Specific and off-target immune responses following COVID-19 vaccination with ChAdOx1-S and BNT162b2 vaccines-an exploratory sub-study of the BRACE trial.

BACKGROUND: The COVID-19 pandemic led to the rapid development and deployment of several highly effective vaccines against SARS-CoV-2. Recent studies suggest that these vaccines may also have off-target effects on the immune system. We sought to determine and compare the off-target effects of the adenovirus vector ChAdOx1-S (Oxford-AstraZeneca) and modified mRNA BNT162b2 (Pfizer-BioNTech) vaccines on immune responses to unrelated pathogens. METHODS: Prospective sub-study within the BRACE trial. Blood samples were collected from 284 healthcare workers before and 28 days after ChAdOx1-S or BNT162b2 vaccination. SARS-CoV-2-specific antibodies were measured using ELISA, and whole blood cytokine responses to specific (SARS-CoV-2) and unrelated pathogen stimulation were measured by multiplex bead array. FINDINGS: Both vaccines induced robust SARS-CoV-2 specific antibody and cytokine responses. ChAdOx1-S vaccination increased cytokine responses to heat-killed (HK) Candida albicans and HK Staphylococcus aureus and decreased cytokine responses to HK Escherichia coli and BCG. BNT162b2 vaccination decreased cytokine response to HK E. coli and had variable effects on cytokine responses to BCG and resiquimod (R848). After the second vaccine dose, BNT162b2 recipients had greater specific and off-target cytokine responses than ChAdOx1-S recipients. INTERPRETATION: ChAdOx1-S and BNT162b2 vaccines alter cytokine responses to unrelated pathogens, indicative of potential off-target effects. The specific and off-target effects of these vaccines differ in their magnitude and breadth. The clinical relevance of these findings is uncertain and needs further study. FUNDING: Bill & Melinda Gates Foundation, National Health and Medical Research Council, Swiss National Science Foundation and the Melbourne Children's. BRACE trial funding is detailed in acknowledgements.

A systems immunology study comparing innate and adaptive immune responses in adults to COVID-19 mRNA and adenovirus vectored vaccines.

Identifying the molecular mechanisms that promote optimal immune responses to coronavirus disease 2019 (COVID-19) vaccination is critical for future rational vaccine design. Here, we longitudinally profile innate and adaptive immune responses in 102 adults after the first, second, and third doses of mRNA or adenovirus-vectored COVID-19 vaccines. Using a multi-omics approach, we identify key differences in the immune responses induced by ChAdOx1-S and BNT162b2 that correlate with antigen-specific antibody and T cell responses or vaccine reactogenicity. Unexpectedly, we observe that vaccination with ChAdOx1-S, but not BNT162b2, induces an adenoviral vector-specific memory response after the first dose, which correlates with the expression of proteins with roles in thrombosis with potential implications for thrombosis with thrombocytopenia syndrome (TTS), a rare but serious adverse event linked to adenovirus-vectored vaccines. The COVID-19 Vaccine Immune Responses Study thus represents a major resource that can be used to understand the immunogenicity and reactogenicity of these COVID-19 vaccines.

Reducing Inpatient Hypoglycemic Events: A Focus on Mealtime Insulin.

Quality Improvement Success Stories are published by the American Diabetes Association in collaboration with the American College of Physicians and the National Diabetes Education Program. This series is intended to highlight best practices and strategies from programs and clinics that have successfully improved the quality of care for people with diabetes or related conditions. Each article in the series is reviewed and follows a standard format developed by the editors of Clinical Diabetes. The following article describes an effort to reduce iatrogenic insulin-associated hypoglycemia at the University of Chicago Medical Center in Chicago, IL.

Screening for PTSD during pregnancy: a missed opportunity.

