Immunization with the C-domain of α-toxin prevents lethal infection, localizes tissue injury, and promotes host response to challenge with Clostridium perfringens

© 2004 by the Infectious Diseases Society of America. All rights reserved.Clostridium perfringens gas gangrene is characterized by rapid tissue destruction, impaired host response, and, often, death. Phospholipase C (α-toxin) is the virulence factor most responsible for these pathologies. The present study investigated the efficacy of active immunization with the C-terminal domain of α-toxin (Cpa247–370) in a murine model of gas gangrene. Primary end points of the study were survival, progression of infection, and tissue perfusion. Secondary end points, which were based on findings of histologic evaluation of tissues, included the extent of tissue destruction and microvascular thrombosis, as well as the magnitude of the tissue inflammatory response. Survival among C-domain–immunized animals was significantly greater than that among sham-immunized control animals. Furthermore, immunization with the C-domain localized the infection and prevented ischemia of the feet. Histopathologic findings demonstrated limited muscle necrosis, reduced microvascular thrombosis, and enhanced granulocytic influx in C-domain–immunized mice. We conclude that immunization with the C-domain of phospholipase C is a viable strategy for the prevention of morbidity and mortality associated with C. perfringens gas gangrene

Synthesising the existing evidence for non-pharmacological interventions targeting outcomes relevant to young people with ADHD in the school setting: systematic review protocol.

BACKGROUND: Children and adolescents with attention-deficit/hyperactivity disorder (ADHD) have impairing levels of difficulty paying attention, impulsive behaviour and/or hyperactivity. ADHD causes extensive difficulties for young people at school, and as a result these children are at high risk for a wide range of poor outcomes. We ultimately aim to develop a flexible, modular 'toolkit' of evidence-based strategies that can be delivered by primary school staff to improve the school environment and experience for children with ADHD; the purpose of this review is to identify and quantify the evidence-base for potential intervention components. This protocol sets out our plans to systematically identify non-pharmacological interventions that target outcomes that have been reported to be of importance to key stakeholders (ADHD symptoms, organisation skills, executive-global- and classroom-functioning, quality of life, self-esteem and conflict with teachers and peers). We plan to link promising individual intervention components to measured outcomes, and synthesise the evidence of effectiveness for each outcome. METHODS: A systematic search for studies published from the year 2000 that target the outcomes of interest in children and young people aged 3-12 will be conducted. Titles and abstracts will be screened using prioritisation software, and then full texts of potentially eligible studies will be screened. Systematic reviews, RCTs, non-randomised and case-series studies are eligible designs. Synthesis will vary by the type of evidence available, potentially including a review of reviews, meta-analysis and narrative synthesis. Heterogeneity of studies meta-analysed will be assessed, along with publication bias. Intervention mapping will be applied to understand potential behaviour change mechanisms for promising intervention components. DISCUSSION: This review will highlight interventions that appear to effectively ameliorate negative outcomes that are of importance for people with ADHD, parents, school staff and experts. Components of intervention design and features that are associated with effective change in the outcome will be delineated and used to inform the development of a 'toolkit' of non-pharmacological strategies that school staff can use to improve the primary school experience for children with ADHD. TRIAL REGISTRATION: PROSPERO number CRD42021233924

Patient-Centered Communication for Discussing Oncotype DX Testing

Oncotype DX testing (ODX), a tumor gene expression test, may improve breast cancer care, however communicating results remains challenging. We identified patient-centered communication strategies/gaps for discussing ODX results. We applied a patient-centered communication framework to analyze qualitative interviews with oncologists about how they communicate about ODX with patients, using template analysis in Atlas.ti. Overall, providers discussed four patient-centered communication domains: exchanging information, assessing uncertainty, making decisions and cross-cutting themes. Providers did not report discussing emotional aspects of managing uncertainty, assessing decision-making preferences, and evaluating decisions. A patient-centered approach may be a model for communicating about tumor gene expression tests

Synthesising the existing evidence for non-pharmacological interventions targeting outcomes relevant to young people with ADHD in the school setting: systematic review protocol.

