), phosphorus and other biochemical markers. The intact FGF23 was measured using an automated Diasorin LIAISON kit. The 1,25(OH)2D measurement was performed using liquid chromatography and mass spectrometry (LC-MS/MS). Results: 70 PHPT patients and 75 healthy individuals (CTRL) were included, and 55 PHPT and 64 CTRL completed the 12-week protocol. At baseline, tCa, PTH, 1,25(OH)2D, and intact FGF23 concentrations were significantly higher in PHTP, with no difference in 25OHD levels. After the intervention, the 25OHD levels increased significantly in both groups (PHPT: 22.6.9±6.1 to 31.5±6.8; CTRL: 20.3±5.7 to 32.5±6.4 ng/mL, p&amp;lt;0.001). There was significative increase in intact FGF23 levels in both groups (PHPT: 47.9±27.1 to 76.3±33.3; CTRL: 40.5±13.9 to 59.8±19.8 pg/mL, p&amp;lt;0.001). After the vitamin D replacement, the tubular reabsorption of phosphate (TRP) was significantly reduced in both groups (PHPT: 85.0±7.4% to 83.6±7.75% CTRL: 89.5±4.5% to 88.7±4.8%, p=0.031), without changes in serum phosphorus levels, possibly indicating phosphaturic response to the intervention. Moreover, this decrease of TRP was positively correlated to the increment of FGF23 in the PHPT group. A paradoxical decrease in 1,25(OH)2D levels after vitamin D supplementation was observed in both groups (PHPT: 94.8±34.6 to 68.9±25.3; CTRL: 68.7±23.5 to 56.4±20.7 pg/mL, p&amp;lt;0.001). The reduction of 1,25(OH) 2 D was inversely correlated with the elevation of FGF23 in both groups (r=-0.302, p=0.028). In both groups, no changes in tCa were observed (PHPT: from 11.02±0.9 to 11.1±0.8; CTRL: 9.6±0.3 to 9.6±0.3 pg/mL, p=0.153), as the same for urinary calcium (p=0.534) and PTH measurements (p=0.516). Conclusion: The weekly administration of 14,000 IU of Vitamin D3 was safe and the increase in 25OHD after supplementation did not change the serum or urinary calcium levels in adults with and without PHPT. In both groups, it was observed a paradoxical decrease in 1,25(OH)2D levels after supplementation, which was associated with significant increase in intact FGF23 levels. This effect can maybe explain the safety response on calcium levels in face of vitamin D supplementation among PHPT patients. Presentation: 6/2/2024

8115 Evaluation Of The Incidence Of Hypoparathyroidism In Patients Undergoing Anterior Cervical Surgery

Abstract Disclosure: L.D. Santos: None. G. Oliveira Martins: None. J.V. Lima: None. L.A. Alvares: None. M.N. Lemos: None. L. Costa Figueiredo: None. E.N. Sakane: None. N. Scalissi: None. Introduction: The consensus published in 2022 suggests that a parathyroid hormone (PTH) level below 10 pg/mL may predict permanent hypoparathyroidism. However, these data have not yet been tested in the Brazilian population.Objective: To assess the clinical and laboratory characteristics of patients undergoing anterior cervical surgery, aiming to identify whether a postoperative PTH level below 10 pg/mL is associated with permanent hypoparathyroidism in a tertiary center in Brazil. Methods: We conducted a retrospective study with a chart review analysis. Results: We analyzed 59 patients who underwent anterior cervical surgery, with a mean age of 53 years (SD= +/- 17). 81% of the patients were alcohol consumers, and 76% were smokers. Regarding the surgical indication, 60.34% were for thyroid cancer, 17.24% for thyroid goiter, 13.79% for Graves' disease, 5.17% for glottic cancer, and 3.45% for primary hyperparathyroidism. Of the total operated patients, 49.15% were diagnosed with permanent hypoparathyroidism. The distribution of patients with permanent hypoparathyroidism was as follows: thyroid cancer 34.5%, Graves' disease 24.1%, goiter 24.1%, glottic cancer 10.3%, and primary hyperparathyroidism 7%. There was no significant difference in the occurrence of post-surgical hypoparathyroidism concerning the type of surgical indication (p&amp;gt;0.05). Regarding PTH 24 hours after surgery, a significant difference was observed between the group with permanent hypoparathyroidism and the group without the disease, with a mean PTH of 5.0 pg/mL and 10 pg/mL, respectively (p&amp;lt;0.05). As for serum calcium collected 24 hours post-surgery, there was no significant difference between the groups with and without permanent hypoparathyroidism (7.5 x 8.0 mg/dL; p&amp;gt;0.05). Conclusion: The PTH measurement in the first 24 hours postoperatively has proven to be more discriminative than the serum calcium measurement during the same period in identifying patients with permanent hypoparathyroidism. Presentation: 6/2/2024

