A structural magnetic resonance imaging study in therapy-naïve transsexual individuals

Background: Transsexuality is explained and defined as a gender-identity disorder, characterised by very strong conviction of belonging to the opposite sex and has been associated with a distinct neuroanatomical pattern. Materials and methods: We performed a structural analysis in search of possible differences in grey matter structures based on magnetic resonance imaging scans of the brains of 26 individuals between 19 and 38 years of age. The participants were divided into two groups of 15 controls and 11 transgender individuals. The segmentation of subcortical grey matter was performed using FIRST model a model-based segmentation/registration tool, from FSL software package. Results: The results showed that the volume of the brain region called nucleus accumbens on the left side was significantly smaller in the group of transgender individuals compared to the control. It was the most important parameter which was shown to make distinction between two examined groups. Conclusions: The results also showed decreased volumes of the left thalamus, right hippocampus and right caudate nucleus

The structure and intensity of self-reported autonomic arousal symptoms across anxiety disorders and obsessive-compulsive disorder

© 2016 Elsevier B.V. All rights reserved. Background Heightened autonomic arousal symptoms (AAS) are assumed to be a central feature of anxiety disorders. However, it is unclear whether the magnitude and profile of AAS vary across anxiety disorders and whether heightened AAS characterises obsessive-compulsive disorder (OCD). Aims We sought to determine whether the intensity and structure of AAS varied across anxiety disorders and OCD. Method A sample of 459 individuals with a primary anxiety disorder or OCD were administered the Symptom Checklist-90R. Nine items referring to prototypic AAS were included in a latent class analysis. Results A 2-class solution (high and low AAS classes) best fitted the data. Participants comprising the high AAS class scored uniformly high across all assessed AAS symptoms. Older age and the presence of panic disorder, social anxiety disorder and generalized anxiety disorder predicted membership in the high AAS class. No OCD symptom dimension was significantly associated with membership in the high AAS class. Limitation AAS were assessed using a self-report measure and replication is needed using other methodologies. Conclusions These findings suggest that OCD may be sufficiently distinct from anxiety disorders and do not support subtyping of anxiety disorders on the basis of the predominant type of AAS. Therapeutic approaches that target AAS might best be applied in the treatment of panic disorder, social anxiety disorder and generalized anxiety disorder

Problematic risk-taking involving emerging technologies: A stakeholder framework to minimize harms

Background and aims Despite the many benefits of technological advancements, problematic use of emerging technologies may lead to consumers experiencing harms. Substantial problems and behavioral addictions, such as gambling and gaming disorders, are recognized to be related to Internet-based technologies, including the myriad of new devices and platforms available. This review paper seeks to explore problematic risk-taking behaviors involving emerging technologies (e.g., online gambling and gaming, online sexual behaviors, and oversharing of personal information via social networking sites) that have the potential to lead to problematic outcomes for individuals. Results and discussion Previous research has focused on policy frameworks for responding to specific issues (e.g., online gambling), but a broader framework is needed to address issues as they emerge, given lags in governments and regulators responding to dynamically evolving technological environments. In this paper, key terms and issues involved are identified and discussed. We propose an initial framework for the relative roles and responsibilities of key stakeholder groups involved in addressing these issues (e.g., industry operators, governments and regulators, community groups, researchers, treatment providers, and individual consumers/end users). Conclusion Multidisciplinary collaboration can facilitate a comprehensive, unified response from all stakeholders that balances individual civil liberties with societal responsibilities and institutional duty of care.This work was supported by an Australian Research Council Discovery Early Career Research Award (DE1060100459) awarded to Associate Professor Sally Gainsbury

Gaming disorder and the COVID-19 pandemic: Treatment demand and service delivery challenges

Gaming activities have conferred numerous benefits during the COVID-19 pandemic. However, someindividuals may be at greater risk of problem gaming due to disruption to adaptive routines, increased anxiety and/or depression, and social isolation. This paper presents a summary of 2019–2021 service data from specialist addiction centers in Germany, Switzerland, Japan, and the United Kingdom. Treatment demand for gaming disorder has exceeded service capacity during the pandemic, with significant service access issues. These data highlight the need for adaptability of gaming disorder services and greater resources and funding to respond effectively in future public health crises

