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Competing Interests: None

Background: There is little data available that examines the activation of the cervical paraspinal muscles that occurs during the bench press. It is intuitive that activation of these muscles may lead to increased loads across the cervical spine and may increase the risk of injury to the intervertebral disks of the cervical spine., Hypothesis: The hypothesis of this study is that by supporting the cervical spine with the "Bench Rite" cervical spine orthosis, there will be less muscular activation of the cervical paraspinal muscles as determined by electromyography when performing the bench press., Study Design: Comparative electromyographic study - Level of evidence III (case-control study)., Methods: Fifteen healthy subjects performed two sets (with and without the cervical orthosis) of five repetitions of a 60 percent maximum repetition on the bench press for each muscle group tested (pectoralis major, deltoid, C5 paraspinal, trapezius). Electromyography was used to determine the maximum isometric contraction and concentric contraction of each muscle with and without the cervical orthosis. The concentric contraction of each muscle group was reported as a percentage of maximum voluntary isometric contraction., Results: The use of the "Bench Rite" cervical spine orthosis resulted in a statistically significant decrease in muscle activation in the C5 paraspinal (37 percent; p=0.0001) and deltoid muscles (9.8 percent; p=0.001) and a significant increase in trapezius muscle activation (9.3 percent; p=0.03). No differences were found in muscle activation of the pectoralis major with or without the use of the cervical spine orthosis (0.8 percent; p=0.90)., Conclusions: Weightlifters may consider utilizing the "Bench Rite" cervical orthosis while performing the bench press to decrease cervical paraspinal muscle activation without impacting the muscle activation of the pectoralis major., (Copyright© South Dakota State Medical Association.)

Schistosomiasis is an inflammatory disease that occurs when schistosome species eggs are deposited in the liver, resulting in fibrosis and portal hypertension. Schistosomes can interact with host inflammasomes to elicit host immune responses, leading to mitochondrial damage, generation of high levels of reactive oxygen species (ROS) and activation of apoptosis during inflammation. This study aims to examine whether ROS and NF-κB (p65) expression elicited other types of inflammasome activation in Schistosoma mansoni-infected mouse livers. We examine the relationship between inflammasome activation, mitochondrial damage and ROS production in mouse livers infected with S. mansoni. We demonstrate a significant release of ROS and superoxides and increased NF-κB (p65) in S. mansoni-infected mouse livers. Moreover, activation of the NLRP3 and AIM2 inflammasomes was triggered by S. mansoni infection. Stimulation of HuH-7 hepatocellular carcinoma cells with soluble egg antigen induced activation of the AIM2 inflammasome pathway. In this study, we demonstrate that S. mansoni infection promotes both NLRP3 and AIM2 inflammasome activation.

Background: This study examined how intracranial large artery stenosis (ILAS), symptomatic and asymptomatic ILAS, and risk factors affect unfavorable outcome events after medical treatment in routine clinical practice., Methods: This was a 24-month prospective observational study of consecutively recruited stroke patients. All participants underwent magnetic resonance angiography, and their clinical characteristics were assessed. Outcome events were vascular outcome, recurrent stroke, and death. Cox regression analyses were performed to identify potential factors associated with an unfavorable outcome, which included demographic and clinical characteristics, the risk factors, and stenosis status., Results: The analysis included 686 patients; among them, 371 were assessed as ILAS negative, 231 as symptomatic ILAS, and 84 as asymptomatic ILAS. Body mass index (p < .05), hypertension (p = .01), and old infarction (p = .047) were factors relating to vascular outcomes. Hypertension was the only factor for recurrent stroke (p = .035). Poor glomerular filtration rate (< 30 mL/min/1.73 m 2 ) (p = .011) and baseline National Institutes of Health Stroke Scale scores (p < .001) were significant predictors of death., Conclusions: This study extended previous results from clinical trials to a community-based cohort study by concurrently looking at the presence/absence of stenosis and a symptomatic/asymptomatic stenotic artery. Substantiated risk factors rather than the stenosis status were predominant determinants of adverse outcome. Although the degree of stenosis is often an indicator for treatment, we suggest risk factors, such as hypertension and renal dysfunction, should be monitored and intensively treated.

Abstract: Objective To explore the distribution of genetic structure of Y-SNP and Y-STR genetic markers in different ethnic groups and its application in forensic science. Methods SNaPshot minisequencing was used to detect the polymorphisms of 12 Y-SNP loci in 439 males from 6 ethnic groups, including Guangxi Han, Guangxi Jing, Guangxi Miao, Guangxi Yao, Guangxi Zhuang and Guangxi Dong. DNATyperTM Y26 kit was used to multiplex-amplify 26 Y-STR loci. The PCR products were analyzed by 3130xl genetic analyzer. The network analysis of Y-STR haplotype under the same Y-SNP haplogroup was analyzed by Network 5.0 software. Results Six haplogroups defined by 12 Y-SNP loci were detected in 6 ethnic groups, and 362 haplotypes were detected in 26 Y-STR loci. The haplotype diversity was 0.996 6. In the C haplogroup, the samples from Guangxi Yao, Guangxi Zhuang and Guangxi Dong were clustered on different branches; in the O1 haplogroup, those from Guangxi Zhuang, Guangxi Miao and Guangxi Jing were relatively independent and clustered separately; in the O2 haplogroup, some samples from Guangxi Miao and Guangxi Yao were gathered in a cluster. Conclusion Based on the Y-STR network analysis of samples with identical haplogroup of Y-SNP, some ethnic groups can be preliminarily distinguished, which could be used to infer male suspects' ethnic group through detecting their genetic markers left in the crime scene., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Forensic Medicine.)

Background and Purpose: Fabry disease is an X-linked disease, and enzyme-based screening methods are not suitable for female patients., Methods: In total, 1000 young stroke patients (18-55 years, 661 with ischaemic stroke and 339 with hypertensive intracerebral hemorrhage) were recruited. The Sequenom iPLEX assay was used to detect 26 Fabry related mutation genes. The frequency of Fabry disease in young stroke was reviewed and compared between Asian and non-Asian countries., Results: Two male patients with ischaemic stroke were found to have a genetic mutation of IVS4+919G>A. There was no α-galactosidase A (GLA) gene mutation in female patients. The frequency in Asian stroke patients was 0.62% (male vs. female 0.63% vs. 0.58%) with 0.72% for ischaemic stroke and none for hemorrhagic stroke, compared to 0.88% (0.77% vs. 1.08%) with 0.83% for ischaemic stroke and 1.40% for hemorrhagic stroke reported in western countries., Conclusion: IVS4+919G>A is the GLA mutation in Taiwanese young ischaemic stroke patients. Fabry disease is more frequent among non-Asian patients compared to Asian patients., (© 2018 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background: Hepatic steatosis (HS) can cause substantial problems for both donors and recipients in living donor liver transplantation. The controlled attenuation parameter (CAP) is a noninvasive method of measuring HS using a process based on transient elastography., Aim: To evaluate the accuracy of CAP in quantifying HS during living donor liver transplantation., Methods: A total of 54 liver donors who received CAP and intraoperative liver biopsy (LB) were enrolled in this study. The performance of CAP compared with LB for diagnosing HS was assessed using areas under receiver operating characteristic curves. HS was defined by the presence of steatosis in >5% of hepatocytes., Results: No HS was found in 47 donors, while the remaining 7 donors showed HS ranging from 10% to 30%. Using CAP, the area under receiver operating characteristic curve was 0.96 (95% CI, 0.91-1; P < .001) for HS; the optimal cutoff value for HS was 257 dB/m (sensitivity: 100%, specificity: 89.4%, positive predictive value: 58.3%, negative predictive value: 100%). Among the 42 candidates with CAP <257 dB/m, none had HS, while of the 12 candidates with CAP ≥257 dB/m, 7 had HS. In a multivariate linear regression analyses, body mass index (β = 0.71, P < .001) was found to be independently associated with CAP in those without HS., Conclusions: CAP might be a promising tool to exclude HS in East Asian living liver donors. Body mass index was found to be independently associated with CAP values in those without HS., (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: To assess the risk factors and effects of delayed diagnosis on tuberculosis (TB) mortality in Hong Kong., Methods: All consecutive patients with TB notified in 2010 were tracked through their clinical records for treatment outcome until 2012. All TB cases notified or confirmed after death were identified for a mortality survey on the timing and causes of death., Results: Of 5092 TB cases notified, 1061 (20.9%) died within 2 years of notification; 211 (4.1%) patients died before notification, 683 (13.4%) died within the first year, and 167 (3.3%) died within the second year after notification. Among the 211 cases with TB notified after death, only 30 were certified to have died from TB. However, 52 (24.6%) died from unspecified pneumonia/sepsis possibly related to pulmonary TB. If these cases are counted, the total TB-related deaths increases from 191 to 243. In 82 (33.7%) of these, TB was notified after death. Over 60% of cases in which TB diagnosed after death involved patients aged ≥80 years and a similar proportion had an advance care directive against resuscitation or investigation. Independent factors for TB notified after death included female sex, living in an old age home, drug abuse, malignancy other than lung cancer, sputum TB smear negative, sputum TB culture positive, and chest X-ray not done., Conclusions: High mortality was observed among patients with TB aged ≥80 years. Increased vigilance is warranted to avoid delayed diagnosis and reduce the transmission risk, especially among elderly patients with co-morbidities living in old age homes.

