Mineral Metabolism Research Articles

#2067 Prediction of gastrointestinal bleeding hospitalization risk in hemodialysis using machine learning techniques

Abstract Background and Aims INitiativeS on advancing Patients’ outcomes In REnal disease (INSPIRE) is an academia and industry collaboration set forth to identify critical investigations needed to advance the practice of medicine in nephrology. Gastrointestinal bleeding (GIB) is one of the most common types of bleeding events in the kidney dialysis population [1]. We aimed to develop a model to predict GIB hospitalization risk in a hemodialysis (HD) patient within 180 days. We evaluated advanced machine learning algorithm (XGBoost) and compared it to traditional machine learning algorithm (logistic regression) modeling techniques. Method We used data from a kidney care network from 2017 through 2020. We included data from adult dialysis patients (age ≥18 years). GIB related hospitalization was defined based on international classification of diseases (ICD) diagnosis codes recorded as the primary, secondary, or tertiary discharge reason for hospitalization. Two distinct models were created using XGBoost and logistic regression algorithms and using the same dataset. Both models were evaluated using metrics such as area under the receiver operating curve (AUROC), accuracy, sensitivity, and specificity. Missing data was imputed using mean for quantitative data and mode for qualitative data. The dataset then was randomly divided into 60% training, 20% validation and 20% test dataset. The test data, comprising unseen patients and data was used to evaluate the performance of the model. This means that the model had never encountered the test data during its learning phase, which included training the model and then validating the model. Results The incidence of 180-day GIB hospitalization was 1.12% in the HD population (n = 5 116 with GIB hospitalization/ n = 451 653 without GIB hospitalization), and consistent in the unseen test dataset (n = 465 with GIB hospitalization/ n = 38586 without GIB hospitalization). The XGBoost model showed higher predictive performance compared to logistic regression (Table). The AUROC was 0.72 (95% confidence interval (CI) 0.69, 0.74) for the XGBoost model. In comparison, the AUROC was 0.615 (95% CI 0.60, 0.64) for the logistic regression model. Specificity was 67% versus 58% for the XGBoost model versus logistic regression model respectively. However, sensitivity for both the models was 65%. The top predictors for major GIB were consistent in both models for many factors, yet some factors showed different importance on outcome prediction (Fig. 1). Higher risk of GIB hospitalization was associated with older age, lower ferritin levels, and recent all-cause hospitalizations in both models. The XGBoost showed high importance on outcome prediction for lower hemoglobin and higher serum 25 hydroxy (25OH) vitamin D values, and the logistic regression model showed high importance for higher amounts of saline delivered during an HD treatment and lower intact parathyroid hormone (iPTH) levels. Conclusion We found advanced machine learning prediction modeling (XGBoost) appears suitable for identifying a HD patient at risk for a GIB hospitalization in the next 180 days, and outperforms traditional machine learning (logistic regression) modeling techniques. Although both models showed identical sensitivity, the XGBoost model had higher specificity. Prospective testing is needed to confirm the model's performance. The association between bone mineral metabolism markers and GIB hospitalization risk is unexpected and warrants further investigation.

#129 Impact of Ramadan fasting on bone mineral metabolism in hemodialysis: a multi-center prospective study

Abstract Background and Aims Fasting is fundamental in several major religions and cultural traditions worldwide. In Islam, Ramadan fasting is characterized by daily complete eating and drinking abstinence from the dawn to sunset for an entire lunar month. Sick patients, including patients with advanced chronic kidney disease are not required to fast, however the majority of them are still choose to fast. The Impact of Ramadan fasting on bone health has not been studied prospectively. This study aims to examine the effect of Ramadan fasting on parameters of bone mineral metabolism in patients on hemodialysis. Method : This is a multi-center prospective study on 138 patients with ESKD who are maintained on intermittent hemodialysis for at least six months. Ninety-three (67%) were fasting while 45 patients (33%) did not fast. All patients' demographics, clinical and laboratory parameters were compared before and after the holy month of Ramadan. Serum biochemical parameters included serum sodium, potassium, bicarbonate, chloride, albumin, calcium, phosphorus, magnesium, intact parathyroid hormone (iPTH), FGF23, klotho, sclerostin, bone-specific alkaline phosphatase (BSAP), and tartrate-resistant alkaline phosphatase 5b (TRAP5b). Results The two groups exhibited comparable demographics and clinical parameters at baseline, except for the mean age, which was significantly lower in the fasting group (45.5 vs. 54.4 years, p-value = 0.003) and the non-smoker habit was significantly higher in the fasting group (71% vs. 56%, p-value = 0.02). There was no change in the clinical parameters by the end of Ramadan in both groups including intra-dialytic hypotension, inter-dialytic weight gain, and hypoglycemia. The basic biochemical parameters did not change significantly at the end of Ramadan in both groups, except there was an increased serum albumin level (p-value = 0.04). The BSAP levels significantly went down by the end of Ramadan in the fasting group (p-value = 0.01). The other novel serum biomarkers (FGF23, klotho, sclerostin, and TRAP5b) did not change significantly in both groups. Conclusion This multi-center prospective study demonstrates that Ramadan fasting does not significantly alter the clinical and biochemical parameters in hemodialysis patients, highlighting its safety in this population. Moreover, our findings reveal a noteworthy reduction of the higher BSAP towards normal levels in fasting patients, suggesting a potential benefit of fasting in improving high bone turnover. Further research is warranted to elucidate this phenomenon's underlying mechanisms and long-term implications, which may hold promise for managing bone health in hemodialysis patients during Ramadan fasting.

