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Aim: After extended left colectomy, traditional colorectal anastomosis is often not feasible because of insufficient length of the remaining colon to perform a tension‐free anastomosis. Total colectomy with ileorectal anastomosis could be an alternative but this can lead to unsatisfactory quality of life. Trans‐mesenteric colorectal anastomosis or inverted right colonic transposition (the so‐called Deloyers procedure) are two possible solutions for creating a tension‐free colorectal anastomosis after extended left colectomy. Few studies have reported their results of these two techniques and mostly via laparotomy. The aim of this study was to describe the trans‐mesenteric colorectal anastomosis and the inverted right colonic transposition procedure via a laparoscopic approach and report the outcome in a series of 13 consecutive patients. Method: This was retrospective chart review of laparoscopic colorectal surgery with trans‐mesenteric colorectal anastomosis or the inverted right colonic transposition procedure from January 2015 up to 2019. An accompanying video demonstrates these two techniques. Results: Thirteen consecutive patients underwent either a laparoscopic trans‐mesenteric colorectal anastomosis (n = 9) or an inverted right colonic transposition procedure (n = 4). One patient had intra‐operative presacral bleeding that was stopped successfully without conversion. Two patients had a postoperative intra‐abdominal abscess, but no anastomotic complications were recorded. The median number of bowel movements per day after 6 months was 2 (range 2–5). Conclusions: Trans‐mesenteric colorectal anastomosis or the inverted right colonic transposition procedure is feasible laparoscopically. The now well‐established classical advantages of the laparoscopic approach are associated with good functional outcome after these procedures. [ABSTRACT FROM AUTHOR]

Summary: HBsAg decline during nucleos(t)ide analogue therapy in chronic hepatitis B with lower pretherapy ALT is usually small and slow. This study aimed to investigate why ~10% of such patients showed “rapid HBsAg decline” ≥0.5 log10 IU/mL by month 6 of therapy. Patients with persistent pretherapy ALT <5X ULN who had qHBsAg at baseline, months 6 and 12 of entecavir or tenofovir therapy were studied. “On‐treatment ALT elevation” was defined as >10% increase above baseline to >2X ULN during first 6 months of therapy. Of the 256 patients treated, 51 experienced transient “on‐treatment ALT elevation” [group A], including 30 (11.7%) with ALT elevation to 2‐5X ULN [group A‐1] and 21 (8.2%) flared to >5X ULN [group A‐2]. The magnitude of qHBsAg decline and rate of “rapid HBsAg decline” by month 6 was significantly greater and more frequent in group A (−0.446 vs −0.042 log10 IU/mL; 45.1 vs 8.8%, respectively, P = 0.000) than in the remaining 205 patients without on‐treatment ALT elevation (group B), being greatest in patients with hepatitis flare (group A‐2: −0.559 log10 IU/mL and 57.1%, respectively). In patients with therapy ≥2 years, patients with “on‐treatment ALT elevation” also showed significantly greater annual HBsAg decline, more frequent to <100 IU/mL and 4 times higher HBsAg seroclearance rate. “On‐treatment ALT elevation,” especially flare >5X ULN, during entecavir therapy or tenofovir therapy may enhance/accelerate HBsAg decline, suggesting the effect of immune restoration upon potent viral suppression. [ABSTRACT FROM AUTHOR]

Contents: Amniotic fluid is a rich source of multipotent mesenchymal stem cells (MSCs). Amniotic fluid stem cells (AFSCs) have become a new source of stem cells; they have low immunogenicity and are easily harvested. For this reason, they may be useful in clinical tissue engineering. Moreover, AFSCs have anti‐inflammatory properties and can repair tissues. This study evaluated the utility of AFSC injection to treat bilateral ovarian dystrophy in Holstein‐Friesian cows. Bovine AFSCs (BAFSCs) were collected at slaughter from Holstein‐Friesian cows during the third or fourth month of pregnancy and cultured in vitro. The BAFSCs began to show a fibroblast‐like morphology. They were positive for β‐integrin, CD44, CD73, CD106 and Oct4 and negative for CD34 and CD45. After induction, the cells differentiated into mesodermal lineages. Bilateral ovarian dystrophy was confirmed by ultrasonography in 16 lactating cows. The subsequent experiment lasted 15 weeks. Serum was collected weekly to analyse progesterone concentrations, and weekly ultrasonography recorded ovarian changes. Each cow was equipped with an automatic heat detection system to facilitate oestrus observation and breeding records. The progesterone concentration of two cows in the treatment group (25%) significantly increased during weeks 10–15. On ultrasonography, the treatment group demonstrated mature follicles after BAFSCs injection, and foetuses were visualized approximately 40 days after artificial insemination (AI). Oestrus rates in the control and treatment groups were 0% (0/8) and 50% (4/8), respectively; pregnancy rates were 0% (0/8) and 25% (2/8), respectively. Calves were successfully delivered in both cases of pregnancy. These results show that BAFSCs can alleviate bovine ovarian dystrophy and restore fertility. [ABSTRACT FROM AUTHOR]

Abstract: Retained austenite (RA) transformation in martensitic steels subjected to rolling contact fatigue (RCF) is a well‐established phenomenon. In this investigation, a novel approach is developed to predict martensitic transformations of RA in steels subjected to RCF. In order to achieve the objectives, a 2‐dimensional finite element model was developed to determine subsurface stresses due to rolling contact. These stresses are utilized within a continuum damage mechanics framework to determine RA transformations as a function of depth and cycles. Phase transformations were determined by comparing the required thermodynamic driving force for transformations to the energy dissipation of the microstructure. The results obtained from the combined FEA and continuum damage mechanics model were corroborated to the experimental results for RA decomposition as a function of depth and cycle for SAE 52100 steel. The results obtained are in good agreement with observed RA decomposition and DER formation as compared with the experimental results. [ABSTRACT FROM AUTHOR]

Abstract: Aim: Histamine receptor H3 (HRH3) has substantial neuropharmacological potential. Currently, knockout models of this receptor have been investigated only in mice. We characterized the expression of this receptor in the zebrafish and generated a zebrafish HRH3 knockout line. Using this model, we studied the role of HRH3 in important behaviours. We also analysed the effect of HRH3 knockout on monoaminergic systems, which has not been thoroughly studied in any animal model. Methods: Generation of a mutant zebrafish line using the CRISPR‐Cas9 system. Analysis of locomotor and social behaviour. Expression of HRH3 was characterized using in situ hybridization. Analysis of monoamine networks using HPLC, immunohistochemistry and quantitative PCR. Results: We found that HRH3 knockout zebrafish larvae showed a shorter period of increased locomotion after a sudden onset of darkness, while the knockout larvae had a wild‐type‐like acute response to sudden darkness. Adult knockout fish showed decreased swimming velocity, although locomotor activity of knockout larvae was unaltered. Additionally, levels of dopamine and serotonin were significantly decreased in the knockout fish, while monoamine‐related gene expression and immunohistochemistry patterns were unchanged. Conclusions: Our results show that HRH3 knockout larvae adapt faster to sudden darkness, suggesting a role for this receptor in regulating responses to changes in the environment. The decreased levels of dopamine and serotonin provide the first direct evidence that knockout of HRH3 alters these systems. [ABSTRACT FROM AUTHOR]

