Showing papers by "Taipei Veterans General Hospital published in 2014"

Prevalence of and interventions for sarcopenia in ageing adults: a systematic review. Report of the International Sarcopenia Initiative (EWGSOP and IWGS)

Abstract: OBJECTIVE: to examine the clinical evidence reporting the prevalence of sarcopenia and the effect of nutrition and exercise interventions from studies using the consensus definition of sarcopenia proposed by the European Working Group on Sarcopenia in Older People (EWGSOP).METHODS: PubMed and Dialog databases were searched (January 2000-October 2013) using pre-defined search terms. Prevalence studies and intervention studies investigating muscle mass plus strength or function outcome measures using the EWGSOP definition of sarcopenia, in well-defined populations of adults aged ≥50 years were selected.RESULTS: prevalence of sarcopenia was, with regional and age-related variations, 1-29% in community-dwelling populations, 14-33% in long-term care populations and 10% in the only acute hospital-care population examined. Moderate quality evidence suggests that exercise interventions improve muscle strength and physical performance. The results of nutrition interventions are equivocal due to the low number of studies and heterogeneous study design. Essential amino acid (EAA) supplements, including ∼2.5 g of leucine, and β-hydroxy β-methylbutyric acid (HMB) supplements, show some effects in improving muscle mass and function parameters. Protein supplements have not shown consistent benefits on muscle mass and function.CONCLUSION: prevalence of sarcopenia is substantial in most geriatric settings. Well-designed, standardised studies evaluating exercise or nutrition interventions are needed before treatment guidelines can be developed. Physicians should screen for sarcopenia in both community and geriatric settings, with diagnosis based on muscle mass and function. Supervised resistance exercise is recommended for individuals with sarcopenia. EAA (with leucine) and HMB may improve muscle outcomes.

Carbon dots prepared from ginger exhibiting efficient inhibition of human hepatocellular carcinoma cells

Abstract: Fluorescent carbon nanodots (C-dots; 4.3 ± 0.8 nm) from fresh tender ginger juice provide high suppression of the growth of human hepatocellular carcinoma cells (HepG2), with low toxicity to normal mammary epithelial cells (MCF-10A) and normal liver cells (FL83B). The inhibition is selective to HepG2 over other tested cancer cells, including human lung cancer cell line (A549), human breast cancer cell line (MDA-MB-231), and human cervical cancer cell line (HeLa). Western blot results reveal that the C-dots up-regulate the expression of p53 protein only in the HepG2 cell line. The 50% inhibiting concentration (IC50) value of the C-dots on HepG2 cells is 0.35 mg mL−1. Image cytometry results show significant uptake of C-dots by HepG2 cells that induce intracellular production of reactive oxygen species (ROS, 18.2-fold increased), while other cells remain almost the same in ROS levels after treatment with C-dots (1.11 mg mL−1). The C-dots trigger the pro-apoptotic factor to promote HepG2 cell apoptosis. The C-dots effectively inhibit the growth of tumors in nude mice (104 ± 14 vs. 3.7 ± 0.2 mg with and without treatment within 14 days).

Stroke prevention in atrial fibrillation: An Asian perspective

Abstract: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. In 2050, it is estimated that there will be 72 million AF patients in Asia, accounting for almost 2.9 million patients suffering from AF-associated stroke. Asian AF patients share similar risk factor profiles as non-Asians, except that more Asians have a history of previous stroke. Clinical challenges are evident in the field of stroke prevention in AF, amongst Asians. Existing stroke and bleeding risk scores have not been well-validated in Asians. Asians are prone to bleeding when treated with warfarin, and the optimal international normalised ratio (INR) for warfarin use is yet to be determined in Asians, though Asian physicians tend to keep it in a lower range (e.g. INR 1.6–2.6) for elderly patients despite limited evidence to justify this. In general, warfarin is ‘difficult’ to use in Asians due to higher risk of bleeding and higher stroke rate in Asians than in non-Asians, as shown in randomised controlled trials. Excess of bleeding was not found in Asians when novel oral anticoagulants (NOACs) were used. Besides, the superiority of NOACs to warfarin in reducing thromboembolism was maintained in Asians. Therefore NOACs are preferentially indicated in Asians in terms of both efficacy and safety. Also, some preliminary data suggest that Asian patients with AF might not be the same. Future prospective randomised trials are needed for the selection of NOACs according to different ethnic background.

