Developing hypnotic analogues of clinical delusions : Mirrored-self misidentification

Introduction. Despite current research interest in delusional beliefs, there are no viable models for studying delusions in the laboratory. However, hypnosis offers a technique for creating transient delusions that are resistant to challenge. The aim of this study was to develop an hypnotic analogue of one important delusion, mirrored-self misidentification. Methods. Twelve high hypnotisable participants received an hypnotic suggestion to see either a stranger in the mirror, a mirror as a window, or a mirror as a window with a view to a stranger. Participants' deluded beliefs were challenged, and following hypnosis, Sheehan and McConkey's (1982) Experiential Analysis Technique was used to explore participants' phenomenological experience of the delusion. Results. The majority of participants did not recognise their reflection in the mirror, described the person in the mirror as having different physical characteristics to themselves, and maintained their delusion when challenged. Conclusions. The hypnotic suggestion created a credible, compelling delusion with features strikingly similar to clinical cases of mirrored-self misidentification. Our findings suggest that Factor 2 within Langdon and Coltheart's (2000) two-factor framework may involve a lowering of the criteria used to accept or reject delusional hypotheses.PostprintPeer reviewe

The Jacobi orientation and the two-variable elliptic genus

We explain the relationship between the sigma orientation and Witten genus on the one hand and the two-variable elliptic genus on the other. We show that if E is an elliptic spectrum, then the Theorem of the Cube implies the existence of canonical SU-orientation of the associated spectrum of Jacobi forms. In the case of the elliptic spectrum associated to the Tate curve, this gives the two-variable elliptic genus. We also show that the two-variable genus arises as an instance of the circle-equivariant sigma orientation.Comment: Revised to better exhibit complex orientation of MSU^(CP^\infty_{-infty}

Effect of a proficiency-based progression simulation programme on clinical communication for the deteriorating patient: a randomised controlled trial

Objective: This study aimed to determine the effectiveness of a proficiency-based progression (PBP) training approach to clinical communication in the context of a clinically deteriorating patient.Design This is a randomised controlled trial with three parallel arms.Setting: This study was conducted in a university in Ireland.Participants: This study included 45 third year nursing and 45 final year medical undergraduates scheduled to undertake interdisciplinary National Early Warning Score (NEWS) training over a 3-day period in September 2016.Interventions: Participants were prospectively randomised to one of three groups before undertaking a performance assessment of the ISBAR (Identification, Situation, Background, Assessment, Recommendation) communication tool relevant to a deteriorating patient in a high-fidelity simulation facility. The groups were as follows: (i) E, the Irish Health Service national NEWS e-learning programme only; (ii) E+S, the national e-learning programme plus standard simulation; and (iii) E+PBP, the national e-learning programme plus PBP simulation.Main outcome measures: The primary outcome was the proportion in each group reaching a predefined proficiency benchmark comprising a series of predefined steps, errors and critical errors during the performance of a standardised, high-fidelity simulation assessment case which was recorded and scored by two independent blinded assessors.Results: 6.9% (2/29) of the E group and 13% (3/23) of the E+S group demonstrated proficiency in comparison to 60% (15/25) of the E+PBP group. The difference between the E and the E+S groups was not statistically significant (χ2=0.55, 99% CI 0.63 to 0.66, p=0.63) but was significant for the difference between the E and the E+PBP groups (χ2=22.25, CI 0.00 to 0.00, p<0.000) and between the E+S and the E+PBP groups (χ2=11.04, CI 0.00 to 0.00, p=0.001).Conclusions: PBP is a more effective way to teach clinical communication in the context of the deteriorating patient than e-learning either alone or in combination with standard simulation.Trial registration number: NCT02886754; Results

