Search

BackgroundTraumatic brain injury (TBI) is a major public health problem that may be associated with numerous behavioral problems, including impulsivity, aggression and violence. Rates of self-reported TBI are high within offender populations, but the extent to which TBI is causally implicated in causing illegal behavior is unclear. This study examined the psychological and functional correlates of histories of traumatic brain injury in a sample of impulsive violent offenders.MethodsStudy participants, all men, had been recruited to participate in a randomized controlled trial of sertraline to reduce recidivism. Study entry criteria were an age of at least 18 years, a documented history of two or more violent offenses and a score of 70 or above on the Barratt Impulsiveness Scale. An extensive list of standardized questionnaires was administered to obtain information on previous TBI and other neuropsychiatric conditions or symptoms.ResultsIn the sample of 693 men, 66% were aged between 18 and 35 years old, and 55% gave a history of TBI (“TBI+”). Overall, 55% of study participants reported at least one TBI. High levels of neuropsychiatric symptomatology were reported. In 75% of TBI+ individuals, their most severe TBI (by self-report) was associated with loss of consciousness (LOC)

A common limitation of neuroimaging studies is their small sample sizes. To overcome this hurdle, the Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) Consortium combines neuroimaging data from many institutions worldwide. However, this introduces heterogeneity due to different scanning devices and sequences. ENIGMA projects commonly address this heterogeneity with random-effects meta-analysis or mixed-effects mega-analysis. Here we tested whether the batch adjustment method, ComBat, can further reduce site-related heterogeneity and thus increase statistical power. We conducted random-effects meta-analyses, mixed-effects mega-analyses and ComBat mega-analyses to compare cortical thickness, surface area and subcortical volumes between 2897 individuals with a diagnosis of schizophrenia and 3141 healthy controls from 33 sites. Specifically, we compared the imaging data between individuals with schizophrenia and healthy controls, covarying for age and sex. The use of ComBat substantially increased the statistical significance of the findings as compared to random-effects meta-analyses. The findings were more similar when comparing ComBat with mixed-effects mega-analysis, although ComBat still slightly increased the statistical significance. ComBat also showed increased statistical power when we repeated the analyses with fewer sites. Results were nearly identical when we applied the ComBat harmonization separately for cortical thickness, cortical surface area and subcortical volumes. Therefore, we recommend applying the ComBat function to attenuate potential effects of site in ENIGMA projects and other multi-site structural imaging work. We provide easy-to-use functions in R that work even if imaging data are partially missing in some brain regions, and they can be trained with one data set and then applied to another (a requirement for some analyses such as machine learning).

Two studies applied a social-cognitive interpersonal process model to investigate mechanisms underlying the association of maternal depressive symptoms with maternal relationship satisfaction and maternal verbal behavior. Study 1 participants were 86 mothers of 6-12-year-old children with a history of ADHD. Study 2 participants were 81 mother-child dyads recruited from a children's inpatient unit and the surrounding community. Negative trait perceptions and negative affective reactions mediated the effect of maternal depressive symptoms on both maternal relationship satisfaction and maternal verbal behavior. The link between maternal depression level and negative maternal reactions remained after controlling for the child's psychological problems. Results support the value of applying social-cognitive constructs to clinical problems that are embedded in distressed interpersonal relationships. [ABSTRACT FROM AUTHOR]

The U.S. Air Force asked RAND Project AIR FORCE (PAF) to help assess the well-being of its wounded members and the quality of services provided to facilitate their recovery and reintegration. RAND PAF fielded a survey in the fall of 2016 to assess wounded airmen's functioning in the domains of physical health, mental health, interpersonal relationships, unemployment, and financial status, as well as their utilization and perceptions of Air Force nonmedical programs for wounded airmen. The authors of this study invited all 713 wounded airmen enrolled in the Air Force Wounded Warrior program to complete the survey, and 270 airmen (38 percent) completed it. One-third of airmen reported difficulty obtaining care for physical or mental health conditions, and one-quarter expressed dissatisfaction with coordination of care. Similar proportions of airmen reported barriers to care for physical and mental health conditions. Difficulty scheduling appointments was the most commonly endorsed barrier for both types of conditions. Small but notable proportions of airmen reported potential social support deficits, unemployment, and financial problems. For many of the Air Force's programs for wounded airmen, over 80 percent of program users reported overall program satisfaction. The authors recommend that the Air Force consider focusing on improving care coordination, increasing health care system capacity, continuing employment assistance, and improving marketing of programs with low uptake., (Copyright © 2024 RAND Corporation.)

