Experimental Investigation of the Impact of Niobium Additions on the Structural Characteristics and Properties of Ti-5Cr-xNb Alloys for Biomedical Applications.

In this study, a series of Ti-5Cr-xNb alloys with varying Nb content (ranging from 1 to 40 wt.%) were investigated to assess their suitability as implant materials. Comprehensive analyses were conducted, including phase analysis, microscopy examination, mechanical testing, and corrosion resistance evaluation. The results revealed significant structural alterations attributed to Nb addition, notably suppressing the formation of the ω phase and transitioning from α' + ß + ω to single ß phase structures. Moreover, the incorporation of Nb markedly improved the alloys' plastic deformation ability and reduced their elastic modulus. In particular, the Ti-5Cr-25Nb alloy demonstrated high values in corrosion potential and polarization resistance, signifying exceptional corrosion resistance. This alloy also displayed high bending strength (approximately 1500 MPa), a low elastic modulus (approximately 80 GPa), and outstanding elastic recovery and plastic deformation capabilities. These aggregate outcomes indicate the promising potential of the ß-phase Ti-5Cr-25Nb alloy for applications in orthopedic and dental implants.

Serum Cystatin C Levels Could Predict Rapid Kidney Function Decline in A Community-Based Population.

BACKGROUND: Several biomarkers have been correlated with the prevalence and severity of chronic kidney disease (CKD); however, the association between biomarkers and rapid kidney function decline (RKFD) is unknown. This study aimed to evaluate the predictive performance of biomarkers to determine who is likely to develop RKFD in a healthy population. METHODS: A community-based cohort of 2608 people residing in northern Taiwan were enrolled, and their renal function was followed annually from January 2014 to December 2019. The outcomes of interest were RKFD, defined as a 15% decrease in the estimated glomerular filtration rate (eGFR) within the first 4 years, and a decrease in eGFR without improvement in the fifth year. Clinical variables and potential predictors of RKFD, namely adiponectin, leptin, tumor necrosis factor-alpha, and cystatin C, were measured and analyzed. RESULTS: The incidence of RKFD was 17.0% (105/619). After matching for age and sex at a 1:1 ratio, a total of 200 subjects were included for analysis. The levels of cystatin C and total vitamin D were significantly negatively correlated with eGFR. eGFR was negatively correlated with the levels of cystatin C and total vitamin D. Among the biomarkers, cystatin C showed the best predictive performance for RKFD (area under the receiver operating characteristic curve: 0.789). Lower serum cystatin C was associated with a higher rate of RKFD in healthy subjects. A generalized additive model showed that 0.82 mg/L was an adequate cut-off value of cystatin C to predict RKFD. Multivariable logistic regression analysis further indicated that low cystatin C and eGFR were independent predictors of the possibility of RKFD. CONCLUSIONS: Serum cystatin C level could predict the possibility of RKFD. We suggest that a low cystatin C level should be considered as a risk factor for RKFD in healthy subjects.

Essential Roles of the Histone Demethylase KDM4C in Renal Development and Acute Kidney Injury.

