IL-17A and IL-17F genes variants and susceptibility to childhood asthma in Tunisia

Objectives: IL-17A and IL-17F are new pro-inflammatory cytokines implicated in neutrophilic inflammation and thus, involved in the pathogenesis of asthma. We investigated the possible association among asthma and IL-17A -197G/A (rs2275913), IL-17F 7488A/G (rs763780) and IL-17F 7383A/G (rs2397084).

Methods: The study was performed in 171 patients with asthma (mean age 9.5?years, 105 boys, and 66 girls) and 171 healthy individuals matched with patients in age and sex. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to detect genes’ polymorphisms.

Results: IL-17A -197G/A and IL-17F 7383A/G were associated with asthma in children (p?=?0.008, p?=?0.001, respectively). No association was found with IL-17F 7488A/G polymorphism. Haplotype analysis revealed a significant association between GA and AG haplotypes and asthma (p?=?0.004, p?=?0.02). When patients were stratified according to the atopic status, no significant association was detected with any of the three studied variants.

Conclusion: Our results suggested that SNPs in IL-17A and IL-17F confer susceptibility to childhood asthma in Tunisia.     

Unusual features of Creutzfeldt–Jakob disease followed-up in a memory clinic

Sporadic Creutzfeldt–Jakob disease (sCJD) generally manifests itself by cognitive or rapidly progressive motor symptoms. An atypical onset or an unusual evolution may delay the diagnosis. Among patients with a confirmed diagnosis of sCJD following a post-mortem neuropathological examination at the Neuropathology Centre of Lille, France, those who had presented with atypical cognitive disorders at onset were included in the study. Four patients were included. The first patient (64-years-old) presented early language disorders, later accompanied by apathy and behavioral disorders. The prolonged course suggested a diagnosis of progressive primary aphasia. The second patient (68-years-old) presented with aphasia, apraxia, and ataxia of the right upper limb with parkinsonian syndrome, suggesting corticobasal degeneration. In the two last patients (58- and 61-years-old), the onset was marked by an anxiety–depression syndrome, falls, visual hallucinations, extra-pyramidal syndrome, and fluctuating cognitive decline. The diagnosis raised was probable Lewy body dementia. The 14.3.3 protein was found in two of the four cases. The clinical elements found may initially suggest focal atrophy or Lewy body dementia. A very rapid clinical deterioration generally suggests sCJD, but in the last case, the evolution was particularly slow. The diagnosis of sCJD must be considered in cases of rapid-onset dementia, even if all of the clinical criteria are not present. The detection of the 14.3.3 protein and multifold increase in total-Tau with normal or slightly increased phosphorylated-Tau in the CSF are additional arguments to reinforce the diagnosis. The post-mortem neuropathological examination is important to confirm the diagnosis.     

Fractions of cardiovascular diseases and mental disorders attributable to psychosocial work factors in 31 countries in Europe

Objectives

The aim of this study was to evaluate the fractions of cardiovascular diseases and mental disorders attributable to three psychosocial work factors, job strain, effort-reward imbalance (ERI) and job insecurity, in 31 countries in Europe.

Methods

The prevalence of exposure (Pe) to job strain, ERI and job insecurity was calculated using the sample of 29,680 workers from 31 countries of the 2005 European Working Conditions Survey. Relative risks (RR) were obtained from three published meta-analyses. Pe and RR estimates were used to calculate attributable fractions (AF).

Results

Pe estimates were 26.90, 20.44 and 14.11 % for job strain, ERI and job insecurity in Europe, and significant differences were observed between countries. The job strain and ERI AFs for cardiovascular diseases were, respectively, 4.46 % (significantly different from zero for Europe and all countries, but without any differences between countries) and 18.21 % (not significantly different from zero for Europe and without differences between countries). The significant job strain and job insecurity AFs for mental disorders were 18.16 and 4.53 % in Europe, without any significant difference between countries. The significant ERI AF for mental disorders was 14.81 %, and significant differences were found between countries; the 3 highest AFs were observed in Greece, Slovenia and Turkey, and the 3 lowest in Bulgaria, Ireland and Latvia.