Background: The study aimed to investigate the physiology, psychophysics, pathology and their relationship in reversible nociceptive nerve degeneration, and the physiology of acute hyperalgesia., Methods: We enrolled 15 normal subjects to investigate intraepidermal nerve fibre (IENF) density, contact heat-evoked potential (CHEP) and thermal thresholds during the capsaicin-induced skin nerve degeneration-regeneration; and CHEP and thermal thresholds at capsaicin-induced acute hyperalgesia., Results: After 2-week capsaicin treatment, IENF density of skin was markedly reduced with reduced amplitude and prolonged latency of CHEP, and increased warm and heat pain thresholds. The time courses of skin nerve regeneration and reversal of physiology and psychophysics were different: IENF density was still lower at 10 weeks after capsaicin treatment than that at baseline, whereas CHEP amplitude and warm threshold became normalized within 3 weeks after capsaicin treatment. Although CHEP amplitude and IENF density were best correlated in a multiple linear regression model, a one-phase exponential association model showed better fit than a simple linear one, that is in the regeneration phase, the slope of the regression line between CHEP amplitude and IENF density was steeper in the subgroup with lower IENF densities than in the one with higher IENF densities. During capsaicin-induced hyperalgesia, recordable rate of CHEP to 43 °C heat stimulation was higher with enhanced CHEP amplitude and pain perception compared to baseline., Conclusions: There were differential restoration of IENF density, CHEP and thermal thresholds, and changed CHEP-IENF relationships during skin reinnervation. CHEP can be a physiological signature of acute hyperalgesia., Significance: These observations suggested the relationship between nociceptive nerve terminals and brain responses to thermal stimuli changed during different degree of skin denervation, and CHEP to low-intensity heat stimulus can reflect the physiology of hyperalgesia., (© 2018 European Pain Federation - EFIC®.)

Introduction: Pleural fluid adenosine deaminase level can be applied to rapidly detect tuberculous pleural effusion. We aimed to establish a local diagnostic cut-off value for pleural fluid adenosine deaminase to identify patients with tuberculous pleural effusion, and optimise its utility., Methods: We retrospectively reviewed the medical records of consecutive adults with pleural fluid adenosine deaminase level measured by the Diazyme commercial kit (Diazyme Laboratories, San Diego [CA], United States) during 1 January to 31 December 2011 in a cluster of public hospitals in Hong Kong. We considered its level alongside early (within 2 weeks) findings in pleural fluid and pleural biopsy, with and without applying Light's criteria in multiple scenarios. For each scenario, we used the receiver operating characteristic curve to identify a diagnostic cut-off value for pleural fluid adenosine deaminase, and estimated its positive and negative predictive values., Results: A total of 860 medical records were reviewed. Pleural effusion was caused by congestive heart failure, chronic renal failure, or hypoalbuminaemia caused by liver or kidney diseases in 246 (28.6%) patients, malignancy in 198 (23.0%), non-tuberculous infection in 168 (19.5%), tuberculous pleural effusion in 157 (18.3%), and miscellaneous causes in 91 (10.6%). All those with tuberculous pleural effusion had a pleural fluid adenosine deaminase level of ≤100 U/L. When analysis was restricted to 689 patients with pleural fluid adenosine deaminase level of ≤100 U/L and early negative findings for malignancy and non-tuberculous infection in pleural fluid, the positive predictive value was significantly increased and the negative predictive value non-significantly reduced. Using this approach, neither additionally restricting analysis to exudates by Light's criteria nor adding closed pleural biopsy would further enhance predictive values. As such, the diagnostic cut-off value for pleural fluid adenosine deaminase is 26.5 U/L, with a sensitivity of 87.3%, specificity of 93.2%, positive predictive value of 79.2%, negative predictive value of 96.1%, and accuracy of 91.9%. Sex, age, and co-morbidity did not significantly affect prediction of tuberculous pleural effusion using the cut-off value., Conclusion: We have established a diagnostic cut-off level for pleural fluid adenosine deaminase in the diagnosis of tuberculous pleural effusion by restricting analysis to a level of ≤100 U/L, and considering early pleural fluid findings for malignancy and non-tuberculous infection, but not Light's criteria.

Background: Central venous catheters (CVCs) are frequently used for monitoring haemodynamic status and rapidly delivering fluid therapy during the peri- and postoperative periods. Indwelling CVCs are typically used 7-14 days postoperatively for additional monitoring and treatment, but patients may develop asymptomatic catheter-related thrombosis, leading to life-threatening pulmonary embolism and death. Early detection helps to avoid such complications., Methods: This prospective observational study investigated the risk factors associated with catheter-related right internal jugular vein thrombosis in patients undergoing chest surgery. The study enrolled 24 patients who were scheduled to receive chest surgeries during which catheters were needed. To detect thrombus formation, Doppler ultrasound examinations from the thyroid cartilage level to the supraclavicular region were used after CVC placement and on each of the following days until the catheter was removed., Results: No thrombosis was found in patients before surgery, but it appeared in 75% (18/24) after surgery. The risks of thrombosis increased with a longer duration of anaesthesia, greater amounts of bleeding, and use of postoperative ventilator support., Conclusions: Earlier catheter removal may reduce the risk of catheter-related thrombosis and avoid possibly fatal complications after catheter-related thrombosis., (© The Author 2017. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com)

