The relationship between obsessions and the self: Feared and actual self-descriptions in a clinical obsessive-compulsive disorder sample

Cognitive models of obsessive-compulsive disorder (OCD) posit the relevance of the self in OCD, although the nature of this association is still unclear. We aimed to explore actual and feared selves and its association with obsessions and intrusions in a group of OCD patients. A group of 58 patients with OCD identified their most upsetting obsession and intrusion (non-clinical obsession) experienced in the past 3 months. These cognitions were classified as either moral-based or autogenous (obsessions n = 32; intrusions n = 26) or non-moral-based or reactive, depending on their content. Next, patients described their actual self and their feared self, that is, the person they feared being or becoming, and whether they believed these descriptions were associated with their obsessions/intrusions. Results indicate that individuals with OCD described themselves as insecure, anxious and fearful, but also as good and nice. They particularly feared a selfish, aggressive, bad, liar, coward, insecure and arrogant self. Two-thirds of the patients believed that their obsessions said something about their actual self (65.52%) and that their obsessions brought them closer to the person they do not want to be (62.06%). A third of patients believed their intrusions said something about their actual self (actual self: 30.35%; feared self: 25%), which was a significantly lower percentage than for obsessions. These associations existed independent from the content of the obsession and/or intrusion, although patients with obsessions with moral-based contents more often tended to believe that their obsessions brought them closer to the person they do not want to be. Results suggest the relevance of the real and feared selves in the maintenance of obsessions

Is context a crucial factor in distinguishing between intrusions and obsessions in patients with obsessive-compulsive disorder?

Objective Some cognitive models of obsessive‐compulsive disorder (OCD) posit that intrusions exist on a continuum with obsessions; others consider that they may be unrelated phenomena that differ in the context where they occur. We aimed to examine and compare, at two different moments, the context of the occurrence of intrusions and obsessions. Method Sixty‐eight patients with OCD completed an interview appraising their most upsetting obsession and intrusion. Results At their onset, the obsessions/intrusions were associated with experiencing negative emotional states and life events, and they were more likely to appear in 'inappropriate' contexts. The context of the obsessions/intrusions differed the last time they were experienced. Autogenous obsessions/intrusions occurred more frequently in contexts with an indirect link. Conclusions The context distinguishes between intrusions and obsessions, not when they emerge, but when the obsession is already established. The results support that there is a continuum or progression from intrusions to obsessions

Spanish version of the Inferential Confusion Questionnaire-Expanded Version: Further support for the role of inferential confusion in obsessive-compulsive symptoms

Objective Some cognitive models of obsessive‐compulsive disorder (OCD) posit that intrusions exist on a continuum with obsessions; others consider that they may be unrelated phenomena that differ in the context where they occur. We aimed to examine and compare, at two different moments, the context of the occurrence of intrusions and obsessions. Method Sixty‐eight patients with OCD completed an interview appraising their most upsetting obsession and intrusion. Results At their onset, the obsessions/intrusions were associated with experiencing negative emotional states and life events, and they were more likely to appear in 'inappropriate' contexts. The context of the obsessions/intrusions differed the last time they were experienced. Autogenous obsessions/intrusions occurred more frequently in contexts with an indirect link. Conclusions The context distinguishes between intrusions and obsessions, not when they emerge, but when the obsession is already established. The results support that there is a continuum or progression from intrusions to obsessions

Validation of the Spanish version of the Fear of Self Questionnaire

Cognitive models, from both the appraisal and inferential confusion perspectives, propose that the self is a relevant variable in the development and maintenance of obsessive-compulsive (OC) disorder. In this study, we examined the psychometric properties of the Spanish version of the Fear of Self Questionnaire (FSQ) and analyzed the role of the fear of self (the sort of person we are afraid of becoming) as a predictor of OC beliefs and symptoms. A sample of 359 non-clinical participants completed a set of questionnaires, including the FSQ. Confirmatory factor analysis replicated the original one-factor solution for both the FSQ-8- and 20-item versions. The FSQ demonstrated excellent reliability, and fear of self predicted OC symptoms and cognitions, especially unacceptable obsessions

Chagas Disease, France

Chagas Disease, Franc

Filopodyan: An open-source pipeline for the analysis of filopodia

Filopodia have important sensory and mechanical roles in motile cells. The recruitment of actin regulators, such as ENA/ VASP proteins, to sites of protrusion underlies diverse molecular mechanisms of filopodia formation and extension. We developed Filopodyan (filopodia dynamics analysis) in Fiji and R to measure fluorescence in filopodia and at their tips and bases concurrently with their morphological and dynamic properties. Filopodyan supports high-throughput phenotype characterization as well as detailed interactive editing of filopodia reconstructions through an intuitive graphical user interface. Our highly customizable pipeline is widely applicable, capable of detecting filopodia in four different cell types in vitro and in vivo. We use Filopodyan to quantify the recruitment of ENA and VASP preceding filopodia formation in neuronal growth cones, and uncover a molecular heterogeneity whereby different filopodia display markedly different responses to changes in the accumulation of ENA and VASP fluorescence in their tips over time.J.L. Gallop and V. Urbančič are supported by the Wellcome Trust (WT095829AIA). J. Mason and B. Richier are supported by the European Research Council (281971). C.E. Holt is supported by the Wellcome Trust (program grant 085314) and the European Research Council (advanced grant 322817). The Gurdon Institute is funded by the Wellcome Trust (203144) and Cancer Research UK (C6946/A24843)

