Detailed analysis of Mdivi-1 effects on complex I and respiratory supercomplex assembly.

Several human diseases, including cancer and neurodegeneration, are associated with excessive mitochondrial fragmentation. In this context, mitochondrial division inhibitor (Mdivi-1) has been tested as a therapeutic to block the fission-related protein dynamin-like protein-1 (Drp1). Recent studies suggest that Mdivi-1 interferes with mitochondrial bioenergetics and complex I function. Here we show that the molecular mechanism of Mdivi-1 is based on inhibition of complex I at the IQ site. This leads to the destabilization of complex I, impairs the assembly of N- and Q-respirasomes, and is associated with increased ROS production and reduced efficiency of ATP generation. Second, the calcium homeostasis of cells is impaired, which for example affects the electrical activity of neurons. Given the results presented here, a potential therapeutic application of Mdivi-1 is challenging because of its potential impact on synaptic activity. Similar to the Complex I inhibitor rotenone, Mdivi-1 may lead to neurodegenerative effects in the long term.

Diurnal fluctuations in biochemical parameters related to calcium homeostasis - the Bispebjerg study of diurnal variations.

PURPOSE: This aim of this study was to assess the possible association between diurnal oscillations and biochemical markers associated with calcium homeostasis. This included the markers parathyroid hormone (PTH), total calcium, total alkaline phosphatase, phosphate, and 25-hydroxyvitamin D (25-OH-D). By examining the influence of circadian rhythms on these parameters, the study aimed to deepen the understanding of calcium metabolism dynamics and its clinical implications. PATIENTS AND METHODS: Blood samples from 24 Caucasian male volunteers aged 20 to 40 (mean age 26) with normal pulse, blood pressure, and BMI were analyzed for biochemical markers related to calcium homeostasis. Data was obtained from the Bispebjerg study of diurnal variations. Blood samples were collected every three hours over a 24-hour period. Patients were fasting from 22:00 to 09:00. The participants spent 24 h in the hospital ward, receiving regular meals and engaging in low-intensity activities. They experienced 15 h of daylight and 9 h of complete darkness during sleep. Diurnal oscillations were analyzed using cosinor analysis with statistical significance set at p < 0.05. RESULTS: Total calcium, phosphate, and PTH exhibited significant diurnal variations. Total calcium and PTH were inversely synchronized while PTH and phosphate oscillated in synchronization. The three parameters showed relatively large amplitude/reference range ratios from 25.4% to 41.5%. CONCLUSION: This study found notable fluctuations in total calcium, phosphate, and PTH levels over a 24-hour cycle, while 25-OH-D and total alkaline phosphatase remained consistent. It highlights the importance of considering sampling times for total calcium, PTH, and phosphate in clinical settings.

Characterization of a cohort of patients with hypercalcemia in a tertiary pediatric hospital. / Caracterización de una cohorte de pacientes con hipercalcemia en un centro pediátrico de tercer nivel.

Introduction. Hypercalcemia is infrequent in pediatrics, of diverse etiology, and with multiorgan morbidity. Objective. Describe the etiology, biochemistry, clinical, and treatment in pediatric patients with hypercalcemia. Population and methods. Retrospective and descriptive study of a cohort of patients with hypercalcemia between 2008 and 2022. They were classified into three groups (G): hypercalcemia of iatrogenic cause (G1), parathyroid hormone (PTH) independent (G2), or PTH-dependent (G3). Results. One hundred forty-seven patients were included; 57% were male, with a median age of 3.7 years, median calcemia of 11.8 mg/dl, and mean phosphatemia of 4.9 mg/dl. Symptoms were present in 29% of patients, and 28.6% required additional treatments to those of the first line. In G1, 76 patients (51.7%) were included; in G2, 58 (39.4%), and in G3, 13 (8.8%). Median calcemia was lower in G1 vs. G2 and G3 (11.6 mg/dl, 12.6 mg/dl, and 12.3 mg/dl), and mean phosphatemia was lower in G3 vs. G1 and G2 (3.7 mg/dl, 5.3 mg/dl, and 4.9 mg/dl). Most of the patients with hypercalcemia were asymptomatic and did not require additional treatments. The percentage of symptomatic patients and the percentage requiring additional treatment were lower in G1 than in the other two groups. Conclusions. Iatrogenesis was the most frequent cause, presenting lower calcemia, while PTH-dependent causes presented the lowest phosphatemia. PTH-independent causes represented a diagnostic and therapeutic challenge due to lacking a characteristic biochemical profile.

