Up-regulation of hepatic acyl CoA oxidase and cytochrome P-450 4A1 genes and PPARα activation by dietary oxidized frying oil in rats

[[abstract]]Abstract We previously demonstrated that oxidized frying oil (OFO) activates peroxisome proliferator-activated receptor α (PPARα) and up-regulates hepatic acyl-CoA oxidase (ACO) and cytochrome P450 4A1 (CYP4A1) genes in male rats. As female rats were shown to be less responsive to some peroxisome proliferators (PP), this study compared the expression of a few PPARα target genes in male and female rats fed diets containing OFO. Male and female rats were fed a diet containing 20 g/100 g OFO (O diet) or fresh soybean oil (F diet) for 6 wk. Both male and female rats fed the O diet showed significantly higher liver weight, hepatic ACO and catalase activities, CYP4A protein, and expression of ACO and CYP4A1 mRNA (P<0.05) compared with their control groups. The mRNA expression of two other PPARα target genes, FA-binding protein and HMG-CoA synthase, were marginally increased by dietary OFO (P=0.0669 and 0,0521, respectively). Female rats fed the O diet had significantly lower CYP4A protein than male rats fed the same diet. The remaining OFO-induced effects were not significantly different between male and female rats fed the O diet. These results indicate that dietary OFO, unlike clofibrate or other PP, had minimal sexual dimorphic effect on the induction of hepatic PPARα target gene expressio

Positive outcome expectancy mediates the relationship between social influence and Internet addiction among senior high-school students

Background and aims Based on the foundations of Bandura’s social cognitive theory and theory of triadic influence (TTI) theoretical framework, this study was designed to examine the mediating role of positive outcome expectancy of Internet use in the relationship between social influence and Internet addiction (IA) in a large representative sample of senior high-school students in Taiwan. Methods Using a cross-sectional design, 1,922 participants were recruited from senior high schools throughout Taiwan using both stratified and cluster sampling, and a comprehensive survey was administered. Results Structural equation modeling and bootstrap analyses results showed that IA severity was significantly and positively predicted by social influence, and fully mediated through positive outcome expectancy of Internet use. Discussion and conclusions The results not only support Bandura’s social cognitive theory and TTI framework, but can also serve as a reference to help educational agencies and mental health organizations design programs and create policies that will help in the prevention of IA among adolescents

Bcl-2 expression predicts sensitivity to chemotherapy in breast cancer: a systematic review and meta-analysis

BACKGROUND: Numerous studies have yielded inconclusive results regarding the relationship between anti-apoptotic protein Bcl-2 expression and the sensitivity to chemotherapy in the patients with breast cancer. The purpose of the current study was therefore to elaborate their relationship. METHODS, FINDINGS: A total of 23 previously published eligible studies involving 2,467 cases were identified and included in this meta-analysis. Negative Bcl-2 expression was associated with good chemotherapy response in breast cancer patients (total objective response [OR]: risk ratio [RR] = 1.16, 95% confidence interval [CI] = 1.02-1.32, p = 0.026; total complete response [CR]: RR = 1.67, 95% CI = 1.24-2.24, p = 0.001; pathological CR: RR = 1.92, 95% CI = 1.38-2.69, p < 0.001). In further stratified analyses, this association remained for sub-groups of response in neoadjuvant chemotherapy setting, especially pathological CR. Besides, negative Bcl-2 expression was significantly associated with good OR and pathological CR in anthracycline-based chemotherapy subgroup. Furthermore, there were significant links between negative Bcl-2 expression and taxane-based chemotherapy with pathological CR, but not OR. CONCLUSION: The results of the present meta-analysis suggest that Bcl-2 expression is a predictive factor for chemotherapy sensitivity in breast cancer patients. They could also potentially benefit further clinical treatment for breast cancers

Effects of thyroid dysfunction on the severity of coronary artery lesions and its prognosis

