Recommendations for Clinicians to Combat Environmental Disparities in Pediatric Asthma: A Review.

TOPIC IMPORTANCE: Asthma is a common and complex lung disease in children, with disproportionally higher prevalence and related adverse outcomes among children in racial and ethnic minority groups, and of lower socioeconomic position. Environmental factors, including unhealthy housing and school-based exposures can contribute to increased asthma morbidity and widening disparities. This underscores a significant environmental justice issue and suggests the need for clinical interventions to reduce sources of environmental exposures and ultimately diminish the observed disparities in childhood asthma. REVIEW FINDINGS: Unhealthy housing conditions, including secondhand tobacco smoke, allergen exposure, and indoor air pollution can exacerbate asthma symptoms in children. While unhealthy housing can occur anywhere, such situations most frequently occur in urban, low-income environments where renting is common. To reduce environmental triggers, clinicians can recommend smoking cessation, cleaning techniques to mitigate exposure, and even directly contact landlords to address poor housing conditions. Children spend much of their time in schools, where this built environment is also a source of asthma triggers such as poor ventilation and allergens such as mold and pests, and chemicals. As such, a multidisciplinary approach is needed to adequately address the burden of childhood asthma to equitably reduce disparities to both harmful exposures and negative health outcomes. SUMMARY: Racial, ethnic, and socioeconomic disparities exist in asthma morbidity in children, and such disparities are driven in part by environmental factors at the housing and school level. Clinicians can make evidence-based recommendations to drive effective exposure reduction strategies to mitigate asthma morbidity and reduce observed disparities.

Effectiveness of residential treatment services for veterans with substance use disorders: A propensity score matching evaluation.

BACKGROUND: Prior reviews of substance use disorder (SUD) treatment have found mixed support for residential level of care but are limited by methodology problems and the ethical concerns of randomizing patients with severe SUD to lower levels of care. METHODS: The present study is the first to use a large archival SUD residential sample with a matched comparison group and one-year follow-up period to examine the benefits of residential treatment provided to adults clinically assessed as warranting SUD residential care. We used propensity score matching in our sample (N = 6177) of veterans with a SUD who were screened and accepted for Veterans Affairs (VA) SUD residential treatment between January 1st, 2019 and June 30th, 2019. RESULTS: We found evidence that VA SUD residential treatment saves veteran lives with an average 66% all-cause mortality risk reduction during the study period (b = -1.09, exp(b) = 0.34, p <0.001). Medium-to-large residential pre- to post-treatment self-reported mental health and SUD symptom improvements (|SMDrobust| = 0.54-0.93) were sustained by one-year post-screening. These residential treatment improvements were significantly larger than estimated counterfactual outcomes across self-reported SUD and stress disorder symptoms at one-year post-screening (ps <0.001). We found mixed behavioral, service utilization, and other self-reported mental health outcomes. CONCLUSIONS: We conclude that VA SUD residential treatment is an effective level of care for veterans warranting residential care particularly for SUD symptom improvements and reductions in mortality risk.

Induction of antigen specific intrahepatic CD8+ T cell responses by a secreted heat shock protein based gp96-Ig-PfCA malaria vaccine.

Introduction: A highly efficacious and durable vaccine against malaria is an essential tool for global malaria eradication. One of the promising strategies to develop such a vaccine is to induce robust CD8+ T cell mediated immunity against malaria liver-stage parasites. Methods: Here we describe a novel malaria vaccine platform based on a secreted form of the heat shock protein, gp96-immunoglobulin, (gp96-Ig) to induce malaria antigen specific, memory CD8+ T cells. Gp96-Ig acts as an adjuvant to activate antigen presenting cells (APCs) and chaperone peptides/antigens to APCs for cross presentation to CD8+ T cells. Results: Our study shows that vaccination of mice and rhesus monkeys with HEK-293 cells transfected with gp96-Ig and two well-known Plasmodium falciparum CSP and AMA1 (PfCA) vaccine candidate antigens, induces liver-infiltrating, antigen specific, memory CD8+ T cell responses. The majority of the intrahepatic CSP and AMA1 specific CD8+ T cells expressed CD69 and CXCR3, the hallmark of tissue resident memory T cells (Trm). Also, we found intrahepatic, antigen-specific memory CD8+ T cells secreting IL-2, which is relevant for maintenance of effective memory responses in the liver. Discussion: Our novel gp96-Ig malaria vaccine strategy represents a unique approach to induce liver-homing, antigen-specific CD8+ T cells critical for Plasmodium liver-stage protection.