Adjuvant pegylated interferon plus ribavirin treatment (Peg IFN/ RBV) reduces recurrence and prolongs survival in early stage hepatocellular carcinoma ( HCC) patients with chronic hepatitis C ( CHC) infection receiving resection or ablation. However, the impact of antiviral therapy in intermediate and advanced stage of CHC- HCC patients is uncertain. This study aimed to investigate the impact Peg IFN/ RBV treatment on recurrence-free interval and survival in patients with HCC receiving transarterial chemoembolization ( TACE). From 2010 to 2013, 274 CHC patients from a 1073 patient-based cohort composed of freshly diagnosed HCC and receiving TACE treatment the Chang Gung Memorial Hospital, Linkou Medical Center were recruited. Propensity score matching ( PSM) (age, gender, AST to Platelet Ratio Index ( APRI), tumour size, tumour number and Child-Turcotte-Pugh score) with the ratio 1:2 for patients with and without Peg IFN/ RBV treatment was performed. Statistics were performed with SPSS V.20 ( IBM, USA). After matching, 153 patients were analysed and 27 patients (17.6%) achieved sustained virologic response ( SVR). The 2-year cumulative overall survival rate and recurrence-free survival rate among patients with SVR, non- SVR, and untreated were 85.2% vs 58.3% vs 69.6% ( P=.001) and 73.3% vs 53.8% vs 58.5% ( P=.013). By Cox regression analysis, non- SVR, untreated, increase CTP score and nonresponder to TACE were independent factors related to mortality. The SVR achieved by Peg IFN/ RBV treatment markedly improves survival and reduces tumour recurrence in CHC- HCC patients receiving TACE treatment after complete response. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 30-year-old nulliparous woman who has opted for preimplantation genetic diagnosis (PGD) as she was a carrier of Robertsonian translocation. Topics discussed include performing non-invasive cell-free DNA (cfDNA) testing, identifying confined placental mosaicism (CPM) and diagnosing uniparental disomy (UPD).

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Introduction & Aims Haemophilic arthropathy ( HA) is a major complication in patients with haemophilia ( PWH), but the study of age-specific prevalence and severity of HA is very limited in Asian countries. Materials & Methods This study retrospectively reviewed 146 severe- and moderate-type Taiwanese PWH aged 4-73 years, with roentgenograms of elbows, knees and ankles and calculated Pettersson scores. Results The prevalence of HA, mean number of HAs per patient and mean Pettersson scores of all the joints were 42.8%, 1.3 and 1.9 points in PWH aged 4-10 years; 64.3%, 1.4 and 4.1 points in PWH aged 11-19 years; 97.1%, 2.9 and 15.6 points in PWH aged 20-29 years; 93.1%, 4.4 and 33.1 points in PWH aged 30-39 years; 100%, 5.1 and 46.1 points in PWH aged 40-49 years and 100%, 5 and 49.6 points in PWH aged ≥50 years, respectively. There was a high prevalence of HA for PWH aged ≥20 years. Among PWH aged <20 years, prevalence of HA was low and mild ankle arthropathy was the most common. Besides, in the four age groups aged <40 years, the prevalence of ankle arthropathy was the highest, followed by elbow arthropathy and then knee arthropathy. Conclusions Although severe arthropathy of the six major joints was rare in PWH aged <30 years, it increased rapidly in PWH after 30 years. Analysis of clinical correlates suggested that age, severity of haemophilia, absence of prophylaxis and presence of HCV infection correlated positively with Pettersson scores. [ABSTRACT FROM AUTHOR]

Background Only few studies had investigated the histopathological presentations of drug reaction with eosinophilia with systemic symptoms ( DRESS). The results of these studies were diverse and not conclusive. A characteristic histopathological feature is still lacking. Objective We tempted to identify characteristic histopathological features in DRESS and to correlate them with clinical presentations. Methods We retrospectively collected data from patients treated from 1998 through 2015. Available skin specimens from probable or definite cases according to the Regi SCAR criteria were analysed for histopathological patterns, which were then compared with the patients' clinical presentations. Chi-squared test was used for comparisons, while Bonferroni correction was applied if multiple comparison tests were encountered. Results Fifty-six patients with an average age of 52 years were identified, including 22 definite cases. The single most common histopathological pattern was interface dermatitis (75%). The co-existence of two or more patterns in a skin specimen was common (62.5%). In such cases, the co-existence of three patterns (the eczematous pattern, the interface dermatitis pattern and the vascular damage pattern) was most frequently encountered. It exhibited a significantly higher likelihood of being definite cases ( P = 0.004) and was significantly associated with high grades of cutaneous abnormalities ( P < 0.001). It showed a trend towards having higher grades of haematological abnormalities in patients with co-existence of three patterns ( P = 0.04). In addition, patients with the co-existence of three patterns tended to have a higher rate of reactivation of human herpesvirus-6 than those with other patterns but not statistically significant ( P = 0.052). Conclusion The co-existence of three histopathological patterns in a skin specimen is characteristic in DRESS and shows a significant association with clinical severity. [ABSTRACT FROM AUTHOR]

Background Both spontaneous and nucleos(t)ide analogue (Nuc)-treated hepatitis B surface antigen ( HBsAg) seroclearance are associated with excellent clinical outcomes. Aim To conduct a case-control study to explore whether there is difference of clinical outcomes between these two groups. Methods A total of 312 chronic hepatitis B patients with spontaneous HBsAg seroclearance and 110 patients with Nuc-treated HBsAg seroclearance were recruited retrospectively. Propensity score ( PS) matching method produced 98 patients in each group for comparison. The development of hepatocellular carcinoma ( HCC), hepatic complications and cumulative incidence of antibody to HBsAg (anti- HBs) was compared. Results During a mean follow-up period of 107 months after HBsAg seroclearance, five patients developed HCC after a mean period of 75.3 months (four and one patients with spontaneous and Nuc-treated HBsAg seroclearance, respectively) in overall population. One died of pneumonia with sepsis and one experienced variceal bleeding in Nuc-treated patients but none in spontaneous group. The incidence of anti- HBs seroconversion was comparable between spontaneous and Nuc-treated HBsAg seroclearance (69.6% vs. 66.4%, respectively, P = 0.617). There were no significant differences in HCC development (2% vs. 1.1%), overall mortality (0% vs. 1%), variceal bleeding (0% vs. 4.2%) and 6-year cumulative incidence of anti- HBs seroconversion (62.3% vs. 61.5%) among PS-matched patients with spontaneous and Nuc-treated HBsAg seroclearance. Conclusions The clinical outcomes between patients with spontaneous and Nuc-treated HBsAg seroclearance are comparable. HCC can develop at a low rate during long-term follow-up and periodic surveillance after HBsAg seroclearance is still mandatory. [ABSTRACT FROM AUTHOR]

Background Long-term nucleos(t)ide analogues therapy may reduce hepatocellular carcinoma ( HCC) in chronic hepatitis B patients with advanced fibrosis or cirrhosis. Aim To investigate in a retrospective-prospective study whether this beneficial effect would be reduced in cirrhotic patients who discontinued a successful course of entecavir ( ETV) therapy. Methods The study included 586 hepatitis B e antigen ( HBeAg)-negative patients with compensated cirrhosis, mean age of 53.8 ± 10 years and 81% males, treated with ETV for at least 12 months. After ETV therapy for 46.5 ± 22.9 months, 205 patients who achieved hepatitis B virus ( HBV) DNA suppression discontinued therapy. The clinical outcomes were assessed and HCC incidence was compared between propensity score ( PS)-matched patients who continued and patients who discontinued ETV therapy by Asian Pacific Association for the Study of Liver stopping rule. Results During a mean duration of 59.3 ± 19 months after start of ETV therapy, nine and six HCC developed in an estimated annual incidence of 2.3% and 1.6% in 154 PS-matched patients who continued and who discontinued ETV therapy, respectively ( P = 0.587). Multivariate Cox proportional hazards regression analyses showed that age ( HR 1.065, P < 0.001) and HBV DNA ( HR 1.216, P = 0.048) were the significant factors for HCC development. The rates of adverse clinical outcomes were comparable. Conclusions The clinical outcomes, including HCC, after cessation of a successful course of entecavir therapy in patients with compensated cirrhosis were comparable to those who continued therapy. The results suggest that this strategy of finite therapy is safe and a feasible alternative to indefinite therapy, especially in a low resources setting. [ABSTRACT FROM AUTHOR]

