Decreased Risk of Stroke in People Using Red Yeast Rice Prescriptions (LipoCol Forte®): a Total Population-Based Retrospective Cohort Study.

The influence of red yeast rice (RYR) on the risk of incident stroke remains underexplored. We aimed to compare the risk of stroke between people with and without use of RYR prescriptions. We used research data from the National Health Insurance Program in Taiwan and identified 34,723 adults (aged ≥20 years) who first received the RYR prescription from 2010 to 2014. To select the appropriate control group, we used frequency matching by age and sex (case-control ratio = 1 : 1) and identified a non-RYR cohort that included 34,723 adults who first received lovastatin. Events of an incident stroke that occurred during the follow-up period of 2010-2017 were identified from medical claims. The adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of stroke risk associated with RYR prescription were calculated in the multiple Cox proportional hazard model. Compared with the non-RYR cohort, patients who received RYR prescriptions had a decreased risk of stroke (HR 0.65, 95% CI 0.59-0.71), including hemorrhagic stroke (HR 0.60, 95% CI 0.44-0.83), ischemic stroke (HR 0.49, 95% CI 0.43-0.57), and other types of strokes (HR 0.53, 95% CI 0.42-0.67). The association between RYR prescription and stroke risk was significant in both sexes and in people aged more than 40 years, as well as in those individuals with various medical conditions. The frequency of RYR prescription (HR 0.57, 95% CI 0.50-0.64) was associated with a decreased risk of stroke with a dose-response relationship (p for trend<0.0001). This study showed a potentially positive effect of RYR on the risk of stroke. However, compliance with medication use should be cautioned. The findings of this study require future studies to validate the beneficial effects of RYR prescription on stroke risk.

Genistein Triggers Translocation of Estrogen Receptor-Alpha in Mitochondria to Induce Expressions of ATP Synthesis-Associated Genes and Improves Energy Production and Osteoblast Maturation.

Our previous study showed that estrogen can induce mitochondrial adenosine triphosphate (ATP) synthesis-associated gene expressions and osteoblast maturation. Genistein, a phytoestrogenic isoflavone that is widely found in various foods and traditional herb products, is beneficial for osteogenesis by selectively triggering estrogen receptor alpha (ER[Formula: see text] expression. In this study, we further investigated the mechanisms of genistein-induced energy production and osteoblast activation. Exposure of rat calvarial osteoblasts and human U-2 OS cells to genistein triggered osteoblast activation without affecting cell survival. Treatment with genistein time-dependently induced ER[Formula: see text] mRNA and protein expressions in rat calvarial osteoblasts. Analyses by confocal microscopy and immunoblotting showed that genistein stimulated translocation of ER[Formula: see text] from the cytoplasm to mitochondria. Subsequently, expressions of mitochondrial cytochrome c oxidase (COX) I and II mRNAs and proteins in primary rat osteoblasts were induced after exposure to genistein. Knocking-down ER[Formula: see text] concurrently inhibited genistein-induced COX I and II mRNA expressions. In addition, mitochondrial complex enzyme activities, the mitochondrial membrane potential, and cellular ATP levels in rat calvarial osteoblasts were time-dependently augmented by genistein. Suppressing ER[Formula: see text] expression instantaneously lowered genistein-induced enhancements of mitochondrial energy production and osteoblast activation. Effects of genistein on ER[Formula: see text] translocation, COX I and II mRNA expressions, ATP synthesis, and osteoblast activation were further confirmed in human U-2 OS cells. This study showed that genistein can stimulate energy production and consequent osteoblast activation via inducing ER[Formula: see text]-mediated mitochondrial ATP synthesis-linked gene expressions.

Adverse outcomes after major surgery in children with intellectual disability.

AIM: To evaluate outcomes after major surgery in children and adolescents with intellectual disability. METHOD: We used 2004 to 2013 claims data from Taiwan's National Health Insurance programme to conduct a nested cohort study, which included 220 292 surgical patients aged 6 to 17 years. A propensity score matching procedure was used to select 2173 children with intellectual disability and 21 730 children without intellectual disability for comparison. Logistic regression was used to calculate the adjusted odds ratios (ORs) and 95% confidence intervals (CIs) of the postoperative complications and 30-day mortality associated with intellectual disability. RESULTS: Children with intellectual disability had a higher risk of postoperative pneumonia (OR 2.16, 95% CI 1.48-3.15; p<0.001), sepsis (OR 1.67, 95% CI 1.28-2.18; p<0.001), and 30-day mortality (OR 2.04, 95% CI 1.05-3.93; p=0.013) compared with children without intellectual disability. Children with intellectual disability also had longer lengths of hospital stay (p<0.001) and higher medical expenditure (p<0.001) when compared with children with no intellectual disability. INTERPRETATION: Children with intellectual disability experienced more complications and higher 30-day mortality after surgery when compared with children without intellectual disability. There is an urgent need to revise the protocols for the perioperative care of this specific population. WHAT THIS PAPER ADDS: Surgical patients with intellectual disability are at increased risk of postoperative pneumonia, sepsis, and 30-day mortality. Intellectual disability is associated with higher medical expenditure and increased length of stay in hospital after surgical procedures. The influence of intellectual disability on postoperative outcomes is consistent in both sexes and those aged 10 to 17 years. Low income and a history of fractures significantly impacts postoperative adverse events for patients with intellectual disability.

