Beneficial effects of coconut oil (Cocos nucifera) on hematobiochemicl and histopathological markers in CCL4-intoxicated rabbits / Efeitos benéficos do óleo de coco (Cocos nucifera) em marcadores hematobioquímicos e histopatológicos em coelhos intoxicados com CCL4

The study was designed to investigate the effect of Coconut Oil on the levels of some liver and hematological parameters in carbon tetrachloride intoxicated rabbits. Also the antioxidant capacity of Coconut Oil for various concentrations was assessed on the basis of percent scavenging of (DPPH) free radical. Experimental animals were divided into five groups, eight rabbits in each group. These were: group A (Normal control), group B (Toxic control), group C (Standard control), group D (Treated with Coconut Oil 50 mL/kg body weight after CCl4 intoxication), group E (Treated with Coconut Oil 200 mL/kg body weight after CCl4 intoxication). The effects observed were compared with a standard hepatoprotective drug silymarine (50 mL/kg body weight). The Coconut Oil (200 mL/kg body weight) significantly (P<0.05) reduced the elevated serum levels of alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase (ALP) when compared to a toxic control rabbits. The results of extract treated rabbits were similar to silymarine administered rabbits group. Treatment with Coconut Oil root and silymarine caused no significant changes in RBC, Platelets, (Hb), (MCH) concentration and (HCT) values. However, significant (P<0.05) increase was observed in the total WBC count. The present study suggested that Coconut Oil can be used as an herbal alternative (need further exploration i.e to detect its bioactive compound and its efficacy) for hepatoprotective activit.

O estudo foi desenhado para investigar o efeito do óleo de coco nos níveis de alguns parâmetros hepáticos e hematológicos em coelhos intoxicados com tetracloreto de carbono. Também a capacidade antioxidante do óleo de coco para várias concentrações foi avaliada com base na porcentagem de eliminação de radicais livres (DPPH). Os animais experimentais foram divididos em cinco grupos, oito coelhos em cada grupo. Estes foram: grupo A (controle normal), grupo B (controle tóxico), grupo C (controle padrão), grupo D (tratado com óleo de coco 50 mL/kg de peso corporal após intoxicação por CCl4), grupo E (tratado com óleo de coco 200 mL/kg de peso corporal após intoxicação por CCl4). Os efeitos observados foram comparados com um fármaco hepatoprotetor padrão silimarina (50 mL/kg de peso corporal). O óleo de coco (200 mL/kg de peso corporal) reduziu significativamente (P<0,05) os níveis séricos elevados de alanina transaminase (ALT), aspartato transaminase (AST) e fosfatase alcalina (ALP), quando comparado a um coelho controle tóxico. Os resultados dos coelhos tratados com extrato foram semelhantes aos do grupo de coelhos administrados com silimarina. O tratamento com raiz de óleo de coco e silimarina não causou alterações significativas nos valores de RBC, Plaquetas, (Hb), (MCH) e (HCT). No entanto, observou-se aumento significativo (P<0,05) na contagem total de leucócitos. O presente estudo sugeriu que o óleo de coco pode ser usado como uma alternativa fitoterápica (precisa de mais exploração, ou seja, para detectar seu composto bioativo e sua eficácia) para atividade hepatoprotetora.

Definition, Staging, and Role of Biomarkers in Acute Kidney Injury in the Context of Cardiovascular Interventions.

Acute kidney injury (AKI) is a frequently occurring complication of cardiovascular interventions, and associated with adverse outcomes. Therefore, a clear definition of AKI is of paramount importance to enable timely recognition and treatment. Historically, changes in the serum creatinine and urine output have been used to define AKI, and the criteria have evolved over time with better understanding of the impact of AKI on the outcomes. However, the reliance on serum creatinine for these AKI definitions carries numerous limitations including delayed rise, inability to differentiate between hemodynamics versus structural injury and assay variability to name a few.