Background Sequential human herpes virus ( HHV) reactivation is well known in drug reaction with eosinophilia and systemic symptom ( DRESS), but such a phenomenon has seldom studied in other types of cutaneous adverse drug reactions ( cADRs). Moreover, the association between viral reactivations and cytokine or chemokine changes is largely unknown. We aimed to evaluate the viral reactivation rates of HHV-6, HHV-7, Epstein-Barr virus ( EBV), and cytomegalovirus ( CMV) in different cADRs and their impacts on clinical prognosis. Cytokine and chemokine changes with viral reactivations were also examined. Methods A prospective study was conducted to monitor the viral statuses of patients with different cADRs by polymerase chain reaction and serum-specific antibody titers. Changes in plasma cytokine and chemokine levels were also evaluated by sequential blood samples. Results Among the various cADRs, HHV-6 reactivation was only observed in DRESS, but EBV and CMV could be detected in other cADRs. Many proinflammatory cytokines and chemokines, including interleukin ( IL)-1β, IL-2, IL-6, interferon-γ, tumor necrosis factor-α, were significantly lower in DRESS patients with HHV-6 reactivation when compared to those without HHV-6 reactivation. In addition, these mediators were significantly lower before and during HHV-6 reactivation, compared to cytokine levels after HHV-6 reactivation in the same patient. Conclusion HHV-6 reactivation was only observed in DRESS patients, not in any other cADR. In DRESS patients, some proinflammatory cytokines were significantly lower before or during HHV-6 reactivation. [ABSTRACT FROM AUTHOR]

In this study, large-area and uniform thickness novel nano-sheet structured CuS thin films on ITO glass have been prepared by the one-step electrodeposition method from a dimethyl sulfoxide solution. Thin films of completely preserved nano-sheet like morphology of CuyS (y = 1.75, 1.8, 1.95, and 2.0) are grown by vacuum annealing CuS thin films at 500 °C for different lengths of time. The 500 °C sample heated for 10 hours was nearly converted to single phase of Cu2S with y ∼ 2. The optical direct band gaps of nano-sheet CuyS thin films annealed at 500 °C of 2, 6, and 10 hours in vacuum were found to be 1.94, 1.68, and 1.44 eV, respectively. [ABSTRACT FROM AUTHOR]

Background Cirrhotic patients admitted to intensive care units ( ICUs) have high mortality rates. The Chronic Liver Failure-Sequential Organ Failure Assessment ( CLIF- SOFA) score, a modified Sequential Organ Failure Assessment ( SOFA) score, is a newly developed scoring system exclusively for patients with end-stage liver disease. Aim To externally validate the efficacy of the CLIF- SOFA score and evaluate other scoring systems for 6-month mortality in critically ill cirrhotic patients. Methods This study prospectively recorded and analysed the data for 30 demographical parameters and some clinical characteristic variables on day 1 of 250 cirrhotic patients admitted to a 10-bed specialised hepatogastroenterology ICU in a 2000-bed tertiary care referral hospital during the period from September 2010 to August 2013. Results The overall in-hospital and 6-month mortality rate were 58.8% (147/250) and 78.0% (195/250), respectively. Liver diseases were mostly attributed to hepatitis B virus infection (32%). Multiple Cox logistic regression hazard analysis revealed that Glasgow coma scale, both the CLIF- SOFA and Acute Physiology and Chronic Health Evaluation III ( ACPACHE III) scores determined on the first day of ICU admission were independent predictors of 6-month mortality. Analysis of the area under the receiver operating characteristic curve revealed that the CLIF- SOFA score had the best discriminatory power (0.900 ± 0.020). Moreover, the cumulative 6-month survival rates differed significantly for patients with a CLIF- SOFA score ≤11 and those with a CLIF- SOFA score >11 on the ICU admission day. Conclusion Both CLIF- SOFA and APACHE III scores are excellent prognosis evaluation tools for critically ill cirrhotic patients. [ABSTRACT FROM AUTHOR]

Higher average daily gain, more lean meat yield and less fat yield of porcine carcass increase selling profits for animal producers. Myostatin ( MSTN), previously called GDF8, is a member of transforming growth factor-β ( TGF-β) superfamily. It is a negative regulator for both embryonic development and adult homeostasis of skeletal muscle. In this study, the genotypes of the previously described SNPs MSTN g.435 G> A and g.447 A> G SNPs in 66 Duroc pigs, 33 Landrace pigs, 180 Duroc × Landrace ( DL) pigs and 155 Duroc × Yorkshire × Landrace ( DYL) pigs were determined by Taqman SNP Genotyping Assays. For Duroc and Landrace pigs, MSTN g.435 GG/g.447 AA individual had greater backfat thickness (p < 0.05) than g.435 AA/g.447 GG individual, whereas MSTN g.435 AA/g.447 GG had greater meat (p < 0.05) and meat percentage (p < 0.05) than g.435 GA/g.447 AG individual. For DL and DYL pigs, the MSTN g.435 GG/g.447 AA animals were greater in backfat at ultrasound 10th rib (p < 0.05) and carcass 10th rib (p < 0.01) than g.435 AA/g.447 GG individual. The MSTN g.435 AA/g.447 GG individual also had higher values than g.435 GG/g.447 AA for anterior-end meat (p < 0.05), posterior-end meat (p < 0.01), total meat weight (p < 0.01) and meat percentage (p < 0.01). This study confirmed evidence that MSTN g.435 G> A and g.447 A> G affected carcass traits in pigs. The effects of the mutated alleles were additive with the maximal effects resulting from two copies of the mutated allele. Selection for MSTN g.435 A/g.447 G allele is expected to increase muscle of limb and total meat production and decrease backfat thickness. [ABSTRACT FROM AUTHOR]

The aims of our meta-analysis were (i) to quantify the predictability of childhood overweight and obesity on the risk of incident asthma; and (ii) to evaluate the gender difference on this relationship. The selection criteria included prospective cohort paediatric studies which use age- and sex-specific body mass index ( BMI) as a measure of childhood overweight and the primary outcome of incident asthma. A total of 1,027 studies were initially identified through online database searches, and finally 6 studies met the inclusion criteria. The combined result of reported relative risk from the 6 included studies revealed that overweight children conferred increased risks of incident asthma as compared with non-overweight children (relative risk, 1.19; 95% confidence interval [ CI], 1.03-1.37). The relationship was further elevated for obesity vs. non-obesity (relative risk, 2.02; 95% CI, 1.16-3.50). A dose-responsiveness of elevated BMI on asthma incidence was observed ( P for trend, 0.004). Obese boys had a significantly larger effect than obese girls (relative risk, boys: 2.47; 95% CI, 1.57-3.87; girls: 1.25; 95% CI, 0.51-3.03), with significant dose-dependent effect. Proposed mechanisms of gender difference could be through pulmonary mechanics, sleep disordered breathing and leptin. Further research might be needed to better understand the exact mechanism of gender difference on the obesity-asthma relationship. [ABSTRACT FROM AUTHOR]

