Tissue transglutaminase autoantibodies in children with newly diagnosed type 1 diabetes are related to human leukocyte antigen but not to islet autoantibodies: A Swedish nationwide prospective population-based cohort study

Abstract

Objectives: This study explored the association between tissue transglutaminase autoantibody (tTGA), high-risk human leucocyte antigen (HLA) genotypes and islet autoantibodies in children with newly diagnosed type 1 diabetes (T1D).

Patients and methods: Dried blood spots and serum samples were taken at diagnosis from children <18?years of age participating in Better Diabetes Diagnosis (BDD), a Swedish nationwide prospective cohort study of children newly diagnosed with T1D. We analyzed tTGA, high-risk HLA DQ2 and DQ8 (DQX is neither DQ2 nor DQ8) and islet auto-antibodies (GADA, IA-2A, IAA, and three variants of Zinc transporter; ZnT8W, ZnT8R, and ZnT8QA).

Results: Out of 2705 children diagnosed with T1D, 85 (3.1%) had positive tTGA and 63 (2.3%) had borderline values. The prevalence of tTGA was higher in children with the HLA genotypes DQ2/2, DQ2/X or DQ2/8 compared to those with DQ8/8 or DQ8/X (p?=?.00001) and those with DQX/X (p?≤?.00001). No significant differences were found in relation to islet autoantibodies or age at diagnosis, but the presence of tTGA was more common in girls than in boys (p?=?.018).

Conclusion: tTGA at T1D diagnosis (both positive and borderline values 5.4%) was higher in girls and in children homozygous for DQ2/2, followed by children heterozygous for DQ2. Only children with DQ2 and/or DQ8 had tTGA. HLA typing at the diagnosis of T1D can help to identify those without risk for CD.     

Frontal–striatal connectivity and positive symptoms of schizophrenia: implications for the mechanistic basis of prefrontal rTMS

European Archives of Psychiatry and Clinical Neuroscience - Repetitive transcranial magnetic stimulation (rTMS), when applied to left dorsolateral prefrontal cortex (LDLPFC), reduces negative...     

Tested communication strategies for providing information to patients in medical consultations: A scoping review and quality assessment of the literature

ObjectivesTo systematize the scientific knowledge of empirically tested strategies for verbally providing medical information in patient-physician consultations.MethodsA scoping review searching for terms related to physician, information, oral communication, and controlled study. Four pairs of reviewers screened articles. For each selected study, we assessed the quality and summarized aspects on participants, study, intervention, and outcomes. Information provision strategies were inductively classified by types and main categories.ResultsAfter screening 9422 articles, 39 were included. The methodological quality was moderate. We identified four differently used categories of strategies for providing information: cognitive aid (n = 13), persuasive (n = 8), relationship- (n = 3), and objectivity-oriented strategies (n = 4); plus, one “mixed” category (n = 11). Strategies were rarely theoretically derived.ConclusionsCurrent research of tested strategies for verbally providing medical information is marked by great heterogeneity in methods and outcomes, and lack of theory-driven approaches. The list of strategies could be used to analyse real life communication.Practice implicationsFindings may aid the harmonization of future efforts to develop empirically-based information provision strategies to be used in clinical and teaching settings.     

New population-based exome data are questioning the pathogenicity of previously cardiomyopathy-associated genetic variants

Cardiomyopathies are a heterogeneous group of diseases with various etiologies. We focused on three genetically determined cardiomyopathies: hypertrophic (HCM), dilated (DCM), and arrhythmogenic right ventricular cardiomyopathy (ARVC). Eighty-four genes have so far been associated with these cardiomyopathies, but the disease-causing effect of reported variants is often dubious. In order to identify possible false-positive variants, we investigated the prevalence of previously reported cardiomyopathy-associated variants in recently published exome data. We searched for reported missense and nonsense variants in the NHLBI-Go Exome Sequencing Project (ESP) containing exome data from 6500 individuals. In ESP, we identified 94 variants out of 687 (14%) variants previously associated with HCM, 58 out of 337 (17%) variants associated with DCM, and 38 variants out of 209 (18%) associated with ARVC. These findings correspond to a genotype prevalence of 1:4 for HCM, 1:6 for DCM, and 1:5 for ARVC. PolyPhen-2 predictions were conducted on all previously published cardiomyopathy-associated missense variants. We found significant overrepresentation of variants predicted as being benign among those present in ESP compared with the ones not present. In order to validate our findings, seven variants associated with cardiomyopathy were genotyped in a control population and this revealed frequencies comparable with the ones found in ESP. In conclusion, we identified genotype prevalences up to more than one thousand times higher than expected from the phenotype prevalences in the general population (HCM 1:500, DCM 1:2500, and ARVC 1:5000) and our data suggest that a high number of these variants are not monogenic causes of cardiomyopathy.     

The role of cognitive biases and personality variables in subclinical delusional ideation

Introduction. A number of cognitive biases, most notably a data gathering bias characterised by “jumping to conclusions” (JTC), and the “bias against disconfirmatory evidence” (BADE), have been shown to be associated with delusions and subclinical delusional ideation. Certain personality variables, particularly “openness to experience”, are thought to be associated with schizotypy.

Methods. Using structural equation modelling, we examined the association between two higher order subfactors (“aspects”) of “openness to experience” (labelled “openness” and “intellect”), these cognitive biases, and their relationship to subclinical delusional ideation in 121 healthy, nonpsychiatric controls.

Results. Our results suggest that cognitive biases (specifically the data gathering bias and BADE) and the “openness” aspect are independently associated with subclinical delusional ideation, and the data gathering bias is weakly associated with “positive schizotypy”. “Intellect” is negatively associated with delusional ideation and might play a potential protective role.

Conclusions. Cognitive biases and personality are likely to be independent risk factors for the development of delusions.