BACKGROUND: Children and adolescents with attention-deficit/hyperactivity disorder (ADHD) have impairing levels of difficulty paying attention, impulsive behaviour and/or hyperactivity. ADHD causes extensive difficulties for young people at school, and as a result these children are at high risk for a wide range of poor outcomes. We ultimately aim to develop a flexible, modular 'toolkit' of evidence-based strategies that can be delivered by primary school staff to improve the school environment and experience for children with ADHD; the purpose of this review is to identify and quantify the evidence-base for potential intervention components. This protocol sets out our plans to systematically identify non-pharmacological interventions that target outcomes that have been reported to be of importance to key stakeholders (ADHD symptoms, organisation skills, executive-global- and classroom-functioning, quality of life, self-esteem and conflict with teachers and peers). We plan to link promising individual intervention components to measured outcomes, and synthesise the evidence of effectiveness for each outcome. METHODS: A systematic search for studies published from the year 2000 that target the outcomes of interest in children and young people aged 3-12 will be conducted. Titles and abstracts will be screened using prioritisation software, and then full texts of potentially eligible studies will be screened. Systematic reviews, RCTs, non-randomised and case-series studies are eligible designs. Synthesis will vary by the type of evidence available, potentially including a review of reviews, meta-analysis and narrative synthesis. Heterogeneity of studies meta-analysed will be assessed, along with publication bias. Intervention mapping will be applied to understand potential behaviour change mechanisms for promising intervention components. DISCUSSION: This review will highlight interventions that appear to effectively ameliorate negative outcomes that are of importance for people with ADHD, parents, school staff and experts. Components of intervention design and features that are associated with effective change in the outcome will be delineated and used to inform the development of a 'toolkit' of non-pharmacological strategies that school staff can use to improve the primary school experience for children with ADHD. TRIAL REGISTRATION: PROSPERO number CRD42021233924

The role of emotion in the learning of trustworthiness from eye-gaze : Evidence from facial electromyography.

When perception of gaze direction is congruent with the location of a target, attention is facilitated and responses are faster compared to when incongruent. Faces that consistently gaze congruently are also judged trustworthier than faces that consistently gaze incongruently. However, it’s unclear how gaze-cues elicit changes in trust. We measured facial electromyography (EMG) during an identity-contingent gaze-cueing task to examine whether embodied emotional reactions to gaze-cues mediate trust learning. Gaze-cueing effects were found to be equivalent regardless of whether participants showed learning of trust in the expected direction or did not. In contrast, we found distinctly different patterns of EMG activity in these two populations. In a further experiment we showed the learning effects were specific to viewing faces, as no changes in liking were detected when viewing arrows that evoked similar attentional orienting responses. These findings implicate embodied emotion in learning trust from identity-contingent gaze-cueing, possibly due to the social value of shared attention or deception rather than domain-general attentional orienting

Factors associated with depression, anxiety, and severe mental illness among adults with atopic eczema or psoriasis: a systematic review and meta-analysis

Background: Evidence suggests an association between atopic eczema (AE) or psoriasis and mental illness. However, factors associated with mental illness are unclear. / Objectives: To synthesise and evaluate all available evidence on factors associated with depression, anxiety, and severe mental illness (SMI) among adults with AE or psoriasis. / Methods: We searched electronic databases, grey literature databases, and clinical trial registries from inception to February 2022 for studies in adults with AE or psoriasis. Eligible studies were randomised controlled trials (RCTs), cohort, cross-sectional or case-control studies where effect estimates of factors associated with depression, anxiety, or SMI were reported. We did not apply language or geographical restrictions. We assessed risk of bias using the Quality in Prognosis Studies tool. We synthesised results narratively, and if at least two studies were sufficiently homogenous, we pooled effect estimates in a random-effects meta-analysis. / Results: We included 21 studies (11 observational, 10 RCT). No observational studies in AE fulfilled our eligibility criteria. Observational studies in people with psoriasis mostly investigated factors associated with depression or anxiety – one cross-sectional study investigated factors associated with schizophrenia. Pooled effect estimates suggest being female, and psoriatic arthritis, were associated with depression (female sex:OR = 1.62,95%CI = 1.09-2.40,95%PI = 0.62-4.23, I2 = 24.90%, Tau2 = 0.05; psoriatic arthritis:OR = 2.26,95%CI = 1.56-3.25,95%PI = 0.21-24.23, I2 = 0.00%, Tau2 = 0.00) and anxiety (female sex:OR = 2.59,95%CI = 1.32-5.07,95%PI = 0.00-3956.27, I2 = 61.90%, Tau2 = 0.22; psoriatic arthritis:OR = 1.98,95%CI = 1.33-2.94, I2 = 0.00%, Tau2 = 0.00). Moderate/severe psoriasis was associated with anxiety (OR = 1.14,95%CI = 1.05-1.25, I2 = 0.00%, Tau2 = 0.00), but not depression. Evidence from RCTs suggested adults with AE or psoriasis given placebo had higher depression and anxiety scores compared to comparators given targeted treatment (e.g., biologic agents). / Conclusions: Our review highlights limited existing research on factors associated with depression, anxiety, and SMI in adults with AE or psoriasis. Observational evidence on factors associated with depression or anxiety in people with psoriasis was conflicting or from single studies, but some identified factors were consistent with those in the general population. Evidence on factors associated with SMIs in people with AE or psoriasis was particularly limited. Evidence from RCTs suggested AE and psoriasis treated with placebo was associated with higher depression and anxiety scores compared to skin disease treated with targeted therapy, however, follow-up was limited, therefore long-term effects on mental health are unclear