Introducción. La hipercalcemia es infrecuente en pediatría, de etiología diversa y con morbilidad multiorgánica. Objetivo. Describir etiología, bioquímica, clínica y tratamiento en pacientes pediátricos con hipercalcemia. Población y métodos. Estudio retrospectivo y descriptivo de una cohorte de pacientes con hipercalcemia entre 2008 y 2022. Se clasificaron en tres grupos (G): hipercalcemia de causa iatrogénica (G1), paratohormona (PTH) independiente (G2) o PTH dependiente (G3). Resultados. Se incluyeron 147 pacientes; el 57 % eran varones, edad mediana de 3,7 años, calcemia mediana 11,8 mg/dl y fosfatemia media 4,9 mg/dl. El 29,9 % de los pacientes fueron sintomáticos y el 28,6 % requirió tratamientos adicionales a los de la primera línea. En G1 se incluyeron 76 pacientes (51,7 %); en G2, 58 (39,4 %), y en G3, 13 (8,8 %). La calcemia mediana fue menor en G1 vs. G2 y G3 (11,6 mg/dl, 12,6 mg/dl y 12,3 mg/dl). La fosfatemia media fue menor en G3 vs. G1 y G2 (3,7 mg/dl, 5,3 mg/dl y 4,9 mg/dl). La mayoría de los pacientes con hipercalcemia fueron asintomáticos sin requerimientos de tratamientos adicionales. El porcentaje de pacientes sintomáticos y el de requerimiento de tratamientos adicionales fue menor en G1 que en los otros dos grupos. Conclusiones. La iatrogenia fue la causa más frecuente, y se presentó con calcemias más bajas; mientras que las causas PTH dependientes presentaron las fosfatemias más bajas. Las causas PTH independientes representaron un desafío diagnóstico y terapéutico por la falta de un perfil bioquímico característico.

Calcium deposition in chicken eggshells: role of host genetics and gut microbiota.

Eggshell is predominantly composed of calcium carbonate, making up about 95% of its composition. Eggshell quality is closely related to the amount of calcium deposition in the shell, which requires chickens to maintain a robust state of calcium metabolism. In this study, we introduced a novel parameter, Total Eggshell Weight (TESW), which measures the total weight of eggshells produced by chickens over a period of 10 consecutive d, providing valuable information on the intensity of calcium metabolism in chickens. Genome-wide association study (GWAS) was conducted to explore the genetic determinants of eggshell calcification in a population of 570 Rhode Island Red laying hens at 90 wk of age. This study revealed a significant association between a specific SNP (rs14249431) and TESW. Additionally, using random forest modeling and 2-tailed testing, we identified 3 genera, Lactobacillus in the jejunum, Lactobacillus, and Fournierella in the cecum, that exhibited a significant association with TESW. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis of claudin-1 and occludin genes in individuals with low TESW and high abundance of jejunal Lactobacillus confirmed that the inhibitory effect of jejunal Lactobacillus on calcium uptake was achieved through the up-regulation of tight junctions in intestinal epithelial cells. Notably, both host and microbial factors influence TESW, displaying a mutually influential relationship between them. The microbiome-wide Genome-Wide Association Study (mb-GWAS) identified significant associations between these 3 genera and specific genomic variants, such as rs316115020 and rs316420452 on chromosome 5, rs313198529 on chromosome 11, linked to Lactobacillus in the cecum. Moreover, rs312552529 on chromosome 1 exhibited potential association with Fournierella in the cecum. This study highlights the influence of host genetics and gut microbiota on calcium deposition in eggshells during the late laying phase, providing a foundational reference for studying calcium metabolism in hens.

Clinical and epidemiologic characteristics of hospitalized oncological patients with hypercalcemia: a longitudinal, multicenter study.

BACKGROUND: There are few studies that have analyzed the characteristics of hypercalcemia in hospitalized oncological patients. Our objectives were to describe the clinical characteristics of hospitalized patients with paraneoplastic hypercalcemia and to identify prognostic variables for mortality. METHODS: This was an observational, longitudinal, retrospective, and bicentric study. It included adult patients admitted to two hospitals in Málaga, Spain (2014-2018). The minimum follow-up period was 2 years or until death. RESULTS: A total of 154 patients were included; the majority (71.4%) were admitted to the internal medicine department. The median follow-up was 3.5 weeks (interquartile range [IQR] 1.1-11.5). The mean (standard deviation) age was 67.6 (12.3) years, with a predominance of males (58.4%). The median (IQR) serum calcium at admission was 13.2 (11.8-14.6) mg/dl. The most common neoplasms were pulmonary (27.3%), hematologic (23.4%), urological (13%), and breast (12.3%). Furthermore, 56.5% of cases had a known history of neoplasia at the time of diagnosis. The parathyroid hormone (PTH) level was determined in 24%; of these, 10.8% had elevated levels. In all, 95.5% of patients died during follow-up. The median survival was 3.4 weeks (95% confidence interval 2.6-4.3). Factors associated with higher mortality were age, serum calcium at admission, previous history of neoplasia, etiology other than multiple myeloma, and noncorrection of hypercalcemia. CONCLUSIONS: In hospitalized patients, paraneoplastic hypercalcemia was associated with high short-term mortality. Several factors associated with a worse prognosis were identified in these patients.