Background luminance effects on pupil size associated with emotion and saccade preparation.

Pupil dilation is consistently evoked by affective and cognitive processing, and this dilation can result from sympathetic activation or parasympathetic inhibition. The relative contributions of the sympathetic and parasympathetic systems on the pupillary response induced by emotion and cognition may be different. Sympathetic and parasympathetic activity is regulated by global luminance level. Higher luminance levels lead to greater activation of the parasympathetic system while lower luminance levels lead to greater activation of the sympathetic system. To understand the contributions of the sympathetic and parasympathetic nervous systems to pupillary responses associated with emotion and saccade preparation, emotional auditory stimuli were presented following the fixation cue whose color indicated instruction to perform a pro- or anti-saccade while varying the background luminance level. Pupil dilation was evoked by emotional auditory stimuli and modulated by arousal level. More importantly, greater pupil dilation was observed with a dark background, compared to a bright background. In contrast, pupil dilation responses associated with saccade preparation were larger with the bright background than the dark background. Together, these results suggest that arousal-induced pupil dilation was mainly mediated by sympathetic activation, but pupil dilation related to saccade preparation was primarily mediated by parasympathetic inhibition.

Genistein Improves Bone Healing via Triggering Estrogen Receptor Alpha-Mediated Expressions of Osteogenesis-Associated Genes and Consequent Maturation of Osteoblasts.

Osteoporosis-associated fractures may cause higher morbidity and mortality. Our previous study showed the effects of genistein, a phytoestrogen, on the induction of estrogen receptor alpha (ERα) gene expression and stimulation of osteoblast mineralization. In this study, rat calvarial osteoblasts and an animal bone defect model were used to investigate the effects of genistein on bone healing. Treatment with genistein caused a time-dependent increase in alkaline phosphatase (ALP) activity in rat osteoblasts. Levels of cytosolic and nuclear ERα significantly augmented following exposure to genistein. Subsequently, genistein elevated levels of ALP mRNA and protein in rat osteoblasts. Moreover, genistein induced other osteogenesis-associated osteocalcin and Runx2 mRNA and protein expressions. Knocking-down ERα using RNA interference concurrently inhibited genistein-induced Runx2, osteocalcin, and ALP mRNA expression. Attractively, administration of ICR mice suffering bone defects with genistein caused significant increases in the callus width, chondrocyte proliferation, and ALP synthesis. Results of microcomputed tomography revealed that administration of genistein increased trabecular bone numbers and improved the bone thickness and volume. This study showed that genistein can improve bone healing via triggering ERα-mediated osteogenesis-associated gene expressions and subsequent osteoblast maturation.

Stroke risk and outcomes in epilepsy patients: Two retrospective cohort studies based on National Health Insurance in Taiwan.

BACKGROUND AND AIMS: The risk of stroke in epileptic patients and the impact of epilepsy history on stroke patients' outcome have not been studied completely. Our purpose is to evaluate whether patients with epilepsy have increased risk of stroke or post-stroke mortality. METHODS: In Study I, we conducted a retrospective cohort study of 6746 patients with newly diagnosed epilepsy and 26,984 persons without epilepsy between 2000 and 2008, in the database of National Health Insurance in Taiwan. The incidences and risks of stroke during the follow-up period were compared between cohorts until the end of 2013. In Study II, we conducted a nested cohort study of 484,990 hospitalized patients with newly diagnosed stroke between 2000 and 2009. We compared the short-term mortality and complications during stroke admission between stroke patients with previous epilepsy and those without epilepsy. RESULTS: The epileptic cohort had an increased stroke risk (hazard ratio [HR] 2.24, 95% CI 2.02 to 2.49). The relationship between epilepsy and stroke risk remains significant in every age group and both sexes. Among hospitalized stroke patients, history of epilepsy was associated with complications, including pneumonia (odds ratio [OR] 1.08, 95% CI 1.00 to 1.18), urinary tract infection (OR 1.16, 95% CI 1.08 to 1.26), and longer stay (p < 0.0001) during the index stroke admission. CONCLUSIONS: Epileptic patients face increased stroke risk and adverse outcomes of stroke admission. It is necessary to develop a prevention strategy for stroke in epileptic patients.