Modeling the distributions of tegu lizards in native and potential invasive ranges

Invasive reptilian predators can have substantial impacts on native species and ecosystems. Tegu lizards are widely distributed in South America east of the Andes, and are popular in the international live animal trade. Two species are established in Florida (U.S.A.)-Salvator merianae (Argentine black and white tegu) and Tupinambis teguixin sensu lato (gold tegu)-and a third has been recorded there-S. rufescens (red tegu). We built species distribution models (SDMs) using 5 approaches (logistic regression, multivariate adaptive regression splines, boosted regression trees, random forest, and maximum entropy) based on data from the native ranges. We then projected these models to North America to develop hypotheses for potential tegu distributions. Our results suggest that much of the southern United States and northern México probably contains suitable habitat for one or more of these tegu species. Salvator rufescens had higher habitat suitability in semi-arid areas, whereas S. merianae and T. teguixin had higher habitat suitability in more mesic areas. We propose that Florida is not the only state where these taxa could become established, and that early detection and rapid response programs targeting tegu lizards in potentially suitable habitat elsewhere in North America could help prevent establishment and abate negative impacts on native ecosystems.Fil: Jarnevich, Catherine S.. U.s. Geological Survey; Estados UnidosFil: Hayes, Mark A.. Cherokee Nation Technologies; Estados UnidosFil: Fitzgerald, Lee A.. Department Of Wildlife And Fisheries Sciences; Estados UnidosFil: Yackel Adams, Amy A.. U.s. Geological Survey; Estados UnidosFil: Falk, Bryan G.. U.s. Geological Survey; Estados Unidos. National Park Service; Estados UnidosFil: Collier, Michelle A. M.. National Park Service; Estados Unidos. U.s. Geological Survey; Estados UnidosFil: Bonewell, Lea` R.. U.s. Geological Survey; Estados UnidosFil: Klug, Page E.. U.s. Geological Survey; Estados Unidos. U.S. Department of Agriculture APHIS, Wildlife Services, National Wildlife Research Center, North Dakota Field Station; Estados UnidosFil: Naretto, Sergio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Diversidad y Ecología Animal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto de Diversidad y Ecología Animal; ArgentinaFil: Reed, Robert N.. U.s. Geological Survey; Estados Unido

Ethnic differences in depression and anxiety among adults with atopic eczema: Population-based matched cohort studies within UK primary care.

BACKGROUND: Evidence demonstrates that individuals with atopic eczema (eczema) have increased depression and anxiety; however, the role of ethnicity in these associations is poorly understood. We aimed to investigate whether associations between eczema and depression or anxiety differed between adults from white and minority ethnic groups in the UK. METHODS: We used UK Clinical Practice Research Datalink GOLD to conduct matched cohort studies of adults (≥18 years) with ethnicity recorded in primary care electronic health records (April 2006-January 2020). We matched (age, sex, practice) adults with eczema to up to five adults without. We used stratified Cox regression with an interaction between eczema and ethnicity, to estimate hazard ratios (HRs) for associations between eczema and incident depression and anxiety in individuals from white ethnic groups and a pooled minority ethnic group (adults from Black, South Asian, Mixed and Other groups). RESULTS: We identified separate cohorts for depression (215,073 with eczema matched to 646,539 without) and anxiety (242,598 with eczema matched to 774,113 without). After adjusting for matching variables and potential confounders (age, sex, practice, deprivation, calendar period), we found strong evidence (p < 0.01) of ethnic differences in associations between eczema and depression (minority ethnic groups: HR = 1.33, 95% CI = 1.22,1.45; white ethnic groups: HR = 1.15, 95% CI = 1.12,1.17) and anxiety (minority ethnic groups: HR = 1.41, 95% CI = 1.28,1.55; white ethnic groups: HR = 1.17, 95% CI = 1.14,1.19). CONCLUSIONS: Adults with eczema from minority ethnic groups appear to be at increased depression and anxiety risk compared with their white counterparts. Culturally adapted mental health promotion and prevention strategies should be considered in individuals with eczema from minority ethnic groups

Risk factors for mental illness in adults with atopic eczema or psoriasis: protocol for a systematic review.