Supplementation of the Combination of Quercetin and Vitamin E Alleviates the Effects of Heat Stress on the Uterine Function and Hormone Synthesis in Laying Hens.

Chickens are sensitive to heat stress because their capacity to dissipate body heat is low. Hence, in chickens, excessive ambient temperature negatively influences their reproductive performance and health. Heat stress induces inflammation and oxidative stress, thereby rendering many reproductive organs dysfunctional. In this study, we evaluated the effects of the supplementation of dietary quercetin and vitamin E on the uterine function, eggshell quality via estrogen concentration, calcium metabolism, and antioxidant status of the uterus of laying hens under heat stress. The ambient temperature transformation was set at 34 ± 2 °C for 8 h/d (9:00 am-5:00 pm), which was followed by 22 °C to 28 °C for 16 h/d. Throughout the experiment, the relative humidity in the chicken's pen was at 50 to 65%. A total of 400 Tianfu breeder hens (120-days-old) were randomly divided into four dietary experimental groups, including basal diet (Control); basal diet + 0.4 g/kg quercetin; basal diet + 0.2 g/kg vitamin E; and basal diet + the combination of quercetin (0.4 g/kg) and vitamin E (0.2 g/kg). The results show that the combination of quercetin and vitamin E significantly increased the serum alkaline phosphatase levels and the antioxidant status of the uterus (p < 0.05). In addition, the combination of quercetin and vitamin E significantly increased the concentrations of serum estrogen and progesterone, as well as elevated the expression of hypothalamic gonadotropin-releasing hormone-1 and follicular cytochrome P450 family 19 subfamily A member-1 (p < 0.05). We also found that the calcium levels of the serum and uterus were significantly increased by the synergistic effects of quercetin and vitamin E (p < 0.05), and they also increased the expression of Ca2+-ATPase and the mRNA expression of calcium-binding-related genes in the uterus (p < 0.05). These results are consistent with the increased eggshell quality of the laying hens under heat stress. Further, the combination of quercetin and vitamin E significantly increased the uterine morphological characteristics, such as the height of the uterine mucosal fold and the length of the uterine mucosa villus of the heat-stressed laying hens. These results collectively improve the uterine function, serum and uterine calcium concentration, eggshell strength, and eggshell thickness (p < 0.05) in heat-stressed laying hens. Taken together, we demonstrated in the present study that supplementing the combination of dietary quercetin and vitamin E alleviated the effects of heat stress and improved calcium metabolism, hormone synthesis, and uterine function in the heat-stressed laying hens. Thus, the supplementation of the combination of quercetin and vitamin E alleviates oxidative stress in the eggshell gland of heat-stressed laying hens, thereby promoting calcium concentration in the serum and eggshell gland, etc., in laying hens. Hence, the combination of quercetin and vitamin E promotes the reproductive performance of the laying hens under heat stress and can also be used as a potent anti-stressor in laying hens.

Effects of Dietary Colostrum Basic Protein on Bone Growth and Calcium Absorption in Mice.

Colostrum basic protein (CBP) is a trace protein extracted from bovine colostrum. Previous studies have shown that CBP can promote bone cell differentiation and increase bone density. However, the mechanism by which CBP promotes bone activity remains unclear. This study investigated the mechanism of the effect of CBP on bone growth in mice following dietary supplementation of CBP at doses that included 0.015%, 0.15%, 1.5%, and 5%. Compared with mice fed a normal diet, feeding 5% CBP significantly enhanced bone rigidity and improved the microstructure of bone trabeculae. Five-percent CBP intake triggered significant positive regulation of calcium metabolism in the direction of bone calcium accumulation. The expression levels of paracellular calcium transport proteins CLDN2 and CLDN12 were upregulated nearly 1.5-fold by 5% CBP. We conclude that CBP promotes calcium absorption in mice by upregulating the expression of the calcium-transporting paracellular proteins CLND2 and CLND12, thereby increasing bone density and promoting bone growth. Overall, CBP contributes to bone growth by affecting calcium metabolism.

Longitudinal changes of the femoral bone mineral density from first to third trimester of pregnancy: bone health assessment by means of non-ionizing REMS technology.