p53 mutations with single amino acid changes in cancer often lead to dominant oncogenic changes. Here, we have developed a mouse model of gain-of-function (GOF) p53-driven lung cancer utilizing conditionally active LSL p53-R172H and LSL K-Ras-G12D knock-in alleles that can be activated by Cre in lung club cells. Mutation of the p53 transactivation domain (TAD) (p53-L25Q/W26S/R172H) eliminating significant transactivation activity resulted in loss of tumorigenicity, demonstrating that transactivation mediated by or dependent on TAD is required for oncogenicity by GOF p53. GOF p53 TAD mutations significantly reduce phosphorylation of nearby p53 serine 20 (S20), which is a target for PLK3 phosphorylation. Knocking out PLK3 attenuated S20 phosphorylation along with transactivation and oncogenicity by GOF p53, indicating that GOF p53 exploits PLK3 to trigger its transactivation capability and exert oncogenic functions. Our data show a mechanistic involvement of PLK3 in mutant p53 pathway of oncogenesis.

Depletion of epithelial cells after lung injury prompts proliferation and epithelial mesenchymal transition (EMT) of progenitor cells, and this repopulates the lost epithelial layer. To investigate the cell proliferative function of human oncoprotein MDM2, we generated mouse models targeting human MDM2 expression in either lung Club or alveolar cells after doxycycline treatment. We report that MDM2 expression in lung Club or alveolar cells activates DNA replication specifically in lung progenitor cells only after chemical- or radiation-induced lung injury, irrespective of their p53 status. Activation of DNA replication by MDM2 triggered by injury leads to proliferation of lung progenitor cells and restoration of the lost epithelial layers. Mouse lung with no Mdm2 allele loses its ability to replicate DNA, whereas loss of 1 Mdm2 allele compromises this function, demonstrating the requirement of endogenous MDM2. We show that the p53-independent ability of MDM2 to activate Akt signaling is essential for initiating DNA replication in lung progenitor cells. Furthermore, MDM2 activates the Notch signaling pathway and expression of EMT markers, indicative of epithelial regeneration. This is the first report to our knowledge demonstrating a direct p53-independent participation of MDM2 in progenitor cell proliferation and epithelial repair after lung injury, distinct from a p53-degrading antiapoptotic effect preventing injury.

The current study examined racial/ethnic differences in use of parks and park facilities and features and self-reported park use and perceptions. We conducted observations in a nationally representative sample of 193 neighborhood parks in 27 US cities over a 1-week period between April and August of 2016 using the System of Observing Play and Recreation in Communities (SOPARC). To determine the propensity of different racial/ethnic groups to use parks relative to expectation based on their representation in the surrounding neighborhood, we calculated the percentages of park users of each race/ethnicity and compared these to the percentages of racial/ethnic groups residing in the neighborhood within a 1-mile radius of the park based on 2010 U.S. Census data. In the same parks, we administered an intercept survey to assess park users' self-reported use and perceptions of the park (N = 1872). We examined racial/ethnic differences in self-reported use and perceptions of parks using GEE models that adjusted for several individual- and park-level covariates. Hispanics comprised a disproportionate percentage of observed park users. Racial/ethnic groups generally did not differ in their self-reported park use and perceptions, except for the social context of park visits. In adjusted models, Hispanics had significantly higher odds of visiting with a child family member (OR = 1.44) and lower odds of visiting alone than non-Hispanic whites (OR = .55). Findings highlight Hispanics' greater propensity to use parks and indicate that parks may serve a communal purpose for Hispanics that they do not serve for other racial/ethnic groups.

Background: Online peer support groups are an increasingly common venue for caregivers supporting disabled family members to exchange informational, emotional, and instrumental support. We know very little, however, about who uses these groups and whether they are reaching those with the greatest needs., Objective: To examine whether caregiving factors (ie, caregiving demands and strain, competing demands, access to support and services, and other caregiving characteristics) are related to online community support use and intensity of use., Method: This study used data from a new survey of family caregivers who provide care to disabled military veterans. We used logistic regression models to examine the likelihood of online community support group usage and intensity of use as a function of a variety of caregiving factors., Results: Those with greater caregiving demands were more likely to use online peer support. Specifically, helping the care recipient with more activities was associated with a statistically significantly greater likelihood of visiting an online community support group. Caring for a veteran with a neurological or psychological condition, which, in prior work, suggests more complex care needs, was also positively and significantly related to visiting an online community support group. Hours of care and several other caregiving factors were related to intensity of use., Conclusions: We show that family caregivers with the most caregiving demands are most engaged with online support communities. This suggests that online communities could be used to support the most vulnerable family caregivers. The implications of this work for online support systems are discussed.