Lower Plasma miR-223 Level Is Associated with Clopidogrel Resistance in Acute Coronary Syndrome: A Systematic Review and Meta-Analysis.

Objectives: To evaluate the relationship between the plasma miR-223 expression level and clopidogrel resistance in acute coronary syndrome (ACS) patients. Methods: We performed a search for publications using online databases including PubMed, EMBASE, Cochrane Library, and Chinese Databases (CNKI database, Weipu database, and Wanfang database) from the inception of the databases to June 18, 2023, to identify studies reporting the relationship between the plasma miR-223 level and clopidogrel resistance in ACS patients. Two researchers independently searched and screened to ensure the consistency of the results and assess the quality of the included studies according to the Newcastle-Ottawa scale. A fixed-effects model was used for pooling data with STATA 14.0. Results: Four articles including 399 Chinese ACS patients were eligible for the meta-analysis. Low plasma miR-223 levels were independently correlated with clopidogrel resistance in Chinese ACS patients (OR 0.58, 95% CI: 0.33-1.04). Conclusion: Lower plasma miR-223 levels are associated with clopidogrel resistance in Chinese ACS patients, suggesting that miR-223 may be a potential diagnostic biomarker of clopidogrel resistance.

Adipokines are possible risk markers for aortic stenosis requiring surgery.

OBJECTIVES: Aortic stenosis (AS) is the most prevalent valvular heart disease among adults. The adipocyte-derived hormones, leptin and adiponectin, have profound metabolic actions. We examined whether these adipokines are independently associated with future aortic valve replacement (AVR). DESIGN: In this longitudinal case-control study, we identified 336 cases who had undergone AVR due to AS, and who had previously participated in population-based health surveys. Two referents were matched to each case and leptin and adiponectin concentrations were analysed from stored baseline survey samples. Uni- and multivariable logistic regression analyses were used to estimate the risk of future AVR. An additional cohort was identified for validation including 106 cases with AVR and 212 matched referents. RESULTS: Median age (interquartile range (IQR)) in years at survey was 59.9 (10.4) and at surgery 68.3 (12.7), and 48% were women. An elevated concentration of leptin was not associated with future AVR (odds ratio [95% confidence interval]) (1.10 [0.92-1.32]), although leptin was associated with a higher risk in patients with coronary artery disease (CAD) having more than 5 years between survey and AVR (1.41 [1.08-1.84]). Adiponectin was not associated with higher risk for future AVR (0.95 [0.82-1.11]), although after stratification for age, higher levels were associated with reduced risk for AVR in persons aged ≥60 years at surgery (0.79 [0.64-0.98]). In the validation study, leptin was associated with future AVR whereas adiponectin was not. None of the associations remained significant after adjustment for body mass index (BMI). CONCLUSIONS: The adipokine leptin may promote the development of AS.

An association study of cyclase-associated protein 2 and frailty.

Frailty is a geriatric syndrome that results from multisystem impairment caused by age-associated accumulation of deficits. The frailty index is used to define the level of frailty. Several studies have searched for molecular biomarkers associated with frailty, to meet the needs for personalized care. Cyclase-associated protein 2 (CAP2) is a multifunctional actin-binding protein involved in various physiological and pathological processes, that might reflect frailty's intrinsic complexity. This study aimed to investigate the association between frailty index and circulating CAP2 concentration in 467 community-dwelling older adults (median age: 79; range: 65-92 years) from Milan, Italy. The selected robust regression model showed that circulating CAP2 concentration was not associated with chronological age, as well as sex and education. However, circulating CAP2 concentration was significantly and inversely associated with the frailty index: a 0.1-unit increase in frailty index leads to ~0.5-point mean decrease in CAP2 concentration. Furthermore, mean CAP2 concentration was significantly lower in frail participants (i.e., frailty index ≥0.25) than in non-frail participants. This study shows the association between serum CAP2 concentration and frailty status for the first time, highlighting the potential of CAP2 as a biomarker for age-associated accumulation of deficits.