BACKGROUND: Throughout the pregnancy, there is a substantial transfer of calcium from the maternal skeleton to the fetus, which leads to a transient net reduction of the maternal bone mineral density. AIMS: To assess longitudinally the changes in the bone mineral density at the femoral neck between the first and third trimester of pregnancy in a cohort of healthy participants using Radiofrequency Echographic Multi Spectrometry (REMS) technology. METHODS: Prospective, cohort study conducted at the University hospital of Parma, Italy between July 2022 and February 2023. We recruited healthy participants with an uncomplicated singleton pregnancy before 14 completed weeks of gestation. All included participants were submitted to a sonographic examination of the femoral neck to assess the bone mineral density (and the corresponding Z-score values) using REMS at 11-13 and 36-38 weeks of pregnancy. The primary outcome was the change in the bone mineral density values at the maternal femoral neck between the first and third trimester of pregnancy. RESULTS: Over a period of 7 months, a total of 65 participants underwent bone mineral density measurement at the femoral neck at first and third trimester of the pregnancy using REMS. A significant reduction of the bone mineral density at the femoral neck (0.723 ± 0.069 vs 0.709 ± 0.069 g/cm2; p < 0.001) was noted with a mean bone mineral density change of - 1.9 ± 0.6% between the first and third trimester of pregnancy. At multivariable linear regression analysis, none of the demographic or clinical variables of the study population proved to be independently associated with the maternal bone mineral density changes at the femoral neck. CONCLUSIONS: Our study conducted on a cohort of healthy participants with uncomplicated pregnancy demonstrates that there is a significant reduction of bone mineral density at femoral neck from early to late gestation.

Computer simulations predict the impact of neuronal atrophy on the calcium dynamics in Huntington's disease.

One of the early hallmarks of Huntington's disease (HD) is neuronal cell atrophy, especially in the striatum, underlying motor dysfunction in HD. Here using a computer model, we have predicted the impact of cell shrinkage on calcium dynamics at the cellular level. Our model indicates that as cytosolic volume decreases, the amplitude of calcium transients increases and the endoplasmic reticulum (ER) becomes more leaky due to calcium-induced calcium release and a "toxic" positive feedback mechanism mediated by ryanodine receptors that greatly increases calcium release into the cytosol. The excessive calcium release from ER saturates the calcium buffering capacity of calbindin and forces further accumulation of free calcium in the cytosol and cellular compartments including mitochondria. This leads to imbalance of calcium in both cytosol and ER regions. Excessive calcium accumulation in the cytosol can damage the mitochondria resulting in metabolic dysfunction in the cell consistent with the pathology of HD. Our computational model points toward potential drug targets and can accelerate and greatly help the experimental studies of HD paving the way for treatments of patients suffering from HD.

Effect and Mechanism of Chinese Medicine in Treatment of Osteoporosis / 中国实验方剂学杂志

Osteoporosis （OP） is a common bone disease affecting the quality of life and causing huge medical burden to the patients and society. The occurrence of OP is mainly caused by excessive bone resorption and insufficient bone formation， which are directly influenced by external calcium ion balance. Calcium imbalance can impair bone integrity， reduce the calcium supply to the bone， and lower the calcium content in the bone， thus triggering OP. Drugs are the main anti-OP therapy in modern medicine， which， however， may cause adverse reactions and drug dependence. Chinese medicines have good clinical effects and high safety in treating OP， being suitable for long-term use. Recent studies have shown that Chinese medicines can alleviate estrogen deficiency， regulate bone cell and calcium metabolism， which is crucial for the formation and development of OP. The transient receptor potential cation channel superfamily V members 5 and 6 （TRPV5 and TRPV6， respectively） affect bone homeostasis by mediating the transmembrane calcium ion transport in the intestine （TRPV6） and kidney （TRPV5）. Therefore， TRPV5/6 is one of the key targets to understand the anti-OP mechanisms of the effective parts of Chinese medicines， which is worthy of further study. This paper summarizes the research results about the anti-OP effects of Chinese medicines in the last two decades， especially the mechanism of regulating calcium metabolism， aiming to provide new ideas for the basic research， clinical application， and drug development of OP treatment.

Crucial Role of microRNAs as New Targets for Amelogenesis Disorders Detection.

