Objective To present the case of a Latin man 68 years of age who presented to the emergency department with a rash to the right side of his groin 10 weeks after switching from simvastatin 40 mg daily to atorvastatin 40 mg daily. Background Prior to switching to atorvastatin, the patient had been taking simvastatin for 21 years without rash. The rash progressed bilaterally to his arms and hands, legs, buttocks, back, and trunk before the patient was seen by dermatology and atorvastatin was discontinued. Results Within six weeks of discontinuation of atorvastatin, the rash resolved with remaining pigmentation changes. The adverse effect was documented in the patient's chart, and dermatology recommended avoiding other statins in the future. Settings Ambulatory clinic pharmacy practice, emergency room, or urgent care centers. Practice Considerations Atorvastatin is a 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitor or statin that has been FDA approved for the prevention of atherosclerotic cardiovascular disease (ASCVD) and treatment of hypercholesterolemia since 1996. Despite widespread use of atorvastatin over many years, only a handful of published cases report drug eruption from its use. Previous case reports have found that retrial of statins may cause similar drug eruption. Conclusion Pharmacists should consider HMG-CoA reductase inhibitors as a possible cause of new onset rash and should not retrial an alternative statin.

Purpose: In the last decades we have seen an increase in sedentary behaviors and a decrease in physical activity in children when compared to past generations. This lifestyle is commonly associated with the development of clustering risk factors that define metabolic syndrome (MetS). Knowing that motor competence (MC) development can influence lifelong physical activity habits, it is reasonable to assume that children's MC will directly link to clustered cardiometabolic health outcomes. The aim of this study was to analyze the role of MC in MetS risk factors. Methods: Seventy children with a mean age of 7.49 (SD = 1.28) years were evaluated on motor competence (MCA-Motor Competence Assessment instrument), cardiovascular fitness (PACER test), upper body strength (UBS; handgrip), and the components of MetS, hypertriglyceridemia, hypertension, abdominal obesity, low concentration of high-density lipoprotein cholesterol, and high fasting blood glucose. The composite value of MetS was calculated according to Burns et al. (2017). Multiple standard regressions were performed to explore the effect of different variables on MetS. Motor competence and health-related fitness (cardiovascular fitness and relative upper body strength) were used as independent variables (predictors) and MetS as dependent variable. Results: Overall, the results showed that motor competence (β = -.072; p < .05) is a significant predictor and this model explained 7,1% of the variance in MetS. Conclusion: Although more studies are needed, our results indicate that MC seems to have a positive role in children's health markers.

Increased triglycerides (TG) and decreased high-density lipoprotein cholesterol (HDL-C) are dyslipidemias characteristic of diabetes. Here, we aimed to examine associations of TG/HDL-C ratio with cardiovascular disease (CVD) and kidney dysfunction among patients with diabetic nephropathy. This retrospective observational study consists of patients with biopsy-proven diabetic nephropathy at Nara Medical University Hospital. Exposure of interest was TG/HDL-C ratio measured at kidney biopsy. Outcome variables were kidney histological findings, incident CVD and end-stage kidney disease (ESKD). Multivariable logistic regression models and Cox proportional hazard models were used to examined these associations. A total of 353 subjects were divided into quartiles based on TG/HDL-C ratio: Quartile 1 (reference), <1.96; Quartile 2, 1.96-3.10; Quartile 3, 3.11-4.55; and Quartile 4, ≥4.56. TG/HDL-C ratio was not a predictor of any histological findings in fully adjusted models. During median follow-up periods of 6.2 and 7.3 years, 152 and 90 subjects developed CVD and ESKD, respectively. Higher TG/HDL-C ratio was independently associated with higher incidences of CVD even after adjustments for potential confounders (hazard ratio [95% confidence interval] for Quartile 3 vs. reference; 1.73 [1.08-2.79] and Quartile 4 vs. reference; 1.86 [1.10-3.17]). Although there was a weak association between TG/HDL-C ratio and ESKD in the univariable model, the association was not significant in fully adjusted models. In conclusion, among patients with biopsy-proven diabetic nephropathy, higher TG/HDL-C ratio was independently associated with higher incidences of CVD but not with kidney outcomes, suggesting different impact of TG/HDL-C ratio on cardiorenal outcomes.

Hepatitis B virus (HBV) infection is still one kind of the infectious diseases that seriously threaten human health. Nonalcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease worldwide. HBV infection complicated with NAFLD is increasingly common. This review mainly describes the interaction between HBV infection and NAFLD, the interaction between steatosis and antiviral drugs, and the prognosis of HBV infection complicated with NAFLD. Most studies suggest that HBV infection may reduce the incidence of NAFLD. NAFLD can promote the spontaneous clearance of hepatitis B surface antigen (HBsAg), but whether it affects antiviral efficacy has been reported inconsistently. HBV infection combined with NAFLD can promote the progression of liver fibrosis, especially in patients with severe steatosis. The outcome of HBV infection combined with NAFLD predisposing to the progression of HCC remains controversial.

