Non-alcoholic fatty liver disease and risk of in-stent restenosis after bare metal stenting in native coronary arteries

In-stent restenosis (ISR) remains the most common complication of percutaneous coronary intervention. Due to shared risk factors, it is postulated that non-alcoholic fatty liver disease (NAFLD) patients have an increased risk of ISR. This study aimed to determine the association between NAFLD and ISR in patients after bare metal stenting. This study included a cohort of 210 consecutive patients (150 men and 60 women) undergoing follow-up angiography. The primary end-point was angiographic ISR. Multivariate logistic regression analysis was used to identify independent risk factors for ISR. The cumulative ISR rate during follow-up was analyzed by Kaplan–Meier method. Subgroup analyses were also done for different gender. The ISR rate was 29.5 %. Patients with NAFLD had a significantly higher prevalence of ISR than patients without NAFLD (43.3 vs. 16.0 %, P < 0.001). In logistic regression analysis, NAFLD was associated with increased ISR, independent of low-density lipoprotein cholesterol, body mass index (adjusted odds ratio: 2.688, 95 % confidence intervals: 1.285–5.537, P < 0.001). Male NAFLD patients had a higher prevalence of ISR than patients without NAFLD (48.4 vs. 15.3 %, P < 0.001), while the prevalence of ISR in female patients with and without NAFLD were comparable (7.7 vs. 17.0 %, P = 0.404). Kaplan–Meier analysis showed a significant association between NAFLD and ISR in all patients (log-rank P = 0.008) and in male subgroup (log-rank P = 0.033), but not in female subgroup (log-rank P = 0.313). This preliminary study suggests that NAFLD could independently associate with a high prevalence of ISR, especially in male patients.     

Male-driven evolution

The strength of male-driven evolution - that is, the magnitude of the sex ratio of mutation rate - has been a controversial issue, particularly in primates. While earlier studies estimated the male-to-female ratio (alpha) of mutation rate to be about 4-6 in higher primates, two recent studies claimed that alpha is only about 2 in humans. However, a more recent comparison of mutation rates between a noncoding fragment on Y and a homologous region on chromosome 3 gave an estimate of alpha = 5.3, reinstating strong male-driven evolution in hominoids. Several studies investigated variation in mutation rates among genomic regions that may not be related to sex differences and found strong evidence for such variation. The causes for regional variation in mutation rate are not clear but GC content and recombination are two possible causes. Thus, while the strong male-driven evolution in higher primates suggests that errors during DNA replication in the germ cells are the major source of mutation, the contribution of some replication-independent factors such as recombination may also be important.     

Traditional Chinese medicines benefit to nonalcoholic fatty liver disease: a systematic review and meta-analysis

Evidences from randomized controlled trials (RCTs) for the efficiency of traditional Chinese medicine (TCM) on the treatment of nonalcoholic fatty liver disease (NAFLD) are conflicting. Here we conducted a systematic review and meta-analysis of RCTs to evaluate the efficiency and safety of TCM in the treatment of NAFLD. Studies were searched on PubMed and China National Knowledge Infrastructure from January 1995 to June 2010. RCTs comparing either TCM formulations alone or in combination with placebo, ursodeoxycholic acid, insulin sensitizers, lipid-lowering drugs, or antioxidants were included. The category of most usually used herbs in the treatment of NAFLD was also calculated. Five thousand nine hundred and four patients from 62 RCTs were included for meta-analysis and 25,661 patients from 419 clinical studies were for TCM formulation analysis. Comparing with western medicines mentioned above, TCM had a better effect on the normalization of alanine aminotransferase and disappearance of radiological steatosis in the treatment of NAFLD. Furthermore, 246 kinds of Chinese herbs were included in our present study, with an average of 10 herbs (range 1-31) in each formulation. Hawthorn Fruit (321 times in 17,670 patients) was the most often used herb in the treatment of NAFLD. In conclusion, TCM is of modest benefit to the treatment of NAFLD.     