Efficacy of prefrontal theta-burst stimulation in refractory depression: a randomized sham-controlled study

Abstract: Theta-burst transcranial magnetic stimulation could modulate cortical excitability and has the potential to treat refractory depression. However, there has been a lack of large randomized studies of the antidepressant efficacy of different forms of theta-burst stimulation, such as intermittent and continuous theta-burst stimulation. A randomized sham-controlled study was conducted to investigate antidepressant efficacy of theta-burst stimulation and to compare efficacy among left-prefrontal intermittent theta-burst stimulation, right-prefrontal continuous theta-burst stimulation and a combination of them in patients showing different levels of antidepressant refractoriness. A group of 60 treatment-refractory patients with recurrent major depressive disorder were recruited and randomized to four groups (Group A: continuous theta-burst stimulation; Group B: intermittent theta-burst stimulation; Group C: a combination of continuous and intermittent theta-burst stimulation; and Group D: sham theta-burst stimulation; 15 patients were included in each group). After 2 weeks of theta-burst stimulation treatment, depression improved in all groups. Groups B and C had better antidepressant responses (as reflected by % decreases in depression score) than Groups A and D ( P = 0.001, post hoc analysis: B > A, B > D, C > A, and C > D), even after controlling for age and refractoriness scores. The mean antidepressant effect was highest in Group C and followed by that in Group B. Additionally, a significant placebo effect was found in patients with low refractoriness; this disappeared in patients with moderate-to-high refractoriness. A significant correlation existed between refractoriness scores and treatment responses. Treatment refractoriness was a significant factor negatively predicting efficacy of theta-burst stimulation ( P = 0.039). This randomized sham-controlled study demonstrated that active theta-burst stimulation is a well-tolerated form of repetitive transcranial magnetic stimulation and has good antidepressant efficacy, particularly in depressed subjects within a certain range of treatment refractoriness. * Abbreviations : CGI-S : Clinical Global Impression Scale HDRS : Hamilton Depression Rating Scale TBS : theta-burst stimulation TMS : transcranial magnetic stimulation TRD : treatment-refractory depression

Diabetes Mellitus and the Risk of Alzheimer’s Disease: A Nationwide Population-Based Study

Abstract: Objectives: Possible association between diabetes mellitus (DM) and Alzheimer’s disease (AD) has been controversial. This study used a nationwide population-based dataset to investigate the relationship between DM and subsequent AD incidence. Methods: Data were collected from Taiwan’s National Health Insurance Research Database, which released a cohort dataset of 1,000,000 randomly sampled people and confirmed it to be representative of the Taiwanese population. We identified 71,433 patients newly diagnosed with diabetes (age 58.74614.02 years) since January 1997. Using propensity score, we matched them with 71,311 non-diabetic subjects by time of enrollment, age, gender, hypertension, hyperlipidemia, and previous stroke history. All the patients were followed up to December 31, 2007. The endpoint of the study was occurrence of AD. Results: Over a maximum 11 years of follow-up, diabetic patients experienced a higher incidence of AD than non-diabetic subjects (0.48% vs. 0.37%, p,0.001). After Cox proportional hazard regression model analysis, DM (hazard ratio [HR], 1.76; 95% confidence interval [CI], 1.50–2.07, p,0.001), age (HR, 1.11; 95% CI, 1.10–1.12, p,0.001), female gender (HR, 1.24; 95% CI, 1.06–1.46, p=0.008), hypertension (HR, 1.30; 95% CI, 1.07–1.59, p=0.01), previous stroke history (HR, 1.79; 95% CI, 1.28– 2.50, p,0.001), and urbanization status (metropolis, HR, 1.32; 95% CI, 1.07–1.63, p=0.009) were independently associated with the increased risk of AD. Neither monotherapy nor combination therapy with oral antidiabetic medications were associated with the risk of AD after adjusting for underlying risk factors and the duration of DM since diagnosis. However, combination therapy with insulin was found to be associated with greater risk of AD (HR, 2.17; 95% CI, 1.04–4.52, p=0.039). Conclusion: Newly diagnosed DM was associated with increased risk of AD. Use of hypoglycemic agents did not ameliorate the risk. Citation: Huang C-C, Chung C-M, Leu H-B, Lin L-Y, Chiu C-C, et al. (2014) Diabetes Mellitus and the Risk of Alzheimer’s Disease: A Nationwide Population-Based