#2034 CKD-MBD management: results from a national survey on bone turnover biomarkers practice and therapeutic strategies among Italian nephrologists

Abstract Background and Aims Advanced stages of chronic kidney disease (CKD) are constantly characterized by a mineral and bone disorders (MBD) syndrome concerning a complex systemic condition that includes laboratory abnormalities of bone and mineral metabolism involving calcium, phosphorus, parathyroid hormone (PTH), or vitamin D; abnormalities in bone turnover, mineralization, volume, or strength; extra-skeletal calcifications, such as vascular or other soft tissue. CKD-MBD syndrome determines relevant consequences in terms of fragility fractures, cardiovascular events and higher mortality. The nephrologist's awareness of CKD-MBD diagnostic and management tools and therapeutic strategies is key to improving CKD patients’ prognosis and outcomes. Method A new national survey (composed of 17 online questions) was conducted among Italian nephrologists to investigate the reference laboratory availability of bone turnover markers (BTMs), the clinical attitude on secondary hyperparathyroidism (sHPT) management, and the CKD-MBD therapeutic approach in different stages of CKD and dialysis patients. Results 89 Italian nephrologists participated in the survey. The reference laboratories largely fulfill the biomarkers request of ionized calcium (97.7%), phosphorus (100%), PTH (100%), alkaline phosphatase (ALP) (100%), magnesium (100%), 25-OH and 1,25-OH vitamin D levels (92.1%; 53.9%); while most of the hospital laboratories do not regularly support the availability of specific BTMs, both for diagnosis and monitoring the bone resorption and formation (Fig. 1)—such as bone ALP (75.3%), calcifediol (37.1%), calcitriol (40.5%), fibroblast growth factor-23 (FGF-23) (intact 9% and c-terminal 4.5%), vitamin K (33.7%), Klotho (6.75%, soluble 4.5%), osteocalcin (38.2%), matrix gla protein (10.1%), tartrate-resistant acid phosphatase 5b (TRAP-5b) (6.75%), cross-linked collagen type I peptide (CTX) (32.6%) and procollagen type 1 n-terminal propeptide (P1NP) (10.1%). The nephrologist's attitude to start management and treatment of sHPT is revealed to be mainly led by KDOQI (n = 42, 47%) and KDIGO (n = 39, 44%) guidelines considering their PTH cut-off values; in 53.9% of clinicians the measure of PTH levels is then performed every 3 months according to KDOQI guidelines. In relation to the definition of high turnover metabolic bone disease by BTMs, this metabolic pattern is identified in > 50% and 30-40% of patients with CKD 4-5D by 31.5% and 21.4% of nephrologists, respectively. 65% of clinicians currently considered ALP of equal importance as alterations of PTH as a predictor of fracture events. Other biomarkers, such as FGF-23, P1NP or TRAP-5b, emerge to not be still used in regular clinical practice. In patients diagnosed with CKD-MBD and skeletal fragility, 76.4% of nephrologists consider the AIFA (Italian Medicines Agency) note 79 to support osteoporosis treatment. The therapeutic strategies of CKD-MBD include the administration of vitamin D (e.g. cholecalciferol 27-37.1%, calcifediol 9-12.4%, calcitriol 42.7-55.1%) and its analogues (e.g. paricalcitol 23.6-52.8%) and the use of antiresorptive agents (e.g. alendronate 3.4%-23.6%, denosumab 22.5%-30.3%) with variable frequencies among different advanced CKD stages and for those patients on peritoneal or hemodialysis (Fig. 2). Conclusion Results present a suboptimal use of BTMs and a current heterogeneous therapeutic management of CKD-MBD syndrome and renal osteodystrophy in Italian clinical practice. The survey represents a starting point of work to further implement awareness of diagnostic and therapeutic issues of CKD-MBD.

Dynamics of blood osteomarkers in the treatment of generalized periodontitis

AIM. Study of the dynamics of bone metabolism in the treatment of generalized periodontitis.MATERIALS AND METHODS. 60 patients with chronic generalized periodontitis of moderate to severe severity were examined and treated. A group of 15 healthy individuals without periodontal disease served as a control group. To assess the dynamics of bone formation, blood parameters were measured for bone metabolism: osteocalcin levels, alkaline phosphatase levels, and β-CrossLaps levels. Densitometry of the proximal femoral and lumbar spine regions was also performed.RESULTS. The study revealed increased bone metabolism compared with the control group, an increase in bone metabolism activity was found 3 months after treatment of patients with chronic generalized periodontitis, and after 12 months the values of the studied parameters did not differ from the control group.CONCLUSIONS. Thus, when treating generalized periodontitis, it is necessary to use a treatment regimen that takes into account the individual mineral metabolism of the patient’s bone tissue.

