Anthropometric and reproductive factors and risk of esophageal and gastric cancer by subtype and subsite: Results from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort

Obesity has been associated with upper gastrointestinal cancers; however, there are limited prospective data on associations by subtype/subsite. Obesity can impact hormonal factors, which have been hypothesized to play a role in these cancers. We investigated anthropometric and reproductive factors in relation to esophageal and gastric cancer by subtype and subsite for 476,160 participants from the European Prospective Investigation into Cancer and Nutrition cohort. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox models. During a mean follow-up of 14 years, 220 esophageal adenocarcinomas (EA), 195 esophageal squamous cell carcinomas, 243 gastric cardia (GC) and 373 gastric noncardia (GNC) cancers were diagnosed. Body mass index (BMI) was associated with EA in men (BMI ≥30 vs. 18.5–25 kg/m²: HR = 1.94, 95% CI: 1.25–3.03) and women (HR = 2.66, 95% CI: 1.15–6.19); however, adjustment for waist-to-hip ratio (WHR) attenuated these associations. After mutual adjustment for BMI and HC, respectively, WHR and waist circumference (WC) were associated with EA in men (HR = 3.47, 95% CI: 1.99–6.06 for WHR >0.96 vs. <0.91; HR = 2.67, 95% CI: 1.52–4.72 for WC >98 vs. <90 cm) and women (HR = 4.40, 95% CI: 1.35–14.33 for WHR >0.82 vs. <0.76; HR = 5.67, 95% CI: 1.76–18.26 for WC >84 vs. <74 cm). WHR was also positively associated with GC in women, and WC was positively associated with GC in men. Inverse associations were observed between parity and EA (HR = 0.38, 95% CI: 0.14–0.99; >2 vs. 0) and age at first pregnancy and GNC (HR = 0.54, 95% CI: 0.32–0.91; >26 vs. <22 years); whereas bilateral ovariectomy was positively associated with GNC (HR = 1.87, 95% CI: 1.04–3.36). These findings support a role for hormonal pathways in upper gastrointestinal cancers.     

Neuroanatomy of dyslexia: An allometric approach

Despite evidence for a difference in total brain volume between dyslexic and good readers, no previous neuroimaging study examined differences in allometric scaling (i.e. differences in the relationship between regional and total brain volumes) between dyslexic and good readers. The present study aims to fill this gap by testing differences in allometric scaling and regional brain volume differences in dyslexic and good readers. Object‐based morphometry analysis was used to determine grey and white matter volumes of the four lobes, the cerebellum and limbic structures in 130 dyslexic and 106 good readers aged 8–14 years. Data were collected across three countries (France, Poland and Germany). Three methodological approaches were used as follows: principal component analysis (PCA), linear regression and multiple‐group confirmatory factor analysis (MGCFA). Difference in total brain volume between good and dyslexic readers was Cohen's d = 0.39. We found no difference in allometric scaling, nor in regional brain volume between dyslexic and good readers. Results of our three methodological approaches (PCA, linear regression and MGCFA) were consistent. This study provides evidence for total brain volume differences between dyslexic and control children, but no evidence for differences in the volumes of the four lobes, the cerebellum or limbic structures, once allometry is taken into account. It also finds no evidence for a difference in allometric relationships between the groups. We highlight the methodological interest of the MGCFA approach to investigate such research issues.     

An Innovative Oat‐Based Sterile Emollient Cream in the Maintenance Therapy of Childhood Atopic Dermatitis

Although emollients are recommended in the management of atopic dermatitis (AD), regimens for emollient maintenance therapy are awaiting validation. We conducted an international, multicenter, open‐label trial to assess the effects of a 3‐month maintenance treatment regimen with a sterile, preservative‐free emollient cream containing oat plantlets in children (ages 6 mos–6 yrs) with moderate AD. After a 14‐day run‐in stabilization phase using a topical corticosteroid (TCS) treatment of medium potency, 108 children with a SCORing Atopic Dermatitis (SCORAD) index of 20 or less were included in the study. Emollient was applied twice daily for 3 months. Rescue TCS treatment was used only in cases of flare‐ups. The SCORAD index, Patient‐Oriented SCORAD (PO‐SCORAD) index, number of flares, TCS use, and tolerance were assessed at months 1, 2, and 3 (M1, M2, M3). AD severity improved, with a highly significant decrease in the SCORAD and PO‐SCORAD indexes at M2 and M3 (p < 0.001). Changes from baseline to M3 were 48.6 ± 73.6% for SCORAD and 29.6 ± 125.3% for PO‐SCORAD. The number of flares and TCS use significantly decreased by M3 (both p < 0.001). Very good tolerance was recorded in 100% of children at M2 and M3. Notwithstanding the limitations inherent in open‐label trials, twice daily application of the oat‐based sterile emollient cream led to a significant improvement of clinical symptoms, evidenced by parallel changes in the SCORAD and PO‐SCORAD indexes and fewer flare‐ups. Clinical benefit and less TCS use were maintained at M3. Tolerance was very good.     