Predictive Value of the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society Classification of Lung Adenocarcinoma in Tumor Recurrence and Patient Survival

Abstract: Purpose This study investigated the pattern of recurrence of lung adenocarcinoma and the predictive value of histologic classification in resected lung adenocarcinoma using the new International Association for the Study of Lung Cancer (IASLC)/American Thoracic Society (ATS)/European Respiratory Society (ERS) classification system. Patients and Methods Histologic classification of 573 patients undergoing resection for lung adenocarcinoma was determined according to the IASLC/ATS/ERS classification system, and the percentage of each histologic component (lepidic, acinar, papillary, micropapillary, and solid) was recorded. The pattern of recurrence of those components and their predictive value were investigated. Results The predominant histologic pattern was significantly associated with sex (P .01), invasive tumor size (P .01), T status (P .01), N status (P .01), TNM stage (P .01), and visceral pleural invasion (P .01). The percentage of recurrence was significantly higher in micropapillary- and solid-predominant adenocarcinomas (P .01). Micropapillary- and solid-predominant adenocarcinomas had a significantly higher possibility of developing initial extrathoracic-only recurrence than other types (P .01). The predominant pattern group (micropapillary or solid v lepidic, acinar, or papillary) was a significant prognostic factor in overall survival (OS; P .01), probability of freedom from recurrence (P .01), and disease-specific survival (P .01) in multivariable analysis. For patients receiving adjuvant chemotherapy, solid-predominant adenocarcinoma was a significant predictor for poor OS (P .04). Conclusion

Respiratory Syncytial Virus and Other Respiratory Viral Infections in Older Adults With Moderate to Severe Influenza-like Illness

Abstract: Elderly individuals are at increased risk of morbidity and mortality due to microbial infections because of coexisting chronic disease and immune senescence [1]. The contribution of noninfluenza viral infections to acute respiratory illness in the elderly has not been well studied, partly due to difficulties in diagnosis due to atypical presentations and low viral loads [2–5]. However, identification of respiratory viruses is now possible with the advent of sensitive molecular detection methods, including polymerase chain reaction (PCR) [6, 7]. Respiratory syncytial virus (RSV) is increasingly recognized as an important cause of respiratory infections in adults, particularly affecting the elderly, immunocompromised, and those with underlying chronic cardiopulmonary disease [8]. RSV appears to be a predictable cause of wintertime respiratory illnesses among older adults living in congregate settings such as long-term care or attending daycare and is estimated to infect 5%–10% of nursing home residents per year, with rates of pneumonia and death of 10%–20% and 2%–5%, respectively [9]. Few studies have prospectively assessed etiologies of acute respiratory infections in community-based elderly individuals [8, 10]. Much of the available data describing RSV and other viral infections in the elderly come from a limited number of geographic locations, primarily the United States (US). Different cultures, climates, and intergenerational household members might influence infection rates; thus, global data on RSV and other respiratory viral infections in this population are needed. We used multiplex reverse transcriptase PCR (RT-PCR) to identify viral respiratory pathogens in nasal and throat swabs from episodes of moderate-to-severe influenza-like illness (ILI) in influenza-vaccinated elderly individuals.

