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BackgroundThis retrospective cross-sectional study aims to analyse the keratoconus (KC) stage distribution at different ages within the Homburg Keratoconus Center (HKC).Methods1917 corneae (1000 patients) were allocated to decades of age, classified according to Belin’s ABCD KC grading system and the stage distribution was analysed.Results73 per cent (n=728) of the patients were males, 27% (n=272) were females. The highest KC prevalence occurred between 21 and 30 years (n=585 corneae, 294 patients). Regarding anterior (A) and posterior (B) curvature, the frequency of A was significantly higher than B in all age groups for stage 0, 1 and 2 (A0>B0; A1>B1; A2>B2; p<0.03, Wilcoxon matched-pairs test). There was no significant difference between the number of A3 and B3, but significantly more corneae were classified as B4 than A4 in all age groups (p<0.02). The most frequent A|B combinations were A4|B4 (n=451), A0|B0 (n=311), A2|B4 (n=242), A2|B2 (n=189) and A1|B2 (n=154). Concerning thinnest pachymetry (C), most corneae in all age groups were classified as C0>C1>C2>C3>C4 (p<0.04, Wilcoxon matched-pairs test). For the best distance visual acuity (D), a significantly higher number of corneae were classified as D1 compared to D0 (p<0.008; D1>D0>D2>D3>D4).ConclusionThe stage distributions in all age groups were similar. Early KC rather becomes manifest in the posterior than the anterior corneal curvature whereas advanced stages of posterior corneal curvature coincide with early and advanced stages of anterior corneal curvature. Thus, this study emphasises the necessity of posterior corneal surface assessment in KC as enabled by the ABCD grading system.

ObjectiveImmunoglobulin A vasculitis (IgAV) and nephropathy (IgAN) share common immunological mechanisms. Liver cirrhosis is well known to be associated with IgAN. Here, we aimed to describe the presentation and outcome of IgAV patients with underlying cirrhosis.MethodsWe conducted a French nationwide retrospective study of adult patients presenting with both IgAV and cirrhosis. Baseline characteristics were compared to those of the 260 patients included in the French nationwide IgAV registry (IGAVAS).ResultsTwenty patients were included, and 7 (35%) were female. The mean ± SD age was 62.7 ± 11 years. At baseline, compared with IGAVAS patients, patients with underlying cirrhosis were older (62.7 ± 11 vs 50.1 ± 18, P< 0.01) and displayed more constitutional symptoms (weight loss 25% vs 8%, P= 0.03). Patients with underlying cirrhosis were also more likely to exhibit elevated serum IgA levels (5.6 g/L vs 3.6 g/L, P= 0.02). Cirrhosis and IgAV were diagnosed simultaneously in 12 patients (60%). Cirrhosis was mainly related to alcohol intake (n = 15, 75%), followed by nonalcoholic steato-hepatitis (n = 2), chronic viral hepatitis (n = 1), hemochromatosis (n = 1), and autoimmune hepatitis (n = 1). During follow-up with a median of 17 months (IQR 12–84), 10/13 (77%) exhibited IgAV remission at Month 3. One patient presented a minor relapse. Six patients died, but no deaths were related to IgAV.ConclusionWe report the first case series of IgAV patients with underlining cirrhosis, to our knowledge, which was mainly alcohol related. The liver disease did not seem to affect baseline vasculitis characteristics. Physicians should investigate the existence of liver cirrhosis at IgAV diagnosis, especially in the context of alcohol abuse.

In vitro, Drosophila melanogasterDicer-2 (Dcr-2) uses its helicase domain to initiate processing of dsRNA with blunt (BLT) termini, and its Platform•PAZ domain to initiate processing of dsRNA with 3′ overhangs (ovrs). To understand the relationship of these in vitro observations to roles of Dcr-2 in vivo, we compared in vitro effects of two helicase mutations to their impact on production of endogenous and viral siRNAs in flies. Consistent with the importance of the helicase domain in processing BLT dsRNA, both point mutations eliminated processing of BLT, but not 3′ovr, dsRNA in vitro. However, the mutations had different effects in vivo. A point mutation in the Walker A motif of the Hel1 subdomain, G31R, largely eliminated production of siRNAs in vivo, while F225G, located in the Hel2 subdomain, showed reduced levels of endogenous siRNAs, but did not significantly affect virus-derived siRNAs. In vitro assays monitoring dsRNA cleavage, dsRNA binding, ATP hydrolysis, and binding of the accessory factor Loquacious-PD provided insight into the different effects of the mutations on processing of different sources of dsRNA in flies. Our in vitro studies suggest effects of the mutations in vivo relate to their effects on ATPase activity, dsRNA binding, and interactions with Loquacious-PD. Our studies emphasize the importance of future studies to characterize dsRNA termini as they exist in Drosophilaand other animals.