Understanding veteran barriers to specialty outpatient PTSD clinical care.

OBJECTIVE: Veterans seeking treatment for posttraumatic stress disorder (PTSD) commonly report general and veteran-specific barriers to treatment such as stigma and challenges with navigating the Veterans Health Affairs (VHA) system. This study aimed to characterize barriers endorsed by a national sample of veterans seeking care in VHA PTSD specialty outpatient clinics, as well as to examine the impact of demographics on endorsed barriers. METHODS: This study included 17,069 veterans referred to PTSD specialty outpatient clinics in the VHA during Fiscal Year 2019. Barriers to care, demographics, clinical concerns, and PTSD symptom severity (PCL-5) were assessed at intake. RESULTS: Veterans (mean age=47.6 years, 83.3% male) endorsed an average of 2.39 barriers. The most commonly endorsed barriers included difficulty interacting with others (37.9%), difficulty being in public (33.8%), work (30.3%), concern for finances (20%), and difficulty getting out of bed (19.5%). A significant minority of veterans (22%) endorsed no barriers. Male sex (23.1%) and White race (23.6%) were associated with a greater likelihood of reporting no barriers. CONCLUSIONS: These findings indicate the need for a comprehensive approach to addressing multi-faceted barriers for veterans seeking treatment in PTSD specialty clinics. Findings also highlight the potential importance of tailoring strategies to reduce barriers based on demographic and clinical characteristics such as race, sex, and degree of avoidance. Future research should seek to longitudinally examine the impact of barriers on treatment engagement.

Measurement-based care in Veterans Health Administration mental health residential treatment.

In 2016, the Veterans Health Administration (VHA) launched the Measurement-Based Care (MBC) in Mental Health Initiative to support the use of patient-reported outcome measures (PROMs) across mental health services to increase veteran engagement and promote collaborative treatment planning. The present study reported on the administrations of PROMs across all residential stays within the VHA's Mental Health Residential Rehabilitation Treatment Programs between October 1, 2018, and September 30, 2019 (N = 29,111). We subsequently explored a subsample of veterans attending substance use residential treatment during the same period who completed the Brief Addiction Monitor-Revised (BAM-R; Cacciola et al., 2013) at admission and discharge (n = 2,886) to determine the feasibility of using MBC data for program evaluation. The rate of residential stays with at least one PROM was 84.49%. We also identified moderate to large treatment effects on the BAM-R from admission to discharge (Robust Cohen's d = .76-1.60). There is frequent use of PROMs in VHA mental health residential treatment programs with exploratory analyses demonstrating significant improvements for veterans in substance use disorder residential treatment. Considerations for the appropriate use of PROMs in the context of MBC are discussed. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Comparing carotid endarterectomies with or without shunting in symptomatic and asymptomatic patients.

BACKGROUND: Recent research shows that placement of an intraluminal shunt during a carotid endarterectomy (CEA) can be associated with postoperative complications. Therefore, we compared CEA operations with or without shunting to further analyze their clinical outcomes. METHODS: From the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database, 13,736 cases between 2016 and 2019 were analyzed to compare adult symptomatic and asymptomatic carotid stenosis patients who underwent a CEA operation, with or without shunt placement. RESULTS: Rates of stroke with a neurological deficit (p = 0.012), myocardial infarction (p = 0.021), and urinary tract infection (p = 0.030) were higher among symptomatic patients with shunting. Multivariate logistic regression revealed that risk of CNI was higher among both symptomatic (93.63%, p < 0.001) and asymptomatic (69.58%, p = 0.001) patients with shunting, irrespective of confounding variables. CONCLUSION: Shunting was found to be associated with higher rates of postoperative complications in both symptomatic and asymptomatic patient populations.