Despite of multiple systematic studies of schizophrenia based on proteomics, metabolomics, and genome-wide significant loci, reconstruction of underlying mechanism is still a challenging task. Combination of the advanced data for quantitative proteomics, metabolomics, and genome-wide association study (GWAS) can enhance the current fundamental knowledge about molecular pathogenesis of schizophrenia. In this study, we utilized quantitative proteomic and metabolomic assay, and high throughput genotyping for the GWAS study. We identified 20 differently expressed proteins that were validated on an independent cohort of patients with schizophrenia, including ALS, A1AG1, PEDF, VTDB, CERU, APOB, APOH, FASN, GPX3, etc. and almost half of them are new for schizophrenia. The metabolomic survey revealed 18 group-specific compounds, most of which were the part of transformation of tyrosine and steroids with the prevalence to androgens (androsterone sulfate, thyroliberin, thyroxine, dihydrotestosterone, androstenedione, cholesterol sulfate, metanephrine, dopaquinone, etc.). The GWAS assay mostly failed to reveal significantly associated loci therefore 52 loci with the smoothened p < 10-5 were fractionally integrated into proteome-metabolome data. We integrated three omics layers and powered them by the quantitative analysis to propose a map of molecular events associated with schizophrenia psychopathology. The resulting interplay between different molecular layers emphasizes a strict implication of lipids transport, oxidative stress, imbalance in steroidogenesis and associated impartments of thyroid hormones as key interconnected nodes essential for understanding of how the regulation of distinct metabolic axis is achieved and what happens in the conditioned proteome and metabolome to produce a schizophrenia-specific pattern.

Nickel (Ni) is a widespread environmental pollutant commonly released into effluent due to industrial activities, the use of fuels, or wastewater disposal. Many studies confirm the toxic effects of this heavy metal. However, there is a lack of knowledge and data on bioaccumulation patterns in tissues as well as cellular and molecular responses following the exposure of living organisms to Ni. In this study, Japanese quails were exposed to low (10 μg/L) and high (2000 μg/L) Ni concentrations in the form of nickel(II) chloride via drinking water. Sub-chronic exposure lasted 30 days while nominal concentrations represented average Ni content in drinking water (low dose) and average Ni levels in highly polluted aquatic environments (high dose). It was revealed that a high dose of Ni was correlated with increased water intake and decreased body weight. Overall, Ni exposure induced the development of microcytic anemia and alterations in measured blood indices. Moreover, Ni exposure impaired immunological activation as seen through the increased number of the white blood cells, increased heterophile/lymphocyte (H/L) ratio, and pronounced thrombocytosis. Ni elicited changes in the albumin, glucose, cholesterol, and triglyceride serum levels in a concentration-dependent manner. Alterations of plasma protein fractions suggested liver functional impairment while high levels of urea and creatinine indicated potential kidney injury. Granulation of heterophiles and an increase in erythroblasts in the bone marrow showed that the hematopoietic tissue was also impacted by Ni toxicity. On average each quail bioaccumulated 5.87 μg of Ni per gram of tissue. Moreover, the distribution and bioaccumulation of Ni in terms of relative concentration were as follows: feathers > kidneys > heart > liver > pectoral muscles. Assessed bioaccumulation levels and associated cellular and metabolic alterations have revealed new multilayer toxicological data that will help in the extrapolation of Ni toxicity in other vertebrates, including humans.

Acute gallstone pancreatitis is a rare occurrence in pregnancy and the postpartum period. However, gallstone pancreatitis should be considered in a differential diagnosis for right upper quadrant (RUQ) pain in this population, as the risk of biliary stasis and gallstone formation increases in pregnancy due to high levels of circulating estrogen causing increased cholesterol formation and delayed gallbladder emptying. Although gallstones are the most common cause of acute pancreatitis in pregnancy, alcohol use and hypertriglyceridemia may also be considered. In this case report, we present a G1P0 female pregnant with monochorionic diamniotic twins who developed postpartum acute gallstone pancreatitis status post Cesarean section.