Chlordecone is a synthetic organochlorine pesticide, extensively used in banana plantations of the French West Indies from 1972 to 1993. Due to its environmental persistence and bioaccumulation, it has dramatic public health and socio-economic impact. Here we describe a method for carbon-directed compound specific isotope analysis (CSIA) for chlordecone and apply it to monitor biotic and abiotic reductive transformation reactions, selected on the basis of their distinct product profiles (polychloroindenes versus lower chlorinated hydrochlordecones). Significant carbon isotopic enrichments were observed for all microbially mediated transformations (ebulk= -6.8‰ with a Citrobacterstrain and ebulk= -4.6‰ with a bacterial consortium) and for two abiotic transformations (ebulk= -4.1‰ with zerovalent iron and ebulk= -2.6‰ with sodium sulfide and vitamin B12). The reaction with titanium(III) citrate and vitamin B12, which shows the product profile most similar to that observed in biotic transformation, led to low carbon isotope enrichment (ebulk=-0.8‰). The CSIA protocol was also applied on representative chlordecone formulations previously used in the French West Indies, giving similar chlordecone d13C values from -31.1 ± 0.2‰ to -34.2 ± 0.2‰ for all studied samples. This allows the in situ application of CSIA for the assessment of chlordecone persistence.

ObjectiveTraveller’s diarrhoea (TD) is one of the most frequent illnesses affecting children returning from tropical countries. The purpose of this study was to assess the distribution of pathogens associated with TD in children using a multiplex PCR assay on stool samples.DesignAll the children admitted for TD in two university hospitals from 1 August to 15October during 2014 and 2015 were included in a prospective study. Stool samples were tested by a multiplex PCR FilmArray GI panel detecting 22 pathogens. Performances for the detection of major enteropathogenic bacteria (Salmonella, Shigellaand Campylobacterspp) by multiplex PCR and conventional culture methods were compared. The prevalence of extended spectrum beta-lactamase (ESBL)-producing Enterobacteriaceaewas also determined.ResultsFifty-nine children were included. In 58 cases (98%), at least one pathogen was identified, including 9 different enteropathogenic bacteria, 5 viruses and 2 parasites. Multiplex PCR enhanced the enteropathogenic bacteria detection by 25%. The most frequent pathogens were enteroaggregative Escherichia coli(n=32), enteropathogenic E. coli(n=26), enterotoxigenic E. coli(n=19), Salmonella enterica, enteroinvasive E. coli/Shigella(n=16 each), Cryptosporidium, sapovirus (n=11 each), Campylobacter jejuni,norovirus (n=10 each), rotavirus (n=9), Giardia(n=8) and Shiga-toxin-producing E. coli(n=4). Fifty-two coinfections were observed, notably including bacteria and viruses (n=21), multiple bacteria (n=14), or bacteria and parasites (n=10). ESBL were detected in 28 cases. Multiplex PCR could optimise the number of treated patients by 27% compared with stool cultures.ConclusionMultiplex PCR on stools revealed a high prevalence of diverse enteric pathogens and coinfections in children with TD. Major enteropathogenic bacteria were more frequently detected by multiplex PCR compared with conventional culture. Finally, this technique allows the start of appropriate and early antibiotic treatment and seems to optimise the number of correctly treated patients.

ObjectiveCross-sectional data indicate that systemic inflammation is important in oesophageal adenocarcinoma. We conducted a prospective study to assess whether prediagnostic circulating markers of inflammation were associated with oesophageal adenocarcinoma and to what extent they mediated associations of obesity and cigarette smoking with cancer risk.DesignThis nested case–control study included 296 oesophageal adenocarcinoma cases and 296 incidence density matched controls from seven prospective cohort studies. We quantitated 69 circulating inflammation markers using Luminex-based multiplex assays. Conditional logistic regression models estimated associations between inflammation markers and oesophageal adenocarcinoma, as well as direct and indirect effects of obesity and smoking on risk of malignancy.ResultsSoluble tumour necrosis factor receptor 2 (sTNFR2) (ORsquartile 4 vs 1=2.67, 95% CI 1.52 to 4.68) was significantly associated with oesophageal adenocarcinoma. Additional markers close to the adjusted significance threshold included C reactive protein, serum amyloid A, lipocalin-2, resistin, interleukin (IL) 3, IL17A, soluble IL-6 receptor and soluble vascular endothelial growth factor receptor 3. Adjustment for body mass index, waist circumference or smoking status slightly attenuated biomarker–cancer associations. Mediation analysis indicated that sTNFR2 may account for 33% (p=0.005) of the effect of waist circumference on oesophageal adenocarcinoma risk. Resistin, plasminogen activator inhibitor 1, C reactive protein and serum amyloid A were also identified as potential mediators of obesity–oesophageal adenocarcinoma associations. For smoking status, only plasminogen activator inhibitor 1 was a nominally statistically significant (p<0.05) mediator of cancer risk.ConclusionThis prospective study provides evidence of a link between systemic inflammation and oesophageal adenocarcinoma risk. In addition, this study provides the first evidence that indirect effects of excess adiposity and cigarette smoking, via systemic inflammation, increase the risk of oesophageal adenocarcinoma.