Suicide Intervention Practices: What Is Being Used by Mental Health Clinicians and Mental Health Allies?

OBJECTIVE: Implementation of evidence-based suicide prevention is critical to prevent death by suicide. Contrary to previously held beliefs, interventions including contracting for safety, no-harm contracts, and no-suicide contracts are not best practices and are considered contraindicated. Little is known about the current use of best practices and contraindicated interventions for suicide prevention in community settings. METHODS: Data were collected from 771 individuals enrolled in a suicide prevention training. Both mental health clinicians (n = 613) and mental health allies (e.g., teachers, first responders) (n = 158) reported which best practices (i.e., safety plan, crisis response plan) and contraindicated interventions (i.e., contracting for safety, no-harm contract, no-suicide contract) they use with individuals who presents with risk for suicide. RESULTS: The majority of both mental health clinicians (89.7%) and mental health allies (67.1%) endorsed using at least one evidence-based practice. However, of those who endorsed using evidence-based interventions, ∼40% of both mental health clinicians and allies endorsed using contraindicated interventions as well. CONCLUSION: Contraindicated interventions are being used at high rates and suicide prevention trainings for evidence-based interventions should include a focus on de-implementation of contraindicated interventions. This study examined only a snapshot of what clinicians and allies endorsed using. Additional in depth information about each intervention and when it is used would provide helpful information and should be considered in future studies. Future research is needed to ensure only evidence-based interventions are being used to help prevent death by suicide.Highlights:The majority of both mental health clinicians and mental health allies use evidence-based practices for suicide prevention. This indicates good implementation rates of evidence-based interventions for suicide prevention.Approximately 40% of both mental health clinicians and mental health allies who endorsed using evidence-based practices for suicide preventions also endorsed using contraindicated interventions.A focus on de-implementation of contraindicated suicide interventions is warranted and should be part of the focus on suicide prevention efforts.

Comparative effectiveness of group v. individual trauma-focused treatment for posttraumatic stress disorder in veterans.

BACKGROUND: Cognitive processing therapy (CPT) and prolonged exposure (PE) delivered in an individual setting are efficacious and effective treatments for veterans with posttraumatic stress disorder (PTSD). Group CPT has been shown to be less efficacious than individual CPT, however, evidence regarding real-world effectiveness is limited. METHODS: We conducted a retrospective, observational, comparative effectiveness study including veterans that received at least eight sessions of group CPT, individual CPT, or individual PE, and were discharged from PTSD residential treatment at the Department of Veterans Affairs between 1 October 2015, and 30 September 2020. PTSD symptom severity was assessed with the PTSD Checklist for DSM-5 (PCL-5) and treatments delivered in a group (CPT) or individual (CPT or PE) setting were compared at discharge and 4-month post-discharge follow-up. RESULTS: Of 6735 veterans, 3888 [653 women (17%), median (IQR) age 45 (35-55) years] received individual and 2847 [206 women (7.2%), median (IQR) age 42 (34-54)] received group therapy. At discharge, improvement in PTSD severity was statistically greater among those treated individually (mean difference on the PCL-5, 2.55 (95% CI 1.61-3.49); p = <0.001]. However, the difference was smaller than the minimal clinically important difference of 7.9 points. The groups did not differ significantly at 4-month follow-up [mean difference on the PCL-5, 0.37 (95% CI -0.86 to 1.60); p = 0.551]. CONCLUSION: Group CPT was associated with a slightly smaller reduction of PTSD symptom severity than individual CPT or PE in veterans at the end of residential treatment. There were no differences at 4-month follow-up.

Blood cadmium, lead, manganese, mercury, and selenium levels in American Indian populations: The Strong Heart Study.

