The FOAM study : Is Hysterosalpingo foam sonography (HyFoSy) a cost-effective alternative for hysterosalpingography (HSG) in assessing tubal patency in subfertile women? Study protocol for a randomized controlled trial

This is an investigator initiated trial, VU medical center Amsterdam is the sponsor, contact information: prof. CJM de Groot, Department of Obstetrics and Gynaecology, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands, Tel: + 31-204444444. This study is funded by ZonMw, a Dutch organization for Health Research and Development, project number 837001504. ZonMW gives financial support for the whole project. IQ Medical Ventures provides the ExEm FOAM® kits. The funding bodies have no role in the design of the study; collection, analysis, and interpretation of data; and in writing the manuscript.Peer reviewedPublisher PD

Can hysterosalpingo-foam sonography replace hysterosalpingography as first-choice tubal patency test? A randomized non-inferiority trial

Funding Information: The FOAM study was an investigator-initiated study funded by ZonMw, The Netherlands organization for Health Research and Development (project number 837001504). ZonMw funded the whole project. IQ Medical Ventures provided the ExEm-foamVR kits free of charge. The funders had no role in study design, collection, analysis and interpretation of the data. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.Peer reviewedPublisher PD

Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyper-activity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.Peer reviewe

Characterization of CprK1, a CRP/FNR-Type Transcriptional Regulator of Halorespiration from Desulfitobacterium hafniense

The recently identified CprK branch of the CRP (cyclic AMP receptor protein)-FNR (fumarate and nitrate reduction regulator) family of transcriptional regulators includes proteins that activate the transcription of genes encoding proteins involved in reductive dehalogenation of chlorinated aromatic compounds. Here we report the characterization of the CprK1 protein from Desulfitobacterium hafniense, an anaerobic low-G+C gram-positive bacterium that is capable of reductive dechlorination of 3-chloro-4-hydroxyphenylacetic acid (Cl-OHPA). The gene encoding CprK1 was cloned and functionally overexpressed in Escherichia coli, and the protein was subsequently purified to homogeneity. To investigate the interaction of CprK1 with three of its predicted binding sequences (dehaloboxes), we performed in vitro DNA-binding assays (electrophoretic mobility shift assays) as well as in vivo promoter probe assays. Our results show that CprK1 binds its target dehaloboxes with high affinity (dissociation constant, 90 nM) in the presence of Cl-OHPA and that transcriptional initiation by CprK1 is influenced by deviations in the dehaloboxes from the consensus TTAAT----ATTAA sequence. A mutant CprK1 protein was created by a Val→Glu substitution at a conserved position in the recognition α-helix that gained FNR-type DNA-binding specificity, recognizing the TTGAT----ATCAA sequence (FNR box) instead of the dehaloboxes. CprK1 was subject to oxidative inactivation in vitro, most likely caused by the formation of an intermolecular disulfide bridge between Cys11 and Cys200. The possibility of redox regulation of CprK1 by a thiol-disulfide exchange reaction was investigated by using two Cys→Ser mutants. Our results indicate that a Cys11-Cys200 disulfide bridge does not appear to play a physiological role in the regulation of CprK1

Cannabis and cognitive performance in psychosis:a cross-sectional study in patients with non-affective psychotic illness and their unaffected siblings

Background. The relationship between cannabis use and cognitive functioning in patients with psychosis has yielded contradictory findings. In individuals at genetic high risk for psychosis, information is sparse. The aim of this study was to assess the association between recency and frequency of cannabis use and cognitive functioning in patients with psychosis and their unaffected siblings. Method. We conducted a cross-sectional study in 956 patients with non-affective psychosis, 953 unaffected siblings, and 554 control subjects. Participants completed a cognitive test battery including assessments of verbal learning, set shifting, sustained attention, processing speed, working memory, acquired knowledge, reasoning and problem solving and social cognition. Cannabis use was assessed by urinalysis and by the Composite International Diagnostic Interview. Using random-effect regression models the main effects of cannabis (recency and frequency) and the interaction with status (patient, sibling, control) on cognitive functioning were assessed. Results. Current cannabis use was associated with poorer performance on immediate verbal learning, processing speed and working memory (Cohen's d -0.20 to -0.33, p Conclusions. Lifetime cannabis-using individuals might constitute a subgroup with a higher cognitive potential. The residual effects of cannabis may impair short-term memory and processing speed

