Gene–environment interactions increase the risk of pediatric-onset multiple sclerosis associated with ozone pollution

Background: We previously reported a relationship between air pollutants and increased risk of pediatric-onset multiple sclerosis (POMS). Ozone is an air pollutant that may play a role in multiple sclerosis (MS) pathoetiology. CD86 is the only non-HLA gene associated with POMS for which expression on antigen-presenting cells (APCs) is changed in response to ozone exposure. Objectives: To examine the association between county-level ozone and POMS, and the interactions between ozone pollution, CD86, and HLA- DRB1*15, the strongest genetic variant associated with POMS. Methods: Cases and controls were enrolled in the Environmental and Genetic Risk Factors for Pediatric MS study of the US Network of Pediatric MS Centers. County-level-modeled ozone data were acquired from the CDC’s Environmental Tracking Network. Participants were assigned ozone values based on county of residence. Values were categorized into tertiles based on healthy controls. The association between ozone tertiles and having MS was assessed by logistic regression. Interactions between tertiles of ozone level and the GG genotype of the rs928264 (G/A) single nucleotide polymorphism (SNP) within CD86, and the presence of DRB1*15:01 ( DRB1*15) on odds of POMS were evaluated. Models were adjusted for age, sex, genetic ancestry, and mother’s education. Additive interaction was estimated using relative excess risk due to interaction (RERI) and attributable proportions (APs) of disease were calculated. Results: A total of 334 POMS cases and 565 controls contributed to the analyses. County-level ozone was associated with increased odds of POMS (odds ratio 2.47, 95% confidence interval (CI): 1.69–3.59 and 1.95, 95% CI: 1.32–2.88 for the upper two tertiles, respectively, compared with the lowest tertile). There was a significant additive interaction between high ozone tertiles and presence of DRB1*15, with a RERI of 2.21 (95% CI: 0.83–3.59) and an AP of 0.56 (95% CI: 0.33–0.79). Additive interaction between high ozone tertiles and the CD86 GG genotype was present, with a RERI of 1.60 (95% CI: 0.14–3.06) and an AP of 0.37 (95% CI: 0.001–0.75) compared to the lowest ozone tertile. AP results indicated that approximately half of the POMS risk in subjects can be attributed to the possible interaction between higher county-level ozone carrying either DRB1*15 or the CD86 GG genotype. Conclusions: In addition to the association between high county-level ozone and POMS, we report evidence for additive interactions between higher county-level ozone and DRB1*15 and the CD86 GG genotype. Identifying gene–environment interactions may provide mechanistic insight of biological processes at play in MS susceptibility. Our work suggests a possible role of APCs for county-level ozone-induced POMS risk.

Analytical and numerical comparisons of two methods of estimation of additive × additive × additive interaction of QTL effects

This paper presents the analytical and numerical comparison of two methods of estimation of additive × additive × additive (aaa) interaction of QTL effects. The first method takes into account only the plant phenotype, while in the second we also included genotypic information from molecular marker observation. Analysis was made on 150 doubled haploid (DH) lines of barley derived from cross Steptoe × Morex and 145 DH lines from Harrington × TR306 cross. In total, 153 sets of observation was analyzed. In most cases, aaa interactions were found with an exert effect on QTL. Results also show that with molecular marker observations, obtained estimators had smaller absolute values than phenotypic estimators.

Impact of adiposity on risk of female gout among those genetically predisposed: sex-specific prospective cohort study findings over >32 years

ObjectivesTo evaluate the joint (combined) association of excess adiposity and genetic predisposition with the risk of incident female gout, and compare to their male counterparts; and determine the proportion attributable to body mass index (BMI) only, genetic risk score (GRS) only, and to their interaction.MethodsWe prospectively investigated potential gene-BMI interactions in 18 244 women from the Nurses’ Health Study and compared with 10 888 men from the Health Professionals Follow-Up Study. GRS for hyperuricaemia was derived from 114 common urate-associated single nucleotide polymorphisms.ResultsMultivariable relative risk (RR) for female gout was 1.49 (95% CI 1.42 to 1.56) per 5 kg/m2 increment of BMI and 1.43 (1.35 to 1.52) per SD increment in the GRS. For their joint association of BMI and GRS, RR was 2.18 (2.03 to 2.36), more than the sum of each individual factor, indicating significant interaction on an additive scale (p for interaction <0.001). The attributable proportions of joint effect for female gout were 42% (37% to 46%) to adiposity, 37% (32% to 42%) to genetic predisposition and 22% (16% to 28%) to their interaction. Additive interaction among men was smaller although still significant (p interaction 0.002, p for heterogeneity 0.04 between women and men), and attributable proportion of joint effect was 14% (6% to 22%).ConclusionsWhile excess adiposity and genetic predisposition both are strongly associated with a higher risk of gout, the excess risk of both combined was higher than the sum of each, particularly among women.