Conclusion

This study is the first one to provide fractions of cardiovascular diseases and mental disorders attributable to three psychosocial work factors for the whole Europe and to explore the differences between 31 countries. These results may be useful to guide European and national prevention policies as well as to evaluate the economic costs of diseases attributable to these exposures.     

Migration of murine intestinal dendritic cell subsets upon intrinsic and extrinsic TLR3 stimulation

Initiation of adaptive immunity to particulate antigens in lymph nodes largely depends on their presentation by migratory dendritic cells (DCs). DC subsets differ in their capacity to induce specific types of immunity, allowing subset-specific DC-targeting to influence vaccination and therapy outcomes. Faithful drug design, however, requires exact understanding of subset-specific versus global activation mechanisms. cDC1, the subset of DCs that excel in supporting immunity toward viruses, intracellular bacteria, and tumors, express uniquely high levels of the pattern recognition receptor TLR3. Using various murine genetic models, we show here that both, the cDC1 and cDC2 subsets of cDCs are activated and migrate equally well in response to TLR3 stimulation in a cell extrinsic and TNF-α dependent manner, but that cDC1 show a unique requirement for type I interferon signaling. Our findings reveal common and differing pathways regulating DC subset migration, offering important insights for the design of DC-based vaccination and therapy approaches.     

Exogenous hormone use and cutaneous melanoma risk in women: The European Prospective Investigation into Cancer and Nutrition

Evidence suggests an influence of sex hormones on cutaneous melanoma risk, but epidemiologic findings are conflicting. We examined the associations between use of oral contraceptives (OCs) and menopausal hormone therapy (MHT) and melanoma risk in women participating in the European Prospective Investigation into Cancer and Nutrition (EPIC). EPIC is a prospective cohort study initiated in 1992 in 10 European countries. Information on exogenous hormone use at baseline was derived from country-specific self-administered questionnaires. We used Cox proportional hazards regression models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Over 1992–2015, 1,696 melanoma cases were identified among 334,483 women, whereof 770 cases among 134,758 postmenopausal women. There was a positive, borderline-significant association between OC use and melanoma risk (HR = 1.12, 95% CI = 1.00–1.26), with no detected heterogeneity across countries (p_homogeneity = 0.42). This risk increased linearly with duration of use (p_trend = 0.01). Among postmenopausal women, ever use of MHT was associated with a nonsignificant increase in melanoma risk overall (HR = 1.14, 95% CI = 0.97–1.43), which was heterogeneous across countries (p_homogeneity = 0.05). Our findings do not support a strong and direct association between exogenous hormone use and melanoma risk. In order to better understand these relations, further research should be performed using prospectively collected data including detailed information on types of hormone, and on sun exposure, which may act as an important confounder or effect modifier on these relations.     

Theoretical potential for endometrial cancer prevention through primary risk factor modification: Estimates from the EPIC cohort

Endometrial cancer (EC) incidence rates vary ~10-fold worldwide, in part due to variation in EC risk factor profiles. Using an EC risk model previously developed in the European EPIC cohort, we evaluated the prevention potential of modified EC risk factor patterns and whether differences in EC incidence between a European population and low-risk countries can be explained by differences in these patterns. Predicted EC incidence rates were estimated over 10 years of follow-up for the cohort before and after modifying risk factor profiles. Risk factors considered were: body mass index (BMI, kg/m²), use of postmenopausal hormone therapy (HT) and oral contraceptives (OC) (potentially modifiable); and, parity, ages at first birth, menarche and menopause (environmentally conditioned, but not readily modifiable). Modeled alterations in BMI (to all ≤23 kg/m²) and HT use (to all non-HT users) profiles resulted in a 30% reduction in predicted EC incidence rates; individually, longer duration of OC use (to all ≥10 years) resulted in a 42.5% reduction. Modeled changes in not readily modifiable exposures (i.e., those not contributing to prevention potential) resulted in ≤24.6% reduction in predicted EC incidence. Women in the lowest decile of a risk score based on the evaluated exposures had risk similar to a low risk countries; however, this was driven by relatively long use of OCs (median = 23 years). Our findings support avoidance of overweight BMI and of HT use as prevention strategies for EC in a European population; OC use must be considered in the context of benefits and risks.