Healthy diet and physical activity (PA) prevent and reduce chronic disease. Social cognitive theory delineates multiple attitudes and barriers that influence these behaviors. Understanding covariation in these attitudes and barriers is complex. We examined whether individuals could be grouped into a small number of categories that are easier to study. Interviews were conducted with 982 adults from two low-income, predominantly African American neighborhoods in the same city. Social cognitive constructs, including self-efficacy, social norms, and internal and external barriers to diet and exercise, and walking were self-reported. We measured moderate to vigorous physical activity with accelerometers and diet with 24-hour recalls. We conducted a latent profile analysis of attitudes and barriers to diet and PA and identified four classes: (a) moderate diet and negative exercise attitudes, where participants were roughly average on dietary attitudes but reported exercise-related challenges, including lower social support, outcome expectancies, physical functioning, and self-efficacy; (b) few barriers and benefits of healthy diet and exercise, where participants reported fewer barriers and lower outcome expectancies for diet and PA; (c) moderate overall attitudes, where participants had average scores on most indicators but below-average exercise self-efficacy and slightly more exercise barriers; and (d) positive overall attitudes, characterized by more positive attitudes toward both diet and PA across most domains, particularly regarding self-efficacy to overcome exercise barriers. These profiles could inform efforts to tailor individual-level interventions for diet and PA of persons at high risk of chronic diseases.

We examined individual and environmental influences on park use among residents of two low-income predominantly African American neighborhoods to identify determinants of park use in lower-income urban neighborhoods. We analyzed data from interviews of 1003 individuals randomly selected from the neighborhoods, systematic observations of neighborhood parks, and police-recorded crime incidence within a .5-mi buffer around each park. Most participants (82.4%) had previously visited a neighborhood park, and nearly half (46.2%) had visited one in the past month. However, only 8.5% of participants were aware of their closest park. Compared with the parks closest to home, parks that participants reported visiting most were larger and had more amenities and features and fewer incivilities and reported crimes of a serious nature. Park use among residents of lower-income neighborhoods may be increased by offering more amenities and features and ensuring the presence of a well-appointed park within easy walking distance of residents' homes.

Objective: To examine where residents in an area with limited access to healthy foods (an urban food desert) purchased healthier and less healthy foods., Design: Food shopping receipts were collected over a one-week period in 2013. These were analysed to describe where residents shopped for food and what types of food they bought., Setting: Two low-income, predominantly African-American neighbourhoods with limited access to healthy foods in Pittsburgh, PA, USA., Subjects: Two hundred and ninety-three households in which the primary food shoppers were predominantly female (77·8 %) and non-Hispanic black (91·1 %) adults., Results: Full-service supermarkets were by far the most common food retail outlet from which food receipts were returned and accounted for a much larger proportion (57·4 %) of food and beverage expenditures, both healthy and unhealthy, than other food retail outlets. Although patronized less frequently, convenience stores were notable purveyors of unhealthy foods., Conclusions: Findings highlight the need to implement policies that can help to decrease unhealthy food purchases in full-service supermarkets and convenience stores and increase healthy food purchases in convenience stores.