Antioxidant and osteoinductive properties of organic selenium in microdiets for gilthead seabream (Sparus aurata) larvae

This study investigated the effect of yeast derived selenium (Se) dietary supplementation on larval performance, whole body mineral contents, lipid peroxidation, fatty acid profiles, expression of antioxidants and bone biomarkers genes, mineralization and skeletal anomalies in gilthead seabream (Sparus aurata) larvae. Five experimental microdiets containing 1.4, 6.1, 9.2, 12.0 and 14.0 mg Se/kg diets were fed to triplicate groups of larvae (total length: 7.26 ± 0.83 mm, 30 dph) for 21 days. Larval Se levels increased proportionally to the elevation of dietary Se. Those fed with dietary Se level at 6.1 mg/kg had a higher growth performance than those fed with non-supplemented diet (1.4 mg/kg), then reached a plateau from larvae fed with Se6.1 to Se14 diet although growth was not significantly affected by different diets. In addition, larval survival was not significantly affected. However, larvae fed the lowest Se levels showed a significant increase in lipid peroxidation, the downregulation of antioxidant genes, a reduction in polyunsaturated fatty acids (PUFA) contents and the highest incidence of skeletal anomalies. While increase up to 6.1–12 mg Se/kg, reduced oxidative stress, increased PUFA, vertebral mineralization, up-regulated antioxidant and bone metabolism related genes and contributing to reduce skeletal anomalies of larvae. However, further increase in dietary Se up to 14 mg/kg led to the lowest gpx, cat and alp expressions, in agreement with a lower mineralization. These findings suggest, dietary Se level at 6.1 mg/kg would be the minimum dietary Se level required in microdiets for gilthead seabream larvae. Thus, the study demonstrates the importance of dietary Se for bone metabolism and mineralization due to its antioxidant and osteo-inductive properties.

CYP24A1 and TRPC3 Gene Expression in Kidneys and Their Involvement in Calcium and Phosphate Metabolism in Laying Hens.

Ca and P homeostasis across the egg-laying cycle is a complex process involving absorption in the small intestine, reabsorption/excretion in the kidneys, and eggshell gland secretion. Diets with inadequate calcium and phosphorus can interfere with their absorption and digestibility, resulting in eggshell quality losses and reduced productive life, affecting egg production and welfare. A better understanding of gene expression profiles in the kidneys of laying hens during the late egg-laying period could clarify the renal role in mineral metabolism at this late stage. Therefore, the performance, egg quality and bone integrity-related traits, and expression profiles of kidney candidate genes were evaluated in 73-week-old laying hens receiving different Ca and P ratios in their diet: a high Ca/P ratio (HR, 22.43), a low ratio (LR, 6.71), and a medium ratio (MR, 11.43). The laying hens receiving the HR diet had improved egg production and eggshell quality traits compared to the other two groups. Humerus length was shorter in the HR than in the other groups. The CYP24A1 and TRPC3 genes were differentially expressed (p.adj ≤ 0.05) among the groups. Therefore, their expression profiles could be involved in calcium and phosphate transcellular transport in 73-week-old laying hens as a way to keep mineral absorption at adequate levels.

Exploring the Causal Effects of Mineral Metabolism Disorders on Telomere and Mitochondrial DNA: A Bidirectional Two-Sample Mendelian Randomization Analysis

The aim of this study was to assess the causal relationships between mineral metabolism disorders, representative of trace elements, and key aging biomarkers: telomere length (TL) and mitochondrial DNA copy number (mtDNA-CN). Utilizing bidirectional Mendelian randomization (MR) analysis in combination with the two-stage least squares (2SLS) method, we explored the causal relationships between mineral metabolism disorders and these aging indicators. Sensitivity analysis can be used to determine the reliability and robustness of the research results. The results confirmed that a positive causal relationship was observed between mineral metabolism disorders and TL (p < 0.05), while the causal relationship with mtDNA-CN was not significant (p > 0.05). Focusing on subgroup analyses of specific minerals, our findings indicated a distinct positive causal relationship between iron metabolism disorders and both TL and mtDNA-CN (p < 0.05). In contrast, disorders in magnesium and phosphorus metabolism did not exhibit significant causal effects on either aging biomarker (p > 0.05). Moreover, reverse MR analysis did not reveal any significant causal effects of TL and mtDNA-CN on mineral metabolism disorders (p > 0.05). The combination of 2SLS with MR analysis further reinforced the positive causal relationship between iron levels and both TL and mtDNA-CN (p < 0.05). Notably, the sensitivity analysis did not indicate significant pleiotropy or heterogeneity within these causal relationships (p > 0.05). These findings highlight the pivotal role of iron metabolism in cellular aging, particularly in regulating TL and sustaining mtDNA-CN, offering new insights into how mineral metabolism disorders influence aging biomarkers. Our research underscores the importance of trace element balance, especially regarding iron intake, in combating the aging process. This provides a potential strategy for slowing aging through the adjustment of trace element intake, laying the groundwork for future research into the relationship between trace elements and healthy aging.