BACKGROUND: Many American Indian (AI) communities are in areas affected by environmental contamination, such as toxic metals. However, studies assessing exposures in AI communities are limited. We measured blood metals in AI communities to assess historical exposure and identify participant characteristics associated with these levels in the Strong Heart Study (SHS) cohort. METHOD: Archived blood specimens collected from participants (n = 2014, all participants were 50 years of age and older) in Arizona, Oklahoma, and North and South Dakota during SHS Phase-III (1998-1999) were analyzed for cadmium, lead, manganese, mercury, and selenium using inductively coupled plasma triple quadrupole mass spectrometry. We conducted descriptive analyses for the entire cohort and stratified by selected subgroups, including selected demographics, health behaviors, income, waist circumference, and body mass index. Bivariate associations were conducted to examine associations between blood metal levels and selected socio-demographic and behavioral covariates. Finally, multivariate regression models were used to assess the best model fit that predicted blood metal levels. FINDINGS: All elements were detected in 100% of study participants, with the exception of mercury (detected in 73% of participants). The SHS population had higher levels of blood cadmium and manganese than the general U.S. population 50 years and older. The median blood mercury in the SHS cohort was at about 30% of the U.S. reference population, potentially due to low fish consumption. Participants in North Dakota and South Dakota had the highest blood cadmium, lead, manganese, and selenium, and the lowest total mercury levels, even after adjusting for covariates. In addition, each of the blood metals was associated with selected demographic, behavioral, income, and/or weight-related factors in multivariate models. These findings will help guide the tribes to develop education, outreach, and strategies to reduce harmful exposures and increase beneficial nutrient intake in these AI communities.

Subjective distress, self-harm, and suicidal ideation or behavior throughout trauma-focused cognitive-behavioral therapy in transitional age youth.

OBJECTIVE: Elevations in distress, self-harm, and suicidal ideation or behavior are of significant concern in clinical practice. We examined these in a pilot trial of Trauma Focused-Cognitive Behavioral Therapy (TF-CBT) for transitional age youth (aged 15-25 years) with histories of interpersonal trauma and symptoms of posttraumatic stress disorder. METHOD: Participants were 20 young people (13 females, M = 19.5 years) from a pilot study of TF-CBT. Frequencies of elevated distress, self-harm, and suicidal ideation or behavior were measured throughout treatment sessions and across the treatment phases of TF-CBT. RESULTS: Across the 279 sessions of TF-CBT (m = 15.5 sessions), there were 16 incidents of elevated distress in seven participants (i.e., six in Phase I and five each in Phases II and III); 15 incidents of self-harming behavior in seven participants (five incidents in each of the three phases) and one incident of both elevated distress and suicide ideation (Phase I). CONCLUSION: Findings indicate that there may be a relationship between the experience of in session distress and self-harming behaviors. The importance of safety planning and coping skills (acquired in Phase 1) is stressed to ensure the effective implementation of TF-CBT. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Addressing co-occurring suicidal thoughts and behaviors and posttraumatic stress disorder in evidence-based psychotherapies for adults: A systematic review.

Posttraumatic stress disorder (PTSD) is a well-established risk factor for suicidal thoughts and behaviors. Historically, guidelines for treating PTSD have recommended against the use of trauma-focused therapies for patients who are at high risk for suicide, likely due to concerns about potential suicide-related iatrogenesis, specifically the "triggering" of suicidal behaviors. This systematic review examined evidence of the impact of treatments specifically designed to treat PTSD or suicide on both PTSD- and suicide-related outcomes. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed, and a total of 33 articles met the full inclusion criteria: 23 examining PTSD treatments, four examining suicide-focused treatments, and six examining combined treatments. PTSD and combined treatments reduced both PTSD- and suicide-related outcomes, with most studies focusing on cognitive processing therapy or prolonged exposure. Suicide-focused treatments (e.g., cognitive therapies for suicide prevention) also reduced suicide-related outcomes, but the findings were mixed for their impact on PTSD-related outcomes. Overall, PTSD treatments had the most support, primarily due to a larger number of studies examining their outcomes. This supports current clinical guidelines, which suggest utilizing PTSD treatments for individuals who have PTSD and are at risk for suicide. Suicide-focused and combined treatments also appeared to be promising formats, although additional research is needed. Future research should seek to compare the effectiveness of the approaches to the treatment of PTSD and suicidal thoughts and behaviors concurrently as well as to inform guidelines aimed at supporting decisions about the selection of an appropriate treatment approach.