INTRODUCTION: Evidence indicates that people with the common inflammatory skin diseases atopic eczema or psoriasis are at increased risk of mental illness. However, the reasons for the relationship between skin disease and common mental disorders (ie, depression and anxiety) or severe mental illnesses (ie, schizophrenia, bipolar disorder and other psychoses) are unclear. Therefore, we aim to synthesise the available evidence regarding the risk factors for mental illness in adults with atopic eczema or psoriasis. METHODS AND ANALYSIS: We will conduct a systematic review of randomised controlled trials, cohort, case-control and cross-sectional studies. We will search the following databases from inception to March 2020: Medline, Embase, Global Health, Scopus, the Cochrane Library, Web of Science, Base, PsycInfo, the Global Resource of Eczema Trials, and the grey literature databases Open Grey, PsycExtra and the New York Academy of Medicine Grey Literature Report. We will also search the bibliographies of eligible studies and relevant systematic reviews to identify additional relevant studies. Citation searching of large summary papers will be used to further identify relevant publications. Two reviewers will initially review study titles and abstracts for eligibility, followed by full text screening. We will extract data using a standardised data extraction form. We will assess the risk of bias of included studies using the Quality in Prognosis Studies tool. We will synthesise data narratively, and if studies are sufficiently homogenous, we will consider a meta-analysis. We will assess the quality of the evidence using the Grading of Recommendations, Assessment, Development and Evaluation framework. ETHICS AND DISSEMINATION: Ethical approval is not required for a systematic review. Results of the review will be published in a peer-reviewed journal and disseminated through conferences. PROSPERO REGISTRATION NUMBER: CRD42020163941

Factors associated with depression, anxiety and severe mental illness among adults with atopic eczema or psoriasis: a systematic review and meta-analysis

BACKGROUND: Evidence suggests an association between atopic eczema (AE) or psoriasis and mental illness; however, the factors associated with mental illness are unclear. OBJECTIVES: To synthesize and evaluate all available evidence on factors associated with depression, anxiety and severe mental illness (SMI) among adults with AE or psoriasis. METHODS: We searched electronic databases, grey literature databases and clinical trial registries from inception to February 2022 for studies of adults with AE or psoriasis. Eligible studies included randomized controlled trials (RCTs), cohort, cross-sectional or case-control studies where effect estimates of factors associated with depression, anxiety or SMI were reported. We did not apply language or geographical restrictions. We assessed risk of bias using the Quality in Prognosis Studies tool. We synthesized results narratively, and if at least two studies were sufficiently homogeneous, we pooled effect estimates in a random effects meta-analysis. RESULTS: We included 21 studies (11 observational, 10 RCTs). No observational studies in AE fulfilled our eligibility criteria. Observational studies in people with psoriasis mostly investigated factors associated with depression or anxiety - one cross-sectional study investigated factors associated with schizophrenia. Pooled effect estimates suggest that female sex and psoriatic arthritis were associated with depression [female sex: odds ratio (OR) 1.62, 95% confidence interval (CI) 1.09-2.40, 95% prediction intervals (PIs) 0.62-4.23, I2 = 24.90%, τ2 = 0.05; psoriatic arthritis: OR 2.26, 95% CI 1.56-3.25, 95% PI 0.21-24.23, I2 = 0.00%, τ2 = 0.00] and anxiety (female sex: OR 2.59, 95% CI 1.32-5.07, 95% PI 0.00-3956.27, I2 = 61.90%, τ2 = 0.22; psoriatic arthritis: OR 1.98, 95% CI 1.33-2.94, I2 = 0.00%, τ2 = 0.00). Moderate/severe psoriasis was associated with anxiety (OR 1.14, 95% CI 1.05-1.25, I2 0.00%, τ2 = 0.00), but not depression. Evidence from RCTs suggested that adults with AE or psoriasis given placebo had higher depression and anxiety scores compared with comparators given targeted treatment (e.g. biologic agents). CONCLUSIONS: Our review highlights limited existing research on factors associated with depression, anxiety and SMI in adults with AE or psoriasis. Observational evidence on factors associated with depression or anxiety in people with psoriasis was conflicting or from single studies, but some identified factors were consistent with those in the general population. Evidence on factors associated with SMIs in people with AE or psoriasis was particularly limited. Evidence from RCTs suggested that AE and psoriasis treated with placebo was associated with higher depression and anxiety scores compared with skin disease treated with targeted therapy; however, follow-up was limited. Therefore, long-term effects on mental health are unclear