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

6A3-5/Osa2 is an Early Activated Gene Implicated in the Control of Vascular Smooth Muscle Cell Functions

Vascular smooth muscle cells (VSMC) growth plays a key role in the pathophysiology of vascular diseases. However, the molecular mechanisms controlling gene transcription in VSMC remain poorly understood. We previously identified, by differential display, a new gene (6A3-5) overexpressed in proliferating rat VSMC. In this study, we have cloned the full-length cDNA by screening a rat foetal brain cDNA library and investigated its functions. The 6A3-5 protein shows 4 putative conserved functional motifs: a DNA binding domain called ARID (AT-rich interaction domain), two recently described motifs (Osa Homology Domain), and a nuclear localization signal. The deduced protein sequence was observed to be 85% identical to the recently described human Osa2 gene. Immunolabelling, using an anti-6A3-5/Osa2 monoclonal antibody, showed a nuclear localization of the 6A3-5/Osa2 protein. In addition, PDGF upregulated 6A3-5/Osa2 expression at both the transcript and protein levels in a dose and time-dependent fashion. The pattern of upregulation by PDGF was reminiscent of the early responsive gene c-fos. The PDGF-induced upregulation of 6A3-5/Osa2 and proliferation of VSMC were significantly inhibited in a dose and sequence-dependent fashion by an antisense, but not by sense, scrambled or mismatched oligonucleotides directed against 6A3-5/Osa2. In VSMC of aortas derived from hypertensive (LH) rats, 6A3-5/Osa2 is overexpressed as compared to that in normotensive (LL) rats. The 6A3-5/Osa2-gene expression is downregulated by an ACE inhibitor and upregulated by exogenous AngiotensinII in LH rats. In summary, these results indicate that 6A3-5/Osa2 is an early activated gene that belongs to a new family of proteins involved in the control of VSMC growth

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

Teaching Indigenous History and Heritage. Reviving the Past in the Present: Caribbean Experiences from the Dominican Republic and Dominica

The Caribbean is well-known for its multi-ethnic and multi-cultural population, a consequence of its colonial past and Amerindian, European, African, and Asian influences. The role of this colonial heritage in defining contemporary Caribbean identities has been significant. Nevertheless, the indigenous peoples who inhabited the Caribbean in the past are not frequently referred to in modern-day Caribbean society. It is often believed that the indigenous inhabitants were wiped out soon after European arrival, yet recent archaeological and ethnographic studies have shown the survival of indigenous traditions and expressions in the present Caribbean. There is an indigenous resurgence movement among groups that self-identify with their Amerindian ancestors, and in Dominica the contemporary indigenous population has been officially recognized by the country’s government. These important aspects of Caribbean history are highly relevant for the teaching of the national identity and cultural heritage, and need to be reflected in the school curricula of Social Studies across the region. This paper examines current educational practices regarding indigenous history and heritage in two Caribbean countries, each with a different historical background and development. The first study area lies in the northwest of the Dominican Republic, where Columbus encountered the so-called Taíno in 1492 and founded the first European settlements. The second study area is the Kalinago Territory in Dominica, home of the descendants of the Kalinago indigenous people. The teaching of indigenous history and heritage in the schools of these countries includes the pre-Columbian and colonization periods, reflecting the prevalence of traditional Euro-centered narratives in which the indigenous history ended with the Amerindian “extinction” in past centuries. Contemporary issues receive little or no attention in the curricula. Archaeology of the America