Background: Globally there is a burgeoning epidemic of drug monoresistant tuberculosis (TB), multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB). Almost 20% of all TB strains worldwide are resistant to at least one major TB drug, including isoniazid. In several parts of the world there is an increasing incidence of MDR-TB, and alarmingly, almost a third of MDR-TB cases globally are resistant to either a fluoroquinolone or aminoglycoside. This trend cannot be ignored because drug-resistant TB is associated with greater morbidity compared to drug-susceptible TB, accounts for almost 25% of global TB mortality, is extremely costly to treat, consumes substantial portions of budgets allocated to national TB programmes in TB-endemic countries and is a major threat to healthcare workers, who are already in short supply in resource-poor settings. Even more worrying is the growing epidemic of resistance beyond XDR-TB, including resistance to newer drugs such as bedaquiline and delamanid, as well as the increasing prevalence of programmatically incurable TB in countries like South Africa, Russia, India and China. These developments threaten to reverse the gains already made against TB., Sources: Articles related to MDR-TB and XDR-TB found on PubMed in all languages up to September 2016, published reviews, and files of the authors., Aim and Content: To review the clinical management of adults and children with MDR- and XDR-TB with a particular emphasis on the utility of newer and repurposed drugs such as linezolid, bedaquiline and delamanid, as well as management of MDR- and XDR-TB in special situations such as in HIV-infected persons and in children., Implications: This review informs on the prevention, diagnosis, and clinical management of MDR-TB and XDR-TB., (Copyright © 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Enterobius vermicularis is the most common human intestinal parasite, and its control among school children is an important public health issue. The objective of this study was to document the present situation of E. vermicularis infection in school children in Hualien. The administrative divisions in Hualien county include 13 districts (3 in a mountainous area, 10 in a rural/urban area). Between 2007 and 2012, a total of 41,191 children in 13 districts in Hualien were examined using consecutive 2-day adhesive cellophane paper perianal swabs. Our results showed Enterobius egg-positive infection rates of 5.79% (452/7,089) in 2007, 6.25% (457/7,312) in 2008, 5.37% (385/7,173) in 2009, 4.98% (330/6,804) in 2010, 4.91% (301/6,133) in 2011, and 4.68% (279/5,960) in 2012. Compared to the previously reported national average in Taiwan (range, 1.53-2.23%), the prevalence of E. vermicularis in Hualien is relatively high. The infection rates were 7.55-29.10% in mountainous areas and 0.50- 12.43% in rural/urban areas. All first and fourth grade students in elementary schools in Hualien were selected as study participants. The average infection rate of the first grade students (6.71%) was higher than that of the fourth grade students (4.23%). These results indicate that enterobiasis remains an important parasitic disease among school children in Hualien, especially those in mountainous areas.

Broad-area vertical-cavity surface-emitting lasers (VCSELs) with different cavity sizes are experimentally exploited to manifest the influence of the finite confinement strength on the path-length distribution of quantum billiards. The subthreshold emission spectra of VCSELs are measured to obtain the path-length distributions by using the Fourier transform. It is verified that the number of the resonant peaks in the path-length distribution decreases with decreasing the confinement strength. Theoretical analyses for finite-potential quantum billiards are numerically performed to confirm that the mesoscopic phenomena of quantum billiards with finite confinement strength can be analogously revealed by using broad-area VCSELs.

This study aims to assess the nephrotoxicity and efficacy of tenofovir disoproxil fumarate (tenofovir), telbivudine and entecavir. A retrospective study of 587 patients with chronic hepatitis B treated with tenofovir (n = 170), telbivudine (n = 184) and entecavir (n = 233) for at least 1 year. Renal function and efficacy were assessed. The estimated glomerular filtration rate (eGFR) decreased significantly in the tenofovir group after a mean of 17 months treatment (from 92.2 to 85.6 mL/min/1.73 m(2), p < 0.001), but increased in the telbivudine group after a mean of 32 months of treatment (from 86.1 to 95 mL/min/1.73 m(2), p < 0.001). There was no significant change in eGFR in the entecavir group after a mean of 44 months. By multivariate analysis, pre-existing renal insufficiency (p = 0.003), tenofovir (p = 0.007) and diuretic treatment (p = 0.001) were independent predictors for renal function deterioration. Cumulative virological breakthrough was 0% in tenofovir after 2 years, 3.4% in entecavir after 7 years and 22.9% in telbivudine after 5 years. Liver cirrhosis (p = 0.008) and virological breakthrough (p = 0.040) were independently associated with increased risk of hepatocellular carcinoma development. Tenofovir may lead to deterioration in renal function as assessed by serial eGFR measurements. Although telbivudine appeared to be associated with an improvement in eGFR, it was associated with high rates of virological breakthrough, which was an independent risk factor for HCC development. With low rates of virological breakthrough and preservation of renal function, entecavir could be the best choice among these three agents., (Copyright © 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

To supplement previous state-of-art reviews on anti-tuberculosis treatment and to pave the way forward with reference to the current status, we systematically reviewed published literature on clinical research on tuberculosis (TB) over the past decade in the treatment of drug-susceptible and multidrug-resistant TB (MDR-TB), with a focus on drugs, dosing factors and regimens. Our review was restricted to Phase II/III clinical trials, cohort and case-control studies, and systematic reviews of clinical studies. TB programmatic and patient behavioural factors, non-TB drugs, adjunctive surgery, new vaccines, immunotherapy, antiretroviral therapy and management of latent tuberculous infection are outside the scope of this review. An algorithm was used to systematically search PubMed for relevant articles published in English from 1 January 2005 to 31 December 2014. Articles without evaluated factors (drugs, dosing factors and regimens) or comparative analysis of specified anti-tuberculosis treatment outcomes were excluded. Of the 399 articles initially identified, 294 were excluded. The main findings of the remaining 105 articles are described under two categories: presumed drug-susceptible TB and MDR-TB. Fifty-nine articles included under drug-susceptible TB were divided into 12 subcategories: isoniazid, rifampicin, pyrazinamide, fluoroquinolones, fixed-dose combination drugs, dosing frequency, treatment phases, treatment duration, experimental regimens for pulmonary (surrogate markers vs. clinical outcomes) and extra-pulmonary TB. Forty-nine articles included under MDR-TB were divided into seven subcategories: fluoroquinolones, pyrazinamide, second-line injectable drugs, World Health Organization Group 4 and Group 5 drugs, MDR-TB regimens and novel drugs. Clinical research in the last decade and ongoing trials might furnish new paradigms for improving the treatment of this recalcitrant ancient disease.

Acinetobacter baumannii represents a significant cause of nosocomial infections. Therefore, we combined real-time quantitative polymerase chain reaction (PCR) with the propidium monoazide (PMA-qPCR) to assess the feasibility of detecting viable, airborne A. baumannii. The biological collection efficiencies of three samplers for collecting airborne A. baumannii were evaluated by PMA-qPCR in a chamber study. After sampling, the effects of storage in collection fluid on A. baumannii were evaluated. The results showed that the culturable ratio of A. baumannii measured using the culture method was significantly correlated with the viable ratio measured using PMA-qPCR, but was not significantly correlated with the qPCR results. It was indicated that the AGI-30 impinger and the BioSampler were much more effective than the Nuclepore filter sampler for collecting airborne A. baumannii. The storage temperature was critical for aerosol samples, as the loss of viable A. baumannii was minimized when the PMA-bound DNA was stored at -20°C or if the collected cells were stored at 4°C and subsequently processed by PMA-qPCR within 1 month. The PMA-qPCR method was also to distinguish between colistin-sensitive and colistin-resistant A. baumannii, and no colistin-sensitive A. baumannii was detected by PMA-qPCR upon treatment of the BioSampler collection medium with 2 μg/ml colistin for 5 min., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The automated high-throughput Abbott RealTime MTB real-time PCR assay has been recently launched for Mycobacterium tuberculosis complex (MTBC) clinical diagnosis. This study would like to evaluate its performance. We first compared its diagnostic performance with the Roche Cobas TaqMan MTB assay on 214 clinical respiratory specimens. Prospective analysis of a total 520 specimens was then performed to further evaluate the Abbott assay. The Abbott assay showed a lower limit of detection at 22.5 AFB/ml, which was more sensitive than the Cobas assay (167.5 AFB/ml). The two assays demonstrated a significant difference in diagnostic performance (McNemar's test; P = 0.0034), in which the Abbott assay presented significantly higher area under curve (AUC) than the Cobas assay (1.000 vs 0.880; P = 0.0002). The Abbott assay demonstrated extremely low PCR inhibition on clinical respiratory specimens. The automated Abbott assay required only very short manual handling time (0.5 h), which could help to improve the laboratory management. In the prospective analysis, the overall estimates for sensitivity and specificity of the Abbott assay were both 100 % among smear-positive specimens, whereas the smear-negative specimens were 96.7 and 96.1 %, respectively. No cross-reactivity with non-tuberculosis mycobacterial species was observed. The superiority in sensitivity of the Abbott assay for detecting MTBC in smear-negative specimens could further minimize the risk in MTBC false-negative detection. The new Abbott RealTime MTB assay has good diagnostic performance which can be a useful diagnostic tool for rapid MTBC detection in clinical laboratories.