Changes in Bone Mineral Density in Patients With Non-dialysis-Dependent Chronic Kidney Disease Are Associated With Body Composition

Chronic kidney disease (CKD) and low bone mineral density (BMD) are highly prevalent and can co-exist. Parameters of mineral metabolism are associated with BMD in CKD, but other contributing factors may contribute. The aim of this study was to assess changes in BMD and its determinants in patients with non-dialysis-dependent CKD (NDD-CKD). Body composition and biochemical profiles were assessed in a retrospective hospital-based cohort study of patients with NDD-CKD. BMD, lean soft tissue (LST), appendicular LST (ALST), and percentage fat mass were assessed by dual-energy X-ray absorptiometry (DXA). ALST index (ALSTI, ALST/height2) and load-capacity index (LCI, fat mass/LST) were calculated. Low BMD was defined as t-score ≤-1.0. Mean time between assessments was 2.8±1.3 years, 46 patients were included. A reduction in renal function was observed. Changes in body composition included reductions in ALST (p=0.031), ALSTI (p=0.021) and a trend for BMD (p=0.053); and an increase in percentage fat mass (p=0.044) and LCI (p=0.032). Females had a reduction in BMD (p=0.034), ALST (p=0.026), and ALSTI (p=0.037). Patients with low BMD at baseline had lower LST (p=0.013), ALST (p=0.023), and percentage fat mass (p=0.037) than those with normal BMD. Additionally, reductions in LST (p=0.041), ALST (p=0.006), and ALSTI (p=0.008) were observed in patients who had low BMD at baseline, while no significant changes in body composition were observed in those with normal BMD at baseline. The following body composition parameters at baseline were determinants of BMD status at follow-up: LST (OR:0.899, 95%CI:0.829-0.976, p=0.010), ALST (OR:0.825, 95%CI:0.704-0.967, p=0.017), and ALSTI (OR:0.586, 95%CI:0.354-0.968, p=0.037), independent of fat mass, and LCI. Detrimental body composition changes were observed without changes in body weight; these were more significant in females. Moreover, this is the first longitudinal study showing a protective effect of LST against BMD loss in patients with NDD-CKD.

56 Metabolic status of respiratory disease challenged beef steers altered by intranasal Zn and vitamin A treatments

Abstract Bovine respiratory disease (BRD) is a major cause of morbidity and mortality in the cattle industry. Increasing the ability of a calf to respond to disease is of interest due to the loss of production during disease. Zinc and vitamin A (VA) are key micronutrients involved in many immunologic processes such as cell signaling and mucosal immunity. Angus crossbred steers [n = 48; body weight (BW) = 333 ± 4.2 kg] were utilized in this 14-d BRD challenge investigating intranasal (IN) treatments of Zn and VA. Steers were split into two groups (n = 24) with identical disease challenge and sample collection schedules. Before disease challenge, steers were housed at the Iowa State University Beef Nutrition farm (BNF). Steers were weighed on d -2 and -1 of viral challenge and trucked for 6 h before delivery to the Iowa State University Animal Resource Station. On d 0, steers were challenged with an aerosol inoculation with 104 TCID50 BRSV followed by 5x108 CFU of Mannheimia haemolytica on d 5. On d 4, steers received IN treatments of Zn (ZN; ZnO nanoparticles), VA (VA), Zn and VA (VA+ZN), or control with no IN treatment (CON). For trace mineral and VA analysis, liver biopsies were collected on d -9 and 20 and plasma collected on d 0, 4 (trace mineral only), 5, 7 and 14. Steers were tested for viral shedding on d 0, 4, 5, 7, 10 and 14. RNA was isolated from bronchioalveolar lavage (BAL) cells (d 0 and 7) for gene expression related to inflammation, VA and trace mineral metabolism. Statistical analysis was completed using the GLIMMIX and MIXED procedures in SAS 9.4. Throughout the study, viral shedding was not affected by intranasal treatment (P ≥ 0.59). There were no group × TRT × day effects for plasma trace minerals (Cu, Zn, Fe) or VA concentrations (P ≥ 0.18). Intranasal VA prevented a decrease in plasma VA on d 5, after which all treatments were similar (P < 0.01). There were no TRT × day effects for plasma Zn and Cu (P ≥ 0.50). Post challenge, liver VA was increased in VA treated steers compared with steers not treated with VA (P = 0.04). Liver Mn tended to be increased post challenge in IN ZN treated steers (P = 0.08). IN Zn treated steers tended to have lesser expression of IL-10 in BAL cells on d 7 post infection (P = 0.07). Local IN supplementation of Zn and VA can have systemic and local affects on respiratory disease challenged steers and may support increased response to disease.