Redox regulation of KV7 channels through EF3 hand of calmodulin

Neuronal KV7 channels, important regulators of cell excitability, are among the most sensitive proteins to reactive oxygen species. The S2S3 linker of the voltage sensor was reported as a site-mediating redox modulation of the channels. Recent structural insights reveal potential interactions between this linker and the Ca2+-binding loop of the third EF-hand of calmodulin (CaM), which embraces an antiparallel fork formed by the C-terminal helices A and B, constituting the calcium responsive domain (CRD). We found that precluding Ca2+ binding to the EF3 hand, but not to EF1, EF2, or EF4 hands, abolishes oxidation-induced enhancement of KV7.4 currents. Monitoring FRET (Fluorescence Resonance Energy Transfer) between helices A and B using purified CRDs tagged with fluorescent proteins, we observed that S2S3 peptides cause a reversal of the signal in the presence of Ca2+ but have no effect in the absence of this cation or if the peptide is oxidized. The capacity of loading EF3 with Ca2+ is essential for this reversal of the FRET signal, whereas the consequences of obliterating Ca2+ binding to EF1, EF2, or EF4 are negligible. Furthermore, we show that EF3 is critical for translating Ca2+ signals to reorient the AB fork. Our data are consistent with the proposal that oxidation of cysteine residues in the S2S3 loop relieves KV7 channels from a constitutive inhibition imposed by interactions between the EF3 hand of CaM which is crucial for this signaling.Ministerio de Ciencia e Innovacion PID2021-128286NB-100Wellcome Trust 212302/Z/18/ZMedical Research Centre MR/P015727/1Eusko Jaurlaritza IT1707-22 Ekonomiaren Garapen eta Lehiakortasun Saila, Eusko Jaurlaritza BG2019Ministerio de Ciencia e Innovacion RTI2018-097839-B-100Ministerio de Ciencia e Innovacion RTI2018-101269-B-I00Eusko Jaurlaritza IT1165-19 Ekonomiaren Garapen eta Lehiakortasun Saila,Eusko Jaurlaritza KK-2020/00110Eusko Jaurlaritza PRE_2018-2_0082Eusko Jaurlaritza POS_2021_1_0017Eusko Jaurlaritza PRE_2018-2_012

Computational Protein Design to Re-Engineer Stromal Cell-Derived Factor-1α (SDF) Generates an Effective and Translatable Angiogenic Polypeptide Analog

BACKGROUND: Experimentally, exogenous administration of recombinant stromal cell-derived factor-1α (SDF) enhances neovasculogenesis and cardiac function after myocardial infarction. Smaller analogs of SDF may provide translational advantages including enhanced stability and function, ease of synthesis, lower cost, and potential modulated delivery via engineered biomaterials. In this study, computational protein design was used to create a more efficient evolution of the native SDF protein. METHODS AND RESULTS: Protein structure modeling was used to engineer an SDF polypeptide analog (engineered SDF analog [ESA]) that splices the N-terminus (activation and binding) and C-terminus (extracellular stabilization) with a diproline segment designed to limit the conformational flexibility of the peptide backbone and retain the relative orientation of these segments observed in the native structure of SDF. Endothelial progenitor cells (EPCs) in ESA gradient, assayed by Boyden chamber, showed significantly increased migration compared with both SDF and control gradients. EPC receptor activation was evaluated by quantification of phosphorylated AKT, and cells treated with ESA yielded significantly greater phosphorylated AKT levels than SDF and control cells. Angiogenic growth factor assays revealed a distinct increase in angiopoietin-1 expression in the ESA- and SDF-treated hearts. In addition, CD-1 mice (n=30) underwent ligation of the left anterior descending coronary artery and peri-infarct intramyocardial injection of ESA, SDF-1α, or saline. At 2 weeks, echocardiography demonstrated a significant gain in ejection fraction, cardiac output, stroke volume, and fractional area change in mice treated with ESA compared with controls. CONCLUSIONS: Compared with native SDF, a novel engineered SDF polypeptide analog (ESA) more efficiently induces EPC migration and improves post-myocardial infarction cardiac function and thus offers a more clinically translatable neovasculogenic therapy

The Far-Ultraviolet "Continuum" in Protoplanetary Disk Systems II: CO Fourth Positive Emission and Absorption