The Exploration of Multilingualism: Development of research on L3, multilingualism and multiple language acquisition (book review)

no abstract

A Clinical Model for the Differentiation of Suicidality:Protocol for a Usability Study of the Proposed Model

BACKGROUND: Even though various types of suicidality are observed in clinical practice, suicidality is still considered a uniform concept. To distinguish different types of suicidality and consequently improve detection and management of suicidality, we developed a clinical differentiation model for suicidality. We believe that the model allows for a more targeted assessment of suicidal conditions and improves the use of evidence-based treatment strategies. The differentiation model is based on the experience with suicidality that we have encountered in clinical practice. This model distinguishes 4 subtypes of entrapment leading to suicidality. The earliest description of this model and a proposal for usability research has been previously presented in a book chapter. OBJECTIVE: In this study, we present the most recent version of the 4-type differentiation model of suicidality and a protocol for a study into the usability of the proposed model. METHODS: The 4-type differentiation model of suicidality distinguishes the following subtypes: (1) perceptual disintegration, (2) primary depressive cognition, (3) psychosocial turmoil, and (4) inadequate coping or communication. We plan to test the usability of the 4 subtypes in a pilot study of 25 cases, and subsequently, we will include 75 cases in a follow-up study. We looked at the case notes of 100 anonymized patients with suicidality who presented to mental health care emergency service in The Hague International Center. The summary and conclusions of the letters sent to the patients' general practitioners after suicide risk assessment will be independently rated by 3 psychiatrists and 3 nurse-scientists for absolute and dimensional scores. The Suicidality Differentiation version 2 (SUICIDI-II) instrument, developed for this study, is used for rating all the cases. Intraclass correlation coefficients for absolute and dimensional scores will be calculated to examine type agreement between raters to examine the usability of the model and the feasibility of the SUICIDI-II instrument. RESULTS: We consider the model tentatively valid if the intraclass correlation coefficients are =0.70. Subsequently, if the model turns out to be valid, we plan to rate 75 other cases in a follow-up study, according to a similar or adjusted procedure. Study results are expected to be published by the end of 2023. CONCLUSIONS: The theoretical roots of the differentiation model stem from classic and contemporary theoretical models of suicidality and from our clinical practice experiences with suicidal behaviors. We believe that this model can be used to adjust the diagnosis, management, treatment, and research of suicidality, in addition to distinguishing different dynamics between practitioners and patients with suicidality and their families. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/45438

A first study on the usability and feasibility of four subtypes of suicidality in emergency mental health care

BACKGROUND: Based on clinical experience, a (hypothetical) four-type model of suicidality that differentiates between subtypes with a unique pathway to entrapment ((h)4ME)was developed. The subtypes are: 1) perceptual disintegration (PD), 2) primary depressive cognition (PDC), 3) psychosocial turmoil (PT) and 4) inadequate communication/coping (IC). This study was carried out to examine the usability and feasibility of the subtypes in an absolute and dimensional way with the SUICIDI-2 instrument. OBJECTIVE: A first step was to examine the model and the SUICIDI-2 instrument for usability and feasibility in clinical practice. We aim to investigate the'real life' practical application of the model and hope the feedback we get after practical use of the model will help us with improvements for the model and the SUICIDI-2 instrument. METHODS: Discharge letters to general practitioners of 25 cases of anonymized suicidal emergency patients were independently reviewed by three psychiatrists and three nurses. Using the SUICIDI-2 instrument, describing the proposed subtypes, cases were classified by the psychiatrists and nurses. Intraclass Correlation Coefficients (ICC) for absolute/discrete and dimensional ratings were calculated to examine the model's usability and the instrument's feasibility. The study was approved by the ethical board. RESULTS: All raters were able to recognize and classify the cases in subtypes. We found an average measure of good reliability for absolute/(discrete) subtypes. For dimensional scores, we found excellent average measures for the subtype PDC, and good average measures for the subtypes PD, PT and IC. The reliability of dimensional score for the SUICIDI-2 was relatively lower than an alternative dimensional rating, but had good ICC values for all subtypes. After reviewing the results though, we found some inconsistently assessment between raters. This was ground to narrow down the criteria per subtype to describe the subtypes more precisely. This resulted in adjusted formulations for subtypes PD and IC and agreement was achieved about formulations in the revised SUICIDI-3. CONCLUSIONS: The hypothetical model of entrapment leading to suicidality shows promising results for both the usability and feasibility of the SUICIDI instrument. Follow up studies with participants with a more diverse background may show consistency and validity for the model