Association between a Mixture of Per- and Polyfluoroalkyl Substances (PFAS) and Inflammatory Biomarkers in the Atlanta African American Maternal-Child Cohort.

Per- and polyfluoroalkyl substances (PFAS) have been identified as environmental contributors to adverse birth outcomes. One potential mechanistic pathway could be through PFAS-related inflammation and cytokine production. Here, we examined associations between a PFAS mixture and inflammatory biomarkers during early and late pregnancy from participants enrolled in the Atlanta African American Maternal-Child Cohort (N = 425). Serum concentrations of multiple PFAS were detected in >90% samples at 8-14 weeks gestation. Serum concentrations of interferon-γ (IFN-γ), interleukin 6 (IL-6), interleukin 10 (IL-10), tumor necrosis factor-α (TNF-α), and C-reactive protein (CRP) were measured at up to two time points (8-14 weeks and 24-30 weeks gestation). The effect of the PFAS mixture on each inflammatory biomarker was examined using quantile g-computation, Bayesian kernel machine regression (BKMR), Bayesian Weighted Sums (BWS), and weighted quantile sum (WQS) regression. Across all models, the PFAS mixture was associated with increased IFN-γ, IL-10, and TNF-α at both time points, with the strongest effects being observed at 24-30 weeks. Using quantile g-computation, increasing concentrations of a PFAS mixture were associated with a 29% (95% confidence interval = 18.0%, 40.7%) increase in TNF-α at 24-30 weeks. Similarly, using BWS, the PFAS mixture was associated with increased TNF-α at 24-30 weeks (summed effect = 0.29, 95% highest posterior density = 0.17, 0.41). The PFAS mixture was also positively associated with TNF-α at 24-30 weeks using BKMR [75th vs 50th percentile: 17.1% (95% credible interval = 7.7%, 27.4%)]. Meanwhile, PFOS was consistently the main drivers of overall mixture effect across four methods. Our findings indicated an increase in prenatal PFAS exposure is associated with an increase in multiple pro-inflammatory cytokines, potentially contributing to adverse pregnancy outcomes.

Predictive Value of Serum NGAL and ß2 Microglobulin in Blood and Urine amongst Patients with Acute Pancreatitis and Acute Kidney Injury.

OBJECTIVE: This study aimed to explore the predictive value of neutrophil gelatinase-associated lipocalin (NGAL) and ß2 microglobulin (ß2-MG) in blood and urine amongst patients with acute pancreatitis (AP) and acute kidney injury (AKI). METHODS: The clinical data of 80 patients with AP, who were treated in the study hospital from November 2019, to November 2022, were selected for retrospective analysis. They were divided into AKI group (n = 25) and non-AKI group (n = 55) in accordance with the presence of AKI. The levels of serum NGAL and ß2-MG in blood and urine were compared in both groups. Logistic regression analysis was used to explore the influencing factors of AKI in patients with AP and the receiver operating characteristic (ROC) curve was used to evaluate the predictive efficacy of serum NGAL and ß2-MG in the blood and urine of patients with AKI and AP. RESULTS: The AKI group had higher serum NGAL and ß2-MG in blood and urine than the non-AKI group. Logistic regression analysis showed that the high levels of serum NGAL and ß2-MG in blood and urine were risk factors for AKI in patients with AP (p < 0.05). The areas under the curve (AUC), sensitivity and specificity of the combined prediction were 0.97, 84.00% and 98.20%, respectively, showing a good prediction efficiency. CONCLUSIONS: The increased levels of serum NGAL and ß2-MG in blood and urine have a warning significance for patients with AP and AKI and a certain predictive value. So, their combination detection provides a reliable reference for the identification of clinical AKI.

Follicle-stimulating hormone is negatively associated with nonalcoholic fatty liver disease in a Chinese elderly population: a retrospective observational study.