We exploit the high sensitivity and moderate spectral resolution of the $HST$-Cosmic Origins Spectrograph to detect far-ultraviolet spectral features of carbon monoxide (CO) present in the inner regions of protoplanetary disks for the first time. We present spectra of the classical T Tauri stars HN Tau, RECX-11, and V4046 Sgr, representative of a range of CO radiative processes. HN Tau shows CO bands in absorption against the accretion continuum. We measure a CO column density and rotational excitation temperature of N(CO) = 2 +/- 1 $\times$ 10$^{17}$ cm$^{-2}$ and T_rot(CO) 500 +/- 200 K for the absorbing gas. We also detect CO A-X band emission in RECX-11 and V4046 Sgr, excited by ultraviolet line photons, predominantly HI LyA. All three objects show emission from CO bands at $\lambda$ $>$ 1560 \AA, which may be excited by a combination of UV photons and collisions with non-thermal electrons. In previous observations these emission processes were not accounted for due to blending with emission from the accretion shock, collisionally excited H$_{2}$, and photo-excited H2; all of which appeared as a "continuum" whose components could not be separated. The CO emission spectrum is strongly dependent upon the shape of the incident stellar LyA emission profile. We find CO parameters in the range: N(CO) 10$^{18-19}$ cm$^{-2}$, T_{rot}(CO) > 300 K for the LyA-pumped emission. We combine these results with recent work on photo- and collisionally-excited H$_{2}$ emission, concluding that the observations of ultraviolet-emitting CO and H2 are consistent with a common spatial origin. We suggest that the CO/H2 ratio in the inner disk is ~1, a transition between the much lower interstellar value and the higher value observed in solar system comets today, a result that will require future observational and theoretical study to confirm.Comment: 12 pages, 7 figures, 3 tables. ApJ - accepte

Estimating the subnational prevalence of antimicrobial resistant Salmonella enterica serovars Typhi and Paratyphi A infections in 75 endemic countries, 1990–2019: a modelling study

Background Enteric fever, a systemic infection caused by Salmonella enterica serovars Typhi and Paratyphi A, remains a major cause of morbidity and mortality in low-income and middle-income countries. Enteric fever is preventable through the provision of clean water and adequate sanitation and can be successfully treated with antibiotics. However, high levels of antimicrobial resistance (AMR) compromise the effectiveness of treatment. We provide estimates of the prevalence of AMR S Typhi and S Paratyphi A in 75 endemic countries, including 30 locations without data. Methods We used a Bayesian spatiotemporal modelling framework to estimate the percentage of multidrug resistance (MDR), fluoroquinolone non-susceptibility (FQNS), and third-generation cephalosporin resistance in S Typhi and S Paratyphi A infections for 1403 administrative level one districts in 75 endemic countries from 1990 to 2019. We incorporated data from a comprehensive systematic review, public health surveillance networks, and large multicountry studies on enteric fever. Estimates of the prevalence of AMR and the number of AMR infections (based on enteric fever incidence estimates by the Global Burden of Diseases study) were produced at the country, super-region, and total endemic area level for each year of the study. Findings We collated data from 601 sources, comprising 184 225 isolates of S Typhi and S Paratyphi A, covering 45 countries over 30 years. We identified a decline of MDR S Typhi in south Asia and southeast Asia, whereas in sub-Saharan Africa, the overall prevalence increased from 6·0% (95% uncertainty interval 4·3–8·0) in 1990 to 72·7% (67·7–77·3) in 2019. Starting from low levels in 1990, the prevalence of FQNS S Typhi increased rapidly, reaching 95·2% (91·4–97·7) in south Asia in 2019. This corresponded to 2·5 million (1·5–3·8) MDR S Typhi infections and 7·4 million (4·7–11·3) FQNS S Typhi infections in endemic countries in 2019. The prevalence of third-generation cephalosporin-resistant S Typhi remained low across the whole endemic area over the study period, except for Pakistan where prevalence of third-generation cephalosporin resistance in S Typhi reached 61·0% (58·0–63·8) in 2019. For S Paratyphi A, we estimated low prevalence of MDR and third-generation cephalosporin resistance in all endemic countries, but a drastic increase of FQNS, which reached 95·0% (93·7–96·1; 3·5 million [2·2–5·6] infections) in 2019. Interpretation This study provides a comprehensive and detailed analysis of the prevalence of MDR, FQNS, and third-generation cephalosporin resistance in S Typhi and S Paratyphi A infections in endemic countries, spanning the last 30 years. Our analysis highlights the increasing levels of AMR in this preventable infection and serves as a resource to guide urgently needed public health interventions, such as improvements in water, sanitation, and hygiene and typhoid fever vaccination campaigns. Funding Fleming Fund, UK Department of Health and Social Care; Wellcome Trust; and Bill and Melinda Gates Foundation