Both erectile dysfunction (ED) and herpes simplex virus (HSV) infections are related to cardiovascular events. However, the relationship between ED and HSV infections remains undetermined. The aim of our study was to investigate the possible influence of HSV infections on the development of ED using the Taiwan National Health Insurance database. We identified patients with HSV type 1 or type 2 infections from the 1 000 000 sampling cohort data set. Male patients of age 18 years or older who had been diagnosed as cases of HSV infection since January 1, 2001 were enroled. Patients with previous history of stroke, spinal cord injury or malignancy were excluded. A control group was selected, comprising male patients without HSV infection, stroke, spinal cord injury or malignancy. The age, time of enrolment and comorbidities were matched in the two groups. A total of 1 717 HSV subjects (mean age 43.29 ± 15.97 years) and 6 864 control subjects were enroled. During an average of 3.91 ± 1.93 years' followup, HSV-infected subjects experienced a higher incidence of ED than control subjects (1.7% vs. 0.7%, respectively). The log-rank test showed that patients with HSV infections had a significantly higher incidence of ED than those without HSV infections (p < 0.001). After Cox proportional hazard regression model analysis, HSV infections were independently associated with the increased risk of ED (hazard ratio, 2.90; 95% CI, 1.82-4.63, p < 0.001). In conclusion, HSV infections were associated with risk of ED in this cohort. [ABSTRACT FROM AUTHOR]

Despite the known importance of galanin in the nervous system of vertebrates, the galanin gene structure and expression and the consequences of galanin deficiency in developing zebrafish are unknown. We cloned the galanin gene and analyzed its expression by using in situ hybridization, PCR, and immunocytochemistry throughout the early development of zebrafish until the end of the first week of life. The single zebrafish galanin gene encoded for a single amidated galanin peptide and a galanin message-associated peptide. Two forms resulting from alternative processing were identified. Galanin mRNA was maternally expressed and found in developing fish throughout early development. In situ hybridization showed the first positive neurons in three groups in the brain at 28 hours postfertilization. At 2 days postfertilization, three prosencephalic neuron groups were seen in the preoptic area and in rostral and caudal periventricular hypothalamus. In addition, two other groups of weakly stained neurons were visible, one in the midbrain and another in the hindbrain. Translation inhibition of galanin mRNA with morpholino oligonucleotides caused complete disappearance of galanin immunoreactivity in the brain until 7 dpf and did not induce known cascades of nonspecific pathways or morphological abnormalities. A minor disturbance of sensory ganglia was found. Galanin knockdown did not alter the expression of tyrosine hydroxylases 1 and 2, choline acetyltransferase, histidine decarboxylase, or orexin mRNA. The results suggest that galanin does not regulate the development of these key markers of specific neurons, although galanin-expressing fibers were in a close spatial proximity to several neurons of these neuronal populations. J. Comp. Neurol. 520:3846-3862, 2012. © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Lin S-J, Lu H-K, Lee H-W, Chen Y-C, Li C-L, Wang L-F. Nitric oxide inhibits androgen receptor-mediated collagen production in human gingival fibroblasts. J Periodont Res 2012; 47: 701-710. © 2012 John Wiley & Sons A/S Background and Objective: In our previous study, we found that flutamide [an androgen receptor (AR) antagonist] inhibited the up-regulation of collagen induced by interleukin (IL)-1β and/or nifedipine in gingival fibroblasts. The present study attempted to verify the role of nitric oxide (NO) in the IL-1β/nifedipine-AR pathway in gingival overgrowth. Material and Methods: Confluent gingival fibroblasts derived from healthy individuals ( n = 4) and those with dihydropyridine-induced gingival overgrowth (DIGO) ( n = 6) were stimulated for 48 h with IL-1β (10 ng/mL), nifedipine (0.34 μ m) or IL-1β + nifedipine. Gene and protein expression were analyzed with real-time RT-PCR and western blot analyses, respectively. Meanwhile, Sircol dye-binding and the Griess reagent were, respectively, used to detect the concentrations of total soluble collagen and nitrite in the medium. Results: IL-1β and nifedipine simultaneously up-regulated the expression of the AR and type-I collagen α1 [ Colα1(I)] genes and the total collagen concentration in DIGO cells ( p < 0.05). IL-1β strongly increased the expression of inducible nitric oxide synthase ( iNOS) mRNA and the nitrite concentration in both healthy and DIGO cells ( p < 0.05). However, co-administration of IL-1β and nifedipine largely abrogated the expression of iNOS mRNA and the nitrite concentration with the same treatment. Spearman's correlation coefficients revealed a positive correlation between the AR and total collagen ( p < 0.001), but they both showed a negative correlation with iNOS expression and the NO concentration ( p < 0.001). The iNOS inhibitor, 1400W, enhanced IL-1β-induced AR expression; furthermore, the NO donor, NONOate, diminished the expression of the AR to a similar extent in gingival fibroblasts derived from both healthy patients and DIGO patients ( p < 0.05). Conclusion: IL-1β-induced NO attenuated AR-mediated collagen production in human gingival fibroblasts. The iNOS/NO system down-regulated the axis of AR/ Colα1(I) mRNA expression and the production of AR/total collagen proteins by DIGO cells. [ABSTRACT FROM AUTHOR]

Background and purpose We recently reported a novel −62 G/A polymorphism within ataxin 8 ( ATXN8) gene promoter region, with −62 G displaying significantly higher luciferase activity compared with −62 A. Phenotypic variability in spinocerebellar ataxia type 8 ( SCA8) has been suggested, and large SCA8 repeats were found in patients with Parkinson's disease ( PD). We aimed to investigate the association of ATXN8 −62 G/A polymorphism with the risk of Taiwanese PD, and identify the trans-acting factor modulating the ATXN8 promoter activity. Methods A case-control study in a cohort of 569 PD cases and 547 ethnically matched controls was conducted by polymerase chain reaction ( PCR) and restriction enzyme analysis. The trans-acting factor binding to the ATXN8 promoter was examined by chromatin immunoprecipitation ( Ch IP)- PCR assay, c DNA co-transfection and luciferase reporter assay. Results When genotype distribution was calculated by comparing the rare AA genotype with the GG + GA genotypes (recessive model), a significant difference was found ( P = 0.035, 1 df). Individuals carrying AA genotype exhibited a decreased risk of developing PD (odds ratio: 0.73; 95% CI: 0.55-0.98, P = 0.035). After stratification by age, individuals over 60 years of age carrying AA genotype demonstrated a further decrease in the risk of developing PD (odds ratio: 0.64; 95% CI: 0.43-0.96, P = 0.030). Ch IP- PCR and c DNA over-expression revealed that CCAAT/enhancer-binding protein alpha binds to the ATXN8 proximal promoter to upregulate ATXN8 expression in neuroblastoma SK- N- SH cells. Conclusions Our data suggest that ATXN8 −62 G/A polymorphism plays a role in Taiwanese PD susceptibility. [ABSTRACT FROM AUTHOR]

Aim The aim of this trial was to determine whether whole-body vibration (WBV) induced via a noninvasive oscillation platform could improve symptoms and health-related quality of life (HRQOL) in patients with chronic functional constipation. Method A single-blinded, randomized controlled trial was performed in a single hospital in Taiwan. Patients diagnosed with chronic functional constipation, as per the Rome III diagnostic criteria, were included and randomized to either the WBV treatment or no treatment (control) group. The treatment group received six 15-min sessions of WBV therapy over a 2-week period. Patients received vibrations of 2 mm in amplitude at a frequency of 12 Hz. The primary outcome was whether constipation symptoms improved, assessed by the constipation severity instrument (CSI) and the secondary outcome measure was whether there was an improvement in HRQOL. Results Whole-body vibration therapy over a 2-week period in patients with chronic functional constipation ( n = 14) significantly reduced the total CSI and obstructive defaecation subscale scores compared with control ( n = 13). However, WBV did not improve the pain and chronic inertia subscale scores of the CSI or HRQOL. Conclusion These findings suggest that low-intensity WBV induced via a noninvasive oscillation platform may be an effective therapy for reducing symptom severity in patients with chronic functional constipation. [ABSTRACT FROM AUTHOR]