Interventions to address diet, a modifiable risk factor for diabetes, cancer, and cardiovascular disease, have increasingly emphasized the influence of the physical environment on diet, while more traditional approaches have focused on individual characteristics. We examined environmental and individual influences on diet to understand the role of both. Household interviews were conducted in 2011 with 1372 individuals randomly selected from two low-income, predominantly African American neighborhoods in Pittsburgh, PA. Participants reported their sociodemographic characteristics, food shopping behavior, and dietary intake. Both food shopping frequency at different types of food stores and sociodemographic characteristics showed significant associations with diet in adjusted regression models. More frequent shopping at convenience and neighborhood stores and being younger, male, without a college degree, and receiving SNAP benefits were associated with greater intake of sugar-sweetened beverages (SSBs), added sugars, and discretionary fats. Being older, male, and having a college degree were associated with greater intake of fruits and vegetables. However, while food shopping behavior and sociodemographic characteristics accounted for similar amounts of nonoverlapping variance in fruit and vegetable intake, food shopping behavior accounted for much less variance, and little unique variance, in SSBs, added sugars, and discretionary fats in models with sociodemographic characteristics. The current study reinforces the need for policies and interventions at both the environmental and individual levels to improve diet in food desert residents. Individual interventions to address food choices associated with certain sociodemographic characteristics might be particularly important for curbing intake of SSBs, added sugars, and discretionary fats., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Gain-of-function (GOF) mutants of p53 upregulate genes implicated in cell proliferation and oncogenesis. Here, we report that GOF p53 induces tumorigenicity through simultaneous activation of key oncogenic pathways including those controlling putative tumor-initiating cell functions. We determined that in cells expressing p53-R273H, GOF p53 simultaneously upregulates genes from multiple signaling pathways by recognizing promoters containing distinct transcription factor (TF) binding sites. Our analytical data support a model in which GOF p53 complexes with two TFs on the promoter-a mediator protein, Med17, and a histone acetyl transferase, activating histone acetylation-and enhances gene expression to signal cell proliferation and oncogenesis. Thus, therapeutic inhibition of one GOF p53-induced pathway would be insufficient to prevent tumor growth as the oncoprotein activates a multitude of parallel pathways. This discovery suggests enormous selection advantage for cancer cells with GOF p53 to induce oncogenic growth, highlighting the problems of cancer therapy., (© 2017 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.)

Gain-of-function (GOF) p53 mutations are observed frequently in most intractable human cancers and establish dependency for tumor maintenance and progression. While some of the genes induced by GOF p53 have been implicated in more rapid cell proliferation compared with p53-null cancer cells, the mechanism for dependency of tumor growth on mutant p53 is unknown. This report reveals a therapeutically targetable mechanism for GOF p53 dependency. We have shown that GOF p53 increases DNA replication origin firing, stabilizes replication forks, and promotes micronuclei formation, thus facilitating the proliferation of cells with genomic abnormalities. In contrast, absence or depletion of GOF p53 leads to decreased origin firing and a higher frequency of fork collapse in isogenic cells, explaining their poorer proliferation rate. Following genome-wide analyses utilizing ChIP-Seq and RNA-Seq, GOF p53-induced origin firing, micronuclei formation, and fork protection were traced to the ability of GOF p53 to transactivate cyclin A and CHK1. Highlighting the therapeutic potential of CHK1's role in GOF p53 dependency, experiments in cell culture and mouse xenografts demonstrated that inhibition of CHK1 selectively blocked proliferation of cells and tumors expressing GOF p53. Our data suggest the possibility that checkpoint inhibitors could efficiently and selectively target cancers expressing GOF p53 alleles.

In 2009, RAND launched the Deployment Life Study, a longitudinal study of military families across a deployment cycle in order to assess family readiness. Family readiness refers to the state of being prepared to effectively navigate the challenges of daily living experienced in the unique context of military service. The study surveyed families at frequent intervals throughout a complete deployment cycle---before a service member deploys (sometimes months before), during the actual deployment, and after the service member returns (possibly a year or more after she or he redeployed). It assessed a number of outcomes over time, including: the quality of marital and parental relationshipsthe psychological, behavioral, and physical health of family memberschild and teen well-being (e.g., emotional, behavioral, social, and academic)military integration (e.g., attitudes toward military service, retention intentions).This culminating paper briefly reviews the study design and data collection procedures, presents results from analyses of the longitudinal data collected from some 2,700 military families, and offers recommendations for programs and future research related to military families. The research was jointly sponsored by the Office of the Surgeon General, U.S. Army, and by the Defense Centers of Excellence for Psychological Health and Traumatic Brain Injury.