Bioinformatics models for predicting antigenic variants of influenza A/H3N2 virus

MOTIVATION: Continual and accumulated mutations in hemagglutinin (HA) protein of influenza A virus generate novel antigenic strains that cause annual epidemics. RESULTS: We propose a model by incorporating scoring and regression methods to predict antigenic variants. Based on collected sequences of influenza A/H3N2 viruses isolated between 1971 and 2002, our model can be used to accurately predict the antigenic variants in 1999-2004 (agreement rate = 91.67%). Twenty amino acid positions identified in our model contribute significantly to antigenic difference and are potential immunodominant positions.     

Promotion of the mind through exercise (PROMoTE): a proof-of-concept randomized controlled trial of aerobic exercise training in older adults with vascular cognitive impairment

Background  

Sub-cortical vascular ischaemia is the second most common etiology contributing to cognitive impairment in older adults, and is frequently under-diagnosed and under-treated. Although evidence is mounting that exercise has benefits for cognitive function among seniors, very few randomized controlled trials of exercise have been conducted in populations at high-risk for progression to dementia. Aerobic-based exercise training may be of specific benefit in delaying the progression of cognitive decline among seniors with vascular cognitive impairment by reducing key vascular risk factors associated with metabolic syndrome. Thus, we aim to carry out a proof-of-concept single-blinded randomized controlled trial primarily designed to provide preliminary evidence of efficacy aerobic-based exercise training program on cognitive and everyday function among older adults with mild sub-cortical ischaemic vascular cognitive impairment.     

Increased risk of colorectal malignant neoplasm in patients with nonalcoholic fatty liver disease: a large study

Nonalcoholic fatty liver disease (NAFLD) has been suggested to be a strong risk factor of colorectal benign adenomas and advanced neoplasms. The aim of this large cohort study was to further investigate the prevalence of colorectal malignant neoplasm (CRMN) in patients with NAFLD and determine whether association between NAFLD and CRMN exists. 2,315 community subjects (1,370 males and 945 females) who underwent a routine colonoscopy according to international colorectal cancer screening guideline were recruited. Nature of colorectal lesions determined by biopsy and NAFLD was diagnosed by ultrasound. Binary logistic regression analysis was applied to explore the related associations. Prevalence of CRMN was 29.3 % (77/263) in patients with NAFLD, which was significantly higher than 18.0 % (369/2,052) in the control group (P < 0.05). In addition, malignant neoplasm in NAFLD group occurred more frequently at sigmoid colon than in control group (14.3 vs. 11.9 %). The incidence of highly-differentiated colorectal adenocarcinoma in NAFLD group was significantly higher than control group (62.3 vs. 9.8 %). Univariate analysis showed that NAFLD had strong association with CRMN (OR 2.043; 95 % CI 1.512–2.761; P < 0.05). After adjusting for metabolic and other confounding factors, NAFLD remained as an independent risk factor for CRMN (OR 1.868; 95 % CI 1.360–2.567; P < 0.05). NAFLD was an independent risk factor for CRMN. Sigmoid carcinoma and highly differentiated colorectal adenocarcinoma were more commonly found in NAFLD. (ClinicalTrials.gov number, NCT01657773, website: http://clinicaltrials.gov/ct2/show/NCT01657773?term=zheng+minghua&rank=1).     

Fetal and Childhood Exposure to Phthalate Diesters and Cognitive Function in Children Up to 12 Years of Age: Taiwanese Maternal and Infant Cohort Study