Mechanism of sensory perception unveiled by simultaneous measurement of membrane voltage and intracellular calcium

Measuring neuronal activity is important for understanding neuronal function. Ca2+ imaging by genetically encoded calcium indicators (GECIs) is a powerful way to measure neuronal activity. Although it revealed important aspects of neuronal function, measuring the neuronal membrane voltage is important to understand neuronal function as it triggers neuronal activation. Recent progress of genetically encoded voltage indicators (GEVIs) enabled us fast and precise measurements of neuronal membrane voltage. To clarify the relation of the membrane voltage and intracellular Ca2+, we analyzed neuronal activities of olfactory neuron AWA in Caenorhabditis elegans by GCaMP6f (GECI) and paQuasAr3 (GEVI) responding to odorants. We found that the membrane voltage encodes the stimuli change by the timing and the duration by the weak semi-stable depolarization. However, the change of the intracellular Ca2+ encodes the strength of the stimuli. Furthermore, ODR-3, a G-protein alpha subunit, was shown to be important for stabilizing the membrane voltage. These results suggest that the combination of calcium and voltage imaging provides a deeper understanding of the information in neural circuits.

Cardiovascular Aging and Risk Assessment: How Multimodality Imaging Can Help.

Aging affects the cardiovascular system, and this process may be accelerated in individuals with cardiovascular risk factors. The main vascular changes include arterial wall thickening, calcification, and stiffening, together with aortic dilatation and elongation. With aging, we can observe left ventricular hypertrophy with myocardial fibrosis and left atrial dilatation. These changes may lead to heart failure and atrial fibrillation. Using multimodality imaging, including ultrasound, computed tomography (CT), and magnetic resonance imaging, it is possible to detect these changes. Additionally, multimodality imaging, mainly via CT measurements of coronary artery calcium or ultrasound carotid intima-media thickness, enables advanced cardiovascular risk stratification and helps in decision-making about preventive strategies. The focus of this manuscript is to briefly review cardiovascular changes that occur with aging, as well as to describe how multimodality imaging may be used for the assessment of these changes and risk stratification of asymptomatic individuals.

EFFECT OF PROCESSED CHICKEN FEET CONSUMPTION IN INCREASING BLOOD CALCIUM LEVELS AMONG FEMALE ADOLESCENTS

Objective: This study aims to examine the effect of processed chicken feet consumption for a month in increasing blood calcium levels among female adolescents. Methods: This study was carried out using a quasi-experimental method by measuring blood calcium levels before and after the daily consumption of 100 grams of processed chicken feet for a month. Furthermore, the sample population comprised 105 female adolescents who met the inclusion and exclusion criteria. Blood calcium measurement was performed using the OCP direct colorimetric lab test, data processing used the Intention to Treat (ITT) method, and data analysis was carried out using the Wilcoxon test (α=5%). Results: A significant difference was observed between blood calcium levels before and after the consumption of processed chicken feet over 1 mo, with an average increase of 1.10 mg/Dl. Conclusion: Based on the results, blood calcium levels experienced an increase of 1.01 mg/Dl, equivalent to the consumption of a 500 mg/day calcium tablet.

Association between Chronic Kidney Disease-Mineral and Bone Disorder Biomarkers and Symptom Burden in Older Patients with Advanced Chronic Kidney Disease: Results from the EQUAL Study.

