Genome-wide association analyses identify new susceptibility loci for oral cavity and pharyngeal cancer.

We conducted a genome-wide association study of oral cavity and pharyngeal cancer in 6,034 cases and 6,585 controls from Europe, North America and South America. We detected eight significantly associated loci (P < 5 × 10−8), seven of which are new for these cancer sites. Oral and pharyngeal cancers combined were associated with loci at 6p21.32 (rs3828805, HLA-DQB1), 10q26.13 (rs201982221, LHPP) and 11p15.4 (rs1453414, OR52N2–TRIM5). Oral cancer was associated with two new regions, 2p23.3 (rs6547741, GPN1) and 9q34.12 (rs928674, LAMC3), and with known cancer-related loci—9p21.3 (rs8181047, CDKN2B-AS1) and 5p15.33 (rs10462706, CLPTM1L). Oropharyngeal cancer associations were limited to the human leukocyte antigen (HLA) region, and classical HLA allele imputation showed a protective association with the class II haplotype HLA-DRB1*1301–HLA-DQA1*0103–HLA-DQB1*0603 (odds ratio (OR) = 0.59, P = 2.7 × 10−9). Stratified analyses on a subgroup of oropharyngeal cases with information available on human papillomavirus (HPV) status indicated that this association was considerably stronger in HPV-positive (OR = 0.23, P = 1.6 × 10−6) than in HPV-negative (OR = 0.75, P = 0.16) cancers

Interleukin-1 beta has atheroprotective effects in advanced atherosclerotic lesions of mice

Despite decades of research, our understanding of the processes controlling late-stage atherosclerotic plaque stability remains poor. A prevailing hypothesis is that reducing inflammation may improve advanced plaque stability, as recently tested in the Canakinumab Anti-inflammatory Thrombosis Outcome Study (CANTOS) trial, in which post-myocardial infarction subjects were treated with an IL-1β antibody. Here, we performed intervention studies in which smooth muscle cell (SMC) lineage-tracing Apoe-/- mice with advanced atherosclerosis were treated with anti-IL-1β or IgG control antibodies. Surprisingly, we found that IL-1β antibody treatment between 18 and 26 weeks of Western diet feeding induced a marked reduction in SMC and collagen content, but increased macrophage numbers in the fibrous cap. Moreover, although IL-1β antibody treatment had no effect on lesion size, it completely inhibited beneficial outward remodeling. We also found that SMC-specific knockout of Il1r1 (encoding IL-1 receptor type 1) resulted in smaller lesions nearly devoid of SMCs and lacking a fibrous cap, whereas macrophage-selective loss of IL-1R1 had no effect on lesion size or composition. Taken together, these results show that IL-1β has multiple beneficial effects in late-stage murine atherosclerosis, including promotion of outward remodeling and formation and maintenance of an SMC- and collagen-rich fibrous cap

Level of agreement between objectively determined body composition and perceived body image in 6- To 8-year-old South African children- To Body Composition-Isotope Technique study

To assess the level of agreement between body size self-perception and actual body size determined by body mass index (BMI) z-score and body fatness measured by the deuterium dilution method (DDM) in South African children aged 6-8 years. A cross-sectional sample of 202 children (83 boys and 119 girls) aged 6-8 years from the Body Composition-Isotope Technique study (BC-IT) was taken. Subjective measures of body image (silhouettes) were compared with the objective measures of BMI z-score and body fatness measured by the DDM. The World Health Organization BMI z-scores were used to classify the children as underweight, normal, overweight, or obese. DDM-measured fatness was classified based on the McCarthy centile curves set at 2nd, 85th and 95th in conjunction with fatness cut-off points of 25% in boys and 30% in girls. Data were analyzed using SPSS v26. Of 202 children, 32.2%, 55.1%, 8.8%, and 2.4% perceived their body size as underweight, normal, overweight, and obese, respectively. Based on BMI z-score, 18.8%, 72.8%, 6.9%, and 1.5% were classified as underweight, normal, overweight, and obese, respectively. Body fatness measurement showed that 2.5%, 48.0%, 21.8%, and 29.7% were underweight, normal weight, overweight, and obese, respectively

Involvement of endogenous gabaergic system in the modulation of gonadotropin secretion in normal cycling women.

To investigate whether endogenous GABA participates in the control of gonadotropin secretion during the menstrual cycle, placebo or sodium valproate (DPA), an anticonvulsant drug which enhances endogenous GABA content by blocking GABA degradation, were administered to regularly cycling women both during early follicular and midluteal phase. In a first set of experiments, the effect of DPA administration (400 mg, orally) on basal gonadotropin secretion was evaluated in 13 subjects. During early follicular phase (n = 6), no significant changes in plasma gonadotropin levels were observed after DPA or placebo administration. Conversely, during midluteal phase (n = 7), DPA administration resulted in a significant fall (p less than 0.01) in plasma LH concentrations, with a maximal percent decrease of 41.8 +/- 6.7% after 120 min. No changes in plasma FSH levels were observed. In a second set of experiments, the effect of DPA pretreatment (400 mg, orally) on gonadotropin release stimulated by a pulse of exogenous GnRH (10 micrograms, iv bolus) was studied in 11 subjects. During both follicular (n = 4) and luteal phase (n = 7), DPA did not modify gonadotropin response to GnRH injected 1h after pretreatment. Finally, 8 subjects were submitted to iv injection with 10 micrograms GnRH 2h after pretreatment with DPA (400 mg, orally) or placebo. During both follicular (n = 4) and luteal phase (n = 4), no statistical differences in gonadotropin response to GnRH were found between DPA and placebo pretreatment. These findings demonstrated that during the estrogen-progesterone (midluteal) phase of menstrual cycle, endogenous GABA is involved in the inhibitory regulation of LH secretion at a central level