Ergosta-7, 9 (11), 22-trien-3ß-ol Interferes with LPS Docking to LBP, CD14, and TLR4/MD-2 Co-Receptors to Attenuate the NF-κB Inflammatory Pathway In Vitro and Drosophila.

Ergosta-7, 9 (11), 22-trien-3ß-ol (EK100) was isolated from Cordyceps militaris, which has been used as a traditional anti-inflammatory medicine. EK100 has been reported to attenuate inflammatory diseases, but its anti-inflammatory mechanism is still unclear. We were the first to investigate the effect of EK100 on the Toll-like receptor 4 (TLR4)/nuclear factor of the κ light chain enhancer of B cells (NF-κB) signaling in the lipopolysaccharide (LPS)-stimulated RAW264.7 cells and the green fluorescent protein (GFP)-labeled NF-κB reporter gene of Drosophila. EK100 suppressed the release of the cytokine and attenuated the mRNA and protein expression of pro-inflammatory mediators. EK100 inhibited the inhibitor kappa B (IκB)/NF-κB signaling pathway. EK100 also inhibited phosphatidylinositol-3-kinase (PI3K)/Protein kinase B (Akt) signal transduction. Moreover, EK100 interfered with LPS docking to the LPS-binding protein (LBP), transferred to the cluster of differentiation 14 (CD14), and bonded to TLR4/myeloid differentiation-2 (MD-2) co-receptors. Compared with the TLR4 antagonist, resatorvid (CLI-095), and dexamethasone (Dexa), EK100 suppressed the TLR4/AKT signaling pathway. In addition, we also confirmed that EK100 attenuated the GFP-labeled NF-κB reporter gene expression in Drosophila. In summary, EK100 might alter LPS docking to LBP, CD14, and TLR4/MD-2 co-receptors, and then it suppresses the TLR4/NF-κB inflammatory pathway in LPS-stimulated RAW264.7 cells and Drosophila.

Women With Osteoarthritis Are at Increased Risk of Ischemic Stroke: A Population-Based Cohort Study.

BACKGROUND: Osteoarthritis (OA) is more prevalent in women with age. Comorbidities are prevalent in OA patients. In this study, we conducted a follow-up study to evaluate whether women with OA are at an increased risk of ischemic stroke using insurance claims data of Taiwan. METHODS: We identified 13,520 women with OA aged 20-99 newly diagnosed in 2000-2006 and 27,033 women without OA for comparison, frequency matched by age and diagnosis date. Women with baseline history of hypertension and other disorders associated with stroke were excluded for this study. Incident ischemic stroke was assessed by the end of 2013. A nested case-control analysis was used to identify factors associated with the stroke in the OA cohort. RESULTS: The incidence rate of ischemic stroke in the OA cohort was 1.5-fold greater than that in comparisons (1.93 versus 1.26 per 1,000 person-years), with an adjusted hazard ratio of 1.34 (95% confidence interval [CI], 1.09-1.66). The nested case-control analysis showed that stroke cases were twice as likely to develop hypertension during the follow-up period than controls without stroke. The ischemic stroke risk was significantly associated with hypertension (odds ratio [OR] 1.84; 95% CI, 1.37-2.46) and atrial fibrillation (OR 2.25; 95% CI, 1.24-4.09). Ischemic stroke was not associated with the use of non-steroidal anti-inflammatory drugs or aspirin. CONCLUSION: Women with OA are at an elevated risk of ischemic stroke. A close monitoring of hypertension, atrial fibrillation, and other stroke related comorbidities is required for stroke prevention for OA patients.

Prevalence and Associated Factors of Visual Hallucinations in Patients with Vascular Cognitive Impairment.

Visual hallucinations (VHs) are striking features for dementia, especially dementia with Lewy bodies (DLB). We aimed to study the frequency and associated factors of VH in vascular cognitive impairment (VCI) and investigate the feasibility of clinically diagnosing the mixed pathology of VCI with DLB. This is a multicentre registration study. A consecutive series of VCI patients with and without dementia were enrolled. Frequency of VH and associated factors, including age, gender, education, disease severity, DLB clinical features, vascular risk factors, cognitive function, and neuropsychiatric symptoms, were compared between VCI with VH (VH+) and without VH (VH-). Among the 1281 patients analysed, 155 (12.1%) had VH. The VH+ group was older (t = 5.07; p < 0.001), was more likely to be female (χ 2 = 13.46; p < 0.001), and has a higher clinical dementia rating (χ 2 = 70.51; p < 0.001). After adjusting for age, gender, and disease severity, the VH+ group had poorer cognition and more severe neuropsychiatric symptoms. The VH+ group was more associated with DLB features in fluctuating cognition (OR = 2.48; p < 0.001), parkinsonism (OR = 1.85; p = 0.001), rapid eye movement (REM) behavioral disorder (OR = 4.56; p < 0.001), and ≧2 DLB core features (OR = 26.01; p < 0.001). VCI patients with VH tend to have more severe dementia, neuropsychiatric symptoms, and poorer cognitive function. Additionally, highly associated with clinical DLB features in VCI with VH raised the possibility of mixed pathology with DLB in this group. More than two core features in VCI might help in diagnosing a mixed pathology with DLB.