Patients with advanced chronic kidney disease (CKD) develop numerous symptoms, with a multifactorial origin. Evidence linking mineral disorders (CKD-MBD) and uremic symptoms is scant and mostly limited to dialysis patients. Here we aim to assess the association between CKD-MBD and symptom burden in non-dialysis CKD patients. We used data from the European Quality study, which includes patients aged ≥65 with eGFR ≤20 ml/min/1.73m2 from six European countries, followed up to five years. We used generalized linear mixed-effect models to determine the association between repeated measurements of parathyroid hormone (PTH), phosphate and calcium with the overall symptom number (0-33), the overall symptom severity (0-165), and the presence of 33 CKD-related symptoms. We also analyzed subgroups by sex, age, and diabetes mellitus, and assessed effect mediation and joint effects between mineral biomarkers. The 1396 patients included in the study had a mean of 13±6 symptoms at baseline, with a median overall severity score of 32 (IQR 19-50). The association between PTH levels and symptom burden appeared U-shaped with a lower symptom burden found for mild-to-moderately increased PTH levels. Phosphate and calcium were not independently associated with overall symptom burden. The highest symptom burden was found in patients with a combination of both severe hyperparathyroidism and severe hyperphosphatemia (+2.44 symptoms (0.50, 4.38), P=0.01). The association of both hypocalcemia and hyperphosphatemia with symptom burden seemed to differ by sex and age. In older patients with advanced CKD not on dialysis, mild-to-moderately increased PTH was associated with a lower symptom burden, although the effect size was relatively small (less than one symptom). Neither phosphate nor calcium were associated with the overall symptom burden, except for the combination of severe hyperphosphatemia and severe hyperparathyroidism which was associated with an increased number of symptoms.

Techniques for evaluating the ATP-gated ion channel P2X7 receptor function in macrophages and microglial cells

Resident macrophages are tissue-specific innate immune cells acting as sentinels, constantly patrolling their assigned tissue to maintain homeostasis, and quickly responding to pathogenic invaders or molecular danger signals molecules when necessary. Adenosine triphosphate (ATP), when released to the extracellular medium, acts as a danger signal through specific purinergic receptors. Interaction of ATP with the purinergic receptor P2X7 activates macrophages and microglial cells in different pathological conditions, triggering inflammation. The highly expressed P2X7 receptor in these cells induces cell membrane permeabilization, inflammasome activation, cell death, and the production of inflammatory mediators, including cytokines and nitrogen and oxygen-reactive species. This review explores the techniques to evaluate the functional and molecular aspects of the P2X7 receptor, particularly in macrophages and microglial cells. Polymerase chain reaction (PCR), Western blotting, and immunocytochemistry or immunohistochemistry are essential for assessing gene and protein expression in these cell types. Evaluation of P2X7 receptor function involves the use of ATP and selective agonists and antagonists and diverse techniques, including electrophysiology, intracellular calcium measurements, ethidium bromide uptake, and propidium iodide cell viability assays. These techniques are crucial for studying the role of P2X7 receptors in immune responses, neuroinflammation, and various pathological conditions. Therefore, a comprehensive understanding of the functional and molecular aspects of the P2X7 receptor in macrophages and microglia is vital for unraveling its involvement in immune modulation and its potential as a therapeutic target. The methodologies presented and discussed herein offer valuable tools for researchers investigating the complexities of P2X7 receptor signaling in innate immune cells in health and disease.

Correlation of Parathyroid Hormone Values With Lung Function Parameters in Patients With Chronic Obstructive Pulmonary Disease.

The aim of this study was to determine the disturbances in the concentration of parathyroid hormone (PTH) and 25-hydroxyvitamin D (vitamin D) in patients with stable chronic obstructive pulmonary disease (COPD)and its correlation with airflow obstruction. A prospective study included 200 patients with a confirmed diagnosis of COPD in the Department of Lung Diseases and Tuberculosisand Pulmonology Polyclinic of University Clinical Hospital Mostar in the period of three years, between May 2021 and May 2024. Inclusion criteria were a stable phase of COPD, hemodynamically stable patients older than 40 years, forced vital capacities in the first second (FEV1)/forced vital capacities (FVC)<0.7, and patients with PTH, vitamin D, calcium, and phosphate measurements. Exclusion criteria wereacute exacerbation of COPD in the last month; current treatment with nutritional supplements, vitamins, and statins; lack of availability of lung function data; use of systemic corticosteroids in the previous three months; chronic renal insufficiency, respiratory diseases other than COPD (asthma, pneumonia, tuberculosis, and bronchiectasis), and other diseases (cancerand parathyroid disease). Medical records about demographic data (age and gender), pulmonary function test (FVC, FEV1, FEV1%FVC, mean expiratory flow (MEF)50), body mass index (BMI), COPD assessment test (CAT), Modified Medical Research Council(mMRC) Dyspnea Scale, and serum PTH, vitamin D, calcium, and phosphate levels were obtained. Patients with higher COPD stagehad lower spirometry values,most significantly MEF50. The higher the COPD group (Global Initiative for Chronic Obstructive Lung Disease (GOLD) D), the lower vitamin D ​​and the higher PTH levels were. Calcium and phosphate values ​​were the same for all groups. Vitamin D and PTH levels significantly ​​correlated with MEF50 values. The lower MEF50 level, the higher PTH levels, ​​and lower vitamin D levels were found (P<0.05). Our study showed that the patients in the higher COPD group have lower vitamin D levels ​​and higher PTH levels, indicating that they developed secondary hyperparathyroidism. The levels of vitamin D and PTH correlated the most with MEF50 values while other spirometry parameters did not significantly correlate with vitamin D and PTH levels.