BACKGROUND: Prenatal posttraumatic stress disorder (PTSD) is often overlooked in obstetric care, despite evidence that untreated PTSD negatively impacts both mother and baby. OB-GYN clinics commonly screen for depression in pregnant patients; however, prenatal PTSD screening is rare. Although the lack of PTSD screening likely leaves a significant portion of pregnant patients with unaddressed mental health needs, the size of this care gap has not been previously investigated. METHODS: This retrospective chart review study included data from 1,402 adult, pregnant patients who completed PTSD (PTSD Checklist-2; PCL) and depression (Edinburgh Postnatal Depression Survey; EPDS) screenings during a routine prenatal care visit. Descriptive statistics identified screening rates for PTSD and depression, and logistic regression analyses identified demographic variables associated with screening outcomes and assessed whether screening results (+ PCL/ + EPDS, + PCL/-EPDS, -PCL/ + EPDS, -PCL/-EPDS) were associated with different provider intervention recommendations. RESULTS: 11.1% of participants screened positive for PTSD alone, 3.8% for depression alone, and 5.4% for both depression and PTSD. Black (OR = 2.24, 95% CI [1.41,3.54]) and Latinx (OR = 1.64, 95% CI [1.01,2.66]) patients were more likely to screen positive for PTSD compared to White patients, while those on public insurance were 1.64 times (95% CI [1.21,2.22]) more likely to screen positive compared to those with private insurance. Patients who screened positive for both depression and PTSD were most likely to receive referrals for behavioral health services (44.6%), followed by -PCL/ + EPDS (32.6%), + PCL/-EPDS (10.5%), and -PCL/-EPDS (3.6%). A similar pattern emerged for psychotropic medication prescriptions. CONCLUSIONS: Over ten percent of pregnant patients in the current study screened positive for PTSD without depression, highlighting a critical mental health need left unaddressed by current obstetric standards of care. Routine PTSD screening during prenatal care alongside strategies aimed at increasing referral resources and access to mental health services are recommended.

Immunisation with the BCG and DTPw vaccines induces different programs of trained immunity in mice.

In addition to providing pathogen-specific immunity, vaccines can also confer nonspecific effects (NSEs) on mortality and morbidity unrelated to the targeted disease. Immunisation with live vaccines, such as the BCG vaccine, has generally been associated with significantly reduced all-cause infant mortality. In contrast, some inactivated vaccines, such as the diphtheria, tetanus, whole-cell pertussis (DTPw) vaccine, have been controversially associated with increased all-cause mortality especially in female infants in high-mortality settings. The NSEs associated with BCG have been attributed, in part, to the induction of trained immunity, an epigenetic and metabolic reprograming of innate immune cells, increasing their responsiveness to subsequent microbial encounters. Whether non-live vaccines such as DTPw induce trained immunity is currently poorly understood. Here, we report that immunisation of mice with DTPw induced a unique program of trained immunity in comparison to BCG immunised mice. Altered monocyte and DC cytokine responses were evident in DTPw immunised mice even months after vaccination. Furthermore, splenic cDCs from DTPw immunised mice had altered chromatin accessibility at loci involved in immunity and metabolism, suggesting that these changes were epigenetically mediated. Interestingly, changing the order in which the BCG and DTPw vaccines were co-administered to mice altered subsequent trained immune responses. Given these differences in trained immunity, we also assessed whether administration of these vaccines altered susceptibility to sepsis in two different mouse models. Immunisation with either BCG or a DTPw-containing vaccine prior to the induction of sepsis did not significantly alter survival. Further studies are now needed to more fully investigate the potential consequences of DTPw induced trained immunity in different contexts and to assess whether other non-live vaccines also induce similar changes.

Communal mastery and associations with depressive and PTSD symptomatology among urban trauma-exposed women.

Objective: Racial and ethnic minority women from low-resource urban communities experience disproportionately high rates of trauma exposure. Higher rates of lifetime trauma exposure are strongly associated with subsequent psychological sequela, specifically depression and posttraumatic stress disorder (PTSD). Communal mastery is the ability to cope with challenges and achieve goals by being closely interconnected with friends, family, and significant others. Yet, it is unknown if communal mastery is protective specifically against PTSD and depressive symptoms. Method: Participants (N = 131) were Black and Latina women (88.5% Black, mean monthly income: < $750) recruited from an urban outpatient obstetric-gynecological clinic at an academic medical center. Participants completed an online questionnaire that assessed trauma history, PTSD and depressive symptoms, types of individualistic coping, social support, and communal mastery. Results: Hierarchical multiple regression models demonstrated that communal mastery is uniquely associated with fewer PTSD symptoms (ß = -.23, p = .003). More severe trauma history, more use of passive coping skills, and poorer social support were also significantly associated with PTSD symptoms, explaining over half of the variance in PTSD symptoms. Although significantly correlated, communal mastery was not uniquely associated with fewer depressive symptoms (ß = -.13, p = .201). Conclusions: These findings suggest that connectedness as assessed through communal mastery serves as an important shield against the effects of traumatic stress for Black and Latina women. Future research would benefit by exploring interventions that aim to increase communal mastery in order to help highly trauma-exposed racial and ethnic minority women in low-resource environments. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

The association between social support and posttraumatic stress symptoms among survivors of betrayal trauma: a meta-analysis.