Few studies have examined the association between environmental phthalate exposure and children’s neurocognitive development. This longitudinal study examined cognitive function in relation to pre-and postnatal phthalate exposure in children 2–12 years old. We recruited 430 pregnant women in their third trimester in Taichung, Taiwan from 2001–2002. A total of 110, 79, 76, and 73 children were followed up at ages 2, 5, 8, and 11, respectively. We evaluated the children’s cognitive function at four different time points using the Bayley and Wechsler tests for assessing neurocognitive functions and intelligence (IQ). Urine samples were collected from mothers during pregnancy and from children at each follow-up visit. They were analyzed for seven metabolite concentrations of widely used phthalate esters. These esters included monomethyl phthalate, monoethyl phthalate, mono-butyl phthalate, mono-benzyl phthalate, and three metabolites of di(2-ethylhexyl) phthalate, namely, mono-2-ethylhexyl phthalate, mono(2-ethyl-5-hydroxyhexyl) phthalate, and mono(2-ethyl-5-oxohexyl) phthalate. We constructed a linear mixed model to examine the relationships between the phthalate metabolite concentrations and the Bayley and IQ scores. We found significant inverse associations between the children’s levels of urinary mono(2-ethyl-5-oxohexyl) phthalate and the sum of the three metabolites of di(2-ethylhexyl) phthalate and their IQ scores (β = -1.818; 95% CI: -3.061, -0.574, p = 0.004 for mono(2-ethyl-5-oxohexyl) phthalate; β = -1.575; 95% CI: -3.037, -0.113, p = 0.035 for the sum of the three metabolites) after controlling for maternal phthalate levels and potential confounders. We did not observe significant associations between maternal phthalate exposure and the children’s IQ scores. Children’s but not prenatal phthalate exposure was associated with decreased cognitive development in the young children. Large-scale prospective cohort studies are needed to confirm these findings in the future.     

Further improvements on the phosphotriester synthesis of deoxyribooligonucleotides and the oligonucleotide directed site-specific mutagenesis of E. coli lipoprotein gene.

Two improvements that greatly enhance the rate of phosphotriester oligonucleotide synthesis are described: 1) use of hindered primary amines, e.g. t-butyl amine for decyanoethylation of oligonucleotide triester intermediates, and 2) a simplified isolation procedure that eliminates the tedious bicarbonate extraction after each condensing reaction. Using the improved procedures, oligonucleotide fragments can be synthesized as rapidly as using solid phase chemistry. The final products are purer than those obtained by solid phase chemistry since each intermediate block is purified by chromatography. The technique has been used to synthesize five oligonucleotide fragments (size 15 to 20) for the purpose of performing guided site-specific mutagenesis on a cloned E. coli lipoprotein gene.     

CNBr cleavage of the light chain of human complement factor I and alignment of the fragments.

The primary structure of the second component of human complement (C2) was determined by cDNA cloning and sequence analysis. C2 has 39% identity with the functionally analogous protein Factor B. The C-terminal half of C2a is homologous to the catalytic domains of other serine proteinases. C2b contains three direct repeats of approx. 60 amino acid residues. They are homologous to repeats in Factor B, C4b-binding protein and Factor H, suggesting a functional significance of the repeat in C4b and C3b binding. The repeats are also found in the non-complement proteins beta 2-glycoprotein I and interleukin-2 receptor, and this repeat family may be widespread.     

Asynchronous depression of responses to T- and B-cell mitogens during acute infection with cytomegalovirus in the guinea pig

The nonspecific functional capacity of spleen cells, taken from female guinea pigs with primary acute cytomegalovirus (CMV) infection, was assessed using lipopolysaccharide (LPS), a B-cell mitogen, and concanavalin A (Con A), a T-cell mitogen. Proliferative responses to the two mitogens were found to be significantly depressed in animals inoculated with CMV as compared to control animals. The defect in Con A responsiveness occurred earlier during the course of the infection than the defect in LPS responses. Although responses to the mitogens were depressed at the time of peak virus activity in the spleen, the possibility of lytic destruction of the spleen cells by the virus during in vitro culture was excluded. In addition, the depression in Con A responsiveness was noted with a wide range of Con A concentrations, and preculture studies failed to result in enhanced reactivity of the cells from infected animals. We conclude that reductions of both B- and T-cell functions, which differ in their timing during the course of acute CMV infection, occur concurrently with an enhanced viral specific immune response in guinea pigs acutely infected with CMV.