INTRODUCTION: Amelogenesis imperfecta (AI) refers to a heterogeneous group of conditions with multiple factors which contribute to the hypomineralisation of enamel. Preventive measures are necessary to predict this pathology. Prospects for preventive medicine are closely related to the search for new informative methods for diagnosing a human disease. MicroRNAs are prominent for the non-invasive diagnostic platform. THE AIM OF THE STUDY: The aim of the review is to review the heterogeneous factors involved in amelogenesis and to select the microRNA panel associated with the AI type. METHODS: We used DIANA Tools (algorithms, databases and software) for interpreting and archiving data in a systematic framework ranging from the analysis of expression regulation from deep sequencing data to the annotation of miRNA regulatory elements and targets (https://dianalab. e-ce.uth.gr/). In our study, based on a gene panel associated with the AI types, twenty-four miRNAs were identified for the hypoplastic type (supplement), thirty-five for hypocalcified and forty-- nine for hypomaturation AI. The selection strategy included the microRNA search with multiple targets using the AI type's gene panel. RESULTS: Key proteins, calcium-dependent and genetic factors were analysed to reveal their role in amelogenesis. The role of extracellular non-coding RNA sequences with multiple regulatory functions seems to be the most attractive. We chose the list of microRNAs associated with the AI genes. We found four microRNAs (hsa-miR-27a-3p, hsa-miR-375, hsa-miR-16-5p and hsamiR- 146a-5p) for the gene panel, associated with the hypoplastic type of AI; five microRNAs (hsa- miR-29c-3p, hsa-miR-124-3p, hsa-miR-1343-3p, hsa-miR-335-5p, and hsa-miR-16-5p - for hypocalcified type of AI, and seven ones (hsa-miR-124-3p, hsa-miR-147a, hsa-miR-16-5p, hsamiR- 429, hsa-let-7b-5p, hsa-miR-146a-5p, hsa-miR-335-5p) - for hypomaturation. It was revealed that hsa-miR-16-5p is included in three panels specific for both hypoplastic, hypocalcified, and hypomaturation types. Hsa-miR-146a-5p is associated with hypoplastic and hypomaturation type of AI, which is associated with the peculiarities of the inflammatory response immune response. In turn, hsa-miR-335-5p associated with hypocalcified and hypomaturation type of AI. CONCLUSION: Liquid biopsy approaches are a promising way to reduce the economic cost of treatment for these patients in modern healthcare. Unique data exist about the role of microRNA in regulating amelogenesis. The list of microRNAs that are associated with AI genes and classified by AI types has been uncovered. The target gene analysis showed the variety of functions of selected microRNAs, which explains the multiple heterogeneous mechanisms in amelogenesis. Predisposition to mineralisation problems is a programmed event. Many factors determine the manifestation of this problem. Additionally, it is necessary to remember the variable nature of the changes, which reduces the prediction accuracy. Therefore, models based on liquid biopsy and microRNAs make it possible to take into account these factors and their influence on the mineralisation. The found data needs further investigation.

Modulation of the vitamin D/vitamin D receptor system in osteoporosis pathogenesis: insights and therapeutic approaches.

Osteoporosis is a prevalent bone disorder characterized by low bone mineral density (BMD) and deteriorated bone microarchitecture, leading to an increased risk of fractures. Vitamin D (VD), an essential nutrient for skeletal health, plays a vital role in maintaining bone homeostasis. The biological effects of VD are primarily mediated through the vitamin D receptor (VDR), a nuclear receptor that regulates the transcription of target genes involved in calcium and phosphate metabolism, bone mineralization, and bone remodeling. In this review article, we conduct a thorough literature search of the PubMed and EMBASE databases, spanning from January 2000 to September 2023. Utilizing the keywords "vitamin D," "vitamin D receptor," "osteoporosis," and "therapy," we aim to provide an exhaustive overview of the role of the VD/VDR system in osteoporosis pathogenesis, highlighting the most recent findings in this field. We explore the molecular mechanisms underlying VDR's effects on bone cells, including osteoblasts and osteoclasts, and discuss the impact of VDR polymorphisms on BMD and fracture risk. Additionally, we examine the interplay between VDR and other factors, such as hormonal regulation, genetic variants, and epigenetic modifications, that contribute to osteoporosis susceptibility. The therapeutic implications of targeting the VDR pathway for osteoporosis management are also discussed. By bringing together these diverse aspects, this review enhances our understanding of the VD/VDR system's critical role in the pathogenesis of osteoporosis and highlights its significance as a potential therapeutic target.

Características de los pacientes hospitalizados con hipercalcemia en la provincia de Málaga: estudio longitudinal, retrospectivo y multicéntrico / Characteristics of hospitalized patients with hypercalcemia in the province of Malaga: A longitudinal, retrospective, multicenter study