The Posttraumatic Stress Disorder (PTSD) Checklist (PCL) is commonly used to screen for PTSD in clinical and research contexts. While the PCL is utilized within numerous settings and populations, research has not yet established the extent to which individuals respond similarly across different modes of administration. The use of both telephone and web survey administration modes has numerous potential benefits, including data quality improvement, but may introduce an additional source of measurement error. The current study examined the psychometric properties, including factor structure and measurement invariance, of the PCL across telephone and web administration modes among 455 wounded, ill, or injured airmen who were medically retired or undergoing evaluation for disability caused by injuries and illnesses of a physical or psychological nature. Findings suggest the properties of the PCL were invariant with regard to the mode of administration, such that the overall scale structure and size of the loadings were similar across groups. Corrections were applied to the computation of probable PTSD diagnosis to account for partial scalar invariance. The lack of complete invariance did not affect probable PTSD diagnosis. Finally, differences in latent means across the telephone and web group were nonsignificant and modest in magnitude. These results indicate that although the PCL only achieved partial scalar invariance across administration modes, the practical impact of this difference on rates of probable PTSD is negligible. The practical benefits of administering the PCL over the telephone and on the web do not appear to be outweighed by the potential cost of additional measurement error. (PsycINFO Database Record, ((c) 2016 APA, all rights reserved).)

Purpose: Prior studies suggest that cohesion among members of military units has a positive impact on behavioral and mental health sequelae of combat deployment. However, these studies have not distinguished variation in cohesion across units from variation in perception of cohesion across individuals within units., Methods: A sample of U.S. Marines was assessed before and after deployment to Iraq or Afghanistan in 2010 or 2011. Within-group centering was used to distinguish unit-level from individual-level associations of cohesion with four behavioral and mental health outcomes assessed after deployment: alcohol misuse, violation of the Uniform Code of Military Justice (UCMJ), probable posttraumatic stress disorder (PTSD) and a positive screen for depression., Results: Unit-level cohesion is associated positively with alcohol misuse (OR=1.86, 95% CI 1.05-3.29) and negatively with UCMJ violations (OR=0.41, 95% CI 0.20-0.83) but not with probable PTSD (OR=1.00, 95% CI 0.60-1.6) or a positive screen for depression (OR=1.00 95% CI 0.58-1.72). Lower perception of cohesion relative to the other members of the same unit is associated with higher likelihood of UCMJ violations, probable PTSD and a positive screen for depression., Limitations: Data on all members of the studied units were not available., Conclusions: Distinguishing unit-level from individual-level variation in cohesion among military unit members reveals more varied associations with behavioral and mental health outcomes of deployment than have been reported in previous studies, in which these levels have been collapsed. Associations between individual-level variation in cohesion and mental health outcomes may result from pre-existing traits related to both perception of cohesion and risk for psychiatric disorders., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Major depressive disorder (MDD) is a prevalent condition associated with significant burden in terms of reduced quality of life, lower productivity, increased prevalence of other conditions and increased health care costs. We conducted a systematic review and qualitative summary of randomized controlled trials (RCTs) that assessed the effectiveness and safety of acupuncture for the treatment of MDD. We searched the databases PubMed, CINAHL, PsycINFO, Web of Science, Embase, CDSR, CENTRAL, clinicaltrials.gov, DARE, and PILOTS for English-language RCTs published through January 2015. Two independent reviewers screened the identified literature against inclusion and exclusion criteria, abstracted study level data, and assessed the risk of bias and methodological quality of included studies. The quality of the evidence was assessed using GRADE. Eighteen studies met inclusion criteria. Eleven assessed acupuncture as monotherapy, seven as adjunct depression treatment. Intervention approaches and comparators varied. Evidence on the effectiveness and comparative effectiveness of acupuncture to treat MDD for the outcomes depression improvement, measured as scale score differences and the number of responders, is very weak. Acupuncture may be superior to waitlist (low quality of evidence) but findings for effect estimates compared to other comparators are inconclusive. Few studies reported on patients achieving remission. The effect of acupuncture on relapse rates could not be determined. Too few studies assessed quality of life to estimate treatment effects. Reported adverse events were typically mild in nature, but the assessment lacked rigor and studies were not designed to detect rare events.

Comorbidity of posttraumatic stress disorder (PTSD) and pain is well documented, but the mechanisms underlying their comorbidity are not well understood. Cross-lagged regression models were estimated with 3 waves of longitudinal data to examine the reciprocal associations between PTSD symptom severity, as measured by the Clinician-Administered PTSD Scale (CAPS), and pain, as measured by a brief self-report measure of pain called the PEG (pain intensity [P], interference with enjoyment of life [E], and interference with general activity [G]). We evaluated stress appraisals as a mediator of these associations in a sample of low-income, underserved patients with PTSD (N = 355) at federally qualified health centers in a northeastern metropolitan area. Increases in PTSD symptom severity between baseline and 6-month and 6- and 12-month assessments were independently predicted by higher levels of pain (β = .14 for both lags) and appraisals of life stress as uncontrollable (β = .15 for both lags). Stress appraisals, however, did not mediate these associations, and PTSD symptom severity did not predict change in pain. Thus, the results did not support the role of stress appraisals as a mechanism underlying the associations between pain and PTSD., (Copyright © 2016 International Society for Traumatic Stress Studies.)