Outcomes Following Surgical Fixation of Distal Radius Fractures in Patients With Chronic Kidney Disease

Moderate-to-severe chronic kidney disease (CKD, stages III-IV) and end-stage renal disease (ESRD or CKD stage V) are known to be independent risk factors for fragility fracture. Altered bone and mineral metabolism contributes to greater complications and mortality rates in the setting of fractures, although most existing literature is limited to hip fractures. We hypothesized that patients with moderate-to-severe CKD or ESRD would have greater complication rates after surgical treatment of distal radius fractures compared with those without CKD. We retrospectively identified all patients at a level 1 trauma center between 2008 and 2018 who had a diagnosis of stage III-IV CKD or ESRD at the time of operative fixation of a distal radius fracture. We recorded demographic data, comorbidities, and surgical complications. Data for readmissions within 90 days and 1-year mortality were collected. A 2:1 sex-matched control group without CKD who underwent distal radius fixation was selected for comparison, with age-adjusted analysis. A total of 32 patients with CKD (78.1% CKD stage III/IV, 21.9% ESRD) and 62 without CKD were identified. The mean age was 67 ± 12 years in the CKD group and 55 ± 15 years in the control group. The CKD group had a higher Charlson Comorbidity Index (5.7 vs 2.0). Surgical complication rate in the CKD group was 12.5% (12.0% CKD III/IV; 14.3% ESRD). Neither early nor late surgical complication rates were statistically different from those in patients without CKD. Reoperation rate as well as 30- and 90-day readmission rates were similar between groups. Overall, 1-year mortality was greater in the CKD group (9.4% vs 0%). Surgical complications and readmission rates are similar in patients with and without CKD after distal radius fracture fixation. However, 1-year mortality rate is significantly higher after distal radius fixation in patients with moderate-to-severe CKD or ESRD. Prognostic IIIa.

Identification of proteins differentially associated with Npt2a in the presence and absence of NHERF1

Background: NHERF1 deficient mice are hypophosphatemic and phosphaturic due to failure of functional apical membrane localization of Npt2a. Wild type (WT) and NHERF1 knock out (KO) mice show similar proximal tubule protein expression of Npt2a. Previous studies have shown that dissociation of Npt2a and NHERF1 stimulated by PTH and FGF23 results in lysosomal degradation of Npt2a. The persistence of Npt2a expression in NHERF1 deficiency suggests a defect in Npt2a forward traffcking. Hypothesis: We hypothesized that comparison of Npt2a-associated proteins from WT and KO mouse kidney cortex would identify novel proteins critical for forward traffcking of Npt2a. Methods: We immunoprecipitated homogenized kidney cortex from WT and NHERF1 KO C57Bl6 mice using a polyclonal Npt2a antibody followed by proteomic analysis using liquid chromatography-mass spectrometry and the STRING database of known and predicted protein-protein interactions. Results: We identified 31 proteins that showed statistically significantly greater association with Npt2a in WT kidney cortex and 50 proteins that showed statistically significantly greater association with Npt2a in KO kidney cortex. We did not identify greater association of Npt2a from KO kidney cortex with any of the other known PDZ proteins known to associate with Npt2a including PDZK1 and PIST. Among the proteins more highly associated with Npt2a in KO were 14-3-3 and valacyclovir hydrolase. STRING analysis of the WT-associated proteins identified membrane transport, phosphate ion homeostasis, and oxidative phosphorylation as important biological processes. Analysis of the KO-associated proteins identified DNA unwinding, regulation of cytoplasmic translation, and clathrin-dependent endocytosis were identified as important biological processes in the absence of NHERF1. Conclusions: We conclude that the aberrantly-traffcked Npt2a in KO has successfully traversed the Golgi and is correctly folded but may interact with 14-3-3 through its PDZ binding motif, preventing forward traffcking. We also conclude that the function of Npt2a may significantly change when the cotransporter does not properly forward traffc in the absence of NHERF1 expression. Support for EDL from Dept Veterans Affairs CX0001614 and the Pak Mineral Metabolism Center. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Serum Biomarkers and Their Association with Myocardial Function and Exercise Capacity in Cardiac Transthyretin Amyloidosis.

Transthyretin cardiac amyloidosis (ATTR amyloidosis) is a frequent etiology of heart failure. Inflammation and mineral metabolism are associated with myocardial dysfunction and clinical performance. Cardiac global longitudinal strain (GLS) allows function assessment and is associated with prognosis. Our aim was to describe possible correlations between GLS, biomarker levels and clinical performance in ATTR amyloidosis. Thirteen patients with ATTR amyloidosis were included. Clinical characteristics; echocardiographic features, including strain assessment and 6 min walk test (6MWT); and baseline inflammatory, mineral metabolism and cardiovascular biomarker levels were assessed. Of the 13 patients, 46.2% were women, and the mean age was 79 years. TAPSE correlated with NT-ProBNP (r -0.65, p < 0.05) and galectin-3 (r 0.76, p < 0.05); E/E' ratio correlated with hsCRP (r 0.58, p < 0.05). Left ventricular GLS was associated with NT-ProBNP (r 0.61, p < 0.05) (patients have a better prognosis if the strain value is more negative) and left atrial GLS with NT-ProBNP (r -0.73, p < 0.05) and MCP1 (r 0.55, p < 0.05). Right ventricular GLS was correlated with hsTnI (r 0.62, p < 0.05) and IL6 (r 0.881, p < 0.05). Klotho levels were correlated with 6MWT (r 0.57, p < 0.05). While inflammatory biomarkers were correlated with cardiac function, klotho levels were associated with clinical performance in the population with TTR-CA.