BACKGROUND: Several studies have explored the connection between follicle-stimulating hormone (FSH) and nonalcoholic fatty liver disease (NAFLD). However, the impact of FSH elevation on NAFLD remains a topic of debate. Hence, this investigation aimed to evaluate the potential correlation between FSH levels and NAFLD in the aging population. METHODS: This was a retrospective observational cross-sectional study between July 2017 and August 2018 in our hospital. We used data obtained from 455 patients over 60 years old. Anthropometrics and laboratory tests were performed for each patient. NAFLD was diagnosed by sonographic features and the fatty liver index (LFI). RESULTS: Of the 455 patients, 200 (43.96%) had NAFLD on their ultrasound and 169 (37.14%) had NAFLD according to the LFI. An intraclass correlation coefficient of the two methods was 80.4% (P < 0.001). People with NAFLD on their ultrasound showed lower FSH levels (52.68 vs. 61.39 IU/L) and more unfavorable metabolic profiles. FSH was negatively correlated with age, alanine aminotransferase, estradiol, testosterone, systolic blood pressure, waist, body mass index, fasting blood glucose, postload plasma glucose and positive associated with total cholesterol, high-density lipoprotein-cholesterol and low-density lipoprotein-cholesterol by Spearman correlation analysis (all P < 0.05). By controlling for all confounding factors, the odds ratios (OR) of FSH for NAFLD were determined in elderly individuals, both men and women, aged 60-70 years and over 70 years. These ORs were found to be 0.937, 0.982, 0.983, and 0.973, respectively, with corresponding 95% confidence intervals (CI) of 0.892-0.984 (P = 0.009), 0.971-0.993 (P = 0.002), 0.967-0.999 (P = 0.033), and 0.958-0.989 (P = 0.001). In addition, our findings demonstrated no significant correlation between FSH and advanced fibrosis when adjusting for potential covariates. The OR for advanced fibrosis was 0.979 (95% CI, 0.938-1.022, P = 0.339). Additionally, ROC curve analysis showed an optimal cut-off value of 66.91 for women and 15.25 for men for NAFLD diagnosis. CONCLUSIONS: There was an inverse relationship observed between levels of FSH in the blood serum and NAFLD in the elderly population. These findings suggest that reduced FSH levels might serve as a potential risk factor or biomarker for NAFLD in the elderly.

Plasma long non-coding RNAs ASMTL-AS1, AP001363.1, AC005730.3 and AL133415.1 as a potential biomarker for Alzheimer's disease.

BACKGROUND: Long non-coding RNAs (lncRNAs) play critical role in the pathogenesis of neurodegenerative diseases. Human plasma contains lncRNAs that are present in the blood, and their disease-specific profile has been considered a potential biomarker in some diseases. METHODS: This study reports screening of the plasma levels of lncRNAs between Alzheimer disease(AD) (n = 45) and matched healthy controls (n = 45). The plasma samples of 5 AD patients and 5 matched healthy controls were randomly selected for expression levels of lncRNAs using the TruSeq RNA Sample Prep Kit (Illumina). The receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to study the potential of lncRNAs as biomarkers. RESULTS: The differential expression profiles of plasma showed that 514 lncRNAs were upregulated, whereas 499 lncRNAs were downregulated.We found that the lncRNAs AL133415.1, AC020916.1, ENST00000654948, ASMTL-AS, AC005730.3, and AP001363.1 levels in the plasma of the AD patients were significantly lower compared to the control group (p1 = 0.0006, p2 < 0.001, p3 < 0.001, p4 = 0.039, p5 = 0.006, p6 < 0.001, respectively). ROC curve analysis revealed that the AUC of AL133415.1 was 0.635 (95% CI]: 0.507-0.763, p = 0.036), the AUC of ASMTL-AS1 was 0.658 (95% CI: 0.513-0.785, p = 0.015), the AUC of AC005730.3 was 0.627 (95%CI: 0.498-0.756, p = 0.049), and the AUC of AP001363.1 was 0.708 (95%CI: 0.595-0.822, p = 0.001). CONCLUSION: This study indicated that the plasma levels of the lncRNAs ASMTL-AS1, AP001363.1, AC005730.3, and AL133415.1 might be considered potential biomarkers for AD in the Chinese Population.