In Vitro Interactions of Costus speciosus (J. Koenig) Sm., Cymbopogon citratus (Dc. Ex Nees) Stapf. and Tabernaemontana coronaria (L.) Willd. with First-Line Anti-Tuberculosis Drugs Against Mycobacterium tuberculosis H37rv

Global tuberculosis (TB) burden underscores the importance of developing new effective anti-TB drugs. This study was concerned with prospecting for potential anti-TB agents from Malaysian medicinal plants. In our previous study, we have reported that n-hexane fractions of Costus speciosus (C. speciosus) (J. Koening) Sm., Cymbopogon citratus (C. citratus ) (DC.) Stapf. and Tabernaemontana coronaria (T. coronaria) (Jacq.) posses promising anti-TB activity against Mycobacterium tuberculosis (M. tuberculosis) H37Rv with minimum inhibitory concentrations (MICs) of 200–100 µg/mL. This study aimed to investigate the interactions of these active fractions with first-line anti-TB drugs (isoniazid, rifampicin, ethambutol and streptomycin) against M. tuberculosis H37Rv using the microdilution checkerboard method. C. citratus (stem-rhizome) n-hexane fraction exhibited synergism with all drugs except ethambutol which showed additive interaction. Synergistic was also observed when C. speciosus (stem-flower) n-hexane and T. coronaria (leaf) n-hexane fractions in combination with rifampicin. C. speciosus (stem-flower) n-hexane and T. coronaria (leaf) n-hexane exhibited additive interaction with isoniazid, ethambutol and streptomycin. Hence, these active plants are worthy of further investigations for the discovery of anti-TB drug leads.

Inequality in Social Support Associated With Mild Cognitive Impairment: A Cross-Sectional Study of Older (≥60 Years) Residents in Shanghai, China

Objective: Social support plays a critical role in the detection and management of mild cognitive impairment (MCI). However, socioeconomic inequalities exist in both social support and health care services. Our study aimed to compare the level of social support received by MCI patients in comparison with those without MCI and to determine its link with income.Methods: Secondary data analyses were performed. Social support was measured using the Duke Social Support Index (DSSI) and satisfaction ratings. Multivariate logistic regression models were constructed to determine the associations of personal income and MCI with social support after adjustment for variations in the sociodemographic and health characteristics of the respondents. The multiplicative and additive interaction effects of income and MCI were further examined through introducing the MCI*Income variable to the regression models and using the relative excess risk due to interaction (RERI) analysis, respectively.Results: The logistic regression models showed that the respondents with MCI had significantly lower social support as measured by the DSSI scores (AOR = 33.03, p &lt; 0.001) and satisfaction ratings (AOR = 7.48, p &lt; 0.001) compared with those without MCI. Similarly, social support decreased with lower personal income (p &lt; 0.001). There existed a significant multiplicative interaction effect between personal income and MCI on social support (AOR = 0.30–0.32, p &lt; 0.01). The gap in social support between those with and without MCI was higher in the higher income group compared with the lower income group (p &lt; 0.001). No significant additive interaction effects on social support were found between MCI and income.Conclusions: There are significant disparities in social support between people living with and without MCI. Such a gap is more profound in people with higher income. The inequality in social support associated with MCI may present a significant challenge to the successful implementation of community MCI detection and management.

IL-1β and TNFα Cooperativity in Regulating IL-6 Expression in Adipocytes Depends on CREB Binding and H3K14 Acetylation

IL-6 was found to be overexpressed in the adipose tissue of obese individuals, which may cause insulin resistance. However, the regulation of IL-6 in adipocytes in obesity setting remains to be explored. Since IL-1β and TNFα are increased in obese adipose tissue and promote inflammation, we investigated whether cooperation between IL-1β and TNFα influences the production of IL-6. Our data show that IL-1β and TNFα cooperatively enhances IL-6 expression in 3T3L-1 adipocytes. Similar results were seen in human adipocytes isolated from subcutaneous and visceral fat. Although adipocytes isolated from lean and obese adipose tissues showed similar responses for production of IL-6 when incubated with IL-1β/TNFα, secretion of IL-6 was higher in adipocytes from obese tissue. TNFα treatment enhanced CREB binding at CRE locus, which was further enhanced with IL-1β, and was associated with elevated histone acetylation at CRE locus. On the other hand, IL-1β treatments mediated C/EBPβ binding to NF-IL-6 consensus, but not sufficiently to mediate significant histone acetylation. Interestingly, treatment with both stimulatory factors amplifies CREB binding and H3K14 acetylation. Furthermore, histone acetylation inhibition by anacardic acid or curcumin reduces IL-6 production. Notably, inhibition of histone deacetylase (HDAC) activity by trichostatin A (TSA) resulted in the further elevation of IL-6 expression in response to combined treatment of adipocytes with IL-1β and TNFα. In conclusion, our results show that there is an additive interaction between IL-1β and TNFα that depends on CREB binding and H3K14 acetylation, and leads to the elevation of IL-6 expression in adipocytes, providing interesting pathophysiological connection among IL-1β, TNFα, and IL-6 in settings such as obesity.