. Patients with decompensated cirrhosis owing to chronic hepatitis B viral (HBV) infection have a high morbidity/mortality rate, and the treatment remains a challenge. We studied the safety and efficacy of telbivudine and lamivudine in such patients. This noninferiority, double-blind trial randomized 232 treatment-naive patients with decompensated HBV (1:1) in 80 academic hospitals to receive once-daily telbivudine 600 mg or lamivudine 100 mg for 104 weeks. Primary composite endpoint was proportion of patients with HBV DNA <10 000 copies/mL, normal alanine aminotransferase (ALT) and Child-Turcotte-Pugh score improvement/stabilization at week 52. Response rates using a post hoc modified endpoint (HBV DNA <300 copies/mL [57 IU/mL] and ALT normalization) in intent-to-treat analysis (missing = failure) were 56.3% vs 38.0% after 76 weeks ( P = 0.018) and 45.6% vs 32.9% after 104 weeks ( P = 0.093) for telbivudine vs lamivudine. Telbivudine treatment was an independent predictive factor for HBV DNA <300 copies/mL and ALT normalization ( P = 0.037). Response rates with protocol-defined composite endpoint in intent-to-treat analysis (M = F) were 56.2 vs 54.0% (noninferiority not achieved) and 39.1% vs 36.4% (noninferiority achieved) in telbivudine and lamivudine groups at 52 and 104 weeks. Telbivudine treatment was associated with a significant improvement in glomerular filtration rate compared to lamivudine treatment and was also associated with a trend for improvement in survival (87% vs 79%). No cases of lactic acidosis were reported. Telbivudine compared to lamivudine was associated with a higher rate of patients with both viral suppression and ALT normalization, a trend towards a higher rate of survival and significant improvement in glomerular filtration. [ABSTRACT FROM AUTHOR]

Background: Adverse drug events (ADE) have been studied widely in hospitalised and emergency department (ED) patients. Less is known about the ED visits of drug-related injury in Taiwan. This study seeks to determine the incidence, risk and patient outcomes of ADE in an ED population. Methods: We conducted a prospective observational cohort study of patients 18 years and older presenting to the ED of an urban, tertiary medical centre. ED visits between 1 March 2009 and 28 February 2010 identified by investigators for suspected ADE were further assessed by using the Naranjo Adverse Drug Reaction probability scale. Outcomes (ED disposition, injury severity and preventability) and associated variables (triage, gender, drug category, number of drugs, Charlson comorbidity index score and ADE mechanism) were measured. Results: Of 58 569 ED visits, 452 patients (0.77%) had physician-documented ADE. 24% of patients with ADE were hospitalised with life-threatening conditions, with a mortality rate of 10.0%. The majority of ADE were considered preventable (73.4%), and the unintentional overdose was the most common cause. Cardiovascular agents accounted for the most ADE (25.8%) and consisted of 65.3% of ADE in patients aged 65 years and older. Risk factors for ADE-related hospitalisation were elderly age (odds ratio (OR) 1.9, 95% confidence interval (CI) 1.1-3.4), severity of ADE (OR 6.9, 95% CI 3.3-14.5) and higher Charlson comorbidity index scores (OR 3.4, 95% CI 2.0-5.7). Conclusion: ADE-related ED visits are not uncommon in Taiwan and many cases are preventable. ED-based surveillance may provide useful information for monitoring outpatient ADE. [ABSTRACT FROM AUTHOR]

In contemporary reinforcement learning models, reward prediction error (RPE), the difference between the expected and actual reward, is thought to guide action value learning through the firing activity of dopaminergic neurons. Given the importance of dopamine in reward learning and the involvement of Akt1 in dopamine-dependent behaviors, the aim of this study was to investigate whether Akt1 deficiency modulates reward learning and the magnitude of RPE using Akt1 mutant mice as a model. In comparison to wild-type littermate controls, the expression of Akt1 proteins in mouse brains occurred in a gene-dosage-dependent manner and Akt1 heterozygous (HET) mice exhibited impaired striatal Akt1 activity under methamphetamine challenge. No genotypic difference was found in the basal levels of dopamine and its metabolites. In a series of reward-related learning tasks, HET mice displayed a relatively efficient method of updating reward information from the environment during the acquisition phase of the two natural reward tasks and in the reverse section of the dynamic foraging T-maze but not in methamphetamine-induced or aversive-related reward learning. The implementation of a standard reinforcement learning model and the Bayesian hierarchical parameter estimation show that HET mice have higher RPE magnitudes and that their action values are updated more rapidly among all three test sections in T-maze. These results indicate that Akt1 deficiency modulates natural reward learning and RPE. This study showed a promising avenue for investigating RPE in mutant mice and provided evidence for the potential link from genetic deficiency, to neurobiological abnormalities, to impairment in higher-order cognitive functioning. [ABSTRACT FROM AUTHOR]

In this study, the dual modified organoclay (DMC), was successfully prepared by the successive cationic exchange reactions of the sodium montomorillonite clay (MMT) with two intercalating reagents, hexadecyl-triphenyl-phosphonium bromide and 2-methacryloxy-ethyl-hexadecyl-dimethyl-ammonium bromide. A series of the PMMA/DMC nanocomposite membranes (PDCM) were then prepared with the PMMA matrix and various amounts of DMC via the solution cast method. The results of XRD, TEM, SEM, and UV-VIS measurements of the PDCMs prepared showed that the DMC particles were well dispersed in the PMMA matrix with a highly exfoliated structure. The TGA thermograms indicated that the thermal stabilities of the PDCM membranes are higher than that of the PMMA. Furthermore, the tensile mechanical property and glass transition temperature of the nanocomposites were dramatically increased with increasing the DMC content. The limiting oxygen index of PDCM membranes also indicated that the flame retardancy was significantly enhanced due to the presence of DMC. Moreover, more than 90% of the PMMA's transparency was remained in the nanocomposites. Copyright © 2011 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Summary. Earlier studies addressing the hepatitis B virus (HBV) DNA cut-off level for inactive chronic HBV infection largely involved patients with normal alanine aminotransferase (ALT) for only 1-2 years and based on a single time HBV DNA assay. This study was conducted to address this issue using serial HBV DNA assays in patients with persistently normal ALT (PNALT) over 10 years following spontaneous hepatitis B e antigen (HBeAg) seroconversion. Serial serum specimens (mean 9 samples per patient) of 62 patients with PNALT and no disease progression over 10 years (median 18.1 years) after spontaneous HBeAg seroconversion were assayed for HBV DNA. Excluding assays within 1 year after HBeAg seroconversion, 21% and 82.3% of the patients with PNALT had HBV DNA levels persistently lower than 4 log10 and 5 log10 copies/mL, respectively, and only 8% had a level ≥5 log10 copies/mL in at least two assays. Of the 27 patients with PNALT defined by ALT <30 U/L for male and <19 U/L for female, only 33% had serum HBV DNA level persistently <4 log10 copies/mL. There was no significant difference in the serial HBV DNA changes among patients with different gender, HBV genotype or age at HBeAg seroconversion. Liver biopsy in nine patients invariably showed minimal necroinflammation and one showed Ishak fibrosis score 4. These results suggest that 5 log10 copies/mL (20 000 IU/mL) is a more appropriate cut-off HBV DNA level for inactive chronic HBV infection in the setting of PNALT. [ABSTRACT FROM AUTHOR]

