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Background: Differences exist regarding post-stroke cognitive outcomes. Objective: The aim of this study investigates the potential factors associated with post-stroke cognitive performance and trajectories. Methods: We performed a prospective cohort study using serial monitoring of cognitive function over a 1-year period after a first-ever ischemic stroke. Small vessel disease (SVD) burden and hippocampal atrophy (HA) were evaluated using the modified cerebral small vessel disease scores (mCSVD) and medial temporal atrophy score (MTA) scores. A generalized estimating equation (GEE) model and a group-based trajectory model (GBTM) was used to analyze the potential factors associated with post-stroke cognitive outcomes. Results: A total of 112 patients were enrolled. The GEE model showed that all patients, regardless of initial cognitive performance, had a tendency to show an increase in the Montreal Cognitive Assessment over time. The cognitive performance was better in male patients with higher education levels (p = 0.046 and p

Background Fear of falling (FOF) is a common and major health concern in older adults. The consequences of FOF include reduced physical performance, social activity, and health-related quality of life. Ramsay Hunt syndrome (RHS) is a herpes zoster-related facial nerve dysfunction accompanied by an erythematous vesicular rash on the ear or mouth that may complicate ipsilateral facial paralysis and otalgia, vertigo, tinnitus, hearing loss, and meningoencephalitis. However, repeated falls and subsequent FOF due to RHS have not been reported in older adults. Case presentation A 65-year-old woman diagnosed with RHS experienced repeated falls during hospital admission and after discharge. Despite recovery of balance and no subsequent falls, the patient presented with persistent FOF at the geriatric outpatient follow-up visit 1 year after the RHS episode. The fear sensation impaired the patient’s instrumental daily activities and was confirmed by documentation of serial comprehensive geriatric assessments, especially the Timed Up and Go test scores. Conclusions RHS may cause repeated falls and FOF, leading to impairment in daily activities and psychosocial function in older adults. Therefore, clinicians should be mindful of falls and FOF when caring for older patients with RHS and should develop multidimensional strategies for fall prevention and FOF.

The zinc-finger protein which regulates apoptosis and cell cycle arrest 1 (Zac1), encoded by Plagl1 gene, is a seven-zinc-finger containing transcription factor belonging to the imprinted genome and is expressed in diverse types of embryonic and adult human tissues. Zac1 is postulated to be a tumor suppressor by inducing cell cycle arrest and apoptosis through interacting and modulating transcriptional activity of p53 as it was named. Correspondingly, the reduction or loss of Zac1 expression is associated with the incidence and progression of several human tumors, including cervical cancer, breast cancer, ovarian cancer, pituitary tumors, and basal cell carcinoma, implying the rationality of utilizing Zac1 expression as novel a biomarker for the evaluation of cervical cancer prognosis. However, to date, it has not been elucidated whether Zac1 expression is related to the prognosis of patients in clinical cervical cancer tumor samples. To address the questions outlined above, we report here a comprehensive investigation of Zac1 expression in biopsies of clinical cervical carcinoma. By analyzing Zac1 expression in various gene expression profiling of cervical cancer databases, we show the association between high Zac1 expression and poor prognosis of cervical cancer. Functional enrichment analysis showed that high Zac1 expression was associated with epithelial-mesenchymal transition (EMT), which was further observed in clinical characteristics and metastatic carcinoma samples using immunohistochemical staining. Correspondingly, hypomethylation of CpG island on Zac1 promoter was observed in samples with high Zac1 expression in cervical carcinoma. Finally, overexpression of Zac1 in a variety of cervical cancer cell lines increase their mesenchymal biomarker expression and migration, strengthening the correlation between cervical cancers with high Zac1 expression and metastasis in clinical. In summary, this research firstly revealed that identifying Zac1 expression or the methylation status of CpG site on Zac1 promoter may provide us with novel indicators for the evaluation of cervical cancer metastasis.

Vocal fold nodules (VFNs) are the most frequent cause of hoarseness. The management comprised medical, surgical and physical therapy but the effectiveness is not always satisfactory. In this study, we try to figure out an alternative treatment from our clinical experience summary. We retrospectively reviewed VFNs patients who received traditional Chinese medicine (TCM) treatments from July 2018 to August 2020 and traced their Chinese Voice Handicap Index-10 (VHI-C10) and multidimensional voice program (MDVP) analysis results. For further evaluation, we conducted an inflammatory response of porcine vocal fold epithelial (PVFE) cells with 50 ng/mL TNF-alpha. The inflamed PVFE cells were separately cultured in the aqueous extract of Glycyrrhiza glabra (

Background: Hypomimia is a clinical feature of Parkinson’s disease (PD). Based on the embodied simulation theory, the impairment of facial mimicry may worsen facial emotion recognition; however, the empirical results are inconclusive. Objective: We aimed to explore the worsening of emotion recognition by hypomimia. We further explored the relationship between the hypomimia, emotion recognition, and social functioning. Methods: A total of 114 participants were recruited. The patients with PD and normal controls (NCs) were matched for demographic characteristics. All the participants completed the Mini-Mental State Examination and the Chinese Multi-modalities Emotion Recognition Test. In addition to the above tests, the patients were assessed with the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale and Parkinson’s Disease Social Functioning Scale (PDSFS). Results: Patients with PD with hypomimia had worse recognition of disgust than NCs (p = 0.018). The severity of hypomimia was predictive of the recognition of disgust (β= –0.275, p = 0.028). Facial emotion recognition was predictive of the PDSFS score of PD patients (β= 0.433, p = 0.001). We also found that recognizing disgust could mediate the relationship between hypomimia and the PDSFS score (β= 0.264, p = 0.045). Conclusion: Patients with hypomimia had the worst disgust facial recognition. Hypomimia may affect the social function of PD patients, which is related to recognizing the expression of disgust. Emotion recognition training may improve the social function of patients with PD.