Anandamide modulation of monocyte-derived Langerhans cells: implications for immune homeostasis and skin inflammation.

The endocannabinoid system (ECS), named after the chemical compounds found in the cannabis plant, is a regulatory network of neurotransmitters, receptors, and enzymes that plays crucial roles in skin health and disease. Endogenous ligands of the ECS, called endocannabinoids, have proven to be important regulators of immune responses. One of the most prevalent endocannabinoids, arachidonoylethanolamide (also known as anandamide), is known for its anti-inflammatory effects. Langerhans cells (LCs) are the sole antigen-presenting cells present in the human epidermis. They serve as the first line of defense against pathogens and are essential for the skin's specific immune responses and play a critical role in maintaining tissue homeostasis; however, little is known about the effect of endocannabinoids on these cells. Our research aimed to provide the connection between monocyte-derived Langerhans cells (moLCs) and the ECS, shedding light on their collaborative roles in immune homeostasis and inflammation. Human monocytes were differentiated into moLCs using established protocols. Anandamide was applied during the differentiation process to test its effect on the viability, marker expression, and cytokine production of the cells, as well as in short term treatments for intracellular calcium measurement. TLR ligands applied after the differentiation protocol were used to activate moLCs. The impact of anandamide on the functionality of moLCs was further assessed using differential gene expression analysis of bulk RNA-Seq data, moLC-T cell cocultures, while ELISpot was employed to determine polarization of T cells activated in the aforementioned cocultures. Anandamide did not significantly affect the viability of moLCs up to 10 µM. When applied during the differentiation process it had only a negligible effect on CD207 expression, the prototypic marker of LCs; however, there was an observed reduction in CD1a expression by moLCs. Anandamide had no significant effects on the maturation status of moLCs, nor did it affect the maturation induced by TLR3 and TLR7/8 agonists. MoLCs differentiated in the presence of anandamide did however show decreased production of CXCL8, IL-6, IL-10 and IL-12 cytokines induced by TLR3 and TLR7/8 activation. Anandamide-treated moLCs showed an increased capability to activate naïve T cells; however, not to the level seen with combined TLR agonism. RNA sequencing analysis of moLCs differentiated with anandamide showed modest changes compared to control cells but did reveal an inhibitory effect on oxidative phosphorylation specifically in activated moLCs. Anandamide also promoted the polarization of naïve T cells towards a Th1 phenotype. Our results show that anandamide has nuanced effects on the differentiation, maturation, cytokine secretion, metabolism and function of activated moLCs. Among these changes the decrease in CD1a expression on moLCs holds promise to selectively dampen inflammation induced by CD1a restricted T cells, which have been implicated as drivers of inflammation in common inflammatory skin conditions such as psoriasis, atopic dermatitis and contact dermatitis.

Parvalbumin-expressing basal forebrain neurons mediate learning from negative experience

Parvalbumin (PV)-expressing GABAergic neurons of the basal forebrain (BFPVNs) were proposed to serve as a rapid and transient arousal system, yet their exact role in awake behaviors remains unclear. We performed bulk calcium measurements and electrophysiology with optogenetic tagging from the horizontal limb of the diagonal band of Broca (HDB) while male mice were performing an associative learning task. BFPVNs responded with a distinctive, phasic activation to punishment, but showed slower and delayed responses to reward and outcome-predicting stimuli. Optogenetic inhibition during punishment impaired the formation of cue-outcome associations, suggesting a causal role of BFPVNs in associative learning. BFPVNs received strong inputs from the hypothalamus, the septal complex and the median raphe region, while they synapsed on diverse cell types in key limbic structures, where they broadcasted information about aversive stimuli. We propose that the arousing effect of BFPVNs is recruited by aversive stimuli to serve crucial associative learning functions.