Objective: To examine the impact of immigrant populations on the epidemiology of tuberculosis in Hong Kong., Design: Longitudinal cohort study., Setting: Hong Kong., Participants: Socio-demographic and disease characteristics of all tuberculosis notifications in 2006 were captured from the statutory tuberculosis registry and central tuberculosis reference laboratory. Using 2006 By-census population data, indirect sex- and age-standardised incidence ratios by place of birth were calculated. Treatment outcome at 12 months was ascertained from government tuberculosis programme record forms, and tuberculosis relapse was tracked through the notification registry and death registry up to 30 June 2013., Results: Moderately higher sex- and age-standardised incidence ratios were observed among various immigrant groups: 1.06 (Mainland China), 2.02 (India, Pakistan, Bangladesh), 1.59 (Philippines, Thailand, Indonesia, Nepal), and 3.11 (Vietnam). Recent Mainland migrants had a lower sex- and age-standardised incidence ratio (0.51 vs 1.09) than those who immigrated 7 years ago or earlier. Age younger than 65 years, birth in the Mainland or the above Asian countries, and previous treatment were independently associated with resistance to isoniazid and/or rifampicin. Older age, birth in the above Asian countries, non-permanent residents, previous history of treatment, and resistance to isoniazid and/or rifampicin were independently associated with poor treatment outcome (other than cure/treatment completion) at 1 year. Birth outside Hong Kong was an independent predictor of relapse following successful completion of treatment (adjusted hazard ratio=1.76; 95% confidence interval, 1.07-2.89; P=0.025)., Conclusion: Immigrants carry with them a higher tuberculosis incidence and/or drug resistance rate from their place of origin. The higher drug resistance rate, poorer treatment outcome, and excess relapse risk raise concern over secondary transmission of drug-resistant tuberculosis within the local community.

Background/objectives: Chronic kidney diseases are associated with changes in cardiometabolic risk (CMR) factors in which body composition parameters have been used as sensitive predictors. This study aimed to explore the associations of anthropometric indicators, body fat (BF), body mass index (BMI) and waist circumference (WC) with estimated glomerular filtration rate (eGFR) in an adult healthy Chinese population., Subjects/methods: A cross-sectional study was conducted for the subjects undergoing annual health examinations. The associations of subjects with body composition parameters were analyzed using the cutoff values of BMI, BF and WC in accordance with the criteria for Asian or Taiwanese population by gender., Results: A total of 3473 subjects, aged 30-45 years, who received physical examinations in 2007 were analyzed. The levels of CMR factors were significantly higher in males than in females. eGFR was negatively associated with BMI but positively related to BF. The additional roles of BMI and WC were observed in the subjects who were categorized according to BF. Females with normal weight obese were associated with increased eGFR, whereas a higher eGFR was found in males with low/normal BF and BMI or normal WC., Conclusions: Our data provided evidence that anthropometric parameters were associated with changes of eGFR in relatively healthy adults. Higher eGFR was observed in females with normal weight obese in whom hyperfiltration may be suspected, and this finding deserves further studies.

Objectives: The aim of this study was to explore the possible association between dermatomyositis/polymyositis (DM/PM) and subsequent acute coronary syndrome (ACS) risk., Method: We used data from the National Health Insurance (NHI) system of Taiwan to address the research topic. The exposure cohort contained 2029 patients with new diagnoses of DM/PM. Each patient was randomly frequency-matched according to sex and age with four participants from the general population who did not have a history of ACS at the index date (control group). Cox proportional hazard regression analyses were conducted to estimate the relationship between DM/PM and subsequent ACS risk., Results: Among patients with DM/PM, the overall risk for developing subsequent ACS was significantly higher than that of the control group [adjusted hazard ratio (aHR) 1.98, 95% confidence interval (CI) 1.17-3.35]. Further analysis indicated a higher risk in patients who were male, older, or diagnosed with comorbidities., Conclusions: The findings from this population-based retrospective cohort study suggest that DM/PM is associated with an increased subsequent ACS risk.

MicroRNAs (miRNAs) comprise a class of short, non-coding RNAs that regulate protein synthesis through posttranscriptional modifications. In this study, we found significant upregulation of miR-18a in prostate cancer specimens and prostate cancer cell lines compared with the normal controls. MiRNAs can be separated into two groups based on whether they regulate tumor suppressors or oncogenes. In our previous study, we found that miR-18a, which belongs to the miR17-92 cluster, is upregulated in prostate cancer; the objective of this study was to investigate the associated regulatory mechanisms. We found that miR-18a is upregulated in clinical tumor specimens and cancer cell lines. Our bioinformatics analysis showed that the serine/threonine-protein kinase 4 (STK4) 3' untranslated region contains a highly conserved binding site for the miR-18a seed region. Luciferase reporter assays were performed to indicate that STK4 is a direct target of miR-18a. Interestingly, miR-18a knockdown decreased cell growth in prostate cancer cells and significantly decreased prostate tumor growth in in vivo nude mice experiments through STK4-mediated dephosphorylation of AKT and thereby inducing apoptosis. Our results suggest that miR-18a acts as an oncomiR targeting STK4 in prostate cancer, and inhibition of miR-18a expression may offer therapeutically beneficial option for prostate cancer treatment.

The chromosomal passenger complex (CPC) plays a pivotal role in controlling accurate chromosome segregation and cytokinesis during cell division. Aurora-B, one of the chromosomal passenger proteins, is important for the mitotic spindle assembly checkpoint (SAC). Previous reports noted that Aurora-C is predominantly expressed in male germ cells and has the same subcellular localization as Aurora-B. Increasing evidence indicates that Aurora-C is overexpressed in many somatic cancers, although its function is uncertain. Our previous study showed that the aberrant expression of Aurora-C increases the tumorigenicity of cancer cells. Here, we demonstrate that overexpressed Aurora-C displaces the centromeric localization of CPCs, including INCENP, survivin, and Aurora-B. When cells were treated with nocodazole to turn on SAC, both the Aurora-B protein stability and kinase activity were affected by overexpressed Aurora-C. As a result, the activation of spindle checkpoint protein, BubR1, and phosphorylation of histone H3 and MCAK were also eliminated in Aurora-C-overexpressing cells. Thus, our results suggest that aberrantly expressed Aurora-C in somatic cancer cells may impair SAC by displacing the centromeric localization of CPCs.