OBJECTIVES Whether early medication reconciliation and integration can reduce polypharmacy and potentially inappropriate medication (PIM) in the emergency department (ED) remains unclear. Polypharmacy and PIM have been recognized as significant causes of adverse drug events in older adults. Therefore, this pilot study was conducted to delineate this issue. DESIGN An interventional study. SETTING A medical center in Taiwan. PARTICIPANTS Older ED patients (aged ≥65 years) awaiting hospitalization between December 1, 2017, and October 31, 2018 were recruited in this study. A multidisciplinary team and a computer-based and pharmacist-assisted medication reconciliation and integration system were implemented. MEASUREMENTS The reduced proportions of major polypharmacy (≥10 medications) and PIM at hospital discharge were compared with those on admission to the ED between pre- and post-intervention periods. RESULTS A total of 911 patients (pre-intervention = 243 vs post-intervention = 668) were recruited. The proportions of major polypharmacy and PIM were lower in the post-intervention than in the pre-intervention period (-79.4% vs -65.3%; P

Venous thromboembolism (VTE) is associated with a high risk of morbidity and mortality. However, data on the association between oral anticoagulants and the hazards of VTE complications in Taiwanese patients with VTE is limited. This study aimed to compare the hazards of recurrent VTE, bleeding, and mortality between patients with VTE receiving rivaroxaban, a non-vitamin K antagonist oral anticoagulant (NOAC), and those receiving heparin or low-molecular-weight heparin (LMWH) followed by warfarin. Patients with VTE treated with rivaroxaban, or heparin or LMWH followed by warfarin were enrolled from 2 million random samples from Taiwan's National Health Insurance database between 2013 and 2016. Hazards of recurrent VTE (deep vein thrombosis and pulmonary embolism), major bleeding, and mortality in rivaroxaban and warfarin users were investigated. Survival analyses were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Users of rivaroxaban (183) and warfarin (456) were included in the study. Patients receiving rivaroxaban did not have significantly lower hazards of developing recurrent VTE (HR, 0.72 [CI, 0.37-1.37], P = .31) and mortality (HR, 0.86 [CI, 0.49-1.50], P = .59) than those receiving heparin or LMWH followed by warfarin. In addition, the hazard ratio of major bleeding was not significantly different between the 2 regimens (HR, 1.80 [CI, 0.39-8.29], P = .45). Rivaroxaban was not associated with lower risks of recurrent VTE and mortality and higher hazards of major bleeding than heparin or LMWH followed by warfarin in Taiwanese patients with VTE. Clinicians may tailor oral anticoagulants for VTE patients according to the patient's characteristics, cost-effectiveness and healthcare system policy.

The aim of this study was to use a network meta-analysis (NWA) to evaluate the relative efficacy and safety of various neuraminidase inhibitors (NAIs) in reducing the duration of influenza symptoms, and thereby, informing the selection of suitable therapeutic regimens for patients with influenza. We conducted a systematic review of randomized controlled trials comparing the clinical effects of four NAIs administered to patients with influenza and placebo. Relevant studies were found in the PubMed and Cochrane databases. Unpublished studies were collected from the ClinicalTrials.gov registry and through hand searching. We carried out NWA to compare the different regimens with each other and across subgroups of age and medical status (high-risk patients). A total of 58 two-arm studies were identified. Five regimens were efficacious in reducing the time to alleviation of influenza symptoms in all populations; this efficacy was comparable. No significant improvements were seen in combination therapy groups. The mean difference in the time to alleviation of symptoms ranged from 12.78 to 19.51 h. According to the summarized mean difference and surface under the cumulative ranking curve (SUCRA), peramivir (SUCRA = 82.6%), zanamivir (SUCRA = 64%), and oseltamivir (SUCRA = 55.1%) were the three top-ranking drugs for treating influenza. Zanamivir and peramivir were the preferred pharmacologic intervention among all investigated interventions based on the calculated "value preference of SUCRA." This study is a network meta-analysis to explore the therapeutic effects of NAIs in patients with influenza. Peramivir might be the best choice for reducing the time to alleviation of symptoms.

The integral membrane, Kunitz-type, serine protease inhibitors, HAI-1 and HAI-2, closely resemble one another structurally and with regard to their specificity and potency against proteases. Structural complementarity between the Kunitz domains and serine protease domains renders the membrane-associated serine proteases, matriptase and prostasin, the primary target proteases of the HAIs. The shared biochemical enzyme-inhibitor relationships are, however, at odds with their behavior at the cellular level, where HAI-1 appears to be the default inhibitor of these proteases and HAI-2 a cell-type-selective inhibitor, even though they are widely co-expressed. The limited motility of these proteins caused by their membrane anchorages may require their co-localization within a certain distance to allow the establishment of a cellular level functional relationship between the proteases and the inhibitors. The differences in their subcellular localization with HAI-1 both inside the cell and on the cell surface, compared to HAI-2 predominately in intracellular granules has, therefore, been implicated in the differential manner of their control of matriptase and prostasin proteolysis. The targeting signals present in the intracellular domains of the HAIs are systematically investigated herein. Studies involving domain swap and point mutation, in combination with immunocytochemistry and cell surface biotinylation/avidin depletion, reveal that the different subcellular localization between the HAIs can largely be attributed to differences in the intracellular Arg/Lys-rich and EHLVY motifs. These intrinsic differences in the targeting signal render the HAIs as two independent rather than redundant proteolysis regulators.