Summary We report here an HLA-A allele, A*11:90, found in a Taiwanese cord blood sample using DNA sequence-based typing (SBT) protocol after observing an anomalous reaction pattern in a sequence-specific oligonucleotide (SSO) typing exercise. The sequence of A*11:90 is identical to A*11:01:01, the most predominant A*11 variant in Taiwanese, in exon 2 but differs from A*11:01:01 in exon 3 by two nucleotide substitutions at codon 163 (c.487C>G and c.488G>A), resulting R163E. In comparison with the sequence of A*11:02:01, the second most predominant subtype of A*11 in Taiwanese A*11:90 has one nucleotide difference at codon 19 (c.55A>G) in exon 2 resulting K19E and two nucleotides variations at codon 163 (c.487C>G and c.488G>A) in exon 3 resulting R163E. HLA-A*11:90-B*40:02-DRB1*11:01 is the deduced probable HLA haplotype in association with A*11:90. The generation of A*11:90 is thought to involve a DNA recombination event between alleles A*11:01:01 and A*80:01 where A*80:01 donated a fragment of the DNA sequence (from n.t. 487 to n.t. 497) to the recipient sequence of A*11:01:01. [ABSTRACT FROM AUTHOR]

Summary We report here two novel HLA-B alleles, B*46:13:03 and B*15:189, discovered in two Taiwanese volunteer bone marrow donors. The sequence of B*15:189 has a nucleotide sequence possibly derived from a recombination event between HLA-B*39:01:01 and B*15:01:01:01, while the origin of the sequence B*46:13:03 was less obvious to postulate, considering the low frequency of B*46:13 in the general population and the silent mutations involved. Our report here adds further HLA polymorphism to the growing lists of HLA-B*46 and HLA-B*15 and provides an additional HLA information for donor search programme for patients undergoing transplant. [ABSTRACT FROM AUTHOR]

Summary A spectrograph with continuous wavelength resolution has been integrated into a frequency-domain fluorescence lifetime-resolved imaging microscope (FLIM). The spectral information assists in the separation of multiple lifetime components, and helps resolve signal cross-talking that can interfere with an accurate analysis of multiple lifetime processes. This extends the number of different dyes that can be measured simultaneously in a FLIM measurement. Spectrally resolved FLIM (spectral-FLIM) also provides a means to measure more accurately the lifetime of a dim fluorescence component (as low as 2% of the total intensity) in the presence of another fluorescence component with a much higher intensity. A more reliable separation of the donor and acceptor fluorescence signals are possible for Förster resonance energy transfer (FRET) measurements; this allows more accurate determinations of both donor and acceptor lifetimes. By combining the polar plot analysis with spectral-FLIM data, the spectral dispersion of the acceptor signal can be used to derive the donor lifetime - and thereby the FRET efficiency - without iterative fitting. The lifetime relation between the donor and acceptor, in conjunction with spectral dispersion, is also used to separate the FRET pair signals from the donor alone signal. This method can be applied further to quantify the signals from separate FRET pairs, and provide information on the dynamics of the FRET pair between different states. [ABSTRACT FROM AUTHOR]

Summary [ABSTRACT FROM AUTHOR]

Please cite this paper as: Cheng W-F, Chen Y-L, You S-L, Chen C-J, Chen Y-C, Hsieh C-Y, Chen C-A. Risk of gynaecological malignancies in cytologically atypical glandular cells: follow-up study of a nationwide screening population. BJOG 2011;118:34-41. To investigate the relationship between screening status, clinical characteristics and risk of gynaecological malignancies in women with a cytological diagnosis of atypical glandular cells (AGC). Prospective study of a screened population. Case series from nationwide screening population. The 8281 women who were diagnosed with cytological AGC for the first time were divided into screened (5386 women) and unscreened (2895 cases) groups according to their screening status. Follow-up histological reports were analysed. Diagnosis of cervical, uterine, or ovarian cancers. Of the 323 women who developed gynaecological malignancies, 271 had invasive cervical cancers, 40 had uterine cancers and 12 had ovarian cancers, with a mean follow up of 1.9 years and 50 740 person-years. Previous screening status was a strong risk predictor of gynaecological malignancies (hazard ratio 1.69, P = 0.0027). Compared with the general screening population, women with a first diagnosis of cytological AGC had significantly increased ratios of developing gynaecological malignancies (17.85-fold for cervical cancer, 5.68-fold for uterine cancer, and 2.04-fold for ovarian cancer, P < 0.05). When compared with women aged <35 years, those in other age groups had a significantly higher risk of developing gynaecological cancers (age ≥60 years, hazard ratio 1.99, 95% CI 1.20-2.37, P = 0.016). Comprehensive evaluation for women with cytological AGC, including pelvic examination, ultrasonography, colposcopy, endocervical curettage, cervical biopsy and endometrial biopsy needs to be considered, especially for those with risk factors (i.e. >60 years old, lower educational status, previous Papanicolaou smear interval longer than 2 years, or no previous Papanicolaou smear). [ABSTRACT FROM AUTHOR]

Haemophilia A (HA) is an X-linked bleeding disorder caused by mutations in the factor VIII (FVIII) gene. Identification of these mutations is becoming increasingly important in a variety of clinical settings. The purpose of this report is to describe our experience of FVIII gene mutation analysis in the largest cohort of patients in Taiwan including the discovery of 21 novel mutations. We tested 115 HA patients from 91 unrelated families, including 79 severe, 15 moderate and 21 mild types starting with an assay for the intron 22 inversion by long range-PCR followed if necessary by additional genetic studies. Intron 22 inversion accounted for 27.8% of the total and 36.7% of severe HA patients respectively while intron 1 inversion comprised 7.6% of severe patients. These were clearly different from the known data in caucasian populations. Of 75 patients without intron 22 or 1 inversion, 70 from 62 unrelated families revealed 56 different mutations by denaturing high-performance liquid chromatography (DHPLC), of which 21 were novel. Also, the only female patient with severe HA was found to have heterozygous non-sense mutation (c.6683G>A) of exon 24. Seven patients, including five without amplified PCR product and two without encoded DNA defect turned out to have exon(s) deletion or insertion by reverse transcript PCR (RT-PCR). In our study, the combination of various molecular techniques including LR-PCR, multiplex PCR, DHPLC and RT-PCR analysis enabled definitive detection of the causative FVIII gene defects in 112 of 113 (99%) HA patients. [ABSTRACT FROM AUTHOR]

Eur J Clin Invest 2010; 40 (3): 220–225 Background The previous studies regarding the association between endogenous dehydroepiandrosterone (DHEA) sulphate level and metabolic syndrome are inconsistent. This study aimed to investigate such relationship in elderly Taiwanese men. Materials and methods Five hundred and eighty-five elderly Taiwanese men (mean age 68·7 ± 8·3 years) were enrolled as the baseline cohort population in 2000. In addition to a questionnaire, body mass index (BMI), blood pressure, fasting blood glucose, lipids, albumin and serum DHEA-S levels were measured for each participant. Metabolic syndrome was based on the definition by the America Heart Association/National Heart Lung Blood Institute. Results The prevalence of metabolic syndrome was 33·3%. Using multivariate logistic regression analyses with adjustments for age, smoking, alcohol, physical activities, albumin and BMI, there was a positive relationship between serum DHEA-S level and metabolic syndrome. The highest DHEA-S quartile group had increased risk for metabolic syndrome (odds ratio = 2·68, 95% confidence interval: 1·44–5·01, P < 0·01) compared with the lowest quartile group. The mean serum DHEA-S level increased with increasing number of metabolic syndrome components. Conclusions The prevalence of metabolic syndrome increases with elevated DHEA-S levels among elderly Taiwanese men. Thus, elevated serum DHEA-S level should be treated as an important risk factor for metabolic syndrome in elderly men. [ABSTRACT FROM AUTHOR]

A case study is presented of a 56-year-old man with severe-type haemophilia A, who had haemophilic arthropathies of both knees and received on-demand therapy with recombinant FVIII (rFVIII). Topics include successful multivessel percutaneous coronary intervention (PCI) perfomed for acute coronary syndrome in the human immunodeficiency viruses (HIV)-positive severe haemophiliac and multiple bleeding risks existed in the patient during and after PCI in addition to underlying haemophilia.