A nationwide survey of mild cognitive impairment and dementia, including very mild dementia, in Taiwan

Abstract: An increasing population of dementia patients produces substantial societal impacts. We assessed the prevalence of mild cognitive impairment (MCI) and all-cause dementia, including very mild dementia (VMD), in Taiwan. In a nationwide population-based cross-sectional survey, participants were selected by computerized random sampling from all 19 Taiwan counties and were enrolled between December 2011 and March 2013. Cases were identified through in-person interviews based on the National Institute on Aging-Alzheimer’s Association clinical criteria. Demographic data and histories involving mental status and function in daily living were collected. The principal objective assessments were the Taiwanese Mental Status Examination and Clinical Dementia Rating. In all, 10,432 people aged 65 years or older (mean age 76.2±6.7, 52.3% women) were interviewed. The age-adjusted prevalence of all-cause dementia was 8.04% (95% CI 7.47–8.61), including a 3.25% (95% CI 2.89–3.61) prevalence of VMD; that of MCI was 18.76% (95% CI 17.91–19.61). Women had a higher prevalence than men of both all-cause dementia (9.71% vs. 6.36%) and MCI (21.63% vs. 15.57%). MCI affects a considerable portion of the population aged 65 and above in Taiwan. The inclusion of VMD yields dementia prevalence rates higher than those previously reported from Taiwan. Old age, female gender, and a low educational level are significant associated factors.

Meta-analysis of genome-wide association studies in East Asian-ancestry populations identifies four new loci for body mass index

Abstract: Recent genetic association studies have identified 55 genetic loci associated with obesity or body mass index (BMI). The vast majority, 51 loci, however, were identified in European-ancestry populations. We conducted a meta-analysis of associations between BMI and ∼2.5 million genotyped or imputed single nucleotide polymorphisms among 86 757 individuals of Asian ancestry, followed by in silico and de novo replication among 7488-47 352 additional Asian-ancestry individuals. We identified four novel BMI-associated loci near the KCNQ1 (rs2237892, P = 9.29 × 10(-13)), ALDH2/MYL2 (rs671, P = 3.40 × 10(-11); rs12229654, P = 4.56 × 10(-9)), ITIH4 (rs2535633, P = 1.77 × 10(-10)) and NT5C2 (rs11191580, P = 3.83 × 10(-8)) genes. The association of BMI with rs2237892, rs671 and rs12229654 was significantly stronger among men than among women. Of the 51 BMI-associated loci initially identified in European-ancestry populations, we confirmed eight loci at the genome-wide significance level (P < 5.0 × 10(-8)) and an additional 14 at P < 1.0 × 10(-3) with the same direction of effect as reported previously. Findings from this analysis expand our knowledge of the genetic basis of obesity.

Renoprotective Effect of Renin-Angiotensin-Aldosterone System Blockade in Patients With Predialysis Advanced Chronic Kidney Disease, Hypertension, and Anemia

Abstract: Importance The benefit of using a renin-angiotensin-aldosterone system blocker such as an angiotensin-converting enzyme inhibitor (ACEI) or an angiotensin II receptor blocker (ARB) for patients with advanced chronic kidney disease (CKD) remains undetermined. Objective To assess the effectiveness and safety of ACEI/ARB use for advanced predialysis CKD in patients with hypertension and anemia. Design Prospective cohort study. Setting Taiwan. Participants From January 1, 2000, through June 30, 2009, we selected 28 497 hypertensive adult patients with CKD. Serum creatinine levels were greater than 6 mg/dL, hematocrit levels were less than 28%, and patients were treated with erythropoiesis-stimulating agents. Interventions Users (n = 14 117) and nonusers (n = 14 380) of ACEIs/ARBs. Main Outcomes and Measures We used Cox proportional hazards regression models to estimate hazard ratios (HRs) for commencement of long-term dialysis and all-cause mortality for ACRI/ARB users vs nonusers. Results In a median follow-up of 7 months, 20 152 patients (70.7%) required long-term dialysis and 5696 (20.0%) died before progression to end-stage renal disease requiring dialysis. Use of ACEIs/ARBs was associated with a lower risk for long-term dialysis (HR, 0.94 [95% CI, 0.91-0.97]) and the composite outcome of long-term dialysis or death (0.94 [0.92-0.97]). The renal benefit of ACEI/ARB use was consistent across most patient subgroups, as was that of ACEI or ARB monotherapy. Compared with nonusers, the ACEI/ARB users had a higher hyperkalemia-associated hospitalization rate, but the risk of predialysis mortality caused by hyperkalemia was not significantly increased (HR, 1.03 [95% CI, 0.92-1.16]; P = .30). Conclusions and Relevance Patients with stable hypertension and advanced CKD who receive therapy with ACEIs/ARBs exhibit an association with lower risk for long-term dialysis or death by 6%. This benefit does not increase the risk of all-cause mortality.

