Case study of a performance-active changing trans* male singing voice

A professional classical singer of more than 25 years (AZ) in his early 50s requested this voice researcher’s consultation and assistance in early 2014. He was about to start living full time as a trans* man. Despite his intention to be included in the low start/gradual increase testosterone option of the Trans* Male (previously, “FTM”) Singing Voice Program, the request contained a rather unconventional aspect: AZ would continue to sing while his voice was changing. The above request was integral with his singing history. After the introduction of safeguards and his informed consent, AZ was accepted onto the Program. Due to the highly individual circumstances, his participation was recorded as a case study. The study has aimed to replicate the particulars of the slow hormonal changes and continuing singing ability found in certain cisgender male adolescent voices. Despite dealing with an adult trans* male individual, the progress has been comparable. This has been achieved by carefully monitoring AZ’s low start/gradual increase testosterone administration in communication with the medical practitioner. The participant’s vocal health remained safeguarded and promoted by carefully individualized vocal tuition. This article will discuss the collective results of the case study, including the recordings and the data analysis

Exploring the genetics of irritable bowel syndrome: A GWA study in the general population and replication in multinational case-control cohorts

OBJECTIVE: IBS shows genetic predisposition, but adequately powered gene-hunting efforts have been scarce so far. We sought to identify true IBS genetic risk factors by means of genome-wide association (GWA) and independent replication studies. DESIGN: We conducted a GWA study (GWAS) of IBS in a general population sample of 11\u2005326 Swedish twins. IBS cases (N=534) and asymptomatic controls (N=4932) were identified based on questionnaire data. Suggestive association signals were followed-up in 3511 individuals from six case-control cohorts. We sought genotype-gene expression correlations through single nucleotide polymorphism (SNP)-expression quantitative trait loci interactions testing, and performed in silico prediction of gene function. We compared candidate gene expression by real-time qPCR in rectal mucosal biopsies of patients with IBS and controls. RESULTS: One locus at 7p22.1, which includes the genes KDELR2 (KDEL endoplasmic reticulum protein retention receptor 2) and GRID2IP (glutamate receptor, ionotropic, delta 2 (Grid2) interacting protein), showed consistent IBS risk effects in the index GWAS and all replication cohorts and reached p=9.31 710(-6) in a meta-analysis of all datasets. Several SNPs in this region are associated with cis effects on KDELR2 expression, and a trend for increased mucosal KDLER2 mRNA expression was observed in IBS cases compared with controls. CONCLUSIONS: Our results demonstrate that general population-based studies combined with analyses of patient cohorts provide good opportunities for gene discovery in IBS. The 7p22.1 and other risk signals detected in this study constitute a good starting platform for hypothesis testing in future functional investigations. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions

Pemeriksaan Klinis : Pedoman Diagnosis Fisik

xxiv, 443 p.; 24 cm

Hypothesis driven research and molecular mechanisms in functional dyspepsia: The beginning of a beautiful friendship in research and practice?

There is accumulating evidence of a genetic predisposition in at least a subset of patients with functional GI symptoms. Hence, hunting for genes in irritable bowel syndrome and functional dyspepsia has become fashionable of late. Unfortunately, as in other fields, replication of gene association studies has most often been problematic. In this issue of the Journal, independent corroboration of an association of dyspepsia with GNbeta3 is reported. Other carefully selected putative genes including polymorphisms in the alpha2A adrenoreceptor, the serotonin reuptake transporter, and the 5-HT1A receptor were not associated. The study raises three key questions all considered in this editorial: (a) if GNbeta3 is truly associated with functional and uninvestigated dyspepsia, why might this be the case, (b) what molecular mechanisms may be of most relevance, and (c) perhaps most importantly, does or will this finding translate into clinical practice in terms of diagnosis or treatment? New knowledge of gene associations like GNbeta3 and their pathophysiological relevance may ultimately lead to better targeted therapy as well as new disease modifying treatments.Gerald Holtmann and Nicholas J. Talle

Minimum Clinically Important Difference for the Nepean Dyspepsia Index, a Validated Quality of Life Scale for Functional Dyspepsia

6 page(s

An update on irritable bowel syndrome: from diagnosis to emerging therapies

Purpose of review: irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder characterized by abdominal discomfort or pain that is accompanied by a disturbance in defecation. Although the exact etiopathogenesis is not completely understood, recent advances in the understanding of the biochemical, physiologic, and biopsychosocial mechanisms of IBS have resulted in exciting new insights as well as therapies. This article will review the recent developments in pathogenesis, diagnosis, and treatment. Recent findings: IBS may be the product of various pathogenic mechanisms which include IBS as a serotonergic disorder; the role of genetics; IBS as an inflammatory state and the potential role of mast cells; IBS as a result of bacterial overgrowth and altered gastrointestinal microbiome; and abnormal pain processing and pain memory. Emerging therapies have developed targeting these mechanisms. Summary: IBS remains a symptom-based diagnosis that can usually be made comfortably based on clinical history without testing in the absence of alarm features. Novel and emerging therapies that are based upon the evolving understanding of the pathophysiology of IBS hold significant promise and for the first time there are potential therapies that may alter the natural history of this disorder