Untargeted metabolomics revealed the mechanism of aucubin on glucocorticoid-induced osteoporosis in mice through modulating arachidonic acid metabolism

Glucocorticoid-induced osteoporosis (GIOP) represents the most prevalent form of secondary osteoporosis. Aucubin (AU), a principal active component found in traditional herbal medicines such as Eucommia ulmoides, has been demonstrated to enhance osteoblast differentiation. Nonetheless, the precise therapeutic effects of AU on GIOP and the complex underlying regulatory mechanisms warrant further investigation. We first established a GIOP model in female mice and then assessed the therapeutic effects of AU using micro-CT analysis, biomechanical testing, measurements of serum calcium (Ca) and phosphorus (P) levels, and histological analyses using Hematoxylin and Eosin (HE) and Masson staining. Subsequently, non-targeted metabolomics was employed in order to study the effects of AU on serum metabolites in GIOP mice. The levels of the factors related to these metabolites were quantified using real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) and western blot analyses. Finally, the effects of AU on osteoblastic and osteoclastic differentiation were examined. We found that AU significantly ameliorated bone microarchitecture and strength in GIOP mice. It mitigated pathological damages such as impairment of trabecular bone structure and reduction in collagen fibers, while concurrently elevating serum levels of Ca and P. Non-targeted metabolomics revealed that Arachidonic acid (AA) metabolism serves as a common pathway between the control and GIOP groups, as well as between the high-dose AU (AUH) and GIOP groups. AU notably upregulates prostaglandin-endoperoxide synthase 2 (PTGS2) and microsomal prostaglandin-E synthase 1 (PTGES) expression and downregulates prostaglandin-H2 D-isomerase (PTGDS) expression. Furthermore, AU treatment increased the expression of runt-related transcription factor 2 (Runx2) and transcription factor Sp7 (Osterix), enhanced serum alkaline phosphatase (ALP) activity, and reduced osteoclast expression. These results indicate that AU is a potential drug for treating GIOP, and its mechanism is related to regulating AA metabolism and promoting osteoblast differentiation. However, the key targets of AU in treating GIOP still need further exploration.

Clinical, Biochemical and Surgical Outcomes of Primary Hyperparathyroidism in the Present Era: A Prospective Study From a Tertiary Care Hospital.

Introduction Primary hyperparathyroidism (PHPT) has undergone a considerable change from being symptomatic to asymptomatic.This is the first large study from North Indiato study the clinical and biochemical features and surgical outcomes in thepresent era. Study design This is across-sectional study that was conducted in the Department of Endocrinology (SKIMS) from February 2021 to December 2022, in which 103 patients diagnosed with PHPT were included. Evaluation included measurement of total calcium, phosphorus,alkaline phosphate, intact parathyroid hormone, 25-hydroxy vitamin, 24-hour urinary calcium, radiological survey of hands and skull, Dual Energy X-ray absorptiometry, and ultrasonography (USG) of the abdomen. USG neck and technetium-99m sestamibi scans were usedfor preoperative localization; however, in cases of discordance between these investigations or suspicions of multi-glandular disease, four-dimensional computerized tomography of the neck was used. Patients were subjected to surgery according to the guidelines and monitored post-surgeryfor complications like hypocalcemia and hungry bone syndrome and to document the cure. Results The mean age of patients was 42.8±14.73 years, with a female-to-male ratio of 4.4:1.The mean eGFR of patientswas 99.1±30.87 ml/min, with 55 (53.4%) of themhaving renal disease.Osteoporosis and fractures were present in 41 (39.8%) and 5 (4.8%) patients, respectively. Cholelithiasis and pancreatitis were present in 25 (24.3%) and 5 (4.9%) patients, respectively.Hypertension (HTN) and diabetes mellitus (DM) were the commonest comorbidities, which were present in 34 (33.1%) and 15 (14.5%) patients, respectively.Mean preoperative levels of calcium, phosphorus (PO4), alkaline phosphate (ALP), intact parathyroid hormone (iPTH), 25(OH)vitamin D, and 24-hour urinary calcium were 12.1 mg/dl, 2.35 mg/dl, 210.2 U/L, 332.9 pg/ml, 25.7 ng/ml, and 452.1 mg/day, respectively. The most commontype was right inferior parathyroid adenoma, present in45 cases (43.7%), followed by left inferior parathyroid adenoma in31 cases (30.1%). A total of 75 patients (72.8%) underwent minimally invasive parathyroidectomy, with 68 patients (90.7%) achieving a biochemical cure. The mean adenoma weight was 3.19±2.25 g. There was no statistically significant correlation (r) between preoperative biochemical parameters and adenoma weight. Conclusion Despite improvements in imaging and the easy availability of immunoassays for early diagnosis, renal disease continued to be the most common presentation, followed by skeletal involvement in our population. In developing countrieslike India, any patient presenting with nephrolithiasis or nephrocalcinosis, low bone mass, or fragility fractures should be evaluated for PHPT.