Paediatric head CT scan and subsequent risk of malignancy and benign brain tumour: a nation-wide population-based cohort study

Abstract: Paediatric head CT scan and subsequent risk of malignancy and benign brain tumour: a nation-wide population-based cohort study

Clinical and microbiological characteristics of tigecycline non-susceptible Klebsiella pneumoniae bacteremia in Taiwan

Abstract: Resistance among Klebsiella pneumoniae to most antibiotics is on the rise. Tigecycline has been considered as one of the few therapeutic options available to treat multidrug-resistant bacteria. We investigated the clinical and microbiological characteristics of tigecycline non-susceptible K. pneumoniae bacteremia. Adult patients with tigecycline non-susceptible K. pneumoniae bacteremia at a medical center in Taiwan over a 3-year period were enrolled. K. pneumoniae isolates were identified by the E-test using criteria set by the US Food and Drug Administration (FDA). Data on the clinical features of patients were collected from medical records. Genes for β-lactamases, antimicrobial susceptibilities and pulsed-field gel electrophoresis (PFGE) results were determined for all isolates. Of 36 patients, 27 had nosocomial bacteremia. Overall 28-day mortality was 38.9%. The MIC50 and MIC90 of tigecycline were 6 and 8 mg/L, respectively. No carbapenemase was detected among the 36 isolates. Twenty isolates carried extended spectrum β-lactamases and/or DHA-1 genes. No major cluster of isolates was found among the 36 isolates by PFGE. Intensive care unit onset of tigecycline non-susceptible Klebsiella pneumoniae bacteremia was the only independent risk factor for 28-day mortality. The high mortality of patients with tigecycline non-susceptible K. pneumoniae bacteremia may suggest a critical problem. Further study to identify the possible risk factors for its development and further investigation of this type of bacteremia is necessary.

Biological pacemaker created by minimally invasive somatic reprogramming in pigs with complete heart block

Abstract: Somatic reprogramming by reexpression of the embryonic transcription factor T-box 18 (TBX18) converts cardiomyocytes into pacemaker cells. We hypothesized that this could be a viable therapeutic avenue for pacemaker-dependent patients afflicted with device-related complications, and therefore tested whether adenoviral TBX18 gene transfer could create biological pacemaker activity in vivo in a large-animal model of complete heart block. Biological pacemaker activity, originating from the intramyocardial injection site, was evident in TBX18-transduced animals starting at day 2 and persisted for the duration of the study (14 days) with minimal backup electronic pacemaker use. Relative to controls transduced with a reporter gene, TBX18-transduced animals exhibited enhanced autonomic responses and physiologically superior chronotropic support of physical activity. Induced sinoatrial node cells could be identified by their distinctive morphology at the site of injection in TBX18-transduced animals, but not in controls. No local or systemic safety concerns arose. Thus, minimally invasive TBX18 gene transfer creates physiologically relevant pacemaker activity in complete heart block, providing evidence for therapeutic somatic reprogramming in a clinically relevant disease model.