The influence of semantic and phonological factors on syntactic decisions: An event-related brain potential study

During language production and comprehension, information about a word's syntactic properties is sometimes needed. While the decision about the grammatical gender of a word requires access to syntactic knowledge, it has also been hypothesized that semantic (i.e., biological gender) or phonological information (i.e., sound regularities) may influence this decision. Event-related potentials (ERPs) were measured while native speakers of German processed written words that were or were not semantically and/or phonologically marked for gender. Behavioral and ERP results showed that participants were faster in making a gender decision when words were semantically and/or phonologically gender marked than when this was not the case, although the phonological effects were less clear. In conclusion, our data provide evidence that even though participants performed a grammatical gender decision, this task can be influenced by semantic and phonological factors

Human DNA polymerase β polymorphism, Arg137Gln, impairs its polymerase activity and interaction with PCNA and the cellular base excision repair capacity

DNA polymerase β (Pol β) is a key enzyme in DNA base excision repair, and an important factor for maintaining genome integrity and stability. More than 30% of human tumors characterized to date express DNA Pol β variants, many of which result from a single nucleotide residue substitution. However, in most cases, their precise functional deficiency and relationship to cancer susceptibility are still unknown. In the current work, we show that a polymorphism encoding an arginine to glutamine substitution, R137Q, has lower polymerase activity. The substitution also affects the interaction between Pol β and proliferating cell nuclear antigen (PCNA). These defects impair the DNA repair capacity of Pol β in reconstitution assays, as well as in cellular extracts. Expression of wild-type Pol β in pol β−/− mouse embryonic fibroblast (MEF) cells restored cellular resistance to DNA damaging reagents such as methyl methanesulfonate (MMS) and N-methyl-N-nitrosourea (MNU), while expression of R137Q in pol β−/− MEF cells failed to do so. These data indicate that polymorphisms in base excision repair genes may contribute to the onset and development of cancers

A weak scientific basis for gaming disorder: let us err on the side of caution

We greatly appreciate the care and thought that is evident in the 10 commentaries that discuss our debate paper, the majority of which argued in favor of a formalized ICD-11 gaming disorder. We agree that there are some people whose play of video games is related to life problems. We believe that understanding this population and the nature and severity of the problems they experience should be a focus area for future research. However, moving from research construct to formal disorder requires a much stronger evidence base than we currently have. The burden of evidence and the clinical utility should be extremely high, because there is a genuine risk of abuse of diagnoses. We provide suggestions about the level of evidence that might be required: transparent and preregistered studies, a better demarcation of the subject area that includes a rationale for focusing on gaming particularly versus a more general behavioral addictions concept, the exploration of non-addiction approaches, and the unbiased exploration of clinical approaches that treat potentially underlying issues, such as depressive mood or social anxiety first. We acknowledge there could be benefits to formalizing gaming disorder, many of which were highlighted by colleagues in their commentaries, but we think they do not yet outweigh the wider societal and public health risks involved. Given the gravity of diagnostic classification and its wider societal impact, we urge our colleagues at the WHO to err on the side of caution for now and postpone the formalization

A multicentre matched case control study of risk factors for Preeclampsia in healthy women in Pakistan

<p>Abstract</p> <p>Background</p> <p>Preeclampsia is one of the leading causes of maternal and perinatal morbidity and mortality world-wide. The risk for developing preeclampsia varies depending on the underlying mechanism. Because the disorder is heterogeneous, the pathogenesis can differ in women with various risk factors. Understanding these mechanisms of disease responsible for preeclampsia as well as risk assessment is still a major challenge. The aim of this study was to determine the risk factors associated with preeclampsia, in healthy women in maternity hospitals of Karachi and Rawalpindi.</p> <p>Methods</p> <p>We conducted a hospital based matched case-control study to assess the factors associated with preeclampsia in Karachi and Rawalpindi, from January 2006 to December 2007. 131 hospital-reported cases of PE and 262 controls without history of preeclampsia were enrolled within 3 days of delivery. Cases and controls were matched on the hospital, day of delivery and parity. Potential risk factors for preeclampsia were ascertained during in-person postpartum interviews using a structured questionnaire and by medical record abstraction. Conditional logistic regression was used to estimate matched odds ratios (ORs) and 95% confidence intervals (95% CIs).</p> <p>Results</p> <p>In multivariate analysis, women having a family history of hypertension (adjusted OR 2.06, 95% CI; 1.27-3.35), gestational diabetes (adjusted OR 6.57, 95% CI; 1.94 -22.25), pre-gestational diabetes (adjusted OR 7.36, 95% CI; 1.37-33.66) and mental stress during pregnancy (adjusted OR 1.32; 95% CI; 1.19-1.46, for each 5 unit increase in Perceived stress scale score) were at increased risk of preeclampsia. However, high body mass index, maternal age, urinary tract infection, use of condoms prior to index pregnancy and sociodemographic factors were not associated with higher risk of having preeclampsia.</p> <p>Conclusions</p> <p>Development of preeclampsia was associated with gestational diabetes, pregestational diabetes, family history of hypertension and mental stress during pregnancy. These factors can be used as a screening tool for preeclampsia prediction. Identification of the above mentioned predictors would enhance the ability to diagnose and monitor women likely to develop preeclampsia before the onset of disease for timely interventions and better maternal and fetal outcomes.</p