Patients with end-stage renal disease (ESRD) may demonstrate secondary hyperparathyroidism (SHPT), characterized by parathyroid hormone oversecretion in response to electrolyte imbalance (e.g., hypocalcemia and hyperphosphatemia). Moreover, this electrolyte imbalance may affect vocal cord muscle contraction and lead to voice change. Here, we explored the effects of SHPT on the voices of patients with ESRD. We used data of 147,026 patients with ESRD from the registry for catastrophic illness patients, a sub-database of Taiwan National Health Insurance Research Database. We divided these patients into 2 groups based on whether they had hyperparathyroidism (HPT) and compared vocal dysfunction (VD) incidence among them. We also prospectively included 60 ESRD patients with SHPT; 45 of them underwent parathyroidectomy. Preoperatively and postoperatively, voice analysis was used to investigate changes in vocal parameters. In the real-world database analysis, the presence of HPT significantly increased VD incidence in patients with ESRD (p = 0.003): Cox regression analysis results indicated that patients with ESRD had an approximately 1.6-fold increased VD risk (p = 0.003). In the clinical analysis, the “jitter” and “shimmer” factors improved significantly after operation, whereas the aerodynamic factors remained unchanged. In conclusion, SHPT was an independent risk factor for VD in patients with ESRD, mainly affecting their acoustic factors.

Epidermal differentiation and barrier function require well-controlled matriptase and prostasin proteolysis, in which the Kunitz-type serine protease inhibitor HAI-1 represents the primary enzymatic inhibitor for both proteases. HAI-1, however, also functions as a chaperone-like protein necessary for normal matriptase synthesis and intracellular trafficking. Furthermore, other protease inhibitors, such as antithrombin and HAI-2, can also inhibit matriptase and prostasin in solution or in keratinocytes. It remains unclear, therefore, whether aberrant increases in matriptase and prostasin enzymatic activity would be the consequence of targeted deletion of HAI-1 and so subsequently contribute to the epidermal defects observed in HAI-1 knockout mice. The impact of HAI-1 deficiency on matriptase and prostasin proteolysis was, here, investigated in HaCaT human keratinocytes. Our results show that HAI-1 deficiency causes an increase in prostasin proteolysis via increased protein expression and zymogen activation. It remains unclear, however, whether HAI-1 deficiency increases "net" prostasin enzymatic activity because all of the activated prostasin was detected in complexes with HAI-2, suggesting that prostasin enzymatic activity is still under tight control in HAI-1-deficient keratinocytes. Matriptase proteolysis is, however, unexpectedly suppressed by HAI-1 deficiency, as manifested by decreases in zymogen activation, shedding of active matriptase, and matriptase-dependent prostasin zymogen activation. This suppressed proteolysis results mainly from the reduced ability of HAI-1-deficient HaCaT cells to activate matriptase and the rapid inhibition of nascent active matriptase by HAI-2 and other yet-to-be-identified protease inhibitors. Our study provides novel insights with opposite impacts by HAI-1 deficiency on matriptase versus prostasin proteolysis in keratinocytes.

Background and aims Renal dysfunction is a potent risk factor for cardiovascular diseases, including stroke. This study aimed to evaluate the impact of admission estimated glomerular filtration rate (eGFR) levels on short-term (1-month) and long-term (1-year) mortality in patients with acute ischemic stroke. Methods From the Taiwan Stroke Registry data, we classified ischemic stroke patients, identified from April 2006 to December 2015, into 5 groups by eGFR at admission: ≥ 90, 60–89, 30–59, 15–29, and Results Among 52,732 ischemic stroke patients, 1480 died within one month. The 1-month mortality rate was over 5-fold greater in patients with eGFR Conclusions After acute ischemic stroke, patients with reduced eGFR are at elevated risks of short-term and long-term deaths in a graded relationship.

We investigated the impact of serum cholesterol levels on 30-day mortality after ischemic stroke in dialysis patients.From the Taiwan Stroke Registry data, we identified 46,770 ischemic stroke cases, including 1101 dialysis patients and 45,669 nondialysis patients from 2006 to 2013.Overall, the 30-day mortality was 1.46-fold greater in the dialysis group than in the nondialysis group (1.75 versus 1.20 per 1000 person-days). The mortality rates were 1.64, .62, 2.82, and 2.23 per 1000 person-days in dialysis patients with serum total cholesterol levels of 120 mg/dL, 120-159 mg/dL, 160-199 mg/dL, and ≥200 mg/dL, respectively. Compared to dialysis patients with serum total cholesterol levels of 120-159 mg/dL, the corresponding adjusted hazard ratios of mortality were 4.20 (95% confidence interval [CI] = 1.01-17.4), 8.06 (95% CI = 2.02-32.2), and 6.89 (95% CI = 1.59-29.8) for those with cholesterol levels of 120 mg/dL, 160-199 mg/dL, and ≥200 mg/dL, respectively.Dialysis patients with serum total cholesterol levels of ≥160 mg/dL or 120 mg/dL on admission are at an elevated hazard of 30-day mortality after ischemic stroke.

In adult brain, new neurons are generated throughout adulthood in the subventricular zone and the dentate gyrus; this process is commonly known as adult neurogenesis. The regulation or modulation of adult neurogenesis includes various intrinsic pathways (signal transduction pathway and epigenetic or genetic modulation pathways) or extrinsic pathways (metabolic growth factor modulation, vascular, and immune system pathways). Altered neurogenesis has been identified in Alzheimer’s disease (AD), in both human AD brains and AD rodent models. The exact mechanism of the dysregulation of adult neurogenesis in AD has not been completely elucidated. However, neuroinflammation has been demonstrated to alter adult neurogenesis. The presence of various inflammatory components, such as immune cells, cytokines, or chemokines, plays a role in regulating the survival, proliferation, and maturation of neural stem cells. Neuroinflammation has also been considered as a hallmark neuropathological feature of AD. In this review, we summarize current, state-of-the art perspectives on adult neurogenesis, neuroinflammation, and the relationship between these two phenomena in AD. Furthermore, we discuss the potential therapeutic approaches, focusing on the anti-inflammatory and proneurogenic interventions that have been reported in this field.