Long-term consumption of a high-fat diet (HFD) is an important factor that leads to impaired spermatogenesis exhibiting poor sperm quantity and quality. However, the mechanism of which is yet to be elucidated. Disrupted cholesterol homeostasis is one of many crucial pathological factors which contributed to impaired spermatogenesis. As a negative regulator of cholesterol metabolism, preprotein invertase subtilin 9 (PCSK9) mediates LDLR degradation to the lysosome, thereby reducing the expression of LDLR on the cell membrane and increasing serum LDL-C level, resulting in lipid metabolism disorders. Here, we aim to study whether PCSK9 is a pathological factor of impaired spermatogenesis induced by HFD and the underlying mechanism of which, to meet the purpose of our study, we utilized wild-type of C57/B6 male mice and PCSK9 knockout mice with same background as experimental subjects and alirocumab, a PCSK9 inhibitor, was used for treatment. Results indicated that HFD induced higher PCSK9 expression in serum, liver and testes, and serum PCSK9 is negatively correlated with spermatogenesis, while both PCSK9 inhibitor treatment and PCSK9 knockout methodologies ameliorated impaired lipid metabolism and spermatogenesis of mice fed with HFD, which could be due to the over-expression of PCSK9 induced by HFD led to dyslipidemia, resulting in testicular lipotoxicity, thus activating the Bcl-2-Bax-Caspase3 apoptosis signaling pathway in testes, particularly in Leydig cells. Our study demonstrates that PCSK9 is an important pathological factor in the dysfunction of spermatogenesis in mice induced by HFD, which provides innovative ideas for the diagnosis and treatment of male infertility.

The antioxidant effect of caffeine, associated with its ability to upregulate the nuclear factor-E2-related factor-2 (Nrf2)-signaling pathway, was explored as a possible mechanism for the attenuation of liver damage. Nonalcoholic steatohepatitis (NASH) was induced in rats by the administration of a high-fat, high-sucrose, high-cholesterol diet (HFSCD) for 15 weeks. Liver damage was induced in rats by intraperitoneal administration of thioacetamide (TAA) for six weeks. Caffeine was administered orally at a daily dose of 50 mg/kg body weight during the period of NASH induction to evaluate its ability to prevent disease development. Meanwhile, rats received TAA for three weeks, after which 50 mg/kg caffeine was administered daily for three weeks with TAA to evaluate its capacity to interfere with the progression of hepatic injury. HFSCD administration induced hepatic steatosis, decreased Nrf2 levels, increased oxidative stress, induced the activation of nuclear factor-κB (NF-κB), and elevated proinflammatory cytokine levels, leading to hepatic damage. TAA administration produced similar effects, excluding steatosis. Caffeine increased Nrf2 levels; attenuated oxidative stress markers, including malondialdehyde and 4-hydroxynonenal; restored normal, reduced glutathione levels; and reduced NF-κB activation, inflammatory cytokine levels, and damage. Our findings suggest that caffeine may be useful in the treatment of human liver diseases.

Genetic and environmental factors lead to the manifestation of Parkinson's disease (PD) but related mechanisms are only rudimentarily understood. Cytochromes P450 (P450s) are involved in the biotransformation of toxic compounds and in many physiological processes and thus predestinated to be involved in PD. However, so far only SNPs (single nucleotide polymorphisms) in CYP2D6 and CYP2E1 have been associated with the susceptibility of PD. Our aim was to evaluate the role of all 57 human P450s and their redox partners for the etiology and pathophysiology of PD and to identify novel potential players which may lead to the identification of new biomarkers and to a causative treatment of PD. The PPMI (Parkinson's Progression Markers Initiative) database was used to extract the gene sequences of all 57 P450s and their three redox partners to analyze the association of SNPs with the occurrence of PD. Applying statistical analyses of the data, corresponding odds ratios (OR) and confidence intervals (CI) were calculated. We identified SNPs significantly over-represented in patients with a genetic predisposition for PD (GPD patients) or in idiopathic PD (IPD patients) compared to HC (healthy controls). Xenobiotic-metabolizing P450s show a significant accumulation of SNPs in PD patients compared with HC supporting the role of toxic compounds in the pathogenesis of PD. Moreover, SNPs with high OR values (>5) in P450s catalyzing the degradation of cholesterol (CYP46A1, CY7B1, CYP39A1) indicate a prominent role of cholesterol metabolism in the brain for PD risk. Finally, P450s participating in the metabolism of eicosanoids show a strong over-representation of SNPs in PD patients underlining the effect of inflammation on the pathogenesis of PD. Also, the redox partners of P450 show SNPs with OR > 5 in PD patients. Taken together, we demonstrate that SNPs in 26 out of 57 P450s are at least 5-fold over-represented in PD patients suggesting these P450s as new potential players in the pathogenesis of PD. For the first time exceptionally high OR values (up to 12.9) were found. This will lead to deeper insight into the origin and development of PD and may be applied to develop novel strategies for a causative treatment of this disease.