Gestational triclosan exposure and infant birth weight: A systematic review and meta-analysis.

BACKGROUND: Exposure to triclosan, an antimicrobial chemical used in some personal care and cleaning products, has been associated with reduced birth weight in some, but not all epidemiological studies. OBJECTIVES: We conducted a systematic review and meta-analysis to characterize the relation of gestational triclosan exposure with infant birth weight and identify sources of heterogeneity between studies. METHODS: We identified original studies measuring urinary triclosan concentrations during pregnancy and reporting their association with infant birth weight, gestational age (GA) adjusted birth weight (g), or GA-standardized birth weight z-scores. Using a random effects model, we estimated differences in these outcomes per 10-fold increase in triclosan concentrations and considered triclosan levels and infant sex as sources of heterogeneity. Using Navigation Guide Methods, we evaluated risk of bias within individual studies and across the body of evidence. RESULTS: Among thirteen studies, median triclosan concentrations varied by almost 2-orders of magnitude (0.6-29 ng/mL), with higher concentrations in North American and some European studies compared to Asian ones. Associations between triclosan and birth weight (ß:-20 g; 95% CI:-65, 26; n = 6) were stronger than those for GA-adjusted birth weight (ß:-12 g; 95% CI:-29, 5; n = 9). Triclosan was not associated with GA-standardized birth weight z-scores (ß:-0.04; 95% CI:-0.16, 0.07; n = 5). The association between triclosan and GA-adjusted birth weight was stronger in studies with median triclosan values ≥10 ng/mL compared to studies with median values < 10 ng/mL (ß:-27 g; 95% CI:-61, 7; n = 4 vs. ß:6g; 95% CI:-20, 31; n = 5). With a limited number of studies, we observed suggestive evidence that inverse associations were more apparent in studies with ≥ 2 prospective triclosan measures compared to those with one measure. DISCUSSION: Available evidence, with "low" risk of bias, provides limited evidence that triclosan exposure and reduces infant birth weight. We observed stronger inverse associations between triclosan concentrations and birth weight in populations with higher triclosan exposure.

The protective role of reasons for living on suicidal cognitions for military affiliated individuals with a positive PTSD screen in primary care settings.

BACKGROUND: Identifying and enhancing protective beliefs is essential in reducing suicide risk among military-affiliated individuals. The goal of this study was to examine if specific reasons for living impact the relationship between PTSD and suicidal cognitions among military-affiliated individuals in primary care settings. METHODS: Participants included 2,685 U.S. military personnel and their adult beneficiaries recruited from primary care clinics. Participants completed the Primary Care Posttraumatic Stress Disorder Screen, Suicide Cognitions Scale, and Brief Reasons for Living Inventory. RESULTS: Responsibility to family and survival and coping beliefs-were related to suicidal cognitions with higher levels associated with less suicidal cognitions and a weaker relationship between PTSD and suicidal cognitions. By contrast, fear of suicide and fear of social disapproval were associated with more suicidal cognitions, and the link between positive PTSD screen and suicidal cognitions was stronger for individuals with higher levels of fear of social disapproval. Moral objection did not predict suicidal cognitions and did not moderate the relationship between PTSD and suicidal cognitions. LIMITATIONS: The limitations of the study include that measures were done in primary care and brief screeners were often used. Additionally, the study is cross-sectional in nature, whereas some of the symptoms and outcome variables likely fluctuate over time. CONCLUSIONS: Findings suggest not all reasons for living are not equally influential and, among military-affiliated individuals with a positive PTSD screen, bolstering reasons for living related to responsibility to family and survival and coping skills could be particularly impactful in reducing suicide cognitions.

Gender-based violence and suicidal ideation among Indian women from slums: An examination of direct and indirect effects of depression, anxiety, and PTSD symptoms.