Objective This meta-analysis was performed to assess the efficacy of cryotherapy and nail solution (NS) use in preventing nail toxicity (NT) induced by taxane-based chemotherapy. Methods PubMed, EMBASE, Cochrane Library and ClinicalTrials.gov registry databases were searched for relevant studies published up to December 2018. The primary outcome was taxane-induced NT. Secondary outcomes were skin toxicity (ST), time to toxicity and patient comfort. Results We reviewed three randomised control trials and six prospective studies with 708 patients. For meta-analysis, taxane-induced NT grading was compared. NT and ST were significantly lower in the cryotherapy patients than in the controls (grade 1 NT: risk ratio [RR] = 0.51, 95% confidence interval [CI] = 0.30-0.89; grade 2-3 NT: RR = 0.36, 95% CI = 0.11-1.12; total NT: RR = 0.49; 95% CI = 0.30-0.79; ST: RR = 0.46, 95% CI = 0.33-0.64). The NS-treated patients exhibited significantly lower NT than the controls. Conclusions Nail solution-treated or cryotherapy patients exhibited lower NT incidence and severity associated with taxane-based chemotherapy than the controls. For patients who can afford and comply with NS use or cryotherapy, these measures represent effective prophylactic management for taxane-induced NT and improve their quality of life and functional statuses. Further studies are needed to establish the routine usage protocols, long-term efficacy and safety for these interventions.

Fluoxetine, a well-known anti-depression agent, may act as a chemosensitizer to assist and promote cancer therapy. However, how fluoxetine regulates cellular signaling to enhance cellular responses against tumor cell growth remains unclear. In the present study, addition of fluoxetine promoted growth inhibition of interferon-alpha (IFN-α) in human bladder carcinoma cells but not in normal uroepithelial cells through lessening the IFN-α-induced apoptosis but switching to cause G1 arrest, and maintaining the IFN-α-mediated reduction in G2/M phase. Activations and signal transducer and transactivator (STAT)-1 and peroxisome proliferator-activated receptor alpha (PPAR-α) were involved in this process. Chemical inhibitions of STAT-1 or PPAR-α partially rescued bladder carcinoma cells from IFN-α-mediated growth inhibition via blockades of G1 arrest, cyclin D1 reduction, p53 downregulation and p27 upregulation in the presence of fluoxetine. However, the functions of both proteins were not involved in the control of fluoxetine over apoptosis and maintained the declined G2/M phase of IFN-α. These results indicated that activation of PPAR-α and STAT-1 participated, at least in part, in growth inhibition of IFN-α in the presence of fluoxetine.

Etifoxine, an 18 kDa translocator protein (TSPO) agonist for the treatment of anxiety disorders in clinic, may be able to cause acute liver injury or cytolytic hepatitis. TSPO has been demonstrated to participate in inflammatory responses in infective diseases as well as to modulate glucose and lipid homeostasis. Hepatitis C virus (HCV) infection disrupts glucose and lipid homoeostasis, leading to insulin resistance (IR). Whether TSPO affects the HCV-induced IR remains unclear. Here, we found that the administration of etifoxine increased the TSPO protein expression and recovered the HCV-mediated lower mitochondrial membrane potential (MMP) without affecting HCV infection. Moreover, etifoxine reversed the HCV-induced lipid accumulation by modulating the expressions of sterol regulatory element-binding protein-1 and apolipoprotein J. On the other hand, in infected cells pretreated with etifoxine, the insulin-mediated insulin receptor substrate-1/Akt signals, forkhead box protein O1 translocation, and glucose uptake were blocked. Taken together, our results pointed out that etifoxine relieved the HCV-retarded MMP and reduced the lipid accumulation but deteriorated the HCV-induced IR by interfering with insulin signal molecules.