Antecedentes y objetivo Existen escasos estudios que analicen la hipercalcemia en pacientes hospitalizados. Nuestros objetivos fueron: describir las características clínicas de los pacientes hospitalizados con hipercalcemia, estimar su prevalencia en el medio hospitalario, analizar la tasa de corrección de la hipercalcemia, e identificar variables pronósticas. Materiales y métodos Estudio observacional, longitudinal, retrospectivo y bicéntrico. Se incluyeron pacientes adultos ingresados en dos hospitales de Málaga (2014-2018) con diagnóstico de hipercalcemia. El seguimiento mínimo fue de 2años o hasta el fallecimiento. Resultados Se incluyeron 205 pacientes con hipercalcemia (incidencia: 0,13%). La edad media (DE) fue de 68,2 (13,1) años, con predominio de varones (55,1%). La calcemia mediana (RIC) al ingreso fue de 13,1 (11,8-14,6) mg/dL. Las etiologías más frecuentes fueron: neoplasias (75,1%), hiperparatiroidismo primario y fármacos (ambas, 8,8%). La mediana (RIC) de seguimiento fue de 5,1 (1,7-60,3) semanas. Los tratamientos más usados fueron: fluidoterapia (86,8%), diuréticos de asa (70,9%), bifosfonatos (60,7%) y glucocorticoides (46,2%). La tasa de corrección de la hipercalcemia fue del 65,2%, con una mediana (RIC) de 6 (3-10) días La tasa de mortalidad fue del 81,5%. La mediana (IC95%) de supervivencia fue de 5,1 (3-7,3) semanas. Los factores asociados a una mayor mortalidad fueron: edad avanzada, etiología neoplásica, calcemia al ingreso y no corrección de la hipercalcemia. Conclusiones La hipercalcemia en pacientes hospitalizados se debe principalmente a procesos neoplásicos y se asocia a una elevada mortalidad. Observamos una baja tasa de seguimiento de las recomendaciones para el manejo de la hipercalcemia (AU)

Background and objective There are limited studies analyzing hypercalcemia in hospitalized patients. Our objectives were to describe the clinical characteristics of hospitalized patients with hypercalcemia, estimate its prevalence in the hospital setting, analyze the rate of correction of hypercalcemia, and identify prognostic variables. Materials and methods Observational, longitudinal, retrospective, and bicentric study. Adult patients admitted to two hospitals in Málaga (2014-2018) with a diagnosis of hypercalcemia were included. The minimum follow-up was 2years or until death. Results A total of 205 patients with hypercalcemia were included (incidence: 0.13%). The mean age (SD) was 68.2 (13.1) years, with a predominance of males (55.1%). The median (IQR) serum calcium at admission was 13.1 (11.8-14.6) mg/dL. The most common etiologies were neoplasms (75.1%), primary hyperparathyroidism, and medications (both 8.8%). The median (IQR) follow-up period was 5.1 (1.7-60.3) weeks. The most commonly used treatments were fluid therapy (86.8%), loop diuretics (70.9%), bisphosphonates (60.7%), and glucocorticoids (46.2%). The rate of correction of hypercalcemia was 65.2%, with a median (IQR) of 6 (3-10) days. The mortality rate was 81.5%. The median (95%CI) survival was 5.1 (3-7.3) weeks. Factors associated with higher mortality were advanced age, neoplastic etiology, serum calcium at admission, and failure to correct hypercalcemia. Conclusions Hypercalcemia in hospitalized patients is mainly due to neoplastic processes and is associated with high mortality. We observed a low rate of adherence to recommendations for the management of hypercalcemia (AU)

Metabolic Imbalances and Bone Remodeling Agents in Adolescent Idiopathic Scoliosis: A Study in Postmenarcheal Girls.

The causes and mechanisms underlying adolescent idiopathic scoliosis (AIS) remain unclear, and the available information regarding metabolic imbalances in AIS is still insufficient. This investigation aimed to evaluate the concentrations of specific bone remodeling-related agents in postmenarcheal girls diagnosed with AIS. The study encompassed thirty-six scoliosis patients and eighteen age-matched healthy individuals assigned to the control group. The patients underwent clinical and radiological examinations to assess the degree of the spinal deformity, type of curvature, and skeletal maturity. Blood and urine samples were collected from all participants and serological markers were measured using an enzyme-linked immunosorbent assay. Our study results demonstrated that the balance of phosphate-calcium and parathormone levels seems normal in individuals with AIS. Furthermore, no statistically significant differences were observed in the content of Klotho protein, osteocalcin, osteoprotegerin, C-terminal telopeptide of type I collagen (CTX), sclerostin, and alkaline phosphatase. Nevertheless, the serum levels of vitamin D (25-OH-D) were lowered, while N-terminal propeptide of type I procollagen (PINP), and fibroblast growth factor-23 (FGF23) were increased in the AIS group, with p-values of 0.044, 0.001, and 0.022, respectively. This finding indicates the potential involvement of these factors in the progression of AIS, which necessitates further studies to uncover the fundamental mechanisms underlying idiopathic scoliosis.

Abnormal changes of bone metabolism markers with age in children with cerebral palsy.