OBJECTIVE: India accounts for 36.6% of suicide-related deaths among women worldwide. One social determinant of suicide in India is gender-based violence (GBV), and it disproportionately affects women from poorer socioeconomic classes. Although Indian women from slums are at high risk of GBV, the direct and indirect relationships between types of GBV and suicidal ideation (SI) for Indian women remain unexplored. This study examined: (a) the direct associations between types of GBV and SI and (b) indirect associations between GBV and risk for SI through depression, anxiety, and posttraumatic stress disorder (PTSD) symptoms. METHOD: Trauma-exposed Indian women were recruited (N = 112); 98 completed a trauma screen, PHQ-9, GAD-7, and PCL-5 in Hindi. Traumatic events were categorized as GBV overlapping with Criterion A trauma (CA-GBV), emotional/economic GBV without Criterion A (E-GBV), and Criterion A without GBV (CA). The relation between trauma types and SI was examined through the indirect role of depression, anxiety, and PTSD symptoms. RESULTS: Logistic regression analyses revealed that CA-GBV was associated with higher odds of SI than other trauma types. This relationship was explained through the indirect role of depression symptom severity after accounting for other trauma types, anxiety, and PTSD symptoms. CONCLUSION: Results align with research showing that CA-GBV is particularly pernicious and affects SI. While anxiety and PTSD symptoms are related to CA-GBV, results suggest the relative importance of depression severity in the relation between CA-GBV and SI. Screening for SI among GBV survivors and treating depression symptoms may reduce the risk of suicide. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Music Therapy for Anxiety and Pain After Spinal Cord Injury: A Pilot Study.

BACKGROUND: Music therapy (MT) programs have been used in various health care settings to reduce patients' pain, anxiety, and stress. However, few studies have investigated its effects on patients with spinal cord injury (SCI), a frequently serious event requiring extensive rehabilitation. OBJECTIVE: This pilot study evaluated the feasibility of offering music-assisted relaxation (MAR) during rehabilitation for patients with SCI. We also measured the effect of MAR on the patients' pain, anxiety, and stress levels. METHODS: Patients were hospitalized at Mayo Clinic (Rochester, Minnesota) from September 2015 through September 2017 for rehabilitation of an SCI. Eligible patients received 2, 20-minute, personalized MAR sessions. Interventions were facilitated by a board-certified music therapist (MT-BC) and included diaphragmatic breathing, guided imagery, and passive muscle relaxation with live guitar accompaniment and spoken, improvised, or singing voice. Two surveys (Generalized Anxiety Disorder [GAD-7] and Perceived Stress Scale [PSS-10]) were used at the time of study consent and again upon hospital dismissal. Pain, anxiety, and relaxation were assessed before and after both MT sessions with visual analog scales (VASs), scored from 0 to 10. Participants completed a 7-question satisfaction survey after the second MAR session. RESULTS: Twenty patients were enrolled (12 men, 8 women); 13 (65%) completed the MAR interventions. The mean (SD) age was 53.7 (17.7) years. VAS scores for pain significantly improved after both sessions (P ≤ .02). VAS scores for anxiety also significantly improved after both sessions (P ≤ .02), as did VAS scores for relaxation (P ≤ .02 for both). The satisfaction survey indicated that patients generally believed that they benefited from MT. Rehabilitation staff indicated that MT did not interfere with routine clinical care. CONCLUSION: MT with live MAR is a feasible treatment for patients with SCI and may be effective for reducing their pain and anxiety.

Using Machine Learning to Predict Suicide Attempts in Military Personnel.

Identifying predictors of suicide attempts is critical in intervention and prevention efforts, yet finding predictors has proven difficult due to the low base rate and underpowered statistical approaches. The objective of the current study was to use machine learning to examine predictors of suicidal behaviors among high-risk suicidal Soldiers who received outpatient mental health services in a randomized controlled trial of Brief Cognitive Behavioral Therapy for Suicide Prevention (BCBT) compared to treatment as usual (TAU). Self-report measures of clinical and demographic variables, administered prior to the start of outpatient treatment to 152 participants with recent suicidal thoughts and/or behaviors were analyzed using machine learning software to identify the best combination of variables for predicting suicide attempts during or after treatment. Worst-point suicidal ideation, history of multiple suicide attempts, treatment group (i.e., BCBT or TAU), suicidogenic cognitions, and male sex were found, in combination, correctly classified 30.8% of patients who attempted suicide during the two-year follow-up period. This combination has higher sensitivity than many models that have previously been used to predict suicidal behavior. Overall, this study provides a combination of variables that can be assessed clinical to help identify high-risk suicidal individuals.