Higher stroke incidence in the patients with pancreatic cancer: A nation-based cohort study in Taiwan.

No study has investigated the role of pancreatic cancer in the stroke risk using population data. We used claims data obtained from a universal health insurance program of Taiwan to evaluate the stroke risk in pancreatic cancer patients.From the catastrophic disease registry of the insurance, we identified 7479 patients with pancreatic malignancy without stroke history from 2000 to 2009. The comparison cohort consisted of 29,916 individuals identified from 1 million insured people without cancer and stroke history, matching with the cancer cohort by propensity score. We followed each selected individual until stroke was diagnosed or until being censored for death or withdrawal from insurance, or for a maximum of 3 follow-up years, or the end of 2011.The pancreatic cancer cohort had a 2.3-fold greater incident stroke than comparisons had (28.5 vs 12.3 per 1000 person-years), with an adjusted hazard ratio (aHR) of 2.74 (95% confidence interval (CI) = 2.31-3.24) after controlling for covariates, or a subdistribution hazard ratio (SHR) of 2.04 (95% CI = 1.74-2.40) accounting for the competing risk of deaths. During the follow-up period, stroke events occurred constantly in comparisons, but declined rapidly in the cancer cohort. The pancreatic cancer cohort had a stroke incidence of 46.6 per 1000 person-years within 6 months postdiagnosis, with an aHR of 4.37 (95% CI = 3.45-5.54) and a SHR of 3.87 (95% CI = 3.08-4.86), relative to comparisons.Our study suggests that patients with pancreatic cancer are at an elevated risk of stroke, patients deserve sufficient follow-up care, particularly in the first 6 months after the diagnosis of the cancer, and for those with comorbidities.

Visual hallucinations in Alzheimer's disease is significantly associated with clinical diagnostic features of dementia with Lewy bodies.

Visual hallucinations (VHs) are among the most striking features of dementia with Lewy bodies (DLB). Given that Lewy body pathology is frequently observed in the brains of patients with AD, we aimed to study factors associated with VHs in AD and examine their association with DLB features. This cross-sectional study enrolled a consecutive series of AD patients who visited the dementia clinic of a regional hospital. Clinically diagnosed possible or probable DLB cases were excluded. VH frequency and associated factors including age, sex, education, disease severity, DLB features, vascular risk factors, cognitive function, and neuropsychiatric symptoms were compared between AD patients with VHs (VH+) and those without VHs (VH-). Among a total of 295 patients analyzed, 42 (14.2%) had VHs. After adjusting for age, sex, and disease severity, DLB features including fluctuations in cognition scores, rapid-eye-movement behavioral disorder (RBD), and severe neuroleptic sensitivity were more frequent in the VH+ group. Furthermore, depression score, total Neuropsychiatric Inventory (NPI) score, and total caregiver burden score as assessed by the NPI were higher in the VH+ group. Among neuropsychiatric symptoms, delusions, hallucinations in the non-visual domains, anxiety, and disinhibition were more frequent in the VH+ group. Conversely, none of the vascular risk factors (VRFs) or cognitive domains of the Cognitive Abilities Screening Instrument (CASI) was associated with VHs in AD. In summary, VHs, albeit occurring at a low rate, had a high impact on AD. Diagnostic features of DLB, including fluctuations, RBD, and severe neuroleptic sensitivity were significantly associated with VHs in AD. AD patients with VHs tended to have more severe neuropsychiatric symptoms and greater caregiver burden.

Increased risk of stroke in contact dermatitis patients: A nationwide population-based retrospective cohort study.