Cerebral palsy (CP) is a broad range of diseases with permanent and nonprogressive motor impairments, carrying a high cost for both the individual and the society. The characteristics of low bone mineral density and high risk of fractures suggest that bone metabolism disorders are present in CP. This study aims to investigate the association between indicators of bone metabolism and children with CP. A total of 139 children (75 children with CP and 64 healthy controls) were included in this cross-sectional study. Participants were divided into three age groups (0-2 years, 2.1-4 years, and 4.1-7 years). All children with CP were diagnosed according to clinical criteria and furtherly divided into clinical subtypes. The levels of total procollagen type I N-terminal propeptide (TPINP), N-MID osteocalcin (OC), beta-crosslaps (ß-CTX), 25-hydroxyvitamin D (25-OHD) and parathyroid hormone (PTH) in the serum were measured with corresponding detection kits according to the manufacturer's instructions. Serum levels of TPINP and 25-OHD were lower with older age, whereas ß-CTX and PTH were higher with older age. In the CP group, TPINP (age 0-2 years and 2.1-4 years) and OC (age 2.1-4 years) levels were higher, while ß-CTX (age 2.1-4 years and 4.1-7 years) and PTH (age 2.1-4 years) values were lower than the control group. In addition, there were no statistically significant differences in the levels of these indicators among the CP subgroups with different clinical characteristics. Our study shows that bone turnover markers, indicators of bone metabolism, in children with CP differ significantly from healthy controls. The indicators we studied changed with age, and they did not correlate with disease severity.

Characteristics of hospitalized patients with hypercalcemia in the province of Malaga: a longitudinal, retrospective, multicenter study.

BACKGROUND AND OBJECTIVE: There are limited studies analyzing hypercalcemia in hospitalized patients. Our objectives were to describe the clinical characteristics of hospitalized patients with hypercalcemia, estimate its prevalence in the hospital setting, analyze the rate of correction of hypercalcemia, and identify prognostic variables. MATERIALS AND METHODS: Observational, longitudinal, retrospective, and bicentric study. Adult patients admitted to two hospitals in Málaga (2014-2018) with a diagnosis of hypercalcemia were included. The minimum follow-up was 2 years or until death. RESULTS: A total of 205 patients with hypercalcemia were included (incidence: 0.13%). The mean age (SD) was 68.2 (13.1) years, with a predominance of males (55.1%). The median (IQR) serum calcium at admission was 13.1 (11.8-14.6) mg/dl. The most common etiologies were neoplasms (75.1%), primary hyperparathyroidism, and medications (both 8.8%). The median (IQR) follow-up period was 5.1 (1.7-60.3) weeks. The most commonly used treatments were fluid therapy (86.8%), loop diuretics (70.9%), bisphosphonates (60.7%), and glucocorticoids (46.2%). The rate of correction of hypercalcemia was 65.2%, with a median (IQR) of 6 (3-10) days. The mortality rate was 81.5%. The median (95% CI) survival was 5.1 (3-7.3) weeks. Factors associated with higher mortality were advanced age, neoplastic etiology, serum calcium at admission, and failure to correct hypercalcemia. CONCLUSIONS: Hypercalcemia in hospitalized patients is mainly due to neoplastic processes and is associated with high mortality. We observed a low rate of adherence to recommendations for the management of hypercalcemia.

The Uncharted Link Between Desogestrel and Hypercalcemia.

This report presents a unique case of hypercalcemia with an elusive etiology. A 37-year-old Caucasian female with a history of gonadotropin-secreting pituitary microadenoma and recurrent nephrolithiasis was found to have hypercalcemia, hypercalciuria, elevated 1,25-dihydroxyvitamin D levels, and low parathyroid hormone levels. Extensive investigations were conducted to identify the cause, including ruling out sarcoidosis and other granulomatous disorders. Imaging and diagnostic testing revealed normal results. The patient's condition considerably improved after the cessation of an oral contraceptive pill containing desogestrel. This surprising association raises the possibility that the use of desogestrel could result in hypercalcemia as one of the side effects. To ensure proper care and avoid consequences linked to severe hypercalcemia, a high index of suspicion is needed to detect the underlying cause of hypercalcemia, even in the absence of usual indications.

Effect of replacing dicalcium phosphate with mono-dicalcium phosphate to supplement phosphorus on laying performance, phosphorus-calcium metabolism and bone metabolism of aged laying hens.