Background: Betrayal traumas have a particularly deleterious effect on mental health. Although social support is a robust predictor of posttraumatic stress disorder (PTSD) symptom severity, it is not clear what factors may impact this relationship among betrayal trauma survivors. Objective: This study sought to describe the association between social support and PTSD symptom severity among survivors of betrayal trauma and examine whether methodological, sample, trauma, and social support characteristics moderated this association. Method: A comprehensive search identified 29 studies that assessed the cross-sectional association between PTSD symptom severity and social support among 6,510 adult betrayal trauma survivors. Results: The average effect size (r = -.25; 95% CI: -.30, -.20) was small to medium, with significant heterogeneity between studies (I2 = 71.86). The association between PTSD and social support was stronger when the trauma was perpetrated by a romantic partner compared to mixed perpetrators, even after accounting for covariates. There was also a significant effect of support type depending on whether the support was provided in the context of trauma disclosure. Specifically, positive reactions to trauma disclosure were not associated with PTSD symptoms whereas general positive social support (not disclosure focused) was associated with fewer PTSD symptoms. Negative reactions to trauma disclosure were associated with more PTSD symptoms. None of the included studies measured general negative social support outside of trauma disclosure. Conclusions: Our findings suggest that social support may be a particularly important buffer against PTSD symptoms when experiencing traumatic betrayal by an intimate partner. Additionally, our results suggest that social support interventions for those experiencing betrayal trauma should focus on reducing negative responses to disclosure and bolstering general satisfaction with social support.

Antecedentes: Los traumas de traición tienen un efecto particularmente perjudicial sobre la salud mental. Aunque el apoyo social es un fuerte predictor de la severidad de los síntomas del trastorno de estrés postraumático (TEPT), no está claro qué factores pueden afectar esta relación entre los sobrevivientes de traumas de traición.Objetivo: Este estudio buscó describir la asociación entre el apoyo social y la severidad de los síntomas del TEPT entre los sobrevivientes de trauma de traición y examinar si las características metodológicas, muestrales, de trauma y de apoyo social moderaron esta asociación.Método: Una búsqueda exhaustiva identificó 29 estudios que evaluaron la asociación transversal entre la gravedad de los síntomas de TEPT y el apoyo social entre 6.510 adultos sobrevivientes de trauma de traición.Resultados: El tamaño del efecto promedio (r = −.25; IC del 95%: −.30, −.20) fue de pequeño a mediano, con heterogeneidad significativa entre los estudios (I2 = 71.86). La asociación entre el TEPT y el apoyo social fue más fuerte cuando el trauma fue perpetrado por una pareja romántica en comparación con perpetradores mixtos, incluso después de tener en cuenta las covariables. También hubo un efecto significativo del tipo de apoyo dependiendo de si el apoyo se proporcionó en el contexto de la revelación del trauma. Específicamente, las reacciones positivas a la revelación del trauma no se asociaron con síntomas de TEPT, mientras que el apoyo social positivo general (no enfocado en la revelación) se asoció con menos síntomas de TEPT. Las reacciones negativas a la revelación del trauma se asociaron con más síntomas de TEPT. Ninguno de los estudios incluidos midió el apoyo social negativo general fuera de la revelación del trauma.Conclusiones: Nuestros hallazgos sugieren que el apoyo social puede ser un amortiguador particularmente importante contra los síntomas del TEPT cuando se experimenta una traición traumática por un compañero íntimo. Además, nuestros resultados sugieren que las intervenciones de apoyo social para quienes experimentan el trauma de traición deben centrarse en reducir las respuestas negativas a la revelación y reforzar la satisfacción general con el apoyo social.

Psychological Intervention and Treatment for Posttraumatic Stress Disorder During Pregnancy: A Systematic Review and Call to Action.