Novel malaria antigen Plasmodium yoelii E140 induces antibody-mediated sterile protection in mice against malaria challenge.

Only a small fraction of the antigens expressed by malaria parasites have been evaluated as vaccine candidates. A successful malaria subunit vaccine will likely require multiple antigenic targets to achieve broad protection with high protective efficacy. Here we describe protective efficacy of a novel antigen, Plasmodium yoelii (Py) E140 (PyE140), evaluated against P. yoelii challenge of mice. Vaccines targeting PyE140 reproducibly induced up to 100% sterile protection in both inbred and outbred murine challenge models. Although PyE140 immunization induced high frequency and multifunctional CD8+ T cell responses, as well as CD4+ T cell responses, protection was mediated by PyE140 antibodies acting against blood stage parasites. Protection in mice was long-lasting with up to 100% sterile protection at twelve weeks post-immunization and durable high titer anti-PyE140 antibodies. The E140 antigen is expressed in all Plasmodium species, is highly conserved in both P. falciparum lab-adapted strains and endemic circulating parasites, and is thus a promising lead vaccine candidate for future evaluation against human malaria parasite species.

Combination of CHEK1/2 inhibition and ionizing radiation results in abscopal tumor response through increased micronuclei formation.

We explore a novel strategy of activating immune signaling through increased micronuclei formation utilizing a cell cycle checkpoint inhibitor to drive cell cycle progression following ionizing radiation. The Chk1/2 inhibitor AZD7762 is used to abrogate radiation therapy (RT)-induced G2/M cell cycle arrest in multiple cell lines and, we find that this therapeutic combination promotes increased micronuclei formation in vitro and subsequently drives increased type I interferon signaling and cytotoxic T-cell activation. In vivo studies using B16-F10 melanoma cancer cells implanted in C57/BL6 mice demonstrate improved rates of tumor control at the abscopal (unirradiated) site, located outside of the radiation field, only in the AZD7762 + RT group, with a corresponding reduction in mean tumor volume, increase in the CD8 T-cell population, and immune activated gene signaling. Our results demonstrate that targeted inhibition of cell cycle checkpoint activation following ionizing radiation drives increased production of immunogenic micronuclei, leading to systemic tumor response with potential future clinical benefit.

Sex Differences in Associations Between Depression and Posttraumatic Stress Disorder Symptoms and Tobacco Use Among Veterans of Recent Conflicts.

Background: Rates of tobacco use, posttraumatic stress disorder (PTSD), and depression are higher for veterans compared to their civilian counterparts. Female veterans have high rates of tobacco use and mental health (MH) conditions; however, little is known about sex differences in the association of depression and PTSD symptoms with postdeployment tobacco use. Methods: Cross-sectional associations and binary logistic regression models were conducted using baseline interview data from the Survey of Experiences of Returning Veterans sample (850 recently returned veterans; 352 women; age mean [standard deviation, SD] = 35.63 [8.94]; 71.2% white). Results: Men were more likely to be tobacco users (39.8% vs. 23.6%; chi square = 24.40; p < 0.001) and had higher postdeployment PTSD symptoms (men mean [SD] = 48.62 [17.93], women mean [SD] = 45.95 [18.22], t = -2.12, p < 0.05), but had similar rates of depression compared to women. In binary logistic models, sex, depression, and PTSD symptoms showed significant main effects in the prediction of postdeployment tobacco use, over and above the effects of demographics, military variables, and alcohol use. Sex moderated the association between PTSD symptoms and tobacco use, such that PTSD symptoms predicted tobacco use for women, but not for men. Sex did not moderate the association between depression and tobacco use. Conclusions: Given the divergent predictors of postdeployment tobacco use for male and female veterans, there may be sex-specific barriers to tobacco-use cessation, including factors related to MH conditions such as PTSD. Further examination of sex differences can help to identify tailored intervention strategies.