We recently reported that grouper iridovirus (GIV) can induce apoptosis in barramundi, Lates calcarifer, muscle (BM) and swim bladder (BSB) cell lines. In this paper, we further characterize the molecular mechanism underlying apoptotic death in BM cells triggered by GIV. DNA-laddering and apoptotic cells were observed in BM cells infected with UV-irradiated or untreated GIV but was absent in cells infected with heat-inactivated GIV, indicating the involvement of viral protein in the apoptosis event. In GIV-infected BM cells, the conversion of procaspase-3 to caspase-3 was evident and the level of caspase-8 and -9 increased as early as 30 min post-infection. When treated with a pancaspase inhibitor, the GIV-induced apoptosis event was abolished. These observations indicate that GIV-induced apoptosis is caspase-dependent, and that both the external and internal routes in the caspase-dependent pathway are likely involved in the apoptosis process. [ABSTRACT FROM AUTHOR]

Background and Purpose: Elevated plasma total homocysteine (tHcy) level has been established as an independent risk factor for cardiovascular diseases. Danshensu, an active ingredient of Salvia miltiorrhiza, shows wide cardiovascular benefit. However, in terms of its own methylation, danshensu could elevate tHcy level, which would act against its cardiovascular benefit, thus posing a 'therapeutic paradox'. As this paradox has not been fully assessed, we have evaluated the effects of danshensu on tHcy levels to uncover the underlying mechanisms. EXPERIMENT APPROACH: We evaluated the influence of danshensu on homocysteine (Hcy) metabolism in rats with normal tHcy levels and in rat models of elevated tHcy (single intravenous methionine loading model and a hyperhomocysteinemic model after 3 weeks methionine dosing, with and without 3 weeks of danshensu treatment). We also quantified some metabolic intermediates (S-adenosyl methionine, S-adenosyl-l-homocysteine, cysteine and glutathione) relevant to Hcy metabolism in rat liver and kidney.Key Results: Acute treatment with a single dose of danshensu in rats with normal tHcy did not change plasma tHcy. In contrast, danshensu significantly lowered tHcy in rats with elevated tHcy. The relatively higher cysteine and glutathione levels after treatment with danshensu indicated that its tHcy-lowering effect was via increased activity of the trans-sulphuration pathway.Conclusions and Implications: Our results suggested that danshensu may act both acutely to increase trans-sulphuration and after chronic exposure to up-regulate the activity of the trans-sulphuration enzymes. The tHcy-lowering effect of danshensu is another cardiovascular benefit provided by S. miltiorrhiza and suggests a potential tHcy-lowering therapy. [ABSTRACT FROM AUTHOR]

Proteins and insolubles were recovered from whole Antarctic krill via novel isoelectric solubilization/precipitation using different pH treatments. The protein recovery yield was 45% to 50% (dry basis). The recovered proteins had higher ( P < 0.05) content of essential amino acids (EAAs) and non-EAAs as well as higher ( P < 0.05) ratio of total EAA/total AA than whole krill. The EAAs constituted almost 50% of total AAs. The least extreme pH treatments (pHs 3 and 12) yielded highest ( P < 0.05) content of EAAs. The quality of recovered proteins was high based on EAAs meeting FAO/WHO/UNU recommendations for adults and infants. The basic pH yielded proteins with the lowest ( P < 0.05) amount of minerals and the highest ( P < 0.05) amount of Ca, P, and Mg in the insolubles when compared to the acidic treatments. However, both basic and acidic treatments effectively removed minerals from recovered proteins without the removal of the exoskeleton before processing. Therefore, besides high-quality proteins, the insolubles may provide a mineral supplement in the animal diet. [ABSTRACT FROM AUTHOR]

Background Peroxisome proliferator-activated receptors (PPAR) mediate inflammatory processes and alter cardiac function. However, it is not clear whether inflammatory cytokines or PPAR ligands regulate PPARs in the cardiomyocytes to modulate cardiac functions. We investigated the effects of tumour necrosis factor-alpha (TNF-α) and PPAR ligands on the expression of PPARs in HL-1 cardiomyocytes. Materials and methods HL-1 cardiomyocytes were incubated with and without TNF-α (1, 10, 25 and 50 ng mL−1) or PPAR ligands (rosiglitazone, pioglitazone and fenofibrate) at concentrations of 0·1, 1 and 10 µm for 24 h. The cells also received SN-50 (NF-κB inhibitor, 50 µg mL−1), ascorbic acid (100 µm) and coenzyme Q10 (10 µm) alone or combined with TNF-α. Results Using reverse transcriptase–polymerase chain reaction and Western blot, we found that incubation of TNF-α (50 ng mL−1) for 24 h decreased PPAR-α, but increased PPAR-γ without altering PPAR-δ. These effects were not changed by co-administration of SN-50. However, co-administration of ascorbic acid prevented the effect of TNF-α both on PPAR-α and PPAR-γ. Coenzyme Q10 partially attenuated the effect of TNF-α on PPAR-γ but did not alter its effect on PPAR-α. The administration of rosiglitazone (10 µm) and pioglitazone (10 µm) for 24 h increased PPAR-γ mRNA, but did not alter PPAR-α or PPAR-δ. Moreover, fenofibrate (0·1, 1 and 10 µm) increased PPAR-γ without any effects on PPAR-α or PPAR-δ. Conclusions Oxidative stress causes the regulations of PPAR-α and PPAR-γ in the TNF-α-treated cardiomyocytes. The up-regulation of PPAR-γ by PPAR ligands may contribute to their anti-inflammation effects. [ABSTRACT FROM AUTHOR]

Posterior lingual glands consist of two sets of minor salivary glands that serve important functions in oral physiology. To investigate the hypothesis that the hypoglossal nerve provides sympathetic innervation to the posterior lingual glands, we examined ultrastructural changes in the glands following hypoglossal denervation. In the posterior deep lingual glands (of von Ebner), the serous acinar cells showed a decrease in the number of secretory granules and an increase in lipofuscin accumulation. The ratios of cells containing lipofuscin granules were 11.39, 36.49 and 50.46%, respectively, of the control, 3- and 7-day post-axotomy glands ( P < 0.001). Intraepithelial phagocytotic activity was increased. The mucous acinar cells in the posterior superficial lingual glands (of Weber) also showed degenerative changes after hypoglossal denervation. One week after nerve transection, marked cytoplasmic vacuolation and fragmentation of organelles were frequently observed. Degenerative changes were also found in unmyelinated axons associated with the glands. We provide the first evidence of the structural and functional connections between the sympathetic component of the hypoglossal nerve and posterior lingual glands. [ABSTRACT FROM AUTHOR]