Association of cognitive impairment, depressive symptoms and sarcopenia among healthy older men in the veterans retirement community in southern Taiwan: A cross-sectional study

Abstract: Aim To evaluate the association of cognitive impairment, depressive mood and sarcopenia among older men living in the veterans retirement community in southern Taiwan Methods This cross-sectional study recruited 353 men aged 65 years and older. In addition to demographic characteristics, all participants were measured for gait speed, handgrip strength and muscle mass by using bioelectrical impedance analysis (BIA). The diagnosis of sarcopenia was made according to the European Working Group on Sarcopenia in Older People criteria. Slow walking speed was defined as ≤0.8 meter/second. Low muscle strength was defined as the handgrip strength less than 22.5 kg which was adjusted according to Taiwanese norms. A height-adjusted muscle mass of 8.87 kg/m2 from a previous Taiwanese study was defined as low muscle mass. Cognitive function was evaluated by the Mini-Mental State Examination (MMSE), and the Geriatric Depression Scale-15 (GDS-15) was used for screening of depressive symptoms. Results Among the 353 participants (mean age 82.7 ± 5.3 years), 30.9% (109/353) were classified as sarcopenic. Multivariate logistic regression showed that sarcopenia was independently associated with cognitive impairment (adjusted OR 3.03, 95% CI 1.63–5.65, P < 0.001) and depressive symptoms (adjusted OR 2.25, 95% CI 1.03–4.89, P = 0.04). Conclusions Sarcopenia was significantly associated with cognitive impairment and depressive symptoms among otherwise healthy older men living in the veterans retirement community. Further outcome study is required to explore the interrelationship of cognition, depressive symptoms and sarcopenia in older adults. Geriatr Gerontol Int 2014; 14 (Suppl. 1): 102–108.

Diagnosis, prevalence estimation and burden measurement in population surveys of headache: presenting the HARDSHIP questionnaire

Abstract: The global burden of headache is very large, but knowledge of it is far from complete and needs still to be gathered. Published population-based studies have used variable methodology, which has influenced findings and made comparisons difficult. The Global Campaign against Headache is undertaking initiatives to improve and standardize methods in use for cross-sectional studies. One requirement is for a survey instrument with proven cross-cultural validity. This report describes the development of such an instrument. Two of the authors developed the initial version, which was used with adaptations in population-based studies in China, Ethiopia, India, Nepal, Pakistan, Russia, Saudi Arabia, Zambia and 10 countries in the European Union. The resultant evolution of this instrument was reviewed by an expert consensus group drawn from all world regions. The final output was the Headache-Attributed Restriction, Disability, Social Handicap and Impaired Participation (HARDSHIP) questionnaire, designed for application by trained lay interviewers. HARDSHIP is a modular instrument incorporating demographic enquiry, diagnostic questions based on ICHD-3 beta criteria, and enquiries into each of the following as components of headache-attributed burden: symptom burden; health-care utilization; disability and productive time losses; impact on education, career and earnings; perception of control; interictal burden; overall individual burden; effects on relationships and family dynamics; effects on others, including household partner and children; quality of life; wellbeing; obesity as a comorbidity. HARDSHIP already has demonstrated validity and acceptability in multiple languages and cultures. Modules may be included or not, and others (eg, on additional comorbidities) added, according to the purpose of the study and resources (especially time) available.

The methodology of population surveys of headache prevalence, burden and cost: Principles and recommendations from the Global Campaign against Headache

Abstract: The global burden of headache is very large, but knowledge of it is far from complete and needs still to be gathered. Published population-based studies have used variable methodology, which has influenced findings and made comparisons difficult. Among the initiatives of the Global Campaign against Headache to improve and standardize methods in use for cross-sectional studies, the most important is the production of consensus-based methodological guidelines. This report describes the development of detailed principles and recommendations. For this purpose we brought together an expert consensus group to include experience and competence in headache epidemiology and/or epidemiology in general and drawn from all six WHO world regions. The recommendations presented are for anyone, of whatever background, with interests in designing, performing, understanding or assessing studies that measure or describe the burden of headache in populations. While aimed principally at researchers whose main interests are in the field of headache, they should also be useful, at least in parts, to those who are expert in public health or epidemiology and wish to extend their interest into the field of headache disorders. Most of all, these recommendations seek to encourage collaborations between specialists in headache disorders and epidemiologists. The focus is on migraine, tension-type headache and medication-overuse headache, but they are not intended to be exclusive to these. The burdens arising from secondary headaches are, in the majority of cases, more correctly attributed to the underlying disorders. Nevertheless, the principles outlined here are relevant for epidemiological studies on secondary headaches, provided that adequate definitions can be not only given but also applied in questionnaires or other survey instruments.