Exploring the link between hair elemental composition and oral and general health of children in Northern and Central Dagestan Russia

Relevance. This article presents data on the level of trace elements in hair and oral and general health among various age groups of children (from 2 to 17 years) in Northern and Central Dagestan. It also reports findings on the relationship between oral health indicators and the content of such macro- and microelements as Ca, Cu, Mg, Mn, Zn, As, Fe, F. Identifying concentrations of macro- and microelements in hair proves to be a promising diagnostic method and aids in creating personalized prevention programs.Objective. To investigate the correlation between the elemental composition in children's hair and their oral and general health conditions in the cities of Kizlyar and Makhachkala, situated in Northern and Central Dagestan, Russia.Materials and methods. Established methods and physicochemical techniques were utilized for oral health evaluations to determine the quality indicators of drinking water, levels of elemental composition in hair, and methods to assess the general health of children (questionnaires, analysis of medical records of children).Results. A correlation was established between the levels of specific chemical elements in hair, the dental hard tissues, and mixed saliva with the oral and general health complications observed in children. Water analysis in Makhachkala, central part of the Republic of Dagestan, revealed an unbalanced presence of essential chemical elements such as fluoride, iron, manganese, zinc, and sulfates. In 74–84% of the examined water samples, the fluoride content was below 0.5 mg/l, and only 13–25% were within the normal range. The levels of fluoride and iron in hair and mixed saliva indicate shifts in mineral metabolism in children's bodies. Fluoride is crucial for iron absorption, and its deficiency results in significantly decreased absorption rates. A substantial reduction in water fluoride levels, compared to standard values, correlates with high rates of dental caries and iron deficiency anemia in children from Makhachkala, occurring in about 87% of cases (P &lt; 0.05). This relationship is substantiated by the analysis of medical records from children aged 2 to 17 from hospitals in both Northern and Central Dagestan, highlighting the connection between iron deficiency anemia and the low fluoride levels in drinking water. Further studies into the oral health of children have shown that the incidence and severity of caries in deciduous teeth are greater in the Northern than in the Central Zone of Dagestan. Moreover, conditions such as cheilitis, aphthous stomatitis, and desquamative glossitis are frequently observed in children during the stages of temporary tooth occlusion, affecting on average 38.5% of cases, and this prevalence increases to 78.2% during the mixed and permanent occlusion stages.Conclusion. The conducted studies revealed that the drinking water supplied to the Dagestan population has elevated permissible levels of iron and arsenic. Additionally, there is a noted deficiency of fluoride, zinc, and copper, as well as low water hardness. Research into the quality of drinking water and the health impacts on the pediatric population of Dagestan established a correlation (R = 0.593) between unbalanced water, dietary intake, the severity of dental caries, and reduced immunity in children. High levels of arsenic, germanium, and molybdenum in the water and children's hair contribute to cumulative health effects. Environmental pollution is also linked to a rise in oral health issues, iron deficiency anemia, and broader health problems. Analyzing the chemical composition of children's hair serves as a diagnostic tool for detecting and preventing diseases related to deficiencies and excesses of macro- and microelements.

Metabolic response of endangered goats fed spineless cactus associated with Tifton-85 hay or Maniçoba hay

The aim of this study was to evaluate the effects of replacement of Tifton-85 hay by maniçoba hay, in spineless cactus-based diets, on markers of energy, protein, mineral metabolism and serum enzyme activity of Moxotó goats. Sixteen uncastrated male Moxotó breed goats, with 20 months old and initial body weight of 21.7 ± 3.92 kg were used in a randomized blocks design, using the initial weight as the criterion for the formation of blocks, with two treatments and eight replicates per treatment. The experimental treatments consisted of two diets: diets containing Miúda spineless cactus associated with Tifton-85 hay (1) or maniçoba hay (2), with roughage:concentrate ratio of 70:30. Blood samples were collected fortnightly (baseline, 15 days, 30 days and 45 days) during the feedlot period. There was a higher serum concentration of total protein and fructosamine (P &lt; 0.05) in goats that received maniçoba hay. However, there was higher serum gamma-glutamyl transferase (GGT) enzyme activity in goats that ingested Tifton-85 hay (P &lt; 0.05). Concerning to the profile of blood metabolites in the different fortnightly collections, it was possible to verify a significant effect for urea, fructosamine, GGT enzyme activity, K and Cl levels (P &lt; 0.05). In conclusion, Tifton-85 hay and maniçoba hay combined with spineless cactus does not cause metabolic disorders in feedlot native goats.

Skeletal parathyroid hormone hyporesponsiveness: a neglected, but clinically relevant reality in chronic kidney disease.