Screening of placenta accreta spectrum disorder using maternal serum biomarkers and clinical indicators: a case-control study.

BACKGROUND: Placenta accreta spectrum (PAS) disorder is a major cause of postpartum hemorrhage-associated maternal and fetal death, and novel methods for PAS screening are urgently needed for clinical application. METHODS: The purpose of this study was to develop new methods for PAS screening using serum biomarkers and clinical indicators. A total of 95 PAS cases and 137 controls were enrolled in a case-control study as cohort one, and 44 PAS cases and 35 controls in a prospective nested case-control study were enrolled as cohort two. All subjects were pregnant women of Chinese Han population. Biomarkers for PAS from maternal blood samples were screened based on high-throughput immunoassay and were further validated in three phases of cohort one. Screening models for PAS were generated using maternal serum biomarkers and clinical indicators, and were validated in two cohorts. The expression levels of biomarkers were analyzed using histopathological and immunohistochemical (IHC) techniques, and gene expression was examined by QPCR in the human placenta. Binary logistic regression models were built, and the area under the curve (AUC), sensitivity, specificity, and Youden index were calculated. Statistical analyses and model building were performed in SPSS and graphs were generated in GraphPad Prism. The independent-sample t test was used to compare numerical data between two groups. For nonparametric variables, a Mann-Whitney U test or a X2 test was used. RESULTS: The results demonstrated that the serum levels of matrix metalloproteinase-1 (MMP-1), epidermal growth factor (EGF), and vascular endothelial growth factor-A (VEGF-A) were consistently higher, while the level of tissue-type plasminogen activator (tPA) was significantly lower in PAS patients compared with normal term controls and patients with pre-eclampsia (PE) and placenta previa (PP). IHC and QPCR analysis confirmed that the expression of the identified biomarkers significantly changed during the third trimester in human placenta. The generated screening model combining serum biomarkers and clinical indicators detected 87% of PAS cases with AUC of 0.94. CONCLUSIONS: Serum biomarkers can be used for PAS screening with low expense and high clinical performance; therefore, it may help to develop a practicable method for clinical prenatal PAS screening.

Pseudohypercreatininemia after surgery for aortic dissection: a case report.

BACKGROUND: Elevated creatinine concentrations often indicate acute renal injury and renal biopsies are considered in this situation. However,pseudohypercreatininemia is potential cause of elevated creatinine concentrations, and invasive interventions should be avoided. CASE PRESENTATION: A 54-year-old woman underwent surgery for descending aortic dissection.Nine days postoperatively, her creatinine concentration increased from 1 mg/dl to 5.78 mg/dl (normal range, 0.47-0.7 mg/dl). Azotemia and hyperkalemia were absent and physical examination findings were unremarkable. Cystatin C concentration was 1.56 mg/l (normal range, 0.56-0.8 mg/l) and pseudohypercreatininemia was suspected. Testing with different reagents showed a creatinine concentration of 0.84 mg/dl. Immunoglobulin (Ig)G was markedly elevated, and creatinine and IgG fluctuated in parallel, suggesting the cause of the pseudohypercreatininemia. IgG4 was also elevated at 844 mg/dl. Immunosuppressive steroid therapy effectively decreased the IgG concentration and resolved the pseudohypercreatininemia. CONCLUSIONS: In cases of elevated creatinine concentration with the presence of abnormal proteins, pseudohypercreatininemia should be considered. We report a rare case of pseudohypercreatininemia caused by polyclonal IgG.

Serum levels of serum amyloid A, interleukin-6 and C-reactive protein correlate with severity of hidradenitis suppurativa.