Posttraumatic stress disorder (PTSD) during pregnancy is a significant global mental health concern that affects up to 1 in 5 trauma-exposed pregnant women and is associated with an increased risk of adverse maternal and infant complications and health outcomes. This systematic literature review, conducted in accordance with PRISMA guidelines, examined findings from studies of psychological interventions and treatments for prenatal PTSD to inform recommendations for future research. Relevant evidence was identified from reference reviews and electronic databases (i.e., PubMed, Google Scholar, PsychInfo, and Scopus). Included studies reported on the effect of nonpharmacological intervention or treatment of PTSD symptomatology delivered during pregnancy, with at least one postintervention follow-up collected during pregnancy to assess prenatal treatment outcomes. The systematic review was augmented with a discussion of lower-level evidence. Of the 954 articles screened, six peer-reviewed, quantitative reports met the inclusion criteria and featured three empirically based interventions, including two randomized controlled trials: Two psychoeducation interventions for PTSD and one treatment study of interpersonal psychotherapy in trauma-exposed pregnant women. Effect sizes for PTSD symptom change ranged from small to large, Cohen's d/ηp 2 = 0.16-0.78. No studies examined evidence-based PTSD treatments (e.g., exposure therapy, cognitive processing therapy). A risk of bias assessment indicated variability in study quality. This review demonstrates that research on prenatal PTSD symptoms, diagnosis, and treatment is extremely limited despite a clear link between prenatal PTSD and perinatal complications. Early evidence supports further scientific inquiry into psychoeducation, psychotherapy treatments (e.g., exposure therapy), integrated prenatal care approaches, and community-based approaches.

Examining moderators of the relationship between social support and self-reported PTSD symptoms: A meta-analysis.

Social support is one of the most robust predictors of posttraumatic stress disorder (PTSD). Yet, little is known about factors that moderate the relationship between social support and PTSD symptom severity. This meta-analysis estimated the overall effect size of the relationship between self-reported social support and PTSD severity and tested meaningful demographic, social support, and trauma characteristics that may moderate this association using both cross-sectional and longitudinal effect sizes. A comprehensive search identified 139 studies with 145 independent cross-sectional effect sizes representing 62,803 individuals and 37 studies with 38 independent longitudinal effect sizes representing 25,792 individuals. Study samples had to comprise trauma-exposed, nonclinical adult populations to be included in the analysis. Cross-sectional and longitudinal analyses revealed a near medium overall effect size (rcross = -.27; 95% CI [-.30, -.24]; rlong = -.25; 95% CI [-.28, -.21]) with a high degree of heterogeneity (cross-sectional I2 = 91.6, longitudinal I2 = 86.5). Both cross-sectional and longitudinal moderator analyses revealed that study samples exposed to natural disasters had a weaker effect size than samples exposed to other trauma types (e.g., combat, interpersonal violence), studies measuring negative social reactions had a larger effect size than studies assessing other types of social support, and veteran samples revealed larger effect sizes than civilian samples. Several other methodological and substantive moderators emerged that revealed a complex relationship between social support and PTSD severity. These findings have important clinical implications for the types of social support interventions that could mitigate PTSD severity. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

The immunotoxicity, but not anti-tumor efficacy, of anti-CD40 and anti-CD137 immunotherapies is dependent on the gut microbiota.

Immune agonist antibodies (IAAs) are promising immunotherapies that target co-stimulatory receptors to induce potent anti-tumor immune responses, particularly when combined with checkpoint inhibitors. Unfortunately, their clinical translation is hampered by serious dose-limiting, immune-mediated toxicities, including high-grade and sometimes fatal liver damage, cytokine release syndrome (CRS), and colitis. We show that the immunotoxicity, induced by the IAAs anti-CD40 and anti-CD137, is dependent on the gut microbiota. Germ-free or antibiotic-treated mice have significantly reduced colitis, CRS, and liver damage following IAA treatment compared with conventional mice or germ-free mice recolonized via fecal microbiota transplant. MyD88 signaling is required for IAA-induced CRS and for anti-CD137-induced, but not anti-CD40-induced, liver damage. Importantly, antibiotic treatment does not impair IAA anti-tumor efficacy, alone or in combination with anti-PD1. Our results suggest that microbiota-targeted therapies could overcome the toxicity induced by IAAs without impairing their anti-tumor activity.

Self-reported PTSD symptoms and social support in U.S. military service members and veterans: a meta-analysis.

