Genetic polymorphisms in the Toll-like receptor signalling pathway in Helicobacter pylori infection and related gastric cancer

Background

Gastric cancer (GC) is a progressive process initiated by Helicobacter pylori-induced inflammation. Initial recognition of H. pylori involves Toll-like receptors (TLRs), central molecules in the host inflammatory response. Here, we investigated the association between novel polymorphisms in genes involved in the TLR signalling pathway, including TLR2, TLR4, LBP, MD-2, CD14 and TIRAP, and risk of H. pylori infection and related GC.

Methods

A case-control study comprising 310 ethnic Chinese individuals (87 non-cardia GC cases and 223 controls with functional dyspepsia) was conducted. Twenty-five polymorphisms were detected by MALDI-TOF mass spectrometry, PCR, PCR–RFLP and real-time PCR.

Results

Seven polymorphisms showed significant associations with GC (TLR4 rs11536889, TLR4 rs10759931, TLR4 rs1927911, TLR4 rs10116253, TLR4 rs10759932, TLR4 rs2149356 and CD14 −260 C/T). In multivariate analyses, TLR4 rs11536889 remained a risk factor for GC (OR: 3.58, 95% CI: 1.20–10.65). TLR4 rs10759932 decreased the risk of H. pylori infection (OR: 0.59, 95% CI: 0.41–0.86). Statistical analyses assessing the joint effect of H. pylori infection and the selected polymorphisms revealed strong associations with GC (TLR2, TLR4, MD-2, LBP and TIRAP polymorphisms).

Conclusions

Novel polymorphisms in TLR2, TLR4, MD-2, LBP, CD14 and TIRAP, genes encoding important molecules of the TLR signalling pathway, showed clear associations with H. pylori-related GC in Chinese.     

Gracilaria changii(Rhodophyta) alleviates bisphenol A-induced adverse reproductive abnormalities in mice

Objective: To evaluate the potential of Gracilaria changii extract in ameliorating the potential adverse effects of bisphenol A. Methods: The antioxidant capacity of Gracilaria changii extracted using different solvents(methanol, ethanol, and aqueous) was studied. The mice were administered by oral gavage with bisphenol A(60 mg/kg body weight) for 6 weeks with or without Gracilaria changii aqueous extract. Thereafter, the mice were either euthanized for histology and immunohistochemistry studies or mated to evaluate the pregnancy rate. Results: Gracilaria changii aqueous extract showed the highest antioxidant properties compared with extract using methanol and ethanol. The aqueous extract of Gracilaria changii improved the uterus index and uterine lipid peroxidation after bisphenol A exposure, although the uterine expressions of estrogen receptors and complement C3 were not improved. Histological evaluation of the uterus during the estrus stage has revealed that the extract could mitigate bisphenol A-induced adverse effects in the uterus as there was a lower percentage of mice showing abnormalities like decreased eosin staining in the myometrium, and decrease in the number of eosinophil and endometrial glands in the endometrium. Besides, Gracilaria changii aqueous extract improved the pregnancy rate of mice administered with bisphenol A. Conclusions: Gracilaria changii extract protects against bisphenol A-induced female reproductive abnormalities in mice which may be mediated via modulation of eosinophil migration, endometrial gland formation, and protein expressions associated with prostaglandins in the myometrium.     

Exploring the reasons for low pertussis vaccine effectiveness in Ontario,Canada, 2006–2008: a Canadian Immunization Research Network study

ObjectivesAlthough pertussis vaccines have been widely used for many decades, a burden of illness persists. Resurgences in Ontario, Canada, have not been substantial in the past decade, but an outbreak of pertussis occurred in Toronto between 1 October 2005 and 31 March 2006. Previous Ontario studies found high vaccine effectiveness (VE) in the initial years post-immunization. In order to explore the impact of outbreaks and external factors on VE, we investigated pertussis VE during the period 2006–2008.MethodsWe assessed pertussis VE using a frequency-matched case-control study for the period 1 March 2006 to 31 December 2008. We used logistic regression to estimate VE by age, time since last vaccination, and vaccination status according to the Ontario recommended schedule. We compared analyses including and excluding cases from Toronto, and to two recent Ontario pertussis VE studies.ResultsWe included 1797 confirmed cases and 7188 matched controls. Most cases were under 4 years of age during the study period. Pertussis VE was 3.8% (95% CI: − 21.0, 24.0) in the period 15–364 days following the last pertussis vaccine dose, and increased with increasing time since vaccination. Pertussis VE in the first 15–364 days excluding Toronto increased to 57.1% (95% CI: 26.0, 75.1), but the trend of increasing VE with time since vaccination persisted. Although VE was higher in older (6–11 years) than younger (0–5 years) children, it was lower at 12–13 years than after 14 years.ConclusionVE was lower in comparison with other studies conducted in Ontario, particularly in younger children. Various factors occurring during the study period may have influenced the results, including clinical testing of asymptomatic contacts, laboratory testing and methods and reporting practice, and a sensitive case definition. Further studies are needed to optimize methods for measuring VE to inform pertussis vaccine policy.     