Dermatologic diseases are not traditional risk factors of stroke, but recent studies show atopic dermatitis, psoriasis, and bullous skin disease may increase the risk of stroke and other cardiovascular diseases. No previous studies have focused on the association between contact dermatitis and stroke.We established a cohort comprised of 48,169 contact dermatitis patients newly diagnosed in 2000-2003 and 96,338 randomly selected subjects without the disorder, frequency matched by sex, age, and diagnosis year, as the comparison cohort. None of them had a history of stroke. Stroke incidence was assessed by the end of 2011 for both cohorts.The incidence stroke was 1.1-fold higher in the contact dermatitis cohort than in the comparison cohort (5.93 vs 5.37 per 1000 person-years, P < 0.01). The multivariable Cox method analyzed adjusted hazard ratios (aHRs) were 1.12 (95% confidence interval [CI], 1.05-1.19) for all stroke types and 1.12 (95% CI, 1.05-1.20) for ischemic stroke and 1.11 (95% CI, 0.94-1.30) for hemorrhagic stroke. The age-specific aHR of stroke for contact dermatitis cohort increased with age, from 1.14 (95% CI, 1.03-1.27) for 65 to 74 years; to 1.27 (95% CI, 1.15-1.42) for 75 years and older. The aHR of stroke were 1.16 (95% CI, 1.07-1.27) and 1.09 (95% CI, 1.00-1.18) for men and women, respectively.This study suggests that patients with contact dermatitis were at a modestly increased risk of stroke, significant for ischemic stroke but not for hemorrhagic stroke. Comorbidity, particularly hypertension, increased the hazard of stroke further.

Chronic Influences of Obstructive Sleep Apnea on Cerebral Venous Flow.

OBJECTIVES: Evidence reveals a pathophysiologic link between sleep apnea syndrome and cerebrovascular diseases. It is known that obstructive sleep apnea (OSA) may cause serial hemodynamic changes and structural abnormalities in the cerebral and cardiac arterial systems, but its effect on the cerebral venous system has remained unclear. The purpose of this study was to compare internal jugular vein hemodynamics between patients with OSA and healthy individuals. METHODS: Patients with OSA and age-, body mass index-, and sex-matched healthy control participants were recruited for a jugular venous duplex study and neurologic examination. The luminal area of the internal jugular vein, jugular venous flow volume, time-averaged mean velocity, and presence of jugular venous reflux were recorded. These flow characteristics were obtained at different respiratory statuses, and we analyzed the differences between patients and controls. RESULTS: In the OSA group, there was an increasing flow volume in total internal jugular veins at rest. The frequency of venous reflux in patients compared with controls was significantly decreased (26.7% versus 53.3%, respectively; P < .05). The internal jugular vein drainage dominance was greater on the left side in the OSA group (right versus left: 48.8% versus 51.2%), whereas it was greater on the right side in the control group (right versus left: 61.7% versus 38.3%). CONCLUSIONS: Our data showed peculiar internal jugular vein hemodynamics at baseline and different respiratory statuses in patients with OSA. These characteristics imply that cerebral venous drainage conditions might be involved in the pathophysiologic mechanisms of OSA syndrome.

Neuropsychological functions in patients with bipolar I and bipolar II disorder.

UNLABELLED: The literature reports persistent cognitive impairments in patients with bipolar disorder even after prolonged remission. However, a majority of studies have focused only on bipolar I disorder (BP-I), primarily because bipolar II disorder (BP-II) is often underdiagnosed or misdiagnosed. More attention should be paid to the differences between BP-I and BP-II, especially the aspects of neuropsychological functioning. We examined the different neuropsychological functions in BP-I and BP-II patients and compared them with those of healthy controls. METHODS: The study included 67 patients with interepisode bipolar disorder (BP-I: n = 30; BP-II: n = 37) and 22 healthy controls compared using a battery of neuropsychological tests that assessed memory, psychomotor speed, and certain aspects of frontal executive function. RESULTS: The BP-I group performed poorly on verbal memory, psychomotor speed, and executive function compared to the BP-II and control groups. Both bipolar groups performed significantly less well than the control group on measures of working memory and psychomotor speed, while the BP-II group showed an intermediate level of performance in psychomotor speed compared to the BP-I and control groups. There was no difference between the groups on visual memory. CONCLUSIONS: BP-I was characterized by reduced performance in verbal memory, working memory, psychomotor speed, and executive function, while BP-II patients showed a reduction only in working memory and psychomotor speed. Cognitive impairment existed in both subtypes of bipolar disorder, and was greater in BP-I patients. Rehabilitation interventions should take into account potential cognitive differences between these bipolar subtypes.