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BackgroundTissue inflammation in inflammatory bowel diseases (IBD) is associated with a decrease in local pH. The gene encoding G-protein-coupled receptor 65 (GPR65) has recently been reported to be a genetic risk factor for IBD. In response to extracellular acidification, proton activation of GPR65 stimulates cAMP and Rho signalling pathways. We aimed to analyse the clinical and functional relevance of the GPR65 associated single nucleotide polymorphism (SNP) rs8005161.Methods1138 individuals from a mixed cohort of IBD patients and healthy volunteers were genotyped for SNPs associated with GPR65 (rs8005161, rs3742704) and galactosylceramidase (rs1805078) by Taqman SNP assays. 2300 patients from the Swiss IBD Cohort Study (SIBDC) were genotyped for rs8005161 by mass spectrometry based SNP genotyping. IBD patients from the SIBDC carrying rs8005161 TT, CT, CC and non-IBD controls (CC) were recruited for functional studies. Human CD14+ cells were isolated from blood samples and subjected to an extracellular acidic pH shift, cAMP accumulation and RhoA activation were measured.ResultsIn our mixed cohort, but not in SIBDC patients, the minor variant rs8005161 was significantly associated with UC. In SIBDC patients, we observed a consistent trend in increased disease severity in patients carrying the rs8005161-TT and rs8005161-CT alleles. No significant differences were observed in the pH associated activation of cAMP production between IBD (TT, CT, WT/CC) and non-IBD (WT/CC) genotype carriers upon an acidic extracellular pH shift. However, we observed significantly impaired RhoA activation after an extracellular acidic pH shift in IBD patients, irrespective of the rs8005161 allele.ConclusionsThe T allele of rs8005161 might confer a more severe disease course in IBD patients. Human monocytes from IBD patients showed impaired pH associated RhoA activation upon an acidic pH shift.

Normal-hearing listeners use acoustic cues in speech to interpret a speaker's emotional state. This study investigates the effect of hearing aids on the perception of the emotion dimensions arousal (aroused/calm) and valence (positive/negative attitude) in older adults with hearing loss. More specifically, we investigate whether wearing a hearing aid improves the correlation between affect ratings and affect-related acoustic parameters. To that end, affect ratings by 23 hearing-aid users were compared for aided and unaided listening. Moreover, these ratings were compared to the ratings by an age-matched group of 22 participants with age-normal hearing.For arousal, hearing-aid users rated utterances as generally more aroused in the aided than in the unaided condition. Intensity differences were the strongest indictor of degree of arousal. Among the hearing-aid users, those with poorer hearing used additional prosodic cues (i.e., tempo and pitch) for their arousal ratings, compared to those with relatively good hearing. For valence, pitch was the only acoustic cue that was associated with valence. Neither listening condition nor hearing loss severity (differences among the hearing-aid users) influenced affect ratings or the use of affect-related acoustic parameters. Compared to the normal-hearing reference group, ratings of hearing-aid users in the aided condition did not generally differ in both emotion dimensions. However, hearing-aid users were more sensitive to intensity differences in their arousal ratings than the normal-hearing participants.We conclude that the use of hearing aids is important for the rehabilitation of affect perception and particularly influences the interpretation of arousal

BACKGROUND: Predisposition is responsible for approximately 50 % of age-related cataracts. Investigation of inherited forms of cataract provides the opportunity to identify the genes that may play a role in age-related cataract as well. PATIENTS AND METHODS: We describe the phenotype of a Swiss family with juvenile cataract, associated with microcornea and renal glucosuria. 11 of 17 family members in three generations underwent ophthalmic assessment and urine analysis. Medical records or questionnaires were evaluated in the remaining six cases. RESULTS: Eleven family members had progressive juvenile cataract. Eight affected members available for clinical examination had bilateral microcornea, not associated with microphthalmos. Furthermore, renal glucosuria was demonstrated in six of these persons. The mode of inheritance is autosomal-dominant. CONCLUSIONS: We have defined a new syndrome, consisting of the association of juvenile cataract, microcornea and renal glucosuria. The pattern of inheritance is autosomal-dominant. Genotyping is ongoing.

Background Genetic variations within the regulatory region of the gene encoding NOD-like receptor pyrin domain containing 3 (NLRP3) have been associated with Crohn’s Disease (CD). NLRP3 is part of the NLRP3-inflammasome that mediates the maturation of IL-1β and IL-18. Carrying the major allele of the single nucleotide polymorphisms (SNPs) rs10733113, rs4353135 and rs55646866 is associated with an increased risk for CD. We here studied the impact of these polymorphisms on clinical characteristics in patients of the Swiss IBD Cohort Study (SIBDCS). Methods We included 981 Crohn’s disease (CD) patients and 690 ulcerative colitis (UC) patients of the SIBDCS. We analyzed whether three CD-associated NLRP3 polymorphisms have an impact on the clinical disease course in these patients. Results In CD patients presence of the major allele (G) of rs10733113 was associated with less surgeries and lower maximal CDAI and a similar trend was observed for rs55646866 and rs4353135. Presence of the major allele of all three SNPs was negatively correlated to maximal CDAI. In UC patients homozygous genotype for the major allele (CC) for rs55646866 was associated with a higher age at diagnosis and a higher MTWAI index. Homozygous genotype for the major allele of all three polymorphisms was associated with a higher number of ambulatory visits and longer hospital stays. Conclusions In CD patients presence of the major allele of all three polymorphisms was associated with markers of a less severe disease course, while in UC the homozygous genotype for all major alleles suggested a more severe disease activity.