Exposure to ambient air pollution and the incidence of lung cancer and breast cancer in the Ontario Population Health and Environment Cohort

Lung and female breast cancers are highly prevalent worldwide. Although the association between exposure to ambient fine particulate matter (PM_2.5) and lung cancer has been recognized, there is less evidence for associations with other common air pollutants such as nitrogen dioxide (NO₂) and ozone (O₃). Even less is known about potential associations between these pollutants and breast cancer. We conducted a population-based cohort study to investigate the associations of chronic exposure to PM_2.5, NO₂, O₃ and redox-weighted average of NO₂ and O₃ (O_x) with incident lung and breast cancer, using the Ontario Population Health and Environment Cohort (ONPHEC), which includes all long-term residents aged 35–85 years who lived in Ontario, Canada, 2001–2015. Incident lung and breast cancers were ascertained using the Ontario Cancer Registry. Annual estimates of exposures were assigned to the residential postal codes of subjects for each year during follow-up. We used Cox proportional-hazards models adjusting for personal- and neighborhood-level covariates. Our cohorts for lung and breast cancer analyses included ~4.9 million individuals and ~2.5 million women, respectively. During follow-up, 100,146 incident cases of lung cancer and 91,146 incident cases of breast cancer were diagnosed. The fully adjusted analyses showed positive associations of lung cancer incidence with PM_2.5 (hazard ratio [HR] = 1.02 [95% CI: 1.01–1.05] per 5.3 μg/m³) and NO₂ (HR = 1.05 [95% CI: 1.03–1.07] per 14 ppb). No associations with lung cancer were observed for O₃ or O_x. Relationships between PM_2.5 and NO₂ with lung cancer exhibited a sublinear shape. We did not find compelling evidence linking air pollution to breast cancer.     

Voxel-based analysis of MRI detects abnormal visual cortex in children and adults with amblyopia

Amblyopia, sometimes called "lazy eye," is a relatively common developmental visual disorder well characterized behaviorally; however, the neural substrates associated with amblyopia in humans remain unclear. We hypothesized that abnormalities in the cerebral cortex of subjects with amblyopia exist, possibly as a result of experience-dependent neuronal plasticity. Anatomic magnetic resonance imaging (MRI) and psychophysical vision testing was carried out on 74 subjects divided into two age ranges, 7-12 years and 18-35 years, and three diagnoses, strabismic amblyopia, anisometropic amblyopia, and normal vision. We report a behavioral impairment in contrast sensitivity for subjects with amblyopia, consistent with previous reports. When the high-resolution MRI brain images were analyzed quantitatively with optimized voxel-based morphometry, results indicated that adults and children with amblyopia have decreased gray matter volume in visual cortical regions, including the calcarine sulcus, known to contain primary visual cortex. This finding was confirmed with a separate region-of-interest analysis. For the children with amblyopia, additional gray matter reductions in parietal-occipital areas and ventral temporal cortex were detected, consistent with recent reports that amblyopia can result in spatial location and object processing deficits. These data are the first to provide possible neuroanatomic bases for the loss of binocularity and visual sensitivity in children and adults with amblyopia.     

Ultrafiltration for acute decompensated heart failure: A systematic review and meta-analysis of randomized controlled trials

Background

Current clinical guidelines recommend ultrafiltration (UF) for patients with acute decompensated heart failure (ADHF) who are unresponsive or resistant to diuretics. We systematically reviewed the latest randomized evidence on the efficacy and safety of UF in ADHF.

Methods

MEDLINE, EMBASE and the Cochrane database were searched in January 2013 for eligible randomized controlled trials (RCTs) evaluating UF in patients with ADHF. A Mantel–Haenszel random-effects model was used to calculate mean differences (MDs) and odds ratios (ORs) for continuous and dichotomous data, respectively, with 95% confidence intervals (CIs).

Results

Data of 12 studies (n = 659) were meta-analyzed; follow-up duration ranged from 36 h to 12 months. Compared to control, treatment of UF was associated with significant fluid removal (MD 1.28, 95% CI 0.43 to 2.12, P = 0.003) and weight loss (MD 1.23, 95% CI 0.03 to 2.44, P = 0.04), with no significant effects on all-cause mortality (OR 1.08, 95% CI 0.63 to 1.86, P = 0.77) or all-cause rehospitalization (OR 0.89, 95% CI 0.39 to 2.00, P = 0.77). No significant differences were observed in the analyses of change in serum creatinine or unscheduled medical care; analysis of adverse effects was inconclusive since only one study provided usable data.

Conclusions

For patients with ADHF, UF is effective in reducing fluid retention and body weight, with no significant benefits in mortality or rehospitalization. The current limited randomized evidence highlights the need for further well-conducted randomized studies of adequate power to establish the role of UF in ADHF patients for whom conventional HF treatment is unsuccessful or contraindicated.