The objective of this study was to evaluate the effect of replacing dicalcium phosphate (DCP) with mono-dicalcium phosphate (MDCP) to formulate low-phosphorus (P) diets on laying performance, egg quality, phosphorus-calcium metabolism, and bone metabolism of 69-78-week-old aged laying hens. Hy-Line Brown laying hens (n = 1,350, 69 weeks old) were randomly assigned to six treatments, each with five replicates of 45 hens. A corn-soybean meal-based diet was formulated to contain 0.12% non-phytate phosphorus (NPP), 3.81% calcium (Ca), and 1,470 FTU/kg phytase. The control group (CON) was supplemented with DCP inorganic phosphorus (Pi) at the NPP level of 0.20% (dietary NPP levels of 0.32%). Test groups (T1-T5) were supplemented with MDCP Pi at NPP levels of 0.07%, 0.11%, 0.15%, 0.18, and 0.20% (dietary NPP levels of 0.19, 0.23, 0.27, 0.30, and 0.32%, respectively). Calcium carbonate levels were adjusted to ensure all experimental diets contained the same Ca levels (3.81%). The feeding trial lasted 10 weeks, with hens increasing in age from 69 to 78 weeks. When supplemented with 1,470 FTU/kg phytase, extra DCP Pi or MDCP Pi did not affect (p > 0.05) laying performance (day laying rate, average egg weight, feed intake, feed-to-egg mass ratio, broken egg rate), egg quality (eggshell strength, albumen height, haugh units), or serum P, Ca, copper (Cu), iron (Fe), zinc (Zn), and manganese (Mn) levels. However, when laying hens were fed MDCP Pi (NPP levels of 0.07 to 0.20%), yolk color improved (p = 0.0148). The tibia breaking strength was significantly higher (p < 0.05) in the 0.18 and 0.20% NPP MDCP Pi groups than in the 0.20% NPP DCP Pi group. The breaking strength, Ca content, and P content of tibia in 0.11% and 0.15% NPP MDCP Pi hens were not significantly (p > 0.05) different from those in 0.20% NPP DCP Pi hens. Hens fed 0.07% NPP MDCP Pi had higher (p < 0.01) serum levels of osteoprotegerin (OPG), type-I collagen c-telopeptide (CTX-I), and tartrate-resistant acid phosphatase 5b (TRACP-5b) than those in all other groups. Serum levels of TRACP-5b and CTX-I in the 0.11% and 0.15% NPP MDCP Pi group were significantly lower than those in 0.18 and 0.20% NPP MDCP Pi groups and the 0.20% NPP DCP Pi group (p < 0.0001). Hens fed 0.07% and 0.11% NPP MDCP Pi had higher (p < 0.05) serum levels of parathyroid hormone (PTH) than those in all other groups. No differences were detected in serum calcitonin (CT), 1,25-dihydroxy-vitamin D3 (1,25-(OH)2D3), bone alkaline phosphatase (BAP), osteocalcin(OCN), and osteopontin (OPN) among all groups (p > 0.05). The expression of P transporters type IIa Na/Pi cotransporter (NaPi-IIa) in 0.11% and 0.15% NPP MDCP Pi hens were higher than those in 0.20% NPP MDCP Pi group and 0.20% NPP DCP Pi group (p < 0.05). The results indicated that both renal P reabsorption and bone resorption were involved in adapting to a low-P diet. In summary, when MDCP was used instead of DCP to supplement P, NPP levels could be reduced to 0.11% (dietary NPP level of 0.23%) without negative effects on laying performance and skeletal health of aged hens. In addition, MDCP was more beneficial than DCP for tibia quality. The results of the current study would provide references for the application of MDCP in low-P diets of aged laying hens.

Calcium regulation by SERC-A before and during Alzheimer disease / Regulación del calcio por SERC-A antes de la enfermedad de Alzheimer y durante la misma

There are many factors involved in the incidence of Alzheimer's disease that, in combination, impede or hinder normal neuronal functions. Little is currently known about calcium regulation before and during the disease. Internal instability of calcium levels is associated with increased vascular risk, a prevalent condition in a high number of individuals already compromised by Alzheimer's disease. This review provides a reevaluation of the molecular mechanism of the sarcoendoplasmic reticulum calcium ATPase (SERC-A) in the disease and discusses salient aspects of voltage-gated calcium channel function; in these way new alternatives could be open for its treatment. These regulation mechanisms are clinically relevant since the irregular functions of SERC+A has been implicated in pathologies of brain function.

Hay muchos factores implicados en la incidencia de la enfermedad de Alzheimer que, en combinación, terminan por impedir o dificultar las funciones neuronales normales. Actualmente, poco se conoce sobre la regulación del calcio, antes de la enfermedad y durante la misma. La inestabilidad interna de los niveles de calcio se asocia a un mayor riesgo vascular, condición prevalente en un gran número de individuos ya comprometidos por la enfermedad de Alzheimer. Esta revisión proporciona una reevaluación de los mecanismos moleculares de la ATPasa dependiente de Ca2+ del retículo sarcoendoplásmico (SERC-A) en la enfermedad y analiza los aspectos más destacados de la función de los canales de calcio dependientes de voltaje; de esta manera, se podrán abrir nuevas alternativas de tratamiento. Estos mecanismos de regulación son clínicamente relevantes, ya que se ha implicado la función irregular de SERC-A en diversas alteraciones de la función cerebral.