There are limited data comparing the clinical outcomes between telbivudine and entecavir. We consecutively enrolled 115 telbivudine-naive and 115 entecavir-naive chronic hepatitis B patients, who were matched for age, sex, hepatitis B e antigen (HBeAg) status and cirrhosis, and treated for at least 2 years or less than 2 years but had developed resistance. Except for the rate of HBeAg seroconversion, which was similar, patients in the entecavir group had better clinical outcomes than those in the telbivudine group for alanine aminotransferase normalization (85.2% vs 78.4%, p <0.048), undetectable HBV DNA (96.5% vs 74.8%, p <0.001), and viral resistance (0.9% vs 21.7%, p <0.001) after 2 years of treatment, After applying roadmap or super-responders concepts, entecavir still had better outcomes than telbivudine in undetectable HBV DNA and viral resistance. The cumulative incidence of hepatocellular carcinoma development was similar between telbivudine-naive and entecavir-naive patients (p 0.565). In renal function analysis, there were significantly more patients with estimated glomerular filtration rate (eGFR) category improvement in both the telbivudine and entecavir groups at year 1 (p 0.006 and p 0.047, respectively). The rate of virological improvement was significantly higher with entecavir than with telbivudine after 2 years of treatment, whether applying the concepts of roadmap or super-responders. The incidence of hepatocellular carcinoma was similar between telbivudine and entecavir. Both telbivudine and entecavir were associated with eGFR improvement, especially in patients with renal insufficiency., (© 2013 The Authors Clinical Microbiology and Infection ©2013 European Society of Clinical Microbiology and Infectious Diseases.)

Recent studies have indicated that amino acid (aa) substitutions in the core region and NS5A interferon sensitivity-determining region (ISDR) of hepatitis C virus (HCV) as well as genetic polymorphisms in the interleukin-28B (IL-28B) locus affect the outcome of interferon (IFN)-based therapies. We aimed to investigate the role of these factors on response to peginterferon plus ribavirin in a prospective study of response-guided therapy. The aa sequences in core region and ISDR and rs12979860 genotypes were analysed in 115 HCV-1 patients. The treatment was 24 weeks for patients achieving a rapid virological response (RVR), 48 weeks for those with an early virological response (EVR) and early terminated in those without an EVR. A sustained virological response (SVR) was achieved in 82% of 34 RVR patients, 45% of 74 EVR patients and 0% of seven non-EVR patients. Logistic regression analysis showed that ISDR mutation (≥2) [odds ratio(OR): 6.024], double core 70/91 mutations (OR: 0.136), and platelet counts≥15×10(4) /μL (OR: 3.119) were independent pretreatment factors associated with SVR. Apart from rs12979860 CC genotype, low viral load and ISDR mutation (≥2) were significant factors predictive of RVR. Combination of rs12979860 genotype and baseline viral characteristics (viral load and core/ISDR mutations) could predict RVR and SVR with positive predictive value of 100% and 91%, and negative predictive value of 80% and 54%, respectively. In conclusion, pretreatment screening rs12979860 genotype and aa substitutions in the core region and ISDR could help identifying patients who are good candidates for peginterferon plus ribavirin therapy., (© 2013 John Wiley & Sons Ltd.)

Background: Interferon (IFN)-based therapies could eradicate hepatitis C (HCV) and reduce the risk of hepatocellular carcinoma (HCC). However, HCC could still happen after sustained virological response (SVR). We aimed to develop a simple scoring system to predict the risk of HCC development among HCV patients after antiviral therapies., Methods: From 1999 to 2009, 1879 patients with biopsy-proven HCV infection treated with IFN-based therapies were analyzed., Results: Multivariable analysis showed old age (adjusted HR (aHR)=1.73, 95% CI=1.13-2.65 for aged 60-69 and aHR=2.20, 95% CI=1.43-3.37 for aged ≥ 70), Male gender (aHR=1.74, 95% CI=1.26-2.41), platelet count <150 × 10(9)/l (HR=1.91, 95% CI=1.27-2.86), α-fetoprotein ≥ 20 ng ml(-1) (HR=2.23, 95% CI=1.58-3.14), high fibrotic stage (HR=3.32, 95% CI=2.10-5.22), HCV genotype 1b (HR=1.53, 95% CI=1.10-2.14), and non SVR (HR=2.40, 95% CI=1.70-3.38) were independent risk factors for HCC. Regression coefficients were used to build up a risk score and the accuracy was evaluated by using the area under the receiver operating characteristic curve (AUC). Three groups as low-, intermediate-, and high-risk are classified based on the risk scores. One hundred sixty patients (12.78%) in the derivation and 82 patients (13.08%) in the validation cohort developed HCC with AUC of 79.4%, sensitivity of 84.38%, and specificity of 60.66%. In the validation cohort, the 5-year HCC incidence was 1.81%, 12.92%, and 29.95% in low-, intermediate-, and high-risk groups, with hazard ratios 4.49 in intermediate- and 16.14 in high-risk group respectively. The risk reduction of HCC is greatest in patients with SVR, with a 5-year and 10-year risk reduction of 28.91% and 27.99% respectively., Conclusion: The risk scoring system is accurate in predicting HCC development for HCV patients after antiviral therapies.

Transarticular screw fixation with autograft is an established procedure for the surgical treatment of atlantoaxial instability. Removal of the posterior arch of C1 may affect the rate of fusion. This study assessed the rate of atlantoaxial fusion using transarticular screws with or without removal of the posterior arch of C1. We reviewed 30 consecutive patients who underwent atlantoaxial fusion with a minimum follow-up of two years. In 25 patients (group A) the posterior arch of C1 was not excised (group A) and in five it was (group B). Fusion was assessed on static and dynamic radiographs. In selected patients CT imaging was also used to assess fusion and the position of the screws. There were 15 men and 15 women with a mean age of 51.2 years (23 to 77) and a mean follow-up of 7.7 years (2 to 11.6). Stable union with a solid fusion or a stable fibrous union was achieved in 29 patients (97%). In Group A, 20 patients (80%) achieved a solid fusion, four (16%) a stable fibrous union and one (4%) a nonunion. In Group B, stable union was achieved in all patients, three having a solid fusion and two a stable fibrous union. There was no statistically significant difference between the status of fusion in the two groups. Complications were noted in 12 patients (40%); these were mainly related to the screws, and included malpositioning and breakage. The presence of an intact or removed posterior arch of C1 did not affect the rate of fusion in patients with atlantoaxial instability undergoing C1/C2 fusion using transarticular screws and autograft.

MicroRNAs (miRNAs) are a type of endogenous noncoding small RNAs involved in the regulation of multiple biological processes. Recently, miR-29 was found to participate in myogenesis. However, the underlying mechanisms by which miR-29 promotes myogenesis have not been identified. We found here that miR-29 was significantly upregulated with age in postnatal mouse skeletal muscle and during muscle differentiation. Overexpression of miR-29 inhibited mouse C2C12 myoblast proliferation and promoted myotube formation. miR-29 specifically targeted Akt3, a member of the serine/threonine protein kinase family responsive to growth factor cell signaling, to result in its post-transcriptional downregulation. Furthermore, knockdown of Akt3 by siRNA significantly inhibited the proliferation of C2C12 cells, and conversely, overexpression of Akt3 suppressed their differentiation. Collectively and given the inverse endogenous expression pattern of rising miR-29 levels and decreasing Akt3 protein levels with age in mouse skeletal muscle, we propose a novel mechanism in which miR-29 modulates growth and promotes differentiation of skeletal muscle through the post-transcriptional downregulation of Akt3.