Made available in DSpace on 2019-10-04T12:41:37Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-07-02 National Health and Medical Research Council of Australia Background-The uptake of proven stroke treatments varies widely. We aimed to determine the association of evidence-based processes of care for acute ischemic stroke (AIS) and clinical outcome of patients who participated in the HEADPOST (Head Positioning in Acute Stroke Trial), a multicenter cluster crossover trial of lying flat versus sitting up, head positioning in acute stroke. Methods and Results-Use of 8 AIS processes of care were considered: reperfusion therapy in eligible patients; acute stroke unit care; antihypertensive, antiplatelet, statin, and anticoagulation for atrial fibrillation; dysphagia assessment; and physiotherapist review. Hierarchical, mixed, logistic regression models were performed to determine associations with good outcome (modified Rankin Scale scores 0-2) at 90 days, adjusted for patient and hospital variables. Among 9485 patients with AIS, implementation of all processes of care in eligible patients, or defect-free care, was associated with improved outcome (odds ratio, 1.40; 95% CI, 1.18-1.65) and better survival (odds ratio, 2.23; 95% CI, 1.62-3.09). Defect-free stroke care was also significantly associated with excellent outcome (modified Rankin Scale score 0-1) (odds ratio, 1.22; 95% CI, 1.04-1.43). No hospital characteristic was independently predictive of outcome. Only 1445 (15%) of eligible patients with AIS received all processes of care, with significant regional variations in overall and individual rates. Conclusions-Use of evidence-based care is associated with improved clinical outcome in AIS. Strategies are required to address regional variation in the use of proven AIS treatments. Univ New South Wales, Fac Med, George Inst Global Hlth, Sydney, NSW, Australia Ctr Estudios Clin, Inst Ciencias & Innovac Med, Santiago, Chile Clin Alemana Univ Desarrollo, Fac Med, Serv Neurol, Dept Neurol & Psiquiatria, Santiago, Chile Peking Univ, Hlth Sci Ctr, George Inst Global Hlth, Beijing, Peoples R China Australian Catholic Univ, Nursing Res Inst, St Vincents Hlth Australia Sydney, Sydney, NSW, Australia Univ Cent Lancashire, Fac Hlth & Wellbeing, Preston, Lancs, England Univ Chile, Fac Med, Dept Ciencias Neurol, Santiago, Chile Univ Sao Paulo, Ribeirao Preto Med Sch, Stroke Serv Neurol Div, Ribeirao Preto, Brazil Fukuoka Univ, Fac Med, Dept Prevent Med & Publ Hlth, Fukuoka, Fukuoka, Japan Univ Leicester, Dept Cardiovasc Sci, Leicester Biomed Res Ctr, Leicester, Leics, England Univ Leicester, Natl Inst Hlth Res, Leicester Biomed Res Ctr, Leicester, Leics, England Univ Edinburgh, Ctr Clin Brain Sci, Edinburgh, Midlothian, Scotland George Inst Global Hlth, Sydney, NSW, Australia Univ Desarrollo, Serv Neurol, Dept Neurol & Psiquiatria Clin Alemana Santiago, Santiago, Chile St Vincents Hlth Australia Sydney, Sydney, NSW, Australia Australian Catholic Univ, Sydney, NSW, Australia Univ Cent Lancashire, Stroke Practice Res Unit, Sch Hlth, Lancashire Clin Trials Unit, Preston, Lancs, England Univ Leicester, Dept Cardiovasc Sci, Cardiovasc Res Ctr, British Heart Fdn, Leicester, Leics, England Univ Kelaniya, Dept Pharmacol, Fac Med, Colombo, Sri Lanka Christian Med Coll & Hosp, Dept Neurol, Ludhiana, India Kaohsiung Med Univ & Hosp, Dept Neurol, Kaohsiung, Taiwan Linkou Chang Gung Mem Hosp, Dept Neurol, Taipei, Taiwan Peking Union Med Coll Hosp, Beijing, Peoples R China Univ Sao Paulo, Ribeirao Preto Sch Med, Ribeirao Preto, Brazil Monash Univ, Dept Epidemiol & Prevent Med, Melbourne, Vic, Australia Univ Cent Lancashire, Sch Hlth Sci, Coll Hlth & Wellbeing, Preston, Lancs, England Univ Desarrollo, Santiago, Chile Univ New South Wales, Neurosci Res Australia, Sydney, NSW, Australia Natl Univ Singapore, Dept Pharmacol, Singapore, Singapore Bradford Royal Infirm, Bradford Inst Hlth Res, Leeds, W Yorkshire, England Christian Med College, Ludhiana, Punjab, India RemediumOne Pvt Ltd, Kandy, Sri Lanka Kaohsiung Med Univ, Chung Ho Mem Hosp, Kaohsiung, Taiwan Calvary Publ Hosp Bruce, Bruce, Australia Royal North Shore Hosp, St Leonards, NSW, Australia Royal Prince Alfred Hosp, Camperdown, NSW, Australia Concord Repatriat Gen Hosp, Camperdown, NSW, Australia Fiona Stanley Hosp, Camperdown, NSW, Australia Macquarie Base Hosp, Melbourne, Vic, Australia Univ Sao Paulo, Fac Med Ribeirao Preto, Hosp Clin, Sao Paulo, Brazil Hosp Governador Celso Ramos, Florianopolis, SC, Brazil Sao Paulo State Univ, Hosp Fac Med Botucatu, UNESP, Sao Paulo, Brazil Yangquan Coalmine Grp Gen Hosp, Yangquan, Peoples R China Nanjing Med Univ, Nanjing Hosp 1, Nanjing, Jiangsu, Peoples R China 85 Hosp Peoples Liberat Army, Beijing, Peoples R China Chifeng Univ, Affiliated Hosp, Chifeng, Peoples R China Beijing Pinggu Hosp, Beijing, Peoples R China Wenzhou Med Univ, Affiliated Hosp 1, Wenzhou, Peoples R China Soochow Univ, Affiliated Hosp 2, Suzhou, Peoples R China Hebei Med Univ, Hosp 3, Shijiazhuang, Hebei, Peoples R China Capital Med Univ, Xuanwu Hosp, Beijing, Peoples R China Jining Med Univ, Affiliated Hosp, Jining, Peoples R China Third Peoples Hosp Huizhou, Huizhou, Peoples R China Second Cangzhou Cent Hosp, Cangzhou, Peoples R China Shanghai Jiao Tong Univ, Hosp Affiliated, Sch Med, Shanghai, Peoples R China Baogang Hosp, Baotou, Peoples R China Harbin Med Univ, Affiliated Hosp 1, Harbin, Heilongjiang, Peoples R China Shanghai Jiao Tong Univ Sch, Tong Ren Hosp, Peoples Hosp Hejian City, Shanghai, Peoples R China Peking Univ, Shougang Hosp, Beijing, Peoples R China Guangzhou Med Univ, Affiliated Hosp 3, Guangzhou, Guangdong, Peoples R China Second Hosp Nanchang, Nanchang, Jiangxi, Peoples R China Bethune Int Peace Hosp, Beijing, Peoples R China Hua Henan Prov Peoples Hosp, Beijing, Peoples R China Hua Henan Prov Peoples Hosp, Zhengzhou, Henan, Peoples R China Shanghai Jiao Tong Univ, Sch Med, Shanghai Ninth Peoples Hosp, Shanghai, Peoples R China Shijiazhuang Cent Hosp, Shijiazhuang, Hebei, Peoples R China Hosp Base San Jos de Osorno, Osorno, Chile Christian Med Coll & Hosp, Ludhiana, Punjab, India Unit Narayana Hrudayalaya Ltd, Mazumdar Shaw Med Ctr, Bangalore, Karnataka, India Dr Ramesh Cardiac & Multispecial Hosp Pvt Ltd, Guntur, India Post Grad Inst Med Educ & Res, Chandigarh, India Baby Mem Hosp Ltd, Calicut, Kerala, India Sree Chitra Tirunal Inst Med Sci & Technol, Thiruvananthapuram, Kerala, India Sri Jayawardenepura Gen Hosp, Sri Jayawardenepura Kott, Sri Lanka Colombo North Teaching Hosp, Colombo, Sri Lanka Colombo South Coching Hosp, Colombo, Sri Lanka Linkou Chang Gung Mem Hosp, Taoyuan, Taiwan Taipei Med Univ, Shuang Ho Hosp, Taipei, Taiwan En Chu Kong Hosp, New Taipei, Taiwan Natl Cheng Kung Univ Hosp, Tainan, Taiwan Queen Alexandra Hosp, Portsmouth, Hants, England Portsmouth Hosp NHS Natl Hlth Serv iTrust, Portsmouth, Hants, England Univ Coll London Hosp NHS Fdn Trust, London, England Univ Hosp Birmingham NHS Fdn Trust, Queen Elizabeth Hosp Birmingham, Birmingham, W Midlands, England Southend Univ Hosp NHS Fdn Trust, Southend On Sea, England Kings Coll Hosp London, London, England York Teaching Hosp NHS Fdn Trust, York, N Yorkshire, England Nottingham Univ Hosp NHS Trust, Nottingham, England Blackpool Teaching Hosp NHS Fdn Trust, Blackpool, England Gloucestershire Hosp NHS Fdn Trust, Gloucestershire Royal Hosp, Gloucester, England Teaching Hospi NHS Fdn Trust, London, England Royal Cornwall Hosp NHS Trust, Truro, England Royal London Hosp, Barts Hlth NHS Trust, London, England Sheffield Teaching Hosp NHS Fdn Trust, Sheffield, S Yorkshire, England Cambridge Univ Hosp NHS Fdn Trust, Addenbrookes Hosp, Cambridge, England Royal Victoria Hosp, Belfast Hlth & Social Care Trust, London, England Pinderfields Gen Hosp, Mid Yorkshire Hosp NHS Trust, Wakefield, England Royal Devon & Exeter NHS Fdn Trust, London, England Bradford Teaching Hosp NHS Fdn Trust, Bradford, W Yorkshire, England Great Western Hosp NHS Fdn Trust, Swindon, Wilts, England Watford Dist Gen Hosp, Watford, England Imperial Coll Healthcare NHS Trust, London, England Medway NHS Fdn Trust, Gillingham, England Royal Liverpool & Broadgreen Univ NHS Trust, Liverpool, Merseyside, England Calderdale & Huddersfield NHS Fdn Trust, Huddersfield, W Yorkshire, England Hywel Dda Univ Hlth Board, Haverfordwest, Wales Chesterfield Royal Hosp NHS Fdn Trust, Calow, England Luton & Dunstable Univ Hosp NHS Fdn Trust, Luton, Beds, England Countess Chester Hosp NHS Fdn Trust, Chester, Cheshire, England Peterborough City Hosp, Peterborough, Cambs, England Univ Hosp Leicester NHS Trust, Leicester Royal Infirm, Leicester, Leics, England Dist Hosp NHS Fdn Trust, London, England Barnsley Hosp NHS Fdn Trust, Barnsley, England Dorset Cty Hosp NHS Fdn Trust, Dorchester, England Royal Bournemouth & Christchurch Hosp NHS Fdn Tru, Royal Bournemouth Hosp, Bournemouth, Dorset, England Southern Hlth & Social Care Trust, Craigavon Area Hosp, Portadown, England United Lincolnshire Hosp NHS Trust, Pilgrim Hosp, Lincoln, England Bedford Hosp NHS Trust, Bedford, England Sao Paulo State Univ, Hosp Fac Med Botucatu, UNESP, Sao Paulo, Brazil National Health and Medical Research Council of Australia: 1066966