Background: The mental health burden of posttraumatic stress disorder (PTSD) is high in U.S. military samples. Social support is one of the most robust protective factors against PTSD and a recent meta-analysis indicates that this relationship is even stronger in military samples compared to civilian samples. Yet no meta-analyses have explored factors impacting this association in veterans and military service members (VSMs). Objective: The current meta-analysis examined demographic, social support, and military characteristics that may moderate the relationship of PTSD severity and social support among U.S. VSMs. Method: A search identified 37 cross-sectional studies, representing 38 unique samples with a total of 18,766 individuals. Results: The overall random effects estimate was -.33 (95% CI: -.38, -.27, Z = -10.19, p <.001), indicating that lower levels of social support were associated with more severe PTSD symptoms. PTSD measures based on the Diagnostic and Statistical Manual (DSM)-III had a larger effect size than measures based on DSM-IV or DSM-5. The social support source was a significant moderator such that support perceived from non-military sources was associated with a larger effect size than support perceived from military sources. This finding held after accounting for covariates. Deployment-era, timing of social support, and age were also significant moderators, but were no longer significantly associated with effect size after adjusting for covariates. Although previous meta-analyses have shown social negativity to be more impactful than positive forms of social support, there were too few studies conducted to evaluate social negativity in moderator analyses. Conclusion: Results suggest that social support received from civilians and in the home environment may play a greater protective role than social support received from military sources on long-term PTSD symptom severity. The literature on social support and PTSD in U.S. VSMs would be strengthened by studies examining the association of social negativity and PTSD symptoms.

Antecedentes: La carga en salud mental del trastorno de estrés post-traumático (TEPT) es alta en muestras militares estadounidenses. El apoyo social es uno de los factores protectores más robustos contra el TEPT, y un meta-análisis reciente indica que esta relación es incluso más fuerte en muestras militares comparada con muestras de civiles. Aunque, ningún meta-análisis ha explorado los factores que impactan esta asociación en veteranos y miembros militares en servicio (VMS).Objetivo: El presente meta-análisis examinó características demográficas, de apoyo social, y militares que puedan moderar la relación de severidad de TEPT y apoyo social en VMS estadounidenses.Método: Una búsqueda identificó 37 estudios transversales, representando 38 muestras únicas con un total de 18.766 individuos.Resultados: La estimación general de efectos aleatorios fue −.33 (95% CI: −.38, −.27, Z=−10.19, p<.001), indicando que niveles más bajos de apoyo social estaban asociados a mayor severidad de síntomas TEPT. Los instrumentos de TEPT basados en el Manual diagnóstico y estadístico de los trastornos mentales (DSM) ­III obtuvieron un tamaño de efecto mayor que los instrumentos basados en DSM-IV o DSM-5. La fuente de apoyo social fue un moderador significativo, de tal forma que el apoyo percibido de fuentes no militares estuvo asociado a un tamaño de efecto más grande que el percibido de fuentes militares. Este efecto se mantuvo luego de controlar covariables. La era de despliegue militar, temporalidad del apoyo social, y edad también fueron moderadores significativos, pero no se mantuvieron significativamente asociados al tamaño de efecto luego de controlar covariables. Aunque meta-análisis previos han demostrado que la negatividad social ha tenido más impacto que las formas positivas de apoyo social, existían muy pocos estudios como para evaluar negatividad social en un análisis de moderación.Conclusión: Los resultados sugieren que el apoyo social recibido de civiles y en el ambiente familiar puede tener un rol protector más relevante que el recibido de fuentes militares en la severidad de síntomas TEPT en el largo plazo. La literatura sobre apoyo social y TEPT en VMS estadounidenses se vería enriquecida por estudios que examinen la asociación de la negatividad social y síntomas TEPT.

Exposure therapy for PTSD during pregnancy: a feasibility, acceptability, and case series study of Narrative Exposure Therapy (NET).