Setting: Elderly persons living in the community in Hong Kong., Objective: To examine the association between tuberculosis (TB) and lung cancer., Design: Elderly clients enrolled in a health programme from 2000 to 2003 were retrospectively cross-matched with the territory-wide TB notification registry for TB before enrolment. The cohort was followed up prospectively through linkage with the territory-wide death registry for cause of death until 31 December 2011. All subjects with suspected malignancy or recent weight loss (≥5%) at enrolment and deaths within the first 2 years of follow-up were excluded., Results: Of the 61,239 subjects included, 516 had TB before enrolment. After 490,258 person-years of follow-up, respectively 1344, 910 and 2003 deaths were caused by lung cancer, other tobacco-related malignancies and non-tobacco-related malignancies. TB before enrolment was associated with death due to lung cancer (Mantel-Haenszel weighted relative risk 2.61, 95%CI 1.82-3.74, P < 0.001) but not other malignancies after stratification by sex. TB remained an independent predictor of lung cancer death (adjusted hazard ratio 2.01, 95%CI 1.40-2.90; P < 0.001), after adjustment for multiple potential confounders., Conclusions: TB was independently associated with subsequent mortality due to lung cancer. This finding calls for intensification of tobacco control and better targeting of lung cancer screening in high TB burden areas.

A farm-scale biogas desulfurization system was designed and tested for H2S removal efficiency from livestock biogas. This work assesses the H2S removal efficiency of a novel farm-scale biogas bio-desulfurization system (BBS) operated for 350 days on a 1,000-head pig farm. Experimental data demonstrated that suitable humidity and temperature can help sulfur-oxidizing bacteria to form active bio-films on the bio-carriers. The daily average removal rate increased to 879.16 from 337.75 g-H2S/d with an average inlet H2S concentration of 4,691 ± 1,532 mg/m(3) in biogas. Thus, the overall (0-350 days) average H2S removal efficiency exceeded 93%. The proposed BBS overcomes limitations of H2S in biogas when utilizing pig farm biogas for power generation and other applications.

IN THIS YEAR-IN-REVIEW ARTICLE, we summarizes 104 articles published on tuberculosis in the International Journal of Tuberculosis and Lung Disease from the January to the August issue in 201, and arbitrarily categorise them according to three subject areas: active TB, latent TB infection (LTBI),and operational research.

Setting: High lung cancer mortality is observed among female never-smokers in Hong Kong., Objective: To examine the relationship between obstructive lung disease (chronic obstructive pulmonary disease and/or asthma) and lung cancer mortality by sex and smoking status., Design: A cohort of elderly clients (aged ≥65 years) in a health maintenance programme were followed prospectively through linkage with the territory-wide death registry for causes of death, using identity card number as the unique identifier., Results: After 516,055 person-years of follow-up, respectively 1297, 872 and 1908 deaths were caused by lung cancer, other tobacco-related malignancies and non-tobacco-related malignancies. In the overall analysis, obstructive lung disease was independently associated with mortality due to lung cancer (aHR 1.86, P < 0.001) after adjustment for potential confounders. However, no association was detected among female never-smokers (HR 0.97, P = 0.909), in sharp contrast with female ever-smokers, male never-smokers and male ever-smokers (HR 1.98, 2.34 and 2.09, respectively, P from 0.047 to <0.001). Consistent results were observed after exclusion of all deaths in the initial 3 years., Conclusion: Obstructive lung disease exerted differential effects on lung cancer mortality across different sex and smoking subgroups in this Asian population, with a conspicuous absence of effect among female never-smokers.

Higenamine mediates cardiotonic, vascular relaxation and bronchodilator effects. The relaxation effects and the mechanism of action of higenamine on the rat corpus cavernosum (CC) were assessed to investigate the effect of higenamine on penile erection. Strips of CC and aorta were used in organ baths for isometric tension studies. Tension was measured with isometric force transducers, and muscle relaxation was expressed as the percent decrease in precontraction induced by phenylephrine (PE). The relaxation reactions were investigated in an endothelial-denuded group and groups pretreated with N(G)-nitro-L-arginine methyl ester (NO synthesis inhibitor), propranolol (β-receptor blocker), indomethacin (COX inhibitor), glibenclamide (K(+)(ATP) channel inhibitor), 4-aminopyridine (membrane potential-dependent potassium channel inhibitor) and methylene blue (guanylyl cyclase inhibitor) for 30 min. Intracavernous pressure (ICP) was assessed in rats after the intravenous administration of higenamine, and changes in guanosine 3',5'-cyclic monophosphate and adenosine 3',5'-cyclic monophosphate (cAMP) concentrations were measured on the basis of the higenamine concentration. Also, the combined reaction of higenamine and the phosphodiesterase type-5 (PDE-5) inhibitors was assessed. Higenamine induced relaxation of the CC and the aortic strips precontracted with PE in a dose-dependent manner. The CC was significantly more relaxed than the aortic rings in response to the same higenamine concentration (P<0.05). The CC relaxation reaction was suppressed by the β-receptor blocker propranolol. The cAMP concentration increased gradually with increased higenamine concentration (P<0.05). The ICP also increased with increased higenamine concentration in vivo (P<0.05). In the group pretreated with 10(-7) M higenamine, the relaxation reaction of CC induced by the PDE-5 inhibitor increased significantly, compared with CC exposed to the PDE-5 inhibitor but not pretreated with higenamine (P<0.05). In conclusion, higenamine induced relaxation of the rat CC in a dose-dependent manner. The effect may be mediated through β-adrenoceptors. The results suggest that higenamine may be valuable as a new lead compound for treating erectile dysfunction.

Background: The sigma-2 receptor has been identified as a biomarker of proliferating cells in solid tumours. In the present study, we studied the mechanisms of sigma-2 ligand-induced cell death in the mouse breast cancer cell line EMT-6 and the human melanoma cell line MDA-MB-435., Methods: EMT-6 and MDA-MB-435 cells were treated with sigma-2 ligands. The modulation of multiple signaling pathways of cell death was evaluated., Results: Three sigma-2 ligands (WC-26, SV119 and RHM-138) induced DNA fragmentation, caspase-3 activation and PARP-1 cleavage. The caspase inhibitor Z-VAD-FMK partially blocked DNA fragmentation and cytotoxicity caused by these compounds. These data suggest that sigma-2 ligand-induced apoptosis and caspase activation are partially responsible for the cell death. WC-26 and siramesine induced formation of vacuoles in the cells. WC-26, SV119, RHM-138 and siramesine increased the synthesis and processing of microtubule-associated protein light chain 3, an autophagosome marker, and decreased the expression levels of the downstream effectors of mammalian target of rapamycin (mTOR), p70S6K and 4EBP1, suggesting that sigma-2 ligands induce autophagy, probably by inhibition of the mTOR pathway. All four sigma-2 ligands decreased the expression of cyclin D1 in a time-dependent manner. In addition, WC-26 and SV119 mainly decreased cyclin B1, E2 and phosphorylation of retinoblastoma protein (pRb); RHM-138 mainly decreased cyclin E2; and 10 μM siramesine mainly decreased cyclin B1 and pRb. These data suggest that sigma-2 ligands also impair cell-cycle progression in multiple phases of the cell cycle., Conclusion: Sigma-2 ligands induce cell death by multiple signalling pathways.

Background: Primary percutaneous coronary intervention (PCI) in patients with ST-elevation myocardial infarction (STEMI) significantly reduces mortality and morbidity, particularly when door-to-balloon (D2B) time is < 90 min. We sought to minimize preventable delays by instituting an on-site cardiology team-based approach in the emergency department (ED)., Methods: The on-site group comprised 146 consecutive patients with STEMI undergoing primary PCI after implementation of the on-site strategy. This new patient care model was compared with the conventional care administered before instituting the on-site cardiology team-based strategy in ED, which included 90 patients (interim group) receiving primary PCI at a catheterization room in the same building as the ED, and 147 patients (pre-on-site group) undergoing primary PCI at a catheterization room two blocks away from the ED., Results: Median D2B time decreased from 107 min in the pre-on-site group to 72 min in the interim group, and to 47 min in the on-site group, respectively (p < 0.001). The percentage of D2B times < 90 min increased from 34% to 78% and 96%, respectively among the three groups (p < 0.001). Hospitalization costs were significantly reduced in the on-site and interim vs. pre-on-site groups ($5944, $5999, and $6581, respectively; p = 0.008). In-hospital mortality did not differ significantly among the three groups (4.8%, 2.2%, and 6.1%, respectively; p = 0.387)., Conclusions: Institution of an on-site cardiology team-based approach in the ED significantly reduces D2B time in STEMI patients eligible for primary PCI., (© 2011 Blackwell Publishing Ltd.)