Significant improvement of stroke symptoms may occur in acute stroke patients due to large artery occlusion (LAO) treated with intravenous thrombolysis (IVT). Directly proceeding with endovascular thrombectomy (EVT) would be a clinical dilemma.A 55-year-old male suddenly suffered from global aphasia and right side hemiplegia at work. Left proximal middle cerebral artery (MCA) occlusion was shown on CT angiography. After IVT, NIHSS significantly improved from 11 to 4 points. EVT was withheld due to rapidly improving symptoms and low NIHSS scores. However, stroke in progression occurred 7 hours after onset with NIHSS scores increasing from 4 to 13 points. A follow-up brain CT scan showed an Alberta Stroke Program Early CT score of 9 and no hemorrhage. Successful recanalization of the left MCA by EVT was performed at 10.5 hours after onset. The patient was discharged with a NIHSS score of 3 and his modified Rankin Scale score was 0 at 3 months.In LAO patients, directly proceeding EVT following IVT may not be hesitated. In addition, while LAO patients with incomplete IV-tPA treatment responses result in transient improvement of neurological symptoms but later reversed, EVT may be a potential rescue therapy in carefully selected patients.

Vitamin D has been identified as an innate anti-hepatitis C virus (HCV) agent but the possible mechanisms for this issue remain unclear. Here, we clarified the mechanisms of calcitriol-mediated inhibition of HCV infection. Calcitriol partially inhibited HCV infection, nitric oxide (NO) release and lipid accumulation in Huh7.5 human hepatoma cells via the activation of vitamin D receptor (VDR). When cells were pretreated with the activators of peroxisome proliferator-activated receptor (PPAR)-α (Wy14643) and -γ (Ly171883), the calcitriol-mediated HCV suppression was reversed. Otherwise, three individual stimulators of PPAR-α/β/γ blocked the activation of VDR. PPAR-β (linoleic acid) reversed the inhibition of NO release, whereas PPAR-γ (Ly171883) reversed the inhibitions of NO release and lipid accumulation in the presence of calcitriol. The calcitriol-mediated viral suppression, inhibition of NO release and activation of VDR were partially blocked by an inhibitor of endoplasmic reticulum-associated degradation (ERAD), kifunensine. Furthermore, calcitriol blocked the HCV-induced expressions of apolipoprotein J and 78 kDa glucose-regulated protein, which was restored by pretreatment of kifunensine. These results indicated that the calcitriol-mediated HCV suppression was associated with the activation of VDR, interference with ERAD process, as well as blockades of PPAR, lipid accumulation and nitrative stress.