Defining the optimal parathyroid hormone (PTH) target in chronic kidney disease (CKD) is challenging, especially for bone outcomes, due to the substantial variability in the skeleton's response to PTH. Although PTH hyporesponsiveness is as integral a component of CKD-mineral bone disorder as elevated PTH levels, clinical awareness of this condition is limited. In this review, we will discuss factors and mechanisms contributing to PTH hyporesponsiveness in CKD. This knowledge may provide clues towards a personalized approach to treating secondary hyperparathyroidism in CKD. Indicates a link between disturbed phosphate metabolism and impaired skeletal calcium sensing receptor signaling as an important mediator of PTH hyporesponsiveness in CKD. Further, cohort studies with diverse populations point towards differences in mineral metabolism control, rather than genetic or environmental factors, as drivers of the variability of PTH responsiveness. Skeletal PTH hyporesponsiveness in CKD has a multifactorial origin, shows important interindividual variability, and is challenging to estimate in clinical practice. The variability in skeletal responsiveness compromises PTH as a biomarker of bone turnover, especially when considering populations that are heterogeneous in ethnicity, demography, kidney function, primary kidney disease and mineral metabolism control, and in patients treated with bone targeting drugs.

Periparturient Mineral Metabolism: Implications to Health and Productivity.

Mineral metabolism, in particular Ca, and to a lesser extent phosphorus (P) and magnesium (Mg), is altered with the onset of lactation because of extensive irreversible loss to synthesize colostrum and milk. The transient reduction in the concentration of Ca in blood, particularly when it lasts days, increases the risk of mineral-related disorders such as hypocalcemia and, to a lesser extent, hypophosphatemia. Although the incidence of clinical hypocalcemia can be reduced by prepartum dietary interventions, subclinical hypocalcemia remains prevalent, affecting up to 60% of the dairy cows in the first 3 d postpartum. More importantly, strong associations exist between hypocalcemia and increased susceptibility to other peripartum diseases and impaired reproductive performance. Mechanistic experiments have demonstrated the role of Ca on innate immune response in dairy cows, which presumably predisposes them to other diseases. Hypocalcemia is not related to inadequate Ca intake as prepartum diets marginal to deficient in Ca reduce the risk of the disease. Therefore, the understanding of how Ca homeostasis is regulated, in particular how calciotropic hormones such as parathyroid hormone and 1,25-dihydroxyvitamin D3, affect blood Ca concentrations, gastrointestinal Ca absorption, bone remodeling, and renal excretion of Ca become critical to develop novel strategies to prevent mineral imbalances either by nutritional or pharmacological interventions. A common method to reduce the risk of hypocalcemia is the manipulation of the prepartum dietary cation-anion difference. Feeding acidogenic diets not only improves Ca homeostasis and reduces hypocalcemia, but also reduces the risk of uterine diseases and improves productive performance. Feeding diets that induce a negative Ca balance in the last weeks of gestation also reduce the risk of clinical hypocalcemia, and recent work shows that the incorporation of mineral sequestering agents, presumably by reducing the absorption of P and Ca prepartum, increases blood Ca at calving, although benefits to production and health remain to be shown. Alternative strategies to minimize subclinical hypocalcemia with the use of vitamin D metabolites either fed prepartum or as a pharmacological agent administered immediately after calving have shown promising results in reducing hypocalcemia and altering immune cell function, which might prove efficacious to prevent diseases in early lactation. This review summarizes the current understanding of Ca homeostasis around parturition, the limited knowledge of the exact mechanisms for gastrointestinal Ca absorption in bovine, the implications of hypocalcemia on the health of dairy cows, and discusses the methods to minimize the risk of hypocalcemia and their impacts on productive performance and health in dairy cows.

Higher prevalence of thyroid-specific autoantibodies (TPOAb and TgAb) is related to a higher prevalence of fractures in females: results from NHANES 2007-2010.

Hashimoto's thyroiditis is characterized by elevated thyroid-specific autoantibodies. It is currently believed that osteoporosis is not only a disease with abnormal mineral metabolism but also with immune abnormalities. This study investigated the relationship between thyroid-specific autoantibodies and osteoporosis, including the bone mineral density (BMD) values and fractures. A retrospective analysis was conducted using data from the National Health and Nutrition Examination Survey (2007-2010). BMD was compared in different thyroid-specific autoantibodies groups. The associations between thyroid-specific autoantibodies and fractures were explored. Strengths of associations were calculated by binary logistic regression models. Candidate variables for binary logistic regression model were selected after screened in univariate analysis(variables with P < 0.05). A total of 3865 study participants were included in this analysis; 224 participants were TgAb positive and 356 were TPOAb positive. A total of 392 participants reported hip, spine or wrist fractures. Participants with higher prevalence of TgAb or TPOAb had lower BMD. In females, significant cigarettes use, higher prevalence of TgAb and TPOAb, and the BMD of the total femur and femoral neck were significantly associated with fractures. Higher prevalence of TPOAb was particularly associated with a higher possibility of hip or spine fractures. In males, significant cigarettes use, 25OHD3, the BMD values of the total femur, femoral neck and total spine were significantly associated with fractures. Higher prevalence of thyroid-specific autoantibodies may lead to decreased BMD. In females, higher prevalence of TgAb and TPOAb significantly associated with fractures and TPOAb especially relating to the fractures of hip and spine. Males patients with vitaminDdeficiencyorinsufficiency associated a higher possibility of fractures.

Prevalence of vitamin D insufficiency in early pregnancies- a Singapore study.