BACKGROUND: Validated biomarkers enabling an objective, dynamic assessment of hidradenitis suppurativa (HS) disease severity do not exist. The aim of our study was to determine the serum concentration of four potential biomarkers with respect to HS disease severity. METHODS: We recruited 50 patients with hidradenitis suppurativa. After obtaining informed consent, patients were requested to fill out multiple questionnaires. Severity of HS was determined based on Hurley and Sartorius scores by an experienced dermatologist. Blood sampling included Serum Amyloid A (SAA), Interleukin-6 (IL-6), C-reactive protein (CRP) and S100 protein (S100) in a certified laboratory. RESULTS: Moderate and statistically significant correlations of SAA, IL-6 and CRP with the clinical scores Hurley and Sartorius were observed. The respective Spearman's correlation coefficients (r) were: Hurley 0.38, 0.46, 0.35 and Sartorius 0.51, 0.48, 0.48. No relevant changes were detected when comparing S100 to both Hurley (r=0.06) and Sartorius (r=0.09). CONCLUSIONS: Our data suggest that an association between SAA, IL-6, CRP and HS disease severity could exist. Further research is needed to define their potential as biomarkers for quantifying and monitoring disease activity and response to treatment.

Glycoprotein non-metastatic protein B (GPNMB) plasma values in patients with chronic visceral acid sphingomyelinase deficiency.

Acid sphingomyelinase deficiency (ASMD) is a rare LSD characterized by lysosomal accumulation of sphingomyelin, primarily in macrophages. With the recent availability of enzyme replacement therapy, the need for biomarkers to assess severity of disease has increased. Glycoprotein non-metastatic protein B (GPNMB) plasma levels were demonstrated to be elevated in Gaucher disease. Given the similarities between Gaucher disease and ASMD, the hypothesis was that GPNMB might be a potential biochemical marker for ASMD as well. Plasma samples of ASMD patients were analyzed and GPNMB plasma levels were compared to those of healthy volunteers. Visceral disease severity was classified as severe when splenic, hepatic and pulmonary manifestations were all present and as mild to moderate if this was not the case. Median GPNMB levels in 67 samples of 19 ASMD patients were 185 ng/ml (range 70-811 ng/ml) and were increased compared to 10 healthy controls (median 36 ng/ml, range 9-175 ng/ml, p < 0.001). Median plasma GPNMB levels of ASMD patients with mild to moderate visceral disease compared to patients with severe visceral disease differed significantly and did not overlap (respectively 109 ng/ml, range 70-304 ng/ml and 325 ng/ml, range 165-811 ng/ml, p < 0.001). Correlations with other biochemical markers of ASMD (i.e. chitotriosidase activity, CCL18 and lysosphingomyelin, respectively R = 0.28, p = 0.270; R = 0.34, p = 0.180; R = 0.39, p = 0.100) and clinical parameters (i.e. spleen volume, liver volume, diffusion capacity and forced vital capacity, respectively R = 0.59, p = 0.061, R = 0.5, p = 0.100, R = 0.065, p = 0.810, R = -0.38, p = 0.160) could not be established within this study. The results of this study suggest that GPNMB might be suitable as a biomarker of visceral disease severity in ASMD. Correlations between GPNMB and biochemical or clinical markers of ASMD and response to therapy have to be studied in a larger cohort.

Copeptin is associated with microalbuminuria and renal function in the general Japanese population.

An association between copeptin (precursor molecule of arginine vasopressin) and markers for renal function has been reported, but data on the Japanese population has been limited. In this study, we investigated whether elevated copeptin levels are associated with microalbuminuria and renal dysfunction in the general Japanese population. A total of 1,262 participants (842 female and 420 male) were enrolled. Multiple regression analysis was performed to assess the association of copeptin levels (logarithm) with estimated glomerular filtration rate (eGFR) and the urine albumin-to-creatinine ratio (UACR) after adjusting for age, BMI, and lifestyle variables. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression methods in which chronic kidney disease (CKD) was the dependent variable. The copeptin levels differed significantly with sex, but were not found to be related to age or the span of time from preceding meal to blood sampling. In female participants, copeptin level was negatively correlated with eGFR (beta = -0.100, p-value = 0.006) and positively correlated with UACR (beta = 0.099, p-value = 0.003). In male participants, a negative correlation (beta = -0.140, p-value = 0.008) was observed for eGFR. In both females and males, those with high copeptin levels had more than double the ORs of CKD (OR = 2.1-2.9) adjusted for CKD-related factors. The present study found elevated copeptin levels to be associated with renal function loss in the Japanese population and microalbuminuria in female. Moreover, it was evident that high copeptin levels are associated with CKD. These results suggest that copeptin could be considered a marker of renal function.