Background The impact of leukoaraiosis on the risk of symptomatic intracerebral hemorrhage (SICH) after stroke thrombolysis is conflicting, and the data on Asian populations are lacking. Therefore, in this study, we assessed the association between leukoaraiosis and SICH, and the association between leukoaraiosis and the 90-day functional outcome in the Asian population. Methods Data were collected from a two-center prospective registry of acute ischemic stroke patients given intravenous tissue plasminogen activator between 2006 and 2014. A total of 614 pretreatment brain CT and 455 posttreatment MRI were retrospectively assessed using two different rating scales for the presence of leukoaraiosis. Outcome measures were the occurrence of SICH with three definitions and any hemorrhage after thrombolysis and functional outcome at 3 months. Results Of the 614 patients assessed, 30.3% showed severe leukoaraiosis on the baseline brain CT. The SICH rate was 4.6% - 7.2% based on different definitions, and overall, 24.9% of patients showed any post-tPA hemorrhage. No association was observed between the severity of leukoaraiosis and SICH, regardless of having used different leukoaraiosis rating scales or as assessment using different imaging modalities. However, severe leukoaraiosis was independently associated with poor functional outcome at 3 months (OR 1.96, 95% C1 1.24–3.11, P = 0.004) after adjustment for confounders. Conclusions Our results showed no association between leukoaraiosis and the risk of SICH. Although the presence of severe leukoaraiosis predicted a poor functional outcome after stroke, IV thrombolysis might not be withheld in acute ischemic stroke patients solely based on the presence of severe leukoaraiosis on pre-thrombolytic CT scans.

More than 20% of chronic hepatitis C (CHC) patients receiving interferon-alpha (IFN-α)-based anti-hepatitis C virus (HCV) therapy experienced significant depression, which was relieved by treatment with fluoxetine. However, whether and how fluoxetine affected directly the anti-HCV therapy remained unclear. Here, we demonstrated that fluoxetine inhibited HCV infection and blocked the production of reactive oxygen species (ROS) and lipid accumulation in Huh7.5 cells. Fluoxetine facilitated the IFN-α-mediated antiviral actions via activations of signal transducer and activator of transcription (STAT)-1 and c-Jun amino-terminal kinases (JNK). Alternatively, fluoxetine elevated peroxisome proliferator-activated receptor (PPAR) response element activity under HCV infection. The inhibitory effects of fluoxetine on HCV infection and lipid accumulation, but not production of ROS, were partially reversed by the PPAR-β, -γ, and JNK antagonists. Furthermore, fluoxetine intervention to the IFN-α-2b regimen facilitated to reduce HCV titer and alanine transaminase level for CHC patients. Therefore, fluoxetine intervention to the IFN-α-2b regimen improved the efficacy of anti-HCV treatment, which might be related to blockades of ROS generation and lipid accumulation and activation of host antiviral JNK/STAT-1 and PPARβ/γ signals.

Sphingomyelinase (SMase) regulates an activation of the sphingomyelin cycle. Recent studies have shown that it is a novel modulator of monoamine receptor and transporter functions; however, its mechanisms are not fully understood. Our previous studies have found that interferon-alpha (IFN-α) up-regulates serotonin (5-HT) transporter expression and induces 5-HT uptake via an extracellular signal-regulated kinase (ERK)1/2-dependent pathway in T cells, which is blocked by a selective 5-HT transporter inhibitor fluoxetine. In the present study, we further investigated the roles of various SMase inhibitors in IFN-α-induced 5-HT uptake, including sphingolactone-24 (sph24) for neutral SMase or tricyclodecan-9-yl-xanthogenate (D609) for acid SMase. Pretreatments with Sph24 and D609 inhibited IFN-α-induced 5-HT uptake, and activation of ERK1/2 and signal transducer and transactivator (STAT) 1 and STAT3. The elevated protein levels of pro-inflammatory enzyme cycloxygenase (COX)-2 were observed upon IFN-α stimulation. The COX-2 inhibitor celecoxib blocked IFN-α-induced COX-2 expression, 5-HT uptake and activation of Akt, ERK and STAT. Moreover, a PI3K/Akt inhibitor Wortamannin blocked IFN-α-induced 5-HT uptake and activation of Akt and ERK. D609 also blocked IFN-α-induced COX-2 and Akt activation. Contrarily, sph24 did not result in these effects. Furthermore, fluoxetine as an acid SMase inhibitor lowered IFN-α-induced SMase activity as well as attenuated COX-2, Akt, ERK, and STAT activation. These results suggest that inhibiting SMase attenuates IFN-α-induced ERK and STAT activation to regulate 5-HT uptake. Moreover, inhibition of COX-2 induction and an Akt-dependent pathway are involved in IFN-α-induced 5-HT uptake by the blockade of acid SMase activity.