The H3K9 methyltransferase G9a is a marker of aggressive ovarian cancer that promotes peritoneal metastasis

Abstract: Ovarian cancer (OCa) peritoneal metastasis is the leading cause of cancer–related deaths in women with limited therapeutic options available for treating it and poor prognosis, as the underlying mechanism is not fully understood. The clinicopathological correlation of G9a expression was assessed in tumor specimens of ovarian cancer patients. Knockdown or overexpression of G9a in ovarian cancer cell lines was analysed with regard to its effect on adhesion, migration, invasion and anoikis-resistance. In vivo biological functions of G9a were tested by i.p. xenograft ovarian cancer models. Microarray and quantitative RT-PCR were used to analyze G9a-regulated downstream target genes. We found that the expression of histone methyltransferase G9a was highly correlated with late stage, high grade, and serous-type OCa. Higher G9a expression predicted a shorter survival in ovarian cancer patients. Furthermore, G9a expression was higher in metastatic lesions compared with their corresponding ovarian primary tumors. Knockdown of G9a expression suppressed prometastatic cellular activities including adhesion, migration, invasion and anoikis-resistance of ovarian cancer cell lines, while G9a over-expression promoted these cellular properties. G9a depletion significantly attenuated the development of ascites and tumor nodules in a peritoneal dissemination model. Importantly, microarray and quantitative RT-PCR analysis revealed that G9a regulates a cohort of tumor suppressor genes including CDH1, DUSP5, SPRY4, and PPP1R15A in ovarian cancer. Expression of these genes was also inversely correlated with G9a expression in OCa specimens. We propose that G9a contributes to multiple steps of ovarian cancer metastasis and represents a novel target to combat this deadly disease.

IL-6 enriched lung cancer stem-like cell population by inhibition of cell cycle regulators via DNMT1 upregulation.

Abstract: Tumors are influenced by a microenvironment rich in inflammatory cytokines, growth factors and chemokines, which may promote tumor growth. Interleukin-6 (IL-6) is a multifunctional cytokine and known as a regulator of immune and inflammation responses. IL-6 has also been reported to be associated with tumor progression and chemoresistance in different types of cancers. In our study, we demonstrated that IL-6 enriches the properties of lung cancer stem-like cells in A549 lung cancer cells cultured in spheroid medium. IL-6 also promotes sphere formation and stem-like properties of A549 cells by enhancing cell proliferation. Methylation-specific polymerase chain reaction (PCR) was performed and revealed that IL-6 increased methylation of p53 and p21 in A549 cancer cells. Western blot analysis and quantitative real-time PCR demonstrated that IL-6 increased the expression of DNA methyltransferase 1 (DNMT1) in A549 cells cultured in spheroid medium, but not the expression of DNMT3a or DNMT3b. Knockdown of DNMT1 eliminated IL-6-mediated hypermethylation of cell cycle regulators and enrichment of lung cancer stem-like properties. In conclusion, our study, for the first time, shows that the IL-6/JAK2/STAT3 pathway upregulates DNMT1 and enhances cancer initiation and lung cancer stem cell (CSC) proliferation by downregulation of p53 and p21 resulting from DNA hypermethylation. Upon blockage of the IL-6/JAK2/STAT3 pathway and inhibition of DNMT1, the proliferation of lung CSCs was reduced and their formation of spheres and ability to initiate tumor growth were decreased. These data suggest that targeting of the IL-6/JAK2/STAT3 signaling pathway and DNMT1 may become important strategies for treating lung cancer.