Vitamin D plays an essential role in bone and mineral metabolism. There is increased interest in understanding prevalence of Vitamin D deficiency in pregnancy as many studies report association of low vitamin D levels with obstetric complications and neonatal sequelae. There is a paucity of studies in Singapore evaluating levels of vitamin D levels during the first trimester of pregnancies. We aim to study the prevalence of vitamin D insufficiency in this population. Our study assessed vitamin D levels in these women. Vitamin D (Plasma 25(OH)D concentration) levels in multiracial women during the first trimester were collected via venepuncture at their booking antenatal visit. They were stratified into sufficient ≥30ng/ml, insufficient ≥20ng/ml and <30ng/ml, moderately deficient ≥10ng/ml and <20ng/ml and severely deficient <10ng/ml. 93 women were included in this study. Only 2.2% of our study population had sufficient vitamin D levels. In women who had insufficient levels, the heavier the weight, the more likely to be vitamin D deficient. Interestingly, we also note that the older the patient, the less likely they are to be deficient. In women with periconceptual multivitamin supplementation, the average vitamin D level for those with supplementation was 2.10ng/ml higher than those without. Majority of patients were recruited from a single study member's patient pool who were mostly Chinese. Prevalence of Vitamin D deficiency in general obstetric patients with higher BMI and darker skinned patients may be even lower in Singapore. The high prevalence of Vitamin D insufficiency in our patients prove that it is a prominent problem in our population. We aim to implement screening of vitamin D levels as part of antenatal investigations in the first trimester and recommend supplementation as required. We also hope to evaluate the association of low vitamin D levels with obstetric or neonatal complications further understanding its implications.

Cognitive Impairment Related to Chronic Kidney Disease Is Associated with a Decreased Abundance of Membrane-Bound Klotho in the Cerebral Cortex.

Cognitive impairment (CI) is a complication of chronic kidney disease (CKD) that is frequently observed among patients. The aim of this study was to evaluate the potential crosstalk between changes in cognitive function and the levels of Klotho in the brain cortex in an experimental model of CKD. To induce renal damage, Wistar rats received a diet containing 0.25% adenine for six weeks, while the control group was fed a standard diet. The animals underwent different tests for the assessment of cognitive function. At sacrifice, changes in the parameters of mineral metabolism and the expression of Klotho in the kidney and frontal cortex were evaluated. The animals with CKD exhibited impaired behavior in the cognitive tests in comparison with the rats with normal renal function. At sacrifice, CKD-associated mineral disorder was confirmed by the presence of the expected disturbances in the plasma phosphorus, PTH, and both intact and c-terminal FGF23, along with a reduced abundance of renal Klotho. Interestingly, a marked and significant decrease in Klotho was observed in the cerebral cortex of the animals with renal dysfunction. In sum, the loss in cerebral Klotho observed in experimental CKD may contribute to the cognitive dysfunction frequently observed among patients. Although further studies are required, Klotho might have a relevant role in the development of CKD-associated CI and represent a potential target in the management of this complication.

The role of dietary fiber in functional nutrition

The process of nutrition is a function of the relationship between a person and the environment. Food should contribute to the adaptation of the human body to unfavorable conditions and, in addition to its main function – meeting the physiological needs of the human body for nutrients and energy, also perform preventive and therapeutic tasks. Recently, the popularity of healthy food has increased. Experts predict that the market for functional products is growing every year. In this regard, in many countries, in-depth research is being carried out on the structure, composition, properties of dietary fiber, and the technology of their use as one of the components in the creation of composite food products. Dietary fiber is a large group of polymeric substances of different chemical nature, the sources of which are plant products. The composition of nutrients with a fibrous structure includes large quantities of second-order polysaccharides. Dietary fiber is an active participant in the digestive process, a source of essential nutrients; its deficiency or absence can lead to disruption of homeostasis, the dynamic constancy of the internal environment of the body and pathology. Dietary fiber plays an important role in the functioning of a number of organs and systems of the body and, first of all, affects the function of the colon. They adsorb significant amounts of bile acids, as well as other metabolites, toxins and electrolytes, which helps detoxify the body. For a long time, dietary fiber was considered unnecessary ballast, from which attempts were made to free products to increase their nutritional value. In this regard, a number of refined products have been developed that are completely free of ballast substances. Dietary fiber plays an extremely important role in the functioning of the colon. One of their main properties is the ability to retain water. Water-soluble dietary fibers contained in vegetables and fruits are the most hygroscopic. The ability of dietary fiber to retain water accelerates intestinal transit and peristalsis of the colon, changes intraintestinal pressure, and the concentration of fecal electrolytes. One aspect of the physiological effect of dietary fiber is its effect on mineral metabolism. There is evidence that high dietary fiber intake may disrupt the body's mineral balance. These processes are based on the metabolic properties of ballast substances, which promotes the removal of heavy metal ions, such as lead, strontium, and allows us to consider the possibility of using fiber to remove radionuclides from the body. The use of plant additives from cereals in the development of fermented milk products is of scientific interest and is one of the current trends in the development of functional nutrition products.