Human lung cancers harboring gain-of-function (GOF) p53 alleles express higher levels of the epidermal growth factor receptor (EGFR). We demonstrate that a number of GOF p53 alleles directly upregulate EGFR. Knock-down of p53 in lung cancer cells lowers EGFR expression and reduces tumorigenicity and other GOF p53 properties. However, addiction of lung cancer cells to GOF p53 can be compensated by overexpressing EGFR, suggesting that EGFR plays a critical role in addiction. Chromatin immunoprecipitation (ChIP) using lung cancer cells expressing GOF p53 alleles showed that GOF p53 localized to the EGFR promoter. The sequence where GOF p53 is found to interact by ChIP seq can act as a GOF p53 response element. The presence of GOF p53 on the EGFR promoter increased histone H3 acetylation, indicating a mechanism whereby GOF p53 enhances chromatin opening for improved access to transcription factors (TFs). ChIP and ChIP-re-ChIP with p53, Sp1 and CBP histone acetylase (HAT) antibodies revealed docking of GOF p53 on Sp1, leading to increased binding of Sp1 and CBP to the EGFR promoter. Up-regulation of EGFR can occur via GOF p53 contact at other novel sites in the EGFR promoter even when TAD-I is inactivated; these sites are used by both intact and TAD-I mutated GOF p53 and might reflect redundancy in GOF p53 mechanisms for EGFR transactivation. Thus, the oncogenic action of GOF p53 in lung cancer is highly dependent on transactivation of the EGFR promoter via a novel transcriptional mechanism involving coordinated interactions of TFs, HATs and GOF p53.

The U.S. Air Force, wanting to gain greater insight into the well-being of its members who have sustained mental or physical injuries in combat or combat-related situations, including their quality of life and the challenges they will confront in their reintegration following separation or retirement, asked the RAND Corporation for assistance in gauging the current status of the Air Force's wounded warriors, including their use of and satisfaction with Air Force programs designed to serve them. This article presents the baseline findings from a longitudinal analysis of enrollees in the Air Force Wounded Warrior (AFW2) program who were receiving benefits or undergoing evaluation to receive benefits, the majority of whom had a primary administrative diagnosis of post-traumatic stress disorder (PTSD). A high proportion of the Airmen in the sample screened positive for PTSD (roughly 78 percent) and major depressive disorder (MDD) (roughly 75 percent); 69 percent screened positive for both. Although more than 90 percent of those in the sample who screened positive for PTSD or MDD were receiving treatment, about half indicated that there was at least one instance during the past year in which they desired mental health treatment but did not receive it. Participants reported concerns about stigma, confidentiality, and the quality of available treatment as barriers to receiving mental health care, though the current data do not link these concerns to a particular treatment setting. About 10 percent of Airmen reported a financial situation that could be considered as living in poverty based on U.S. Department of Health and Human Services' poverty guidelines. Similarly, close to 15 percent of those in the labor force could be considered unemployed. Reserve and National Guard Airmen evidenced heightened challenges across examined domains. Respondents were overall satisfied with the services they received from the AFW2 and Air Force Recovery Care Coordinator programs.

The Marine Corps Operational Stress Control and Readiness (OSCAR) program embeds mental health personnel within Marine Corps units and extends their reach by training officers and noncommissioned officers to recognize Marines showing signs of stress and intervene early. RAND Corporation researchers conducted an outcome evaluation of the OSCAR program that included four components: (1) a quasi-experimental study that compared Marines in OSCAR-trained and non-OSCAR-trained battalions on a wide array of stress-related outcomes before and after deployment, (2) a longitudinal pre- and postdeployment survey of perceptions of OSCAR among Marines who attended OSCAR training, (3) focus groups with Marines, and (4) semistructured interviews with commanding officers of battalions that had received OSCAR training. Results indicated that, after the authors adjust for a wide array of baseline characteristics and deployment experiences, Marines in OSCAR-trained battalions were more likely than those in non-OSCAR-trained battalions to report having sought help with stress problems from a peer, leader, or corpsman-behavior that is consistent with OSCAR goals. In addition, Marines