Expert appraisal of criteria for assessing gaming disorder : An international Delphi study

© 2021 The Authors. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (CC-BY-NC-ND - https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.Background and aims: Following the recognition of ‘internet gaming disorder’ (IGD) as a condition requiring further study by the DSM-5, ‘gaming disorder’ (GD) was officially included as a diagnostic entity by the World Health Organization (WHO) in the 11th revision of the International Classification of Diseases (ICD-11). However, the proposed diagnostic criteria for gaming disorder remain the subject of debate, and there has been no systematic attempt to integrate the views of different groups of experts. To achieve a more systematic agreement on this new disorder, this study employed the Delphi expert consensus method to obtain expert agreement on the diagnostic validity, clinical utility and prognostic value of the DSM-5 criteria and ICD-11 clinical guidelines for GD. Methods: A total of 29 international experts with clinical and/or research experience in GD completed three iterative rounds of a Delphi survey. Experts rated proposed criteria in progressive rounds until a pre-determined level of agreement was achieved. Results: For DSM-5 IGD criteria, there was an agreement both that a subset had high diagnostic validity, clinical utility and prognostic value and that some (e.g. tolerance, deception) had low diagnostic validity, clinical utility and prognostic value. Crucially, some DSM-5 criteria (e.g. escapism/mood regulation, tolerance) were regarded as incapable of distinguishing between problematic and non-problematic gaming. In contrast, ICD-11 diagnostic guidelines for GD (except for the criterion relating to diminished non-gaming interests) were judged as presenting high diagnostic validity, clinical utility and prognostic value. Conclusions: This Delphi survey provides a foundation for identifying the most diagnostically valid and clinically useful criteria for GD. There was expert agreement that some DSM-5 criteria were not clinically relevant and may pathologize non-problematic patterns of gaming, whereas ICD-11 diagnostic guidelines are likely to diagnose GD adequately and avoid pathologizing.Peer reviewe

Discovery of a new class of inhibitors for the protein arginine deiminase type 4 (PAD4) by structure-based virtual screening

<p>Abstract</p> <p>Background</p> <p>Rheumatoid arthritis (RA) is an autoimmune disease with unknown etiology. Anticitrullinated protein autoantibody has been documented as a highly specific autoantibody associated with RA. Protein arginine deiminase type 4 (PAD4) is the enzyme responsible for catalyzing the conversion of peptidylarginine into peptidylcitrulline. PAD4 is a new therapeutic target for RA treatment. In order to search for inhibitors of PAD4, structure-based virtual screening was performed using LIDAEUS (Ligand discovery at Edinburgh university). Potential inhibitors were screened experimentally by inhibition assays.</p> <p>Results</p> <p>Twenty two of the top-ranked water-soluble compounds were selected for inhibitory screening against PAD4. Three compounds showed significant inhibition of PAD4 and their IC₅₀values were investigated. The structures of the three compounds show no resemblance with previously discovered PAD4 inhibitors, nor with existing drugs for RA treatment.</p> <p>Conclusion</p> <p>Three compounds were discovered as potential inhibitors of PAD4 by virtual screening. The compounds are commercially available and can be used as scaffolds to design more potent inhibitors against PAD4.</p