Osteomalacia Prevalence, Biochemical Profile, and Histology in Patients with Low-Energy Hip Fractures Over the Age of 45.

Our objective was to determine the prevalence of osteomalacia in low-energy hip fracture patients over the age of 45, based on biochemical and histological measures. This cross-sectional study included 72 patients over 45 with low-energy mechanism hip fractures. Samples of fasting venous blood were taken for hemograms and serum biochemistry analyses. Bicortical biopsies of the iliac crest were obtained, processed, and evaluated by an expert pathologist for osteomalacia. Biochemical osteomalacia (b-OM) is defined according to a distinct criterion. A low level of serum calcium, phosphorus, albumin, and 25OHD was found in 43.1, 16.7, 73.6, and 59.7% of patients, respectively. 50.0% of patients had high serum alkaline phosphatase (ALP) levels. b-OM was found in 30 (41.7%), and no significant association was found with PTH, Cr, Alb, age, sex, fracture type, side of the trauma, and season were not associated with osteomalacia. Osteomalacia was diagnosed on histopathological analysis in 19/72 (26.7%), and 54/72 (75.0%) of all cases fulfilled b-OM criteria. In the histologic evaluation, osteoid seam width, osteoid surface, and osteoid volume were 28.5 µm, 25.6, and 12.1%, respectively. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the biochemical test for detecting osteomalacia were 73.6, 64.2, 42.4, 87.2, and 66.7%, respectively. Up to 30% of elderly patients with low-energy hip fractures are affected by osteomalacia. A biochemical screening along with a bone biopsy and histopathologic evaluation may be logical in a high-risk population for osteomalacia diagnosis.

Statin Therapy Induces Gut Leakage and Neuromuscular Disjunction in Patients With Chronic Heart Failure.

ABSTRACT: Statins are commonly used to limit the risk of cardiovascular diseases, including ischemic heart attack and stroke. However, treatment often leads to myopathy and muscle weakness. Therefore, a better understanding of underlying pathomechanism is needed to improve the clinical outcomes. Here, we assessed the physical performance, including handgrip strength (HGS), gait speed (GS), and short physical performance battery, in 172 patients diagnosed with chronic heart failure (CHF) treated with (n = 50) or without (n = 122) statin and 59 controls. The plasma biomarkers, including sarcopenia marker C-terminal agrin fragment-22 (CAF22), intestinal barrier integrity marker zonulin, and C-reactive protein (CRP), were measured and correlated with the physical performance of patients. The HGS, short physical performance battery scores, and GS were significantly compromised in patients with CHF versus controls. Irrespective of etiology, significant elevation of plasma CAF22, zonulin, and CRP was observed in patients with CHF. There were strong inverse correlations of CAF22 with HGS (r 2 = 0.34, P < 0.0001), short physical performance battery scores (r 2 = 0.08, P = 0.0001), and GS (r 2 = 0.143, P < 0.0001). Strikingly, CAF22 and zonulin were positively correlated with each other (r 2 = 0.10, P = 0.0002) and with the level of CRP in patients with CHF. Further investigations revealed a significant induction of CAF22, zonulin, and CRP in patients with CHF taking statin versus nonstatin group. Consistently, HGS and GS were significantly lower in the statin versus nonstatin CHF patients' group. Collectively, statin therapy adversely affects the neuromuscular junction and intestinal barrier, which potentially induces systemic inflammation and physical disability in patients with CHF. Further prospective confirmation of the findings is required in a well-controlled study.