Ginseng is useful to enhance cardiac contractility in animals.

Ginseng has been shown to be effective on cardiac dysfunction. Recent evidence has highlighted the mediation of peroxisome proliferator-activated receptors (PPARs) in cardiac function. Thus, we are interested to investigate the role of PPARδ in ginseng-induced modification of cardiac contractility. The isolated hearts in Langendorff apparatus and hemodynamic analysis in catheterized rats were applied to measure the actions of ginseng ex vivo and in vivo. In normal rats, ginseng enhanced cardiac contractility and hemodynamic dP/dt(max) significantly. Both actions were diminished by GSK0660 at a dose enough to block PPARδ. However, ginseng failed to modify heart rate at the same dose, although it did produce a mild increase in blood pressure. Data of intracellular calcium level and Western blotting analysis showed that both the PPARδ expression and troponin I phosphorylation were raised by ginseng in neonatal rat cardiomyocyte. Thus, we suggest that ginseng could enhance cardiac contractility through increased PPARδ expression in cardiac cells.

Decreased risk of stroke in patients with traumatic brain injury receiving acupuncture treatment: a population-based retrospective cohort study.

BACKGROUND: Patients with traumatic brain injury (TBI) face increased risk of stroke. Whether acupuncture can help to protect TBI patients from stroke has not previously been studied. METHODS: Taiwan's National Health Insurance Research Database was used to conduct a retrospective cohort study of 7409 TBI patients receiving acupuncture treatment and 29,636 propensity-score-matched TBI patients without acupuncture treatment in 2000-2008 as controls. Both TBI cohorts were followed until the end of 2010 and adjusted for immortal time to measure the incidence and adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) of new-onset stroke in the multivariable Cox proportional hazard models. RESULTS: TBI patients with acupuncture treatment (4.9 per 1000 person-years) had a lower incidence of stroke compared with those without acupuncture treatment (7.5 per 1000 person-years), with a HR of 0.59 (95% CI = 0.50-0.69) after adjustment for sociodemographics, coexisting medical conditions and medications. The association between acupuncture treatment and stroke risk was investigated by sex and age group (20-44, 45-64, and ≥65 years). The probability curve with log-rank test showed that TBI patients receiving acupuncture treatment had a lower probability of stroke than those without acupuncture treatment during the follow-up period (p<0.0001). CONCLUSION: Patients with TBI receiving acupuncture treatment show decreased risk of stroke compared with those without acupuncture treatment. However, this study was limited by lack of information regarding lifestyles, biochemical profiles, TBI severity, and acupuncture points used in treatments.

Genistein induces oestrogen receptor-α gene expression in osteoblasts through the activation of mitogen-activated protein kinases/NF-κB/activator protein-1 and promotes cell mineralisation.

Oestrogen and oestrogen receptors (ER) play critical roles in the maintenance of bone remodelling. Genistein, structurally similar to 17ß-oestradiol, is a phyto-oestrogen that may be beneficial for treating osteoporosis. In the present study, we evaluated the effects of genistein on the regulation of ERα gene expression and osteoblast mineralisation using MC3T3-E1 cells and primary rat calvarial osteoblasts as our experimental models. Exposure of MC3T3-E1 cells and primary rat osteoblasts to genistein at ≤ 10 µm for 24 h did not affect the cell morphology or viability. However, treatment of MC3T3-E1 cells with 10 µm-genistein enhanced the phosphorylation of extracellular signal-regulated kinase 1/2, p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase 1/2 in a time-dependent manner. Sequentially, genistein increased the translocation of NF-κB and c-Jun from the cytoplasm to the nucleus. Consequently, exposure of MC3T3-E1 cells to genistein induced ERα mRNA expression in concentration- and time-dependent manners. In parallel, the amounts of cytosolic and nuclear ERα in MC3T3-E1 cells were increased following genistein administration. Additionally, genistein also increased the levels of ERα mRNA and nuclear ERα protein in rat calvarial osteoblasts. A bioinformatic search revealed that there are several ERα-specific DNA-binding elements in the 5'-promoter regions of the bone morphogenetic protein-6, collagen type I and osteocalcin genes. As a result, genistein could induce the expressions of these osteoblast differentiation-related genes in primary rat osteoblasts. Co-treatment with genistein and traditional differentiation reagents synergistically increased osteoblast mineralisation. Therefore, the present study showed that genistein can induce ERα gene expression via the activation of MAPK/NF-κB/activator protein-1 and accordingly stimulates differentiation-related gene expressions and osteoblast mineralisation.