Molecular Characterization and Toxicity of Heavy Metal Quinary Mixtures on Enterobacter cloacae Isolate from Nworie River

The molecular characterization and toxicity of Cadmium (Cd), Lead (Pb), Zinc (Zn), Chromium (Cr) and Copper (Cu) quinary mixtures on Enterobacter cloacae isolate from Nworie River was investigated. Quinary mixtures of the heavy metals were compounded using fixed ratio (%); and inhibitory effect assessed using inhibition of total dehydrogenase as toxicity response. The mixtures consisted of five heavy metals in the ratios: Pb (20%) + Cr (20%) + Cd (20%) + Zn (20%) + Cu (20%), Pb (30%) + Cr (20%) + Cd (10%) + Zn (30%) + Cu (10%). Pb (10%) + Cr (10%) + Cd (30%) + Zn (40%) + Cu (10%), Pb (15%) + Cr (25%) + Cd (25%) + Zn (15%) + Cu (20%), Pb (40%) + Cr (15%) + Cd (5%) + Zn (20%) + Cu(20%). Result obtained showed that toxicity of the metals against the bacterium ranked in the order Cu > Cr >Zn > Pb > Cd. The quinary mixtures Pb (20%) + Cr (20%) + Cd (20%) + Zn (20%) + Cu (20%), Pb (30%) + Cr (20%) + Cd (10%) + Zn (30%) + Cu (10%) and 10%Pb + 10%Cr + 30%Cd + 40%Zn + 10%Cu showed synergistic interaction, while 15%Pb + 25%Cr + 25%Cd + 15%Zn + 20%Cu and 40%Pb + 15%Cr + 5%Cd + 20%Zn + 20%Cu mixtures were antagonistic and additive respectively. Threshold inhibitory concentration (IC50) of the quinary mixtures was 0.054 ± 0.005mM, 0.053 ± 0.002 mM, 0.038 ± 0.002 mM, 0.077 ± 0.007 mM and 0.058 ± 0.006 mM for the respective mixtures. The toxic index values evaluated for the mixtures exhibited antagonistic, synergistic and additive interaction in the various ratios. The 16S rRNA and ITSF1 sequences obtained of the isolate showed the phylogenetic placement of the 16S rRNA of the isolate was closely related to Enterobacter cloacae strain DL01 (MH168084). The heavy metals mixtures demonstrated diverse toxicity interaction on the isolate depending on their relative composition, thus poses a threat to aquatic microbial diversity.

Nucleon-nucleus inelastic scattering by Manning-Rosen distorted nonlocal potential

Within the framework of non-relativistic quantum scattering theory we treat the charged hadron scattering by replacing the nuclear interaction by a separable nonlocal one and the electromagnetic part by the Manning-Rosen potential. The off-energy-shell scattering is studied by this additive interaction by including the effect of electromagnetic interaction rigorously. The exact analytical expressions for the off-shell solutions and half-shell T-matrix are obtained in maximal reduced form. The half-shell T-matrix for the proton-oxygen system is computed and the resultant phase shifts are found in order.

Influencing mechanisms of lifestyle and dietary factors on chronic diseases among community residents: updated evidence in Shanghai, China

Objectives: This study aimed to determine the risk factors for chronic diseases and identify the potential influencing mechanisms from the perspectives of lifestyle and dietary factors. The findings could provide updated and innovative evidence for the prevention and control of chronic diseases. Design: A cross-sectional study. Setting: Shanghai, China. Participants: 1,005 adults from Yangpu district of Shanghai participated in the study, and responded to questions on dietary habits, lifestyle, and health status. Results: Residents suffering from chronic diseases accounted for 34.99% of the respondents. Logistic regression analysis showed that age, diet quality, amount of exercise and tea drinking were related to chronic diseases. Age>60 and overeating (diet balance index total score >0, DBI_TS) had negative additive interaction on the occurrence of chronic disease, while overexercise (Physical activity index>17.1, PAI) and tea drinking had negative multiplicative interaction and negative additive interaction on the occurrence of chronic disease. Diet quality, physical activity, tea drinking was an incomplete mediator of the relationship between types of medical insurance residents participating in and chronic diseases. Conclusions: The residents in Yangpu District of Shanghai have a high prevalence of chronic diseases. Strengthening access of residents to health education and interventions to prevent chronic diseases and cultivating healthy eating and exercise habits of residents are crucial. The nutritional environment of the elderly population should be considered, the reimbursement level of different types of medical insurance should be designed reasonably to improve the accessibility of medical and health services and reduce the risk of chronic diseases.