Comparison of the accumulation of toxic metal biomarkers in Asian subgroups and other races in the United States: NHANES 2015-2016.

Toxic metals such as lead (Pb), cadmium (Cd), mercury (Hg) and arsenic (As) that lead to many visceral organ and nervous system diseases have attracted global attention due to their gradual accumulation in human bodies. The tolerance levels of exposure to toxic metals among race/ethnic groups are different due to the variance of sociodemographic, dietary, and behavioral characteristics. Few studies focused on investigating the biomarker levels of toxic metals in different race/ethnic groups and the potential mechanisms for controlling the accumulation in human bodies. Therefore, we selected eight biomarkers for four toxic metals from the National Health and Nutrition and Examination Survey (NHANES) in the 2-year data cycle of 2015-2016 to reveal the accumulation levels in different races. According to the NHANES rules, we applied probability sampling weights. The geometric mean levels of these biomarkers were calculated in all five race/ethnic groups (Mexican American, white, black, Asian, and other Hispanic) and two Asian subgroups (U.S.-born Asian, and other-born Asian), and compared with each other. The results showed that all the biomarkers in other-born Asians were 1.1-6.7 times in blood and 1.1-3.6 times in urine higher than other race/ethnic groups. Except Hg and As, the lowest biomarker levels were recorded in U.S.-born Asians, only 0.6-0.9 times of lead and 0.3-0.8 times of cadmium than other race/ethnic groups. Furthermore, the major factors of higher Hg and As biomarker levels in Asians were dietary intake of seafood and rice, indicating different accumulation mechanisms among Asians and other race/ethnic groups, especially for U.S.-born Asians. These findings provided new insight into a deeper understanding the accumulation of toxic metals and human health.

Biliverdin Reductase B Is a Plasma Biomarker for Intraplaque Hemorrhage and a Predictor of Ischemic Stroke in Patients with Symptomatic Carotid Atherosclerosis.

BACKGROUND: Intraplaque hemorrhage (IPH) is a hallmark of atherosclerotic plaque instability. Biliverdin reductase B (BLVRB) is enriched in plasma and plaques from patients with symptomatic carotid atherosclerosis and functionally associated with IPH. OBJECTIVE: We explored the biomarker potential of plasma BLVRB through (1) its correlation with IPH in carotid plaques assessed by magnetic resonance imaging (MRI), and with recurrent ischemic stroke, and (2) its use for monitoring pharmacotherapy targeting IPH in a preclinical setting. METHODS: Plasma BLVRB levels were measured in patients with symptomatic carotid atherosclerosis from the PARISK study (n = 177, 5 year follow-up) with and without IPH as indicated by MRI. Plasma BLVRB levels were also measured in a mouse vein graft model of IPH at baseline and following antiangiogenic therapy targeting vascular endothelial growth factor receptor 2 (VEGFR-2). RESULTS: Plasma BLVRB levels were significantly higher in patients with IPH (737.32 ± 693.21 vs. 520.94 ± 499.43 mean fluorescent intensity (MFI), p = 0.033), but had no association with baseline clinical and biological parameters. Plasma BLVRB levels were also significantly higher in patients who developed recurrent ischemic stroke (1099.34 ± 928.49 vs. 582.07 ± 545.34 MFI, HR = 1.600, CI [1.092-2.344]; p = 0.016). Plasma BLVRB levels were significantly reduced following prevention of IPH by anti-VEGFR-2 therapy in mouse vein grafts (1189 ± 258.73 vs. 1752 ± 366.84 MFI; p = 0.004). CONCLUSIONS: Plasma BLVRB was associated with IPH and increased risk of recurrent ischemic stroke in patients with symptomatic low- to moderate-grade carotid stenosis, indicating the capacity to monitor the efficacy of IPH-preventive pharmacotherapy in an animal model. Together, these results suggest the utility of plasma BLVRB as a biomarker for atherosclerotic plaque instability.