BACKGROUND: Lysine demethylase 4C (KDM4C) is a nuclear protein that is essential for histone modification and acts as an important regulator of several transcription factors. Previous studies have shown that KDM4C may also play a role in mediating stress responses. The purpose of this study was to examine the roles of KDM4C in kidney development and acute kidney injury (AKI). METHODS: The effect of KDM4C on kidney development was assessed by comparing the kidney phenotype between 96 zebrafish embryos treated with kdm4c-morpholino oligonucleotide and 96 untreated zebrafish embryos. We further examined whether KDM4C is essential for maintaining cell survival in AKI. Cultured human renal tubular cells were used for the in vitro study. Wild-type and Kdm4c knockout mice (C57BL/6NTac-Kdm4ctm1a(KOMP)Wtsi) were divided into a sham group and model group, and then subjected to ischemic reperfusion kidney injury (IRI-AKI). Blood samples and kidneys were collected at different time points (day 3, day 7, day 14, and day 28) and were processed for in vivo studies (n = 8 in each group). RESULTS: Kdm4c knockdown significantly decreased zebrafish embryo survival and impaired kidney development. The in vitro study showed that KDM4C inhibition by JIB04 significantly increased cellular apoptosis under oxidative stress conditions. KDM4C knockdown cells had impaired autophagy function under stress conditions. The IRI-AKI mice study showed that KDM4C protein levels dynamically changed and were significantly correlated with HIF-1α levels in AKI. Kdm4c-/- mice had significantly more severe renal impairment and increased kidney fibrosis than the wild-type mice. Cytokine array results also indicated that the kidneys of Kdm4c-/- mice had increased inflammation in AKI compared with the wild-type mice. Further RNA sequence analysis revealed that KDM4C may regulate transcription factors related to mitochondrial dynamics and function. CONCLUSIONS: Our study suggests that KDM4C may play a critical role in regulating mitochondria, which is related to a protective effect on maintaining cell survival in AKI.

Circulating Fibroblast Growth Factor-23 Levels Can Predict Rapid Kidney Function Decline in a Healthy Population: A Community-Based Study.

BACKGROUND: Fibroblast growth factor-23 (FGF-23) associates with decreased kidney function in patients with chronic kidney disease (CKD). However, the correlation between circulating FGF-23 levels and the rate of renal function decline in healthy individuals is largely unknown. We aimed to evaluate the predictive performance of FGF-23 for rapid kidney function decline (RKFD) in a community-based study. METHODS: A total of 2963 people residing in northern Taiwan were enrolled from August 2013 to May 2018 for an annual assessment of kidney function for five years. The baseline estimated glomerular filtration rates (eGFR) were calculated using the 2009 and 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, which aggregates the values of serum creatinine and cystatin C (eGFRcr-cys). The outcome was RKFD-a 15% decrease in estimated glomerular filtration rate (eGFR) within the first four years, and a reduction in eGFR without improvement in the 5th year. A generalized additive model (GAM) was used to determine the cut-off value of FGF-23 to predict RKFD. RESULTS: The incidence of RKFD was 18.0% (114/634). After matching for age and sex at a 1:1 ratio, a total of 220 subjects were analyzed. eGFRcr-cys was negatively correlated with total vitamin D level but seemed irrelevant to FGF-23. Multivariable logistic regression analysis showed that FGF-23, eGFRcr-cys, and urine albumin-to-creatinine ratio (UACR) were independent predictors of the possibility of RKFD. FGF-23 showed the best predictive performance for RKFD (AUROC: 0.803), followed by baseline eGFRcr-cys (AUROC: 0.639) and UACR (AUROC: 0.591). From the GAM, 32 pg/mL was the most appropriate cut-off value of FGF-23 with which to predict RKFD. The subgroup and sensitivity analyses showed consistent results that high-FGF-23 subjects had higher risks of RKFD. CONCLUSIONS: Circulating FGF-23 level could be a helpful predictor for RKFD in this community-based population.

Can Anthropometry and Body Composition Explain Physical Fitness Levels in School-Aged Children?

Physical fitness (PF) is closely related to various health outcomes and quality of life among children. However, the associations between anthropometry, body composition (BC), and PF are not fully elucidated. This cross-sectional study aimed to investigate the associations between demographic metrics (age, sex), anthropometric measures (body mass index z-score (BMI z-score) waist/height ratio (WHtR)), BC parameters (body-fat percentage (BF%), muscle weight), and PF levels (800-m run, sit-and-reach, 1-min sit-ups, standing long jump) in school-aged children. Continuous variables were dichotomized by median splits. The results of 180 girls and 180 boys (mean age: 10.0 ± 0.7 years; mean BMI z-score: 0.366 ± 1.216) were analyzed. Multivariable linear regressions revealed that BF% (regression coefficient (B) = 3.4, 95% confidence interval (CI) = 2.5-4.3) was independently correlated with the 800-m run. Sex (B = 4.6, 95% CI = 3.0-6.3), age (B = 3.1, 95% CI = 1.9-4.3), and BMI z-score (B = -0.7, 95% CI = -1.4--0.1) were independently related to sit-and-reach. Age (B = 3.3, 95% CI = 2.0-4.7), BF% (B = -0.3, 95% CI = -0.4--0.2), and muscle weight (B = 0.7, 95% CI = 0.2-1.2) were independently associated with 1-min sit-ups. In addition to demography, anthropometry and BC provided additional information concerning some PF levels in school-aged children. Weight management and PF promotion should be addressed simultaneously in terms of preventive medicine and health promotion for children.