Public attitudes toward mental illness influence the success with which patients reenter the community. An attitude instrument suitable to the Chinese cultural setting with good reliability and validity is essential to examining public attitudes toward mental illness. Exploring the perspectives of adolescents is relevant because most mental illness occurs during adolescence.This study developed and tested the psychometric quality of the Chinese-version Attitudes Toward Mental Illness (CAMI) scale among senior high school students.The original AMI was translated into Chinese using a back and forth translation method and its content validity was examined. A cross-sectional survey of 479 senior high school students was conducted to assess the construct validity, cross validity, and internal consistency of the CAMI.The CAMI showed adequate content validity. The confirmatory factor analysis support: the appropriateness of CAMI's original two-factor structure of negative attitude and recovery outcomes after deleting items 9 and 11; the measurement of the negative perceptions of mentally ill patients and their risks to community; and the perceptions of recovery of mentally ill patients. The construct validity and cross validity are appropriate and the internal consistency of the total scale and two subscales are acceptable (Cronbach's α: .76, .75, .81).The reliability and validity of the CAMI is appropriate for the sample of senior high students in this study. Future studies should target a broader range of people in order to establish the reliability and validity of the scale in different groups and to build up empirical knowledge on public attitudes toward mental illness. The application of this scale is expected to contribute to the development of anti-stigma interventions and to the creation of friendly communities for mentally ill patients.中文版精神疾病態度量表之信效度研究—以高中生為例民眾對精神疾病的態度將影響精神病患回歸社區。發展適於華人社會且信、效度良好的測量工具，有助於瞭解民眾對於精神疾病之觀感，且由於精神疾病好發於青少年階段，該族群對於精神疾病之看法值得進一步探究。以高中生為例，發展及測試中文版精神疾病態度量表之信、效度。運用來回翻譯法將精神疾病態度量表中文化，並建立內容效度；再採橫斷面研究設計，以479位高中生為樣本進行問卷調查，評估量表之建構效度、複核效度及內在一致性信度。中文版精神疾病態度量表內容效度良好，依據驗證性因素分析刪除第9和11題後，顯示中文版量表支持原量表之兩因素結構：負向態度及復元成效，具有適當之建構效度及複核效度，且總量表及兩次量表之內在一致性信度達可接受範圍（Cronbach’s α分別為.76、.75、.81）。中文版精神疾病態度量表於高中生樣本測試所得信、效度適當，未來宜進一步以成人民眾為對象，建立於不同族群及年齡層之信、效度，藉此可瞭解國人對精神病患的觀感，並發展合宜的介入策略，以建構對精神病友較為友善的社區環境。

Internuclear ophthalmoplegia is caused by a lesion; stroke, multiple sclerosis, brain metastases, or trauma may produce lesions of the medial longitudinal fasciculus (MLF). Imaging techniques, such as DWI, can help identify the site of the lesion in order to speed diagnosis and lead to appropriate treatment. Over an 8-month period, eight consecutive patients with suspected MLF syndrome (most secondary to ischemic stroke) underwent MRI examinations, including DWI sequencing, at an academic center in Taiwan. In all eight patients, abnormal high-signal lesions were found close to the floor of the fourth ventricle on the dorsal side of the pons. A neuroanatomical comparison showed that the location of the lesions was identical to the anatomical position of the MLF. Using DWI, good clinico-radiological correlation was found in all eight ischemic stroke patients diagnosed with MLF syndrome. DWI may broaden the application of MRI in the diagnosis of MLF syndrome.

Quality of life (QOL) is a critical issue in mental health care. The associations between quality of life and schizophrenia patients' stigma perception and stigma coping behavior are not well understood.This study investigated quality of life in schizophrenia patients.We used a cross-sectional, correlational research design; enrolled 119 individuals diagnosed with schizophrenia as participants; and used instruments including a demographics datasheet, perceived stigma scale, stigma coping behavior scale, and the World Health Organization quality of life scale, brief version to collect data. Data were analyzed using SPSS 12.0 for Windows software.(1) Participants had an average QOL index score of 62.40, indicating moderate quality of life; (2) Long working hours, holding rehabilitation-related employment, and receiving social welfare support correlated with lower QOL; (3) Marital issues had the greatest impact on quality of life, with participants who chose secrecy ÷ concealment reporting generally better QOL; (4) Social welfare support, number of working hours, stigma perception, stigma coping, level of job satisfaction, and level of salary satisfaction together accounted for 48.8% of total QOL variance.Findings increase our understanding of the influence of socio-demographics, stigma perception, and stigma coping behavior on quality of life in individuals with schizophrenia. Greater community involvement in schizophrenia treatment programs can enhance patient satisfaction with their jobs and lives.

A selective serotonin reuptake inhibitor fluoxetine not only is widely used in the treatment of depression but also has an anti-inflammatory property. Glycogen synthase kinase-3beta (GSK-3β) is a vital factor in the inflammation process. How fluoxetine interferes with inflammation via a GSK-3β-dependent pathway remains unclear. The aim of this study is to investigate the effects of fluoxetine on lipopolysaccharide (LPS)-induced inflammation. Results showed that fluoxetine decreased mortality rate of the mice. It also inhibited LPS-induced release of nitric oxide (NO) and prostaglandin E2 (PGE2) in serum and RAW264.7 murine macrophages and expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Upon LPS stimulation, fluoxetine caused a delay but increased in the phosphorylated levels of GSK-3β (ser9), whereas it did not affect LPS-induced activation of mitogen-activated protein kinase (MAPK) and generation of reactive oxygen species (ROS). Fluoxetine in combination with phosphatidylinositol 3-kinases/Akt inhibitors (LY294002 and Wortmannin) did not have a synergistic inhibition on LPS-induced NO release and PGE2 production. In addition, peroxisome proliferator-activated receptor γ (PPARγ) antagonist GW9622 showed no reverse effects of this inhibition of fluoxetine. GSK-3β knockdown blocked the inhibitory effects of fluoxetine on LPS-induced iNOS/NO release and COX-2/PGE2 production. These results indicated that GSK-3β regulated anti-inflammatory property of fluoxetine. However, Akt activation, ROS generation, and altered PPARγ activity were not involved in this inhibition of fluoxetine.