HIV/HCV Co-infection: Pathogenesis, Clinical Complications, Treatment, and New Therapeutic Technologies

World-wide, hepatitis C virus (HCV) accounts for approximately 130 million chronic infections, with an overall 3% prevalence. Four to 5 million persons are co-infected with HIV. It is well established that HIV has a negative impact on the natural history of HCV, including a higher rate of viral persistence, increased viral load, and more rapid progression to fibrosis, end-stage liver disease, and death. Whether HCV has a negative impact on HIV disease progression continues to be debated. However, following the introduction of effective combination antiretroviral therapy, the survival of coinfected individuals has significantly improved and HCV-associated diseases have emerged as the most important co-morbidities. In this review, we summarize the newest studies regarding the pathogenesis of HIV/HCV coinfection, including effects of coinfection on HIV disease progression, HCV-associated liver disease, the immune system, kidney and cardiovascular disease, and neurologic status; and effectiveness of current anti-HIV and HCV therapies and proposed new treatment strategies

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Immunoglobulin, glucocorticoid, or combination therapy for multisystem inflammatory syndrome in children: a propensity-weighted cohort study.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C), a hyperinflammatory condition associated with SARS-CoV-2 infection, has emerged as a serious illness in children worldwide. Immunoglobulin or glucocorticoids, or both, are currently recommended treatments. METHODS: The Best Available Treatment Study evaluated immunomodulatory treatments for MIS-C in an international observational cohort. Analysis of the first 614 patients was previously reported. In this propensity-weighted cohort study, clinical and outcome data from children with suspected or proven MIS-C were collected onto a web-based Research Electronic Data Capture database. After excluding neonates and incomplete or duplicate records, inverse probability weighting was used to compare primary treatments with intravenous immunoglobulin, intravenous immunoglobulin plus glucocorticoids, or glucocorticoids alone, using intravenous immunoglobulin as the reference treatment. Primary outcomes were a composite of inotropic or ventilator support from the second day after treatment initiation, or death, and time to improvement on an ordinal clinical severity scale. Secondary outcomes included treatment escalation, clinical deterioration, fever, and coronary artery aneurysm occurrence and resolution. This study is registered with the ISRCTN registry, ISRCTN69546370. FINDINGS: We enrolled 2101 children (aged 0 months to 19 years) with clinically diagnosed MIS-C from 39 countries between June 14, 2020, and April 25, 2022, and, following exclusions, 2009 patients were included for analysis (median age 8·0 years [IQR 4·2-11·4], 1191 [59·3%] male and 818 [40·7%] female, and 825 [41·1%] White). 680 (33·8%) patients received primary treatment with intravenous immunoglobulin, 698 (34·7%) with intravenous immunoglobulin plus glucocorticoids, 487 (24·2%) with glucocorticoids alone; 59 (2·9%) patients received other combinations, including biologicals, and 85 (4·2%) patients received no immunomodulators. There were no significant differences between treatments for primary outcomes for the 1586 patients with complete baseline and outcome data that were considered for primary analysis. Adjusted odds ratios for ventilation, inotropic support, or death were 1·09 (95% CI 0·75-1·58; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids and 0·93 (0·58-1·47; corrected p value=1·00) for glucocorticoids alone, versus intravenous immunoglobulin alone. Adjusted average hazard ratios for time to improvement were 1·04 (95% CI 0·91-1·20; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids, and 0·84 (0·70-1·00; corrected p value=0·22) for glucocorticoids alone, versus intravenous immunoglobulin alone. Treatment escalation was less frequent for intravenous immunoglobulin plus glucocorticoids (OR 0·15 [95% CI 0·11-0·20]; p<0·0001) and glucocorticoids alone (0·68 [0·50-0·93]; p=0·014) versus intravenous immunoglobulin alone. Persistent fever (from day 2 onward) was less common with intravenous immunoglobulin plus glucocorticoids compared with either intravenous immunoglobulin alone (OR 0·50 [95% CI 0·38-0·67]; p<0·0001) or glucocorticoids alone (0·63 [0·45-0·88]; p=0·0058). Coronary artery aneurysm occurrence and resolution did not differ significantly between treatment groups. INTERPRETATION: Recovery rates, including occurrence and resolution of coronary artery aneurysms, were similar for primary treatment with intravenous immunoglobulin when compared to glucocorticoids or intravenous immunoglobulin plus glucocorticoids. Initial treatment with glucocorticoids appears to be a safe alternative to immunoglobulin or combined therapy, and might be advantageous in view of the cost and limited availability of intravenous immunoglobulin in many countries. FUNDING: Imperial College London, the European Union's Horizon 2020, Wellcome Trust, the Medical Research Foundation, UK National Institute for Health and Care Research, and National Institutes of Health

Stroke genetics informs drug discovery and risk prediction across ancestries

Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry(1,2). Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis(3), and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach(4), we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry(5). Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries.</p