Plasticizer-based and polymer-free ion-selective optodes on cellulose paper

Paper-based ion-selective optodes (ISOs) allow for low-cost ion measurements using widely accessible optical detectors such as smartphones, representing an attractive analytical platform for medical testing and environmental monitoring. Previously reported paper-based ISOs rely on plasticized PVC membranes or PVC/plasticizer-free adsorption layers containing hydrophobic sensing chemicals. In this paper, we studied a new format of paper-based ISOs, in which a plasticizer phase containing sensing chemicals is deposited onto cellulose paper without using a hydrophobic polymer like PVC. Compared to ISOs without plasticizers and polymers, the plasticizer-based ISOs show much higher pH sensitivity when using chromoionophore I and tetrakis[3,5-bis(trifluoromethyl)phenyl]borate as the sensing chemicals. When the sensing layer further contains a solid ionophore with high molecular rigidity, the plasticizer-based ISOs for cations also exhibit enhanced sensitivity than the plasticizer-free ISOs. However, when the ionophore is a liquid at room temperature or has a long alkyl chain, the plasticizer-based and plasticizer-free ISOs have comparable responses because the ionophore behaves as a pseudo-plasticizer. Compared to ISOs with both plasticizers and polymers, the elimination of hydrophobic polymers like PVC makes inkjet printing more efficient and preserves the capillary action of the porous paper. By using the newly launched Samba cartridge with smaller nozzles, the plasticizer-based and polymer-free optodes for sodium, potassium, and calcium ions are prepared by inkjet printing for the first time. In an example application, the inkjet-printed plasticizer-based and polymer-free ISOs are used for colorimetric measurements of urine calcium.

Monitoring mitochondrial calcium in cardiomyocytes during coverslip hypoxia using a fluorescent lifetime indicator

An increase in mitochondrial calcium via the mitochondrial calcium uniporter (MCU) has been implicated in initiating cell death in the heart during ischemia-reperfusion (I/R) injury. Measurement of calcium during I/R has been challenging due to the pH sensitivity of indicators coupled with the fall in pH during I/R. The development of a pH-insensitive indicator, mitochondrial localized Turquoise Calcium Fluorescence Lifetime Sensor (mito-TqFLITS), allows for quantifying mitochondrial calcium during I/R via fluorescent lifetime imaging. Mitochondrial calcium was monitored using mito-TqFLITS in neonatal mouse ventricular myocytes (NMVM) isolated from germline MCU-KO mice and MCUfl/fl treated with CRE-recombinase to acutely knockout MCU. To simulate ischemia, a coverslip was placed on a monolayer of NMVMs to prevent access to oxygen and nutrients. Reperfusion was induced by removing the coverslip. Mitochondrial calcium increases threefold during coverslip hypoxia in MCU-WT. There is a significant increase in mitochondrial calcium during coverslip hypoxia in germline MCU-KO, but it is significantly lower than in MCU-WT. We also found that compared to WT, acute MCU-KO resulted in no difference in mitochondrial calcium during coverslip hypoxia and reoxygenation. To determine the role of mitochondrial calcium uptake via MCU in initiating cell death, we used propidium iodide to measure cell death. We found a significant increase in cell death in both the germline MCU-KO and acute MCU-KO, but this was similar to their respective WTs. These data demonstrate the utility of mito-TqFLITS to monitor mitochondrial calcium during simulated I/R and further show that germline loss of MCU attenuates the rise in mitochondrial calcium during ischemia but does not reduce cell death.