BACKGROUND: Prenatal posttraumatic stress disorder (PTSD) is a significant complication of pregnancy linked to increased risk of adverse perinatal outcomes. Although 1 in 5 pregnant trauma-exposed individuals have PTSD, most PTSD treatment trials exclude participants who are pregnant, and none focus on treatment specifically during pregnancy. Moreover, access to mental health treatment is particularly challenging in low-resource settings with high rates of trauma. This study examined implementation of Narrative Exposure Therapy (NET), a short-term evidence-based PTSD treatment, in an urban prenatal care setting. Partial telehealth delivery was used to increase accessibility. Study aims were to examine (a) feasibility, (b) acceptability, and (c) case-based treatment outcomes associated with NET participation. METHOD: Eight pregnant participants (median age = 27, median gestational week in pregnancy = 22.5) received up to six sessions of NET with partial telehealth delivery. PTSD and depression symptoms were assessed at pre-treatment intake (T1), at each session (T2), and 1-week post-treatment (T3). A multiple case study approach was used to examine recruitment and engagement, retention, treatment completion, treatment barriers, use of telehealth, participants' experiences of treatment, and PTSD and depression symptoms. RESULTS: Nine of the 16 participants (56%) who were invited to participate engaged in treatment, and one dropped out after the first session. Eight participants completed the minimum "dose" of 4 NET sessions (N = 8/9, 89%). Seven participants gave the highest ratings of treatment acceptability. The most frequently reported barriers to treatment were competing priorities of work and caring for other children. Pre-post treatment symptom measures revealed clinically meaningful change in PTSD severity for nearly all participants (7/8, 88%). CONCLUSIONS: Results suggest that a brief exposure therapy PTSD treatment can be successfully implemented during pregnancy, suggesting promising results for conducting a larger-scale investigation. Trial registration ClinicalTrials.gov, NCT04525469. Registered 20 August 2020-Retrospectively registered, https://register.clinicaltrials.gov/prs/app/template/EditRecord.vm?epmode=View&listmode=Edit&uid=U00058T2&ts=3&sid=S000A59A&cx=-w1vnvn.

Assessing Trauma History in Pregnant Patients: A Didactic Module and Role-Play for Obstetrics and Gynecology Residents.

Introduction: Assessing and addressing patient histories of trauma constitute a critical component of care for vulnerable populations such as pregnant patients, yet they often go unrecognized in obstetric care. Obstetric providers may feel poorly equipped to address this issue comfortably and effectively. Methods: We designed this didactic module for obstetric residents with previous experience taking patient histories and delivering clinical care. The module was delivered with a faculty member and three additional facilitators with expertise in communication skills training. The session included 60 minutes of background information followed by a 15-minute presentation of a communication template for assessing trauma history. Using a practice case, residents had 45 minutes to practice in small groups, with the facilitators serving as the patient in the role-play. Results: In the 2015-2016 academic year, 21 obstetric residents participated in this module. All residents (100%) endorsed favorable beliefs regarding the importance of assessing trauma history and using trauma-informed care. On average, three-fourths (77%) demonstrated basic awareness of issues related to trauma in medical populations. Most residents (>85%) reported a high sense of efficacy in delivering trauma-informed care in some areas, while fewer (64%) reported efficacy specifically in educating patients about signs and symptoms of traumatic stress. Discussion: The module was well received overall, with participants indicating that clinical training in trauma-informed communication was needed to enhance their sense of efficacy in this area. This learning exercise provided training in a critical communication skill while highlighting areas for further development.

Utilizing an SBAR Workshop With Baccalaureate Nursing Students to Improve Communication Skills.

This study evaluated the effectiveness of the Situation-Background-Assessment-Recommendation (SBAR) technique to reduce anxiety and increase self-confidence levels regarding health care communication among undergraduate nursing students. Baccalaureate nursing students (n = 35) completed anxiety and self-confidence questionnaires before and after an SBAR communication workshop and subsequent simulation. A statistically significant increase in postintervention self-confidence scores was noted with no significant difference in anxiety levels. The findings support the use of SBAR as an organizing tool to promote nursing students' self-confidence during communication; however, further efforts are needed to qualitatively examine how this tool promotes these changes.

High mobility group box protein 1 neutralization therapy in ovine bacteremia: Lessons learned from an ovine septic shock model incorporating intensive care support.

Sepsis is a highly complex and often fatal syndrome which varies widely in its clinical manifestations, and therapies that target the underlying uncontrolled immune status in sepsis are needed. The failure of preclinical approaches to provide significant sepsis survival benefit in the clinic is often attributed to inappropriate animal disease models. It has been demonstrated that high mobility group box protein 1 (HMGB1) blockade can reduce inflammation, mortality and morbidity in experimental sepsis without promoting immunosuppression. Within this study, we explored the use of ovine anti-HMGB1 antibodies in a model of ovine septic shock incorporating intensive care supports (OSSICS). Results: Septic sheep exhibited elevated levels of HMGB1 within 12 h after the induction of sepsis. In this study, sepsis was induced in six anaesthetized adult Border Leicester × Merino ewes via intravenous instillation of E. coli and sheep monitored according to intensive care unit standard protocols for 26 h, with the requirement for noradrenaline as the primary endpoint. Septic sheep exhibited a hyperdynamic circulation, renal dysfunction, deranged coagulation profile and severe metabolic acidosis. Sheep were assigned a severity of illness score, which increased over time. While a therapeutic effect of intravenous anti-HMGB1 antibody could not be observed in this model due to limited animal numbers, a reduced bacterial dose induced a septic syndrome of much lower severity. With modifications including a reduced bacterial dose, a longer timeframe and broad spectrum antibiotics, the OSSICS model may become a robust tool for preclinical assessment of sepsis therapeutics.