Cardiac involvement in systemic lupus erythematosus (SLE) has been well described. However, sinus node involvement with profound sinus bradycardia as an early manifestation of adult SLE has not been reported. A 27-year-old previously healthy female was admitted due to intermittent fever for 4 days. SLE was diagnosed based on clinical manifestations and laboratory data. Profound sinus bradycardia (heart rate = 41/min) with weakness was noted during hospitalization. ECG abnormalities completely resolved after a high-dose intravenous steroid infusion. Sinus node involvement with significant bradycardia is one of the possible complications in the early stage of adult SLE. Close cardiovascular monitoring and serial ECGs are suggested for early detection of this serious complication of adult SLE.

Existence of humoral immunity has been previously demonstrated in malignant ascitic fluids. However, only a limited number of immunogenic tumor-associated antigens (TAAs) were identified, and few of which are associated with ovarian cancer. Here, we identified salt-inducible kinase 3 (SIK3) as a TAA through screening of a random peptide library in the phage display system. Overexpression of SIK3 markedly promoted cell proliferation, attenuated p21(Waf/Cip1) and p27(Kip) expressions in low-grade OVCAR3 cells, and permitted the cells to grow in mice. Decrease in SIK3 expression in high-grade SK-OV3 cells consistently demonstrated its tumorigenic potency by modulating the protein levels of cell cycle regulators. When the expressions of SIK3 and CA125 were compared in cancer tissues, immunohistochemical (IHC) studies indicated that cytoplasm-localized SIK3 was highly expressed in 55% of the ovarian cancer samples. In contrast, it was rarely detected in adenomyosis, leiomyoma and normal ovary tissues, showing its higher specificity (97%) to CA125 (65%) in ovarian cancer. Moreover, experiments using pharmacological inhibitors to block SIK3-induced p21(Waf/Cip1) expression revealed that activation of c-Src and phosphoinositide-3-kinase were critically required for its biological activity, suggesting that they are the downstream signaling mediators of SIK3. These data were further supported by IHC studies, showing coexpression of c-Src with SIK3 in 85% of the ovarian tumor samples stained positive for SIK3. Collectively, our findings indicate that SIK3 is a novel ovarian TAA. Overexpression of SIK3 promotes G1/S cell cycle progression, bestows survival advantages to cancer cells for growth and correlates the clinicopathological conditions of patients with ovarian cancer.

Background: Gefitinib (ZD1839) is a selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor with a significant antitumour effect on various cancers. Skin toxicity induced by gefitinib is common, and has been shown to be related to the inhibition of EGFR signalling pathways. However, other mechanisms may be involved in gefitinib-induced skin toxicity., Objectives: To study the possible EGFR-independent mechanisms of gefitinib-induced skin toxicity., Methods: The human immortalized keratinocyte cell line HaCaT and human lung adenocarcinoma cell lines (A549 and PC9) were treated with different concentrations of gefitinib for 24, 48 and 72 h. Cell viability was measured by MTT assay [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] after EGFR gene silencing. The signalling pathways were investigated by immunoblot analysis. Keratinocyte apoptosis was evaluated by nuclear condensation and flow cytometric analysis., Results: Gefitinib maintained its cytotoxicity to HaCaT cells after EGFR gene silencing, indicating that an EGFR-independent mechanism exists. Increased phosphorylation of p38 mitogen-activated protein kinase and JNK by gefitinib was observed in a dose-dependent manner in HaCaT cells. The JNK inhibitor, SP600125, attenuated the gefitinib-induced cytotoxicity and apoptosis of HaCaT cells. Immunohistochemical examination of patient specimens showed an increased expression of phosphorylated JNK in lesional epidermis compared with nonlesional epidermis., Conclusions: Gefitinib can induce keratinocyte apoptosis through an EGFR-independent JNK activation pathway., (© 2010 The Authors. BJD © 2010 British Association of Dermatologists 2010.)

Activation of peroxisome proliferator-activated receptor (PPAR) delta by GW501516, a specific PPARdelta ligand, significantly inhibited interleukin (IL)-1beta-induced proliferation and migration of vascular smooth muscle cells (VSMCs). This effect of GW501516 was dependent on transforming growth factor-beta, and was mediated through the up-regulation of IL-1 receptor antagonist. The inhibitory effect of GW501516 on VSMC proliferation was associated with cell cycle arrest at the G1 to S phase transition, which was accompanied by the induction of p21 and p53 along with decreased cyclin-dependent kinase 4 expression. Inhibition of cell migration by GW501516 was associated with the down-regulation of matrix metalloproteinase (MMP)-2 and MMP-9 in IL-1beta-treated VSMCs. Inhibition of extracellular signal-regulated kinase significantly reduced the GW501516-mediated inhibition of IL-1beta-stimulated VSMC proliferation. These results suggest that PPARdelta plays an important role in the pathophysiology of diseases associated with the proliferation and migration of VSMCs.

Possible masking of tuberculosis (TB) in treatment of community-acquired respiratory infection by newer fluoroquinolones has not been examined in randomised controlled trials. We undertook a randomised, open-label controlled trial involving adults with community-acquired pneumonia or infective exacerbation of bronchiectasis encountered in government chest clinics in Hong Kong. 427 participants were assigned by random permutated blocks of 20 to receive either amoxicillin clavulanate (n = 212) or moxifloxacin (n = 215). Participants were followed for 1 yr for active pulmonary TB. Excluding three participants with positive baseline culture, 13 developed active pulmonary TB: 10 (4.8%) out of 210 were given amoxicillin clavulanate, and three (1.4%) out of 214 were given moxifloxacin. The difference was significant by both proportion and time-to-event analysis. Post hoc analysis showed a significant decrease in the proportion with active pulmonary TB from 4.8% to 2.4% and 0% among participants given amoxicillin clavulanate (n = 210), moxifloxacin for predominantly 5 days (n = 127) and 10 days (n = 87), respectively. The log rank test for trend also showed a significant difference between the three subgroups. Regression models reaffirmed the linear effect; the adjusted odds ratio (95% confidence interval) of active pulmonary TB after moxifloxacin exposure up to predominantly 10 days was 0.3 (0.1-0.9). Newer fluoroquinolones appear to mask active pulmonary TB.

Aim: To develop an approach to enhance polyhydroxybutyrate (PHB) production via the coexpressed phaCAB and vgb genes controlled by arabinose P(BAD) promoter in Escherichia coli., Method and Results: The polyhydroxyalkanoates (PHAs) synthesis operon, (phaCAB), from Ralstonia eutropha was overexpressed under the regulation of the arabinose P(BAD) promoter in Escherichia coli, and the vgb gene encoding bacterial haemoglobin from Vitreoscilla stercoraria (VHb) was further cloned at downstream of phaCAB to form an artificial operon. The cell dry weight (CDW), PHB content and PHB concentration were enhanced around 1.23-, 1.57-, and 1.93-fold in the engineered cell harbouring phaCAB-vgb (SY-2) upon 1% arabinose induction compared with noninduction (0% arabinose). Furthermore, by using a recombinant strain harbouring P(BAD) promoter-vgb along with native promoter-phaCAB construction, the effect of vgb expression level on PHB biosynthesis was positive correlation., Conclusions: The results exploit the possibility to improve the PHB production by fusing the genes phaCAB-vgb from different species under the arabinose regulation system in E. coli. It also demonstrates that increase in VHb level enhances the PHB production., Significance and Impact of the Study: We were successful in providing a new coexpressed system for PHB synthesis in E. coli. This coexpressed system could be regulated by arabinose inducer, and is more stable and cheaper than other induced systems (e.g. IPTG). Furthermore, it could be applied in many biotechnology or fermentation processes.