Ketoanalogue supplements reduce mortality in patients with pre-dialysis advanced diabetic kidney disease: A nationwide population-based study.

BACKGROUND & AIMS: Metabolism dysregulation and protein energy wasting occur in patients with chronic kidney disease (CKD) and are associated with poor survival, especially in patients prior to starting dialysis. Accumulating evidence indicates that dietary supplementation with ketoanalogues (KAs, a mixture of branched-chain amino acids) exerts a variety of beneficial effects for patients with CKD. However, the role of KAs in diabetic kidney disease (DKD), one of the major causes of CKD, is still controversial. The aim of this study was to explore the impact of KA supplements on survival in patients with stage 5 DKD who have not yet started dialysis (DKD-5-ND). METHODS: We analyzed a nationwide cohort retrieved from the National Health Insurance Research Database in Taiwan to study the long-term impact of KA supplements in patients with DKD-5-ND. We enrolled 15,782 incident pre-dialysis DKD patients between January 1, 2004 and December 31, 2007. Landmark analysis was used to eliminate immortal bias, and overlap weighting was used to balance differences between the KA users and nonusers in the beginning. The primary study endpoint was all-cause mortality, and the occurrence of permanent dialysis (presenting the end-stage renal disease, ESRD) and major adverse cardiovascular events (MACEs) was also evaluated. All patients were followed for five years or until death. RESULTS: The prevalence of KA usage in the DKD-5-ND patients was 6.3%. The 5-year all-cause mortality rate in the KA users was lower than that in the nonusers (34.7% vs 42.7%). After adjusting for known covariates, the KA users still had a lower risk of mortality (adjusted hazard ratio [aHR]: 0.73, 95% confidence interval [CI]: 0.66-0.82). In addition, the incidence of ESRD was also slightly lower among the KA users (90.9% for users vs 91.2% for nonusers, adjusted cause-specific hazard ratio [aCSHR]: 0.65, 95% CI: 0.61-0.69), and the occurrence of MACEs was lower (adjusted incidence rate ratios [aIRR]: 0.76, 95% CI: 0.67-0.86). Although the all-cause mortality was higher among patientsolder than 70 years (60.5% for KA users vs 46.5% for nonusers) the risk reduction seemed prominent among older patients (aHR: 0.65, 95% CI: 0.56-0.76 for patients aged ≥70 years; aHR: 0.82, 95% CI: 0.71-0.96 for patients aged < 70 years). The reduction in risks of mortality was consistent in subgroup analysis and sensitivity tests. CONCLUSIONS: The use of KA supplements seemed to be beneficial for patients with DKD-5-ND; further in-depth analysis of using KA for these patients is warranted.

The Association between Insulin Resistance and Cardiovascular Disease Risk: A Community-Based Cross-Sectional Study among Taiwanese People Aged over 50 Years.