Perceived lack of training moderates relationship between healthcare providers' personality and sense of efficacy in trauma-informed care.

Background and Objectives: Medical patients often have trauma histories that are not routinely assessed, which can adversely affect health outcomes. Despite growing awareness of this issue, there is limited understanding of factors that influence provider competency in trauma-informed care (TIC). The study examined healthcare providers' personality traits in relation to their sense of TIC efficacy, taking into account perceived barriers to TIC and professional quality of life. Study Design: The study used cross-sectional survey methods to examine our central hypothesis that provider personality traits and perceived barriers to TIC would be associated with TIC-efficacy, and to explore interactions among study variables. Methods: Survey data were collected from 172 healthcare providers examining TIC knowledge, TIC-efficacy, perceived barriers to TIC, personality traits, and professional quality of life. Results: TIC-efficacy was positively correlated with "intellectence/openness" and inversely correlated with "neuroticism" and perceived lack of training as a barrier. "Intellectence/openness" interacted with perceived lack of training to predict TIC-efficacy, suggesting that providers with lower "intellectence/openness" report greater TIC-efficacy when lack of training is not perceived as a barrier. Conclusions: Provider personality traits and perceived barriers to TIC appear related to providers' TIC-efficacy. Implications for overcoming barriers to TIC through training and implementation are discussed.

Skin Barrier and Autoimmunity-Mechanisms and Novel Therapeutic Approaches for Autoimmune Blistering Diseases of the Skin.

One of the most important functions of the skin besides regulating internal body temperature includes formation of the barrier between the organism and the external environment, hence protecting against pathogen invasion, chemical and physical assaults and unregulated loss of water and solutes. Disruption of the protective barrier is observed clinically in blisters and erosions of the skin that form in autoimmune blistering diseases where the body produces autoantibodies against structural proteins of the epidermis or the epidermal-dermal junction. Although there is no cure for autoimmune skin blistering diseases, immune suppressive therapies currently available offer opportunities for disease management. In cases where no treatment is sought, these disorders can lead to life threatening complications and current research efforts have focused on developing therapies that target autoantibodies which contribute to disease symptoms. This review will outline the involvement of the skin barrier in main skin-specific autoimmune blistering diseases by describing the mechanisms underpinning skin autoimmunity and review current progress in development of novel therapeutic approaches targeting the underlying causes of autoimmune skin blistering diseases.

Factors associated with women's desire for control of healthcare during childbirth: Psychometric analysis and construct validation.

The desire for control of healthcare is a significant moderator of outcomes related to childbirth. Researchers have shown that a sense of control of healthcare during childbirth is strongly correlated with postpartum maternal well-being. The aims of this study were to examine (a) the psychometric characteristics of an instrument to assess women's desire for control of healthcare during childbirth, and (b) examine desire for control in relation to parity, medical complications of pregnancy, and women's choices of childbirth providers and setting. The study design was cross-sectional using two different samples totaling 385 pregnant women. In Sample 1, (n = 193) we conducted an exploratory factor analysis to reduce the initial item pool. In Sample 2, (n = 192) we conducted a confirmatory factor analysis (CFA) of the final 12-item instrument and examined factors related to the desire for control. Results of the analysis in Sample 1 were supportive of a single-factor structure reflecting women's desire to influence the childbirth healthcare environment and decision-making. The final 12-item instrument had high internal consistency reliability (Cronbach's alpha = 0.93). CFA in Sample 2 was supportive of the single-factor structure with good model fit. The desire for control was directly correlated with an internal locus of control. Nulliparous women reported a lower desire for control compared with multiparous women. The desire for control among women with self-reported medical complications of pregnancy was comparable to that among women without pregnancy complications. The desire for control was a predictor of choosing midwives (vs. obstetricians), home or birth center (vs. hospitals), and professional labor support (e.g., doulas). Implications for future research on the impact of desire for control on maternal health outcomes are discussed.