We present coherent speckled x-ray diffraction patterns obtained from a monolayer of surface atoms. We measured both the specular anti-Bragg reflection and the off-specular hexagonal reconstruction peak for the Au(001) surface reconstruction. We observed fluctuations of the speckle patterns even when the integrated intensity appears static. By autocorrelating the speckle patterns, we were able to identify two qualitatively different surface dynamic behaviors of the hex reconstruction depending on the sample temperature.

Setting: Systematic studies of fluoroquinolones (FQs) and Clostridium difficile-associated diarrhoea (CDAD) are scarce among tuberculosis (TB) patients, in whom fluoroquinolones (FQs) are increasingly used., Objective: To evaluate the relationship between FQs and CDAD among TB patients., Design: Retrospective cohort and nested case-control analyses were conducted among 3319 hospital patients on anti-tuberculosis treatment from 1999 to 2005. Each case of CDAD was matched by three sex- and age-matched controls randomly selected from the rest of the cohort. Not every case was confirmed by C. difficile cytotoxins., Results: Among 38 cases studied, the incidence of CDAD, which was 28.2 (95%CI 20.3-38.3) per 100 000 patient-days overall, increased from 12.9 (95%CI 5.8-25.3) for patients aged <60 years to 26.6 (95%CI 15.5-42.8) for those aged between 60 and 79 years, and 66.9 (95%CI 39.8-106.1) for those aged >79 years. Univariate analysis showed a significant association between CDAD and age, FQs, non-FQ antibiotics, serum albumin level, duration of hospital stay and nasogastric feeding. Only duration of hospital stay and nasogastric feeding remained significant on multivariable analysis., Conclusion: The risk of CDAD due to FQs among TB patients is probably modest after controlling for sex, age, non-FQ antibiotics, serum albumin level, duration of hospital stay and nasogastric feeding.

This study evaluates the effects of breed and sex, together with those of birth weight and litter size, on muscle fibre type characteristics in Texel (TEX) and Scottish Blackface sheep (SBF). The M.longissimus thoracis et lumborum (LTL) of TEX had a significantly higher total muscle cross-sectional area (16%), a higher total fibre number (20%) and a higher muscle CT density (5%) than the SBF but had a similar average muscle fibre size. The frequency of slow fibres in the LTL in TEX was lower than in SBF (7.5% vs. 9.6%). Muscle fibre histochemistry similarly demonstrated that the oxidative fibre frequency in TEX was 10% lower than in SBF. The inter-fibre lipid content in TEX was also significantly lower than in SBF. Correspondingly, TEX displayed higher frequency (91.7% vs. 90.9% in SBF) and higher relative total area (92.5% vs. 90.4% in SBF) of fast fibres. These breed differences in muscle fibre traits indicate underlying genetic variation, and future analyses will evaluate the link of these traits to meat quality and assess the usefulness of these traits in breeding programmes.

Background: Our team previously demonstrated arterial stiffening and cardiac hypertrophy in type 2 diabetic rats at 8 but not 4 weeks after being administered streptozotocin (STZ) and nicotinamide (NA). The present study focused on investigating the effects of type 2 diabetes on cardiac autonomic nerve function in the STZ- and NA-treated animals, using modern spectral estimation technique., Design: An autoregressive process was performed to each detrended signal of heart rate and systolic blood pressure measured in the 4- and 8-week STZ-NA rats with anaesthesia. The power of low-frequency and high-frequency oscillations was automatically quantified with each spectral peak by computing the residuals. The closed-loop baroreflex gain was estimated using the square root of the ratio between heart rate and systolic blood pressure powers in the low-frequency band., Results: Compared with the age-matched controls, both the 4- and 8-week STZ-NA diabetic rats had significantly decreased low-frequency oscillations of heart rate but not systolic blood pressure variability, showing a decline in baroreflex gain (0.451 +/- 0.060 and 0.484 +/- 0.056 vs. 1.196 +/- 0.064 ms mmHg(-1), P < 0.05). On the other hand, the low frequency-high frequency power ratio of the heart period was also diminished in the two diabetic groups, indicating a shift in sympatho-vagal balance of the heart control (0.472 +/- 0.109 and 0.504 +/- 0.090 vs. 1.857 +/- 0.336, P < 0.05)., Conclusions: The cardiac autonomic dysfunction in the absence of any significant changes in vascular dynamics, 4 but not 8 weeks after induction of type 2 diabetes, suggests that the diabetic autonomic neuropathy may precede arterial stiffening and cardiac hypertrophy in the STZ- and NA-treated rats.

The clinical utility of therapeutic drug monitoring in tuberculosis has not been adequately evaluated by controlled clinical trials. To examine the relationship between slow culture conversion and peak plasma rifampicin level (Cmax-rfm) in a case-control study, patients with persistence of positive sputum smear despite at least 8 weeks of directly observed treatment with standard pyrazinamide-containing regimens were enrolled prospectively in government chest clinics from 16 December 2005 to 15 November 2006. Patients with multidrug-resistant tuberculosis, human immunodeficiency virus infection, or poor treatment adherence were excluded. Cases referred to patients with persistence of positive culture whereas controls had negative culture despite positive smear. Blood was checked at 2 and 4 hours post-dosing to capture Cmax-rfm. A cohort of 88 patients was identified. After excluding 16 patients, there were 36 controls and 36 cases. None had symptoms of malabsorption. Cmax-rfm was below 6 mg/l among 47% of controls and 44% of cases. Univariate and multiple logistic regression analyses showed no significant association between slow culture conversion and Cmax-rfm after logarithmic transformation. Thus, there is probably no association between Cmax-rfm and slow culture conversion.

Background and Purpose: Aminoguanidine (AG), an inhibitor of advanced glycation endproducts, has been shown to prevent arterial stiffening and cardiac hypertrophy in streptozotocin (STZ) and nicotinamide (NA)-induced type 2 diabetes in rats. Our aims were to examine whether AG produced benefits on cardiac pumping mechanics in the STZ and NA-treated animals in terms of maximal systolic elastance (E(max)) and theoretical maximum flow (Q(max))., Experimental Approach: After induction of type 2 diabetes, rats received daily injections of AG (50 mg kg(-1), i.p.) for 8 weeks and were compared with age-matched, untreated, diabetic controls. Left ventricular (LV) pressure and ascending aortic flow signals were recorded to calculate E(max) and Q(max), using the elastance-resistance model. Physically, E(max) reflects the contractility of the myocardium as an intact heart, whereas Q(max) has an inverse relationship with the LV internal resistance., Key Results: Both type 2 diabetes and AG affected E(max) and Q(max), and there was an interaction between diabetes and AG for these two variables. The E(max) and Q(max) were reduced in rats with type 2 diabetes, but showed a significant rise after administration of AG to these diabetic rats. Moreover, the increase in Q(max) corresponded to a decrease in total peripheral resistance of the systemic circulation when the STZ and NA-induced diabetic rats were treated with AG., Conclusions and Implications: AG therapy prevented not only the contractile dysfunction of the heart, but also the augmentation in LV internal resistance in rats with STZ and NA-induced type 2 diabetes.