Utility of in situ ion‐exchange membranes to assess nutrient availability, productivity, and fertilizer response of coastal Douglas‐fir of the Pacific Northwest

AbstractDouglas‐fir [Pseudotsuga menziesii (Mirb.) Franco] is the predominant forest plantation species in the Pacific Northwest (PNW), with site productivity and fertilizer response influenced by climate and soil variations. This study investigates the utility of in situ 12‐week supply measurements of nitrogen (N), calcium (Ca), and phosphorus (P) to ion‐exchange resins (specifically Plant Root Simulator [PRS] probes) to estimate carbon (C):N ratios, soil nutrient contents (0–1 m), foliar nutrient concentrations, Douglas‐fir productivity (site index and basal area mean annual increment), and fertilizer volume response. PRS nutrient supply rates were correlated with N, Ca, and P soil nutrient contents (0–1 m), C:N ratios, and foliar nutrient concentrations. Low PRS NO3 supply rates (&lt;25 mg N·m−2·burial period−1) were correlated with lower Douglas‐fir productivity and greater fertilizer volume response. PRS NO3 supply rates performed as well as total soil N contents and foliar N concentrations at estimating volume growth response to fertilizer. Twelve weeks after fertilization, PRS NO3, NH4, and Ca supply rates were significantly elevated compared to the unfertilized treatment. This research found that PRS probes were an effective in situ tool and are recommended for understanding N, Ca, and P nutrient availabilities, site productivity, and fertilizer response in Douglas‐fir plantations and for developing fertilizer prescriptions.

The oxalate-lowering effect of functional stirred yogurt in a rat model

Urolithiasis is a prevalent health issue that can potentially lead to kidney failure. Of the different kinds of kidney stones, the most common kind are calcium oxalate crystals. In this study, we investigated the impact of two probiotic lactobacilli preparations on urinary functions in rats that were fed a high-oxalate diet. Forty male Sprague-Dawley rats in all were split up into five groups, each with eight rats. Two groups were used: one as a positive control group that received a high-oxalate diet, and the other as a negative control group that received a regular, balanced diet. The remaining three groups were administered oral doses of the probiotic preparations in addition to being fed a high-oxalate diet. After 21 days, the rats were sacrificed, and biochemical analysis was conducted on their blood and urine samples, including measurements of creatinine, urea, uric acid, phosphorus, calcium, magnesium, aspartate transaminase (AST), acid and alkaline phosphatase, total proteins, and urine pH. The findings of the study confirmed that these probiotic preparations had a positive impact on kidney functions, potentially by enhancing oxalate metabolism in the intestines and/or reducing oxalate absorption from the gastrointestinal tract. Additionally, the counts of lactobacilli colonies in the fecal samples increased with both preparations, while the counts of coliforms decreased compared to the baseline. These results suggest that lactobacilli could be explored as a promising therapeutic approach in the prevention of urinary stones.

Assessment of Some Biometrics and Biochemical Parameters in Migraine Patients

Background: Migraine is a pulsating and recurrent headache in one or both side. It may be caused by induce of nerves in the brain blood vessels walls and its associates with photophobia. Objectives: Measure of Body mass index (BMI), blood pressure (BP), serum calcium (Ca), magnesium (Mg) and iron (Fe) in migraine patients. Methods: This study performed on 94 persons (64 migraine: 30 control), who visited Al-Duloya General Hospital, Tikrit Educational Hospital, and neurological clinics in Al-Duloya and Tkrit. Also it contains visiting participants to their homes in Salahaddin in Iraq. A socio-demographic characters, length, weight, and BP taken directly. 3-5ml blood sampled for obtaining serum. Biochemical tests analyzed by spectrophotometer in Central laboratory of Tikrit University. The study period extended from 30-7-2023 to 27-9-2023. GraphPrism9 program and T-test used for statistical analysis. Results: Patient age was 34.9(16-63) year. Higher percentages reported in female (79.6%) and family history (68.7%). BMI (29.1±5.5), (27.6±5.3) kg/m2, systolic BP (11.7±1.2), (11.5±1.1), and diastolic BP (7.5±0.8), (7.2±1.0) Cm.Hg, show non-significant elevation in migraine compare with control respectively. Mg reveals significant decrease (1.7±0.7), (2.1±0.6), but Ca (7±0.5), (7.3±0.7) and Iron (82±57), (90±52) mg/dL reveal non-significant decrease in migraine compare with control respectively. Conclusions: BMI and BP show non-significant elevation. While Mg reveals significant decrease, Ca and Iron reveal non-significant decrease in patients.