3D variable‐density SPARKLING trajectories for high‐resolution T2*‐weighted magnetic resonance imaging

We have recently proposed a new optimization algorithm called SPARKLING (Spreading Projection Algorithm for Rapid K‐space sampLING) to design efficient compressive sampling patterns for magnetic resonance imaging (MRI). This method has a few advantages over conventional non‐Cartesian trajectories such as radial lines or spirals: i) it allows to sample the k‐space along any arbitrary density while the other two are restricted to radial densities and ii) it optimizes the gradient waveforms for a given readout time. Here, we introduce an extension of the SPARKLING method for 3D imaging by considering both stacks‐of‐SPARKLING and fully 3D SPARKLING trajectories. Our method allowed to achieve an isotropic resolution of 600 μm in just 45 seconds for T2? ‐weighted ex vivo brain imaging at 7 Tesla over a field‐of‐view of 200 × 200 × 140 mm³ . Preliminary in vivo human brain data shows that a stack‐of‐SPARKLING is less subject to off‐resonance artifacts than a stack‐of‐spirals.     

Bruton's tyrosine kinase regulates TLR9 but not TLR7 signaling in human plasmacytoid dendritic cells

Plasmacytoid dendritic cells (PDCs) represent a key cell type for both innate and adaptive immunity. PDCs express both TLR7 and TLR9 and the recognition of nucleic acids by these two receptors triggers the production of a large amount of type‐I IFN and the induction of PDC maturation into APCs. This unique feature of PDCs is at the basis of clinical development of both TLR7 and TLR9 agonists for infectious diseases, allergy, cancer, and asthma. However, TLR7 and TLR9 recognition of self‐nucleic acids is linked to many autoimmune diseases including lupus, and a better understanding of the signaling pathways of these two receptors in PDCs is thus important. We have identified Bruton's tyrosine kinase (Btk) as an important player for TLR9 but not TLR7 signaling in human PDCs. Blocking Btk using a specific inhibitor leads to the reduction of all TLR9‐induced responses in PDCs, including cytokine production and expression of costimulatory molecules, while this has no impact on the TLR7 response. This identifies Btk as a key molecule in TLR9 signaling in PDCs and is the first demonstration that the TLR7 and TLR9 pathways can be dissociated in human PDCs.     

Dietary intake of total polyphenol and polyphenol classes and the risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort

Polyphenols may play a chemopreventive role in colorectal cancer (CRC); however, epidemiological evidence supporting a role for intake of individual polyphenol classes, other than flavonoids is insufficient. We evaluated the association between dietary intakes of total and individual classes and subclasses of polyphenols and CRC risk and its main subsites, colon and rectum, within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. The cohort included 476,160 men and women from 10 European countries. During a mean follow-up of 14 years, there were 5991 incident CRC cases, of which 3897 were in the colon and 2094 were in the rectum. Polyphenol intake was estimated using validated centre/country specific dietary questionnaires and the Phenol-Explorer database. In multivariable-adjusted Cox regression models, a doubling in total dietary polyphenol intake was not associated with CRC risk in women (HR_log2?=?1.06, 95% CI 0.99–1.14) or in men (HR_log2?=?0.97, 95% CI 0.90–1.05), respectively. Phenolic acid intake, highly correlated with coffee consumption, was inversely associated with colon cancer in men (HR_log2?=?0.91, 95% CI 0.85–0.97) and positively associated with rectal cancer in women (HR_log2?=?1.10, 95% CI 1.02–1.19); although associations did not exceed the Bonferroni threshold for significance. Intake of other polyphenol classes was not related to colorectal, colon or rectal cancer risks. Our study suggests a possible inverse association between phenolic acid intake and colon cancer risk in men and positive with rectal cancer risk in women.