BACKGROUND AND AIMS: Previous studies have implied that insulin resistance (IR) could represent a major underlying abnormality leading to cardiovascular disease (CVD). The aim of this study was to evaluate the relationships between IR (estimated by the homeostasis model assessment of IR (HOMA-IR) index) and CVD risk among middle-aged and elderly Taiwanese individuals. METHODS: In this cross-sectional, community-based study, a total of 320 participants were interviewed to collect demographical parameters and blood samples. The recruited participants were divided into tertiles according to their levels of HOMA-IR. The Framingham risk score (FRS) was calculated according to the 2008 general CVD risk model from the Framingham Heart Study. RESULTS: The HOMA-IR index was significantly correlated with the FRS, with a Pearson's coefficient of 0.22. In the multiple logistic regression model, a higher HOMA-IR level was significantly associated with a high FRS (FRS ≥ 20%) (highest tertile vs. lowest tertile of HOMA-IR, crude OR = 3.69; 95% CI = 1.79-7.62), even after adjusting for smoking, fasting plasma glucose (FPG), and systolic blood pressure (SBP) (highest tertile vs. lowest tertile of HOMA-IR, adjusted OR = 11.51; 95% CI = 2.55-51.94). The area under the receiver operating characteristic curve for the HOMA-IR index as the predictor of high FRS was 0.627, and the optimal HOMA-IR cutoff value was 1.215 (sensitivity = 83.6%, specificity = 42.9%). CONCLUSIONS: We considered that HOMA-IR is an independent factor but that it cannot be used solely for evaluating the CVD risk due to the low AUC value. Further prospective cohort studies are warranted to better assess the relationship between CVD risk and insulin resistance.

Thermal Perception Abnormalities Can Predict Diabetic Kidney Disease in Type 2 Diabetes Mellitus Patients.

BACKGROUND: Previous studies have illustrated clinical associations between diabetic peripheral neuropathy (DPN) and diabetic kidney disease (DKD). Quantitative sensory testing (QST) can accurately detect thermal perception abnormalities and aid in the early diagnosis of asymptomatic small-fiber DPN in patients with type 2 diabetes. The aim of this study was to determine the predictive value of thermal perception abnormalities by QST to detect DKD. METHODS: We prospectively enrolled 432 patients with type 2 diabetes (50.2% male, mean age 57.2 years, and average duration of diabetes 9.9 years) at our hospital between 2016 and 2017. Demographic and clinical data of the patients were recorded and analyzed. Diagnosis and staging of DKD were determined by urinary albumin excretion rate and estimated glomerular filtration rate. The presence of thermal perception abnormalities was determined by QST. Multiple logistic regression and receiver operating characteristic (ROC) analyses were performed to investigate the relationships between thermal perception abnormalities and DKD in these patients. RESULTS: In multiple regression analysis, abnormal cold perception in the lower limbs was associated with an increased risk of advanced DKD. Area under the ROC curve analysis revealed that four-limb cold perception abnormalities had the best discriminatory power (0.741 ± 0.053) to predict advanced DKD. CONCLUSIONS: Our results demonstrate the value of using thermal perception abnormalities to identify patients with type 2 diabetes also at risk of DKD.

The Association between Metabolic Syndrome and Elevated Alanine Aminotransferase Levels in an Indigenous Population in Northern Taiwan: A Community-Based and Cross-Sectional Study.

Our study aims to determine the prevalence of metabolic syndrome (MetS) among the Northern Taiwanese indigenous population and to explore the relationship between MetS and liver enzyme, especially serum alanine transaminase (ALT). This is an observational and cross-sectional study that was conducted in remote villages of an indigenous community in Northern Taiwan between 2010 and 2015. MetS was defined based on the revised NCEP/ATPIII criteria from Taiwan Health Promotion Administration. A total of 454 participants were included in the analysis. There were 277 people with MetS and 177 people without. The prevalence of MetS was 61.01%. The average age was 49.50 years. People with MetS had a significantly higher liver enzyme (ALT) level than those without MetS. In addition, the study showed that participants with higher ALT had a tendency towards a higher prevalence of MetS (76.7% vs. 57.3%, p = 0.001). The adjusted odds ratio (OR) of ALT levels >36 U/L for MetS was 2.79 (95% CI = 1.24-6.27, p = 0.01). The area under the ROC curve (AUC) of the ALT level was 0.63 (95% CI = 0.58-0.68, p < 0.001), which showed that the ALT level was positively associated with MetS. The overall prevalence of MetS was 61.01% in the highland indigenous population in Northern Taiwan; this study indicated that higher serum ALT levels were associated with an increased risk of MetS.