Background and purpose: This study examines whether angiotensin-converting enzyme (ACE) gene polymorphisms are associated with the risk of spontaneous deep intracerebral hemorrhage (SDICH) in Taiwan using a case–control study. Methods: Totally, 217 SDICH patients and 283 controls were recruited. Associations of ACE A-240T and ACE I/D polymorphisms with SDICH were examined under the additive model and adjusted for gender, age, body mass index, total cholesterol level, smoking history, alcohol use, hypertension, and use of ACE inhibitors. Results: Hypertension, diabetes mellitus, family history of spontaneous intracerebral hemorrhage (SICH), and low cholesterol level increase risk of female SDICH, whereas hypertension, alcohol use, smoking history, family history of SICH, and low cholesterol level are an important risk factor for male SDICH. After adjusting for covariates, only haplotype ACE T-D (OR = 2.7, 95% CI, 1.1–6.5, P = 0.02) was associated with female SDICH. Conclusions: This study demonstrates that environmental risk factors play a major role and ACE polymorphisms play a minor role in contributing risk of SDICH in Taiwan. [ABSTRACT FROM AUTHOR]

Two new cell lines have been established from the muscle and swim bladder tissues of barramundi, Lates calcarifer, and designated as BM (barramundi muscle) and BSB (barramundi swimbladder), respectively. The cells multiplied well at 28 °C in Leibovitz’s L-15 medium supplemented with 10% foetal bovine serum, and have been continuously subcultured more than 100 times to date. Morphologically, BM cells were mostly fibroblastic, whereas BSB were mostly epithelial. Both cell lines were susceptible to grouper iridovirus (GIV) and displayed characteristics of apoptosis after viral infection. The induction of apoptosis was further assayed in GIV-infected BM and BSB cells by various methods. The inhibition of cell growth by GIV was demonstrated by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. Morphological observations revealed typical apoptotic features in the infected cells, including cell shrinkage and rounding, chromosome condensation and formation of apoptotic body-like vesicles. Chromosome fragmentation was detected by DNA laddering and TUNEL assays. Finally, the appearance of phosphotidylserine on the outer leaflet of apoptotic cell membranes was confirmed by annexin V staining. This is the first report of apoptosis induced by GIV in fish cells. [ABSTRACT FROM AUTHOR]

The aim of this case control study was to investigate the clinical significance of hepatitis B virus nuclear core antigen (HBcAg) in young cirrhotic patients. Fifteen cirrhotic patients with nuclear HBcAg in the liver biopsies were included. Their clinicopathological parameters as well as the core gene sequences were compared with those of a sex- and age-matched (1 to 2) control group. The mean follow-up periods were 124 ± 80 and 102 ± 43 months, respectively. Expression of nuclear HBcAg in cirrhotic liver was significantly associated with higher aspartate aminotransferase levels ( P = 0.001), alanine aminotransferase levels ( P < 0.001), and alpha-fetoprotein levels ( P = 0.002), as well as a shorter duration to develop hepatocellular carcinoma or liver decompensation (Kaplan–Meier method, P = 0.044). Sequence analysis revealed mutations on the nuclear localization signal (NLS) of core protein in five cirrhotic patients with nuclear HBcAg (Q171K in four and Q179K in one patients). Site-directed mutagenesis experiments demonstrated that both the Q171K and Q179K mutation enhanced nuclear localization of the core protein. In conclusion, expression of nuclear HBcAg in young cirrhotic patients was associated with more severe hepatitis activities as well as an unfavourable long-term outcome. Mutations on the NLS of core protein were selected in some patients with nuclear HBcAg. [ABSTRACT FROM AUTHOR]

Flavobacterium psychrophilum is the aetiological agent of rainbow trout fry syndrome and bacterial cold water disease. This study examined the genetic diversity of F. psychrophilum isolates retrieved from multiple epizootics at rainbow trout, Oncorhynchus mykiss, rearing facilities and from spawning coho salmon, O. kisutch. A total of 139 isolates were confirmed as F. psychrophilum by PCR assay and were further typed using pulsed-field gel electrophoresis (PFGE). Multiple epizootics at three proximally located rainbow trout rearing facilities were numerically dominated by three PFGE profiles, which accounted for 76% of all trout isolates. In coho salmon, 19 PFGE profiles were differentiated by PFGE and four numerically dominant PFGE profiles represented 56% of all coho salmon isolates. PFGE analysis also indicated that the average similarity of macrorestriction patterns of F. psychrophilum isolates was greater in rainbow trout than in coho salmon (88% vs. 70%). Furthermore, it was not unusual to isolate multiple PFGE profiles from a single coho salmon sample whereas only two PFGE profiles were shared between two sample dates separated by 1 month. It is clear that the domestic rainbow trout aquaculture facilities studied here were primarily affected by a complex of genetically related strains whereas spawning coho salmon supported a much more genetically diverse collection of F. psychrophilum. [ABSTRACT FROM AUTHOR]

Iron deficiency anaemia (IDA) is a frequently encountered disease, which can be attributed to menorrhagia. Most female patients with von Willebrand disease (VWD) have menorrhagia. The aim of this study was to investigate the prevalence of VWD in women with both IDA and menorrhagia in Taiwan. From January to December 2005 and November 2006 to January 2007, 56 consecutive patients with both IDA and menorrhagia were enrolled in this study. Their median age was 41 years (range 18–53). IDA was diagnosed by anaemia plus either low ferritin or transferrin saturation. Menorrhagia was evaluated by patient’s menses history. Both von Willebrand factor antigen (VWF:Ag) and ristocetin cofactor activity (VWF:RCo) were measured for each patient. Bleeding time (BT) and platelet function analyser (PFA)-100 assay were determined as ancillary tests. The VWD diagnosis was established if: (i) both VWF:Ag (<50%) and VWF:RCo (<50%) were low; (ii) either VWF:Ag or VWF:RCo was low plus prolonged BT or prolonged PFA closure times. VWF multimer analysis was performed for subtype confirmation of VWD. Nine of the 56 (16.1%) patients were identified to have VWD. VWD patients with menorrhagia might develop IDA at younger age (34.3 vs. 39.7, P = 0.09) and had more IDA recurrence (75% vs. 16%, P = 0.03) than those patients without VWD. Of the eight VWD patients with VWF multimer analyses, all were revealed to have type I VWD. Our study demonstrates that VWD was not uncommon in women with both IDA and menorrhagia in Taiwan. [ABSTRACT FROM AUTHOR]

Background and Purpose: Pulmonary veins are the most important focus for the generation of atrial fibrillation. Abnormal calcium homeostasis with ryanodine receptor dysfunction may underlie the arrhythmogenic activity in pulmonary veins. The preferential ryanodine receptor stabilizer (K201) possesses antiarrhythmic effects through calcium regulation. The purpose of this study was to investigate the effects of K201 on the arrhythmogenic activity and calcium regulation of pulmonary vein cardiomyocytes.Experimental Approach: The ionic currents and intracellular calcium were studied in isolated single cardiomyocytes from rabbit pulmonary vein before and after the administration of K201, by the whole-cell patch clamp and indo-1 fluorimetric ratio techniques.Key Results: K201 (0.1, 0.3, 1 microM) reduced the firing rates in pulmonary vein cardiomyocytes, decreased the amplitudes of the delayed afterdepolarizations and prolonged the action potential duration. K201 decreased the L-type calcium currents, Na(+)/Ca(2+) exchanger currents, transient inward currents and calcium transients. K201 (1 microM, but not 0.1 microM or 0.3 microM) also reduced the sarcoplasmic reticulum calcium content. Moreover, both the pretreatment and administration of K201 (0.3 microM) decreased the isoprenaline (10 nM)-induced arrhythmogenesis in pulmonary veins.Conclusions and Implications: K201 reduced the arrhythmogenic activity of pulmonary vein cardiomyocytes and attenuated the arrhythmogenicity induced by isoprenaline. These findings may reveal the anti-arrhythmic potential of K201. [ABSTRACT FROM AUTHOR]