Risk of dementia after anaesthesia and surgery

Abstract: Background The potential relationship between anaesthesia, surgery and onset of dementia remains elusive. Aims To determine whether the risk of dementia increases after surgery with anaesthesia, and to evaluate possible associations among age, mode of anaesthesia, type of surgery and risk of dementia. Method The study cohort comprised patients aged 50 years and older who were anaesthetised for the first time since 1995 between 1 January 2004 and 31 December 2007, and a control group of randomly selected patients matched for age and gender. Patients were followed until 31 December 2010 to identify the emergence of dementia. Results Relative to the control group, patients who underwent anaesthesia and surgery exhibited an increased risk of dementia (hazard ratio = 1.99) and a reduced mean interval to dementia diagnosis. The risk of dementia increased in patients who received intravenous or intramuscular anaesthesia, regional anaesthesia and general anaesthesia. Conclusions The results of our nationwide, population-based study suggest that patients who undergo anaesthesia and surgery may be at increased risk of dementia.

Risk of Psychiatric Disorders following Polycystic Ovary Syndrome: A Nationwide Population-Based Cohort Study

Abstract: Background Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders among women of reproductive age. A higher prevalence of psychiatric comorbidities, including depressive disorder, anxiety disorder, and bipolar disorder has been proved in patients with PCOS. However, a clear temporal causal relationship between PCOS and psychiatric disorders has not been well established. Objective We explored the relationship between PCOS and the subsequent development of psychiatric disorders including schizophrenia, bipolar disorder, depressive disorder, anxiety disorder, and sleep disorder. Methods We identified patients who were diagnosed with PCOS by an obstetrician-gynecologist in the Taiwan National Health Insurance Research Database. A comparison cohort was constructed of patients without PCOS who were matched according to age and sex. The occurrence of subsequent new-onset psychiatric disorders was evaluated in both cohorts based on diagnoses made by psychiatrists. Results The PCOS cohort consisted of 5431 patients, and the comparison cohort consisted of 21,724 matched control patients without PCOS. The incidence of depressive disorder (hazard ratio [HR] 1.296, 95% confidence interval [CI] 1.084–.550), anxiety disorder (HR 1.392, 95% CI 1.121–1.729), and sleep disorder (HR 1.495, 95% CI 1.176–1.899) were higher among the PCOS patients than among the patients in the comparison cohort. In addition, a higher incidence of newly diagnosed depressive disorder, anxiety disorder, and sleep disorder remained significantly increased in all of the stratified follow-up durations (0–1, 1–5, ≥5 y). Conclusions PCOS might increase the risk of subsequent newly diagnosed depressive disorder, anxiety disorder, and sleep disorder. The risk of newly diagnosed bipolar disorder, which has often been reported in the literature to be comorbid with PCOS, was not significantly elevated.

Updated national and international hypertension guidelines: a review of current recommendations.

Abstract: Despite the availability of effective pharmacological treatments to aid the control of blood pressure, the global rate of uncontrolled blood pressure remains high. As such, further measures are required to improve blood pressure control. Recently, several national and international guidelines for the management of hypertension have been published. These aim to provide easily accessible information for healthcare professionals and patients to aid the diagnosis and treatment of hypertension. In this review, we have compared new and current guidelines from the American and International Societies of Hypertension; the American Heart Association, American College of Cardiology and the US Center for Disease Control and Prevention; the panel appointed to the Eighth Joint National Committee; the European Societies of Hypertension and Cardiology; the French Society of Hypertension; the Canadian Hypertension Education Program; the National Institute for Health and Clinical Excellence (UK); the Taiwan Society of Cardiology and the Chinese Hypertension League. We have identified consensus opinion regarding best practises for the management of hypertension and have highlighted any discrepancies between the recommendations. In general there is good agreement between the guidelines, however, in some areas, such as target blood pressure ranges for the elderly, further trials are required to provide sufficient high-quality evidence to form the basis of recommendations.