AbstractBackgroundAbnormal thyroid hormone metabolism influences the occurrence and progress of coronary heart disease (CHD). The aim of the present study was to analyze the severity of coronary artery lesions and the prognosis of thyroid dysfunction patients admitted for coronary angiography (CAG).MethodsFrom July 2011 to July 2012, 605 consecutive patients with suspected coronary heart disease admitted for CAG were selected. The patients were divided into three groups, based on their thyroid function prior to CAG: euthyroid group (n=455 patients), low T3 syndrome group (n=96 patients), and hypothyroidism group (n=54 patients). All patients underwent CAG. Then the severity of coronary artery lesions was assessed by Gensini scores. All patients were followed up for major adverse cardiac events.ResultsThe prevalence of CHD in low T3 syndrome group and hypothyroidism group was significantly higher than that in the euthyroid group (p<0.001 and p=0.004, respectively). Moreover, the severity of coronary artery lesions in low T3 syndrome group and hypothyroidism group was significantly greater than that in the euthyroid group (all p<0.001). Multinomial logistic regression analysis demonstrated that low T3 syndrome was an independent risk factor of coronary artery moderate [odds ratio (OR)=4.268, 95% CI: 3.294–7.450, p=0.016] and severe (OR=4.294, 95% CI: 2.259–9.703, p<0.001) lesions. The mean duration of follow-up was 15.3±3.8 months; patients with thyroid dysfunction had a significantly worse prognosis as compared to those in the euthyroid group for the composite end-point (p<0.01). Moreover, the incidence of the composite end-point (all-cause death, non-fatal myocardial infarction, and coronary revascularization) was significantly higher in low T3 syndrome group and hypothyroidism group compared with that of in the euthyroid group (all p<0.001).ConclusionsThe patients with hypothyroidism and low T3 syndrome had a high prevalence of CHD, increased severity of coronary artery lesions and poor prognosis

Temporal and Spatial Variations in spatial variations in symbiont communities of catch bowl coral Isopora palifera (Scleractinia: Acroporidae) on reefs in Kenting National Park, Taiwan

Acclimatization through Symbiodinium shuffling is one of potential mechanisms in reef-building corals to survive environmental stress. In our previous study, the catch bowl coral Isopora palifera in Tantzei Bay (TZB), Nanwan, Kenting National Park (KNP), southern Taiwan was demonstrated to shuffle thermal-tolerant Symbiodinium D1a and thermal-sensitive Symbiodinium C3 in response to seasonal variations in sea surface temperatures (SSTs) in 2000 and 2001. In this study, we reexamined the temporal dynamics of the Symbiodinium community of I. palifera in TZB in 2006-2009. In addition, spatial variations in Symbiodinium communities in I. palifera were also examined at 6 other sites of Nanwan, KNP in 2009, including a site located at a nuclear power plant outlet (NPP-OL) in southern Taiwan with a yearly mean SST 0.6-1.5 degrees C higher compared to the other sites. Phylotyping and DNA sequence analyses of Symbiodinium ribosomal 28S and ITS2 markers showed that I. palifera colonies at TZB continued to show seasonal shuffling, but shifted to thermal-sensitive type C3 dominant in 2006-2009. This differed from the symbiont community originally dominated by the thermal-tolerant Symbiodinium D1a in 2000 and 2001 after the 1998 mass-bleaching event. Significant differences in spatial variations of the symbiont community in Nanwan were detected with I. palifera colonies at the NPP-OL dominated by Symbiodinium D1a. Our study results suggest that I. palifera can acclimatize to SST anomalies by shuffling to thermal-tolerant Symbiodinium D1a and can revert to thermal-sensitive C3 when the stress disappears, but will maintain the thermally tolerant Symbiodinium D1a as the dominant symbiont if the heat stress continues

A pathogenic UFSP2 variant in an autosomal recessive form of pediatric neurodevelopmental anomalies and epilepsy

Purpose: Neurodevelopmental disabilities are common and genetically heterogeneous. We identified a homozygous variant in the gene encoding UFM1-specific peptidase 2 (UFSP2), which participates in the UFMylation pathway of protein modification. UFSP2 variants are implicated in autosomal dominant skeletal dysplasias, but not neurodevelopmental disorders. Homozygosity for the variant occurred in eight children from four South Asian families with neurodevelopmental delay and epilepsy. We describe the clinical consequences of this variant and its effect on UFMylation.Methods: Exome sequencing was used to detect potentially pathogenic variants and identify shared regions of homozygosity. Immunoblotting assessed protein expression and post-translational modifications in patient-derived fibroblasts.Results: The variant (c.344T\u3eA; p.V115E) is rare and alters a conserved residue in UFSP2. Immunoblotting in patient-derived fibroblasts revealed reduced UFSP2 abundance and increased abundance of UFMylated targets, indicating the variant may impair de-UFMylation rather than UFMylation. Reconstituting patient-derived fibroblasts with wild-type UFSP2 reduced UFMylation marks. Analysis of UFSP2\u27s structure indicated that variants observed in skeletal disorders localize to the catalytic domain, whereas V115 resides in an N-terminal domain possibly involved in substrate binding.Conclusion: Different UFSP2 variants cause markedly different diseases, with homozygosity for V115E causing a severe syndrome of neurodevelopmental disability and epilepsy

A model for predicting physical function upon discharge of hospitalized older adults in Taiwan—a machine learning approach based on both electronic health records and comprehensive geriatric assessment

BackgroundPredicting physical function upon discharge among hospitalized older adults is important. This study has aimed to develop a prediction model of physical function upon discharge through use of a machine learning algorithm using electronic health records (EHRs) and comprehensive geriatrics assessments (CGAs) among hospitalized older adults in Taiwan.MethodsData was retrieved from the clinical database of a tertiary medical center in central Taiwan. Older adults admitted to the acute geriatric unit during the period from January 2012 to December 2018 were included for analysis, while those with missing data were excluded. From data of the EHRs and CGAs, a total of 52 clinical features were input for model building. We used 3 different machine learning algorithms, XGBoost, random forest and logistic regression.ResultsIn total, 1,755 older adults were included in final analysis, with a mean age of 80.68 years. For linear models on physical function upon discharge, the accuracy of prediction was 87% for XGBoost, 85% for random forest, and 32% for logistic regression. For classification models on physical function upon discharge, the accuracy for random forest, logistic regression and XGBoost were 94, 92 and 92%, respectively. The auROC reached 98% for XGBoost and random forest, while logistic regression had an auROC of 97%. The top 3 features of importance were activity of daily living (ADL) at baseline, ADL during admission, and mini nutritional status (MNA) during admission.ConclusionThe results showed that physical function upon discharge among hospitalized older adults can be predicted accurately during admission through use of a machine learning model with data taken from EHRs and CGAs

Preoperative Proteinuria Is Associated with Long-Term Progression to Chronic Dialysis and Mortality after Coronary Artery Bypass Grafting Surgery

AIMS: Preoperative proteinuria is associated with post-operative acute kidney injury (AKI), but whether it is also associated with increased long-term mortality and end-stage renal disease (ESRD) is unknown. METHODS AND RESULTS: We studied 925 consecutive patients undergoing CABG. Demographic and clinical data were collected prospectively, and patients were followed for a median of 4.71 years after surgery. Proteinuria, according to dipstick tests, was defined as mild (trace to 1+) or heavy (2+ to 4+) according to the results of the dipstick test. A total of 276 (29.8%) patients had mild proteinuria before surgery and 119 (12.9%) patients had heavy proteinuria. During the follow-up, the Cox proportional hazards model demonstrated that heavy proteinuria (hazard ratio [HR], 27.17) was an independent predictor of long-term ESRD. There was a progressive increased risk for mild proteinuria ([HR], 1.88) and heavy proteinuria ([HR], 2.28) to predict all-cause mortality compared to no proteinuria. Mild ([HR], 2.57) and heavy proteinuria ([HR], 2.70) exhibited a stepwise increased ratio compared to patients without proteinuria for long-term composite catastrophic outcomes (mortality and ESRD), which were independent of the baseline GFR and postoperative acute kidney injury (AKI). CONCLUSION: Our study demonstrated that proteinuria is a powerful independent risk factor of long-term all-cause mortality and ESRD after CABG in addition to preoperative GFR and postoperative AKI. Our study demonstrated that proteinuria should be integrated into clinical risk prediction models for long-term outcomes after CABG. These results provide a high priority for future renal protective strategies and methods for post-operative CABG patients