Rheumatoid leptomeningitis presenting with an acute neuropsychiatric disorder

Leptomeningitis is a rare central nervous system manifestation of rheumatoid arthritis, generally in patients with established chronic rheumatoid disease. We report a 41-year-old man without previous rheumatoid arthritis or psychiatric disorder who presented with an acute neuropsychiatric disturbance and polyarthralgia. His MR scan of brain showed asymmetric bifrontal leptomeningitis, confirmed on (18F)-fluoro-D-glucose-positron emission tomography. Other investigations showed highly positive serum and cerebrospinal fluid anti-cyclic citrullinated peptide. A leptomeningeal biopsy showed necrotising leptomeningeal inflammation with ill-defined granulomas and lymphoplasmacytic infiltrate without organisms. Prolonged high-dose corticosteroids and then rituximab resulted in recovery. Chronic leptomeningitis can present with an acute neuropsychiatric disorder. We highlight that early rheumatoid disease can, rarely, cause a chronic leptomeningitis, reversible with immunotherapy

Pathogenesis and shedding of Usutu virus in juvenile chickens

Usutu virus (USUV; family: Flaviviridae, genus: Flavivirus), is an emerging zoonotic arbovirus that causes severe neuroinvasive disease in humans and has been implicated in the loss of breeding bird populations in Europe. USUV is maintained in an enzootic cycle between ornithophilic mosquitos and wild birds. As a member of the Japanese encephalitis serocomplex, USUV is closely related to West Nile virus (WNV) and St. Louis encephalitis virus (SLEV), both neuroinvasive arboviruses endemic in wild bird populations in the United States. An avian model for USUV is essential to understanding zoonotic transmission. Here we describe the first avian models of USUV infection with the development of viremia. Juvenile commercial ISA Brown chickens were susceptible to infection by multiple USUV strains with evidence of cardiac lesions. Juvenile chickens from two chicken lines selected for high (HAS) or low (LAS) antibody production against sheep red blood cells showed markedly different responses to USUV infection. Morbidity and mortality were observed in the LAS chickens, but not HAS chickens. LAS chickens had significantly higher viral titers in blood and other tissues, as well as oral secretions, and significantly lower development of neutralizing antibody responses compared to HAS chickens. Mathematical modelling of virus-host interactions showed that the viral clearance rate is a stronger mitigating factor for USUV viremia than neutralizing antibody response in this avian model. These chicken models provide a tool for further understanding USUV pathogenesis in birds and evaluating transmission dynamics between avian hosts and mosquito vectors.This work was supported by National Science Foundation [grant number: 1813011]; Virginia Polytechnic Institute and State University [grant number: Data and Decisions Proposal, VMCVM Internal Research Competition].S

Genome-wide association analysis reveals KCTD12 and miR-383-binding genes in the background of rumination

Ruminative response style is a passive and repetitive way of responding to stress, associated with several disorders. Although twin and candidate gene studies have proven the genetic underpinnings of rumination, no genome-wide association study (GWAS) has been conducted yet. We performed a GWAS on ruminative response style and its two subtypes, brooding and reflection, among 1758 European adults recruited in the general population of Budapest, Hungary, and Manchester, United Kingdom. We evaluated single-nucleotide polymorphism (SNP)-based, gene-based and gene set-based tests, together with inferences on genes regulated by our most significant SNPs. While no genome-wide significant hit emerged at the SNP level, the association of rumination survived correction for multiple testing with KCTD12 at the gene level, and with the set of genes binding miR-383 at the gene set level. SNP-level results were concordant between the Budapest and Manchester subsamples for all three rumination phenotypes. SNPlevel results and their links to brain expression levels based on external databases supported the role of KCTD12, SRGAP3, and SETD5 in rumination, CDH12 in brooding, and DPYSL5, MAPRE3, KCNK3, ATXN7L3B, and TPH2 in reflection, among others. The relatively low sample size is a limitation of our study. Results of the first GWAS on rumination identified genes previously implicated in psychiatric disorders underscoring the transdiagnostic nature of rumination, and pointed to the possible role of the dorsolateral prefrontal cortex, hippocampus, and cerebellum in this cognitive process

H3K9me2/3 Binding of the MBT Domain Protein LIN-61 Is Essential for Caenorhabditis elegans Vulva Development

MBT domain proteins are involved in developmental processes and tumorigenesis. In vitro binding and mutagenesis studies have shown that individual MBT domains within clustered MBT repeat regions bind mono- and dimethylated histone lysine residues with little to no sequence specificity but discriminate against the tri- and unmethylated states. However, the exact function of promiscuous histone methyl-lysine binding in the biology of MBT domain proteins has not been elucidated. Here, we show that the Caenorhabditis elegans four MBT domain protein LIN-61, in contrast to other MBT repeat factors, specifically interacts with histone H3 when methylated on lysine 9, displaying a strong preference for di- and trimethylated states (H3K9me2/3). Although the fourth MBT repeat is implicated in this interaction, H3K9me2/3 binding minimally requires MBT repeats two to four. Further, mutagenesis of residues conserved with other methyl-lysine binding MBT regions in the fourth MBT repeat does not abolish interaction, implicating a distinct binding mode. In vivo, H3K9me2/3 interaction of LIN-61 is required for C. elegans vulva development within the synMuvB pathway. Mutant LIN-61 proteins deficient in H3K9me2/3 binding fail to rescue lin-61 synMuvB function. Also, previously identified point mutant synMuvB alleles are deficient in H3K9me2/3 interaction although these target residues that are outside of the fourth MBT repeat. Interestingly, lin-61 genetically interacts with two other synMuvB genes, hpl-2, an HP1 homologous H3K9me2/3 binding factor, and met-2, a SETDB1 homologous H3K9 methyl transferase (H3K9MT), in determining C. elegans vulva development and fertility. Besides identifying the first sequence specific and di-/trimethylation binding MBT domain protein, our studies imply complex multi-domain regulation of ligand interaction of MBT domains. Our results also introduce a mechanistic link between LIN-61 function and biology, and they establish interplay of the H3K9me2/3 binding proteins, LIN-61 and HPL-2, as well as the H3K9MT MET-2 in distinct developmental pathways

Lives versus Livelihoods? Perceived economic risk has a stronger association with support for COVID-19 preventive measures than perceived health risk

This paper examines whether compliance with COVID-19 mitigation measures is motivated by wanting to save lives or save the economy (or both), and which implications this carries to fight the pandemic. National representative samples were collected from 24 countries (N = 25,435). The main predictors were (1) perceived risk to contract coronavirus, (2) perceived risk to suffer economic losses due to coronavirus, and (3) their interaction effect. Individual and country-level variables were added as covariates in multilevel regression models. We examined compliance with various preventive health behaviors and support for strict containment policies. Results show that perceived economic risk consistently predicted mitigation behavior and policy support—and its effects were positive. Perceived health risk had mixed effects. Only two significant interactions between health and economic risk were identified—both positive

A genome-wide association study of anorexia nervosa suggests a risk locus implicated in dysregulated leptin signaling

J. Kaprio, A. Palotie, A. Raevuori-Helkamaa ja S. Ripatti ovat työryhmän Eating Disorders Working Group of the Psychiatric Genomics Consortium jäseniä. Erratum in: Sci Rep. 2017 Aug 21;7(1):8379, doi: 10.1038/s41598-017-06409-3We conducted a genome-wide association study (GWAS) of anorexia nervosa (AN) using a stringently defined phenotype. Analysis of phenotypic variability led to the identification of a specific genetic risk factor that approached genome-wide significance (rs929626 in EBF1 (Early B-Cell Factor 1); P = 2.04 x 10(-7); OR = 0.7; 95% confidence interval (CI) = 0.61-0.8) with independent replication (P = 0.04), suggesting a variant-mediated dysregulation of leptin signaling may play a role in AN. Multiple SNPs in LD with the variant support the nominal association. This demonstrates that although the clinical and etiologic heterogeneity of AN is universally recognized, further careful sub-typing of cases may provide more precise genomic signals. In this study, through a refinement of the phenotype spectrum of AN, we present a replicable GWAS signal that is nominally associated with AN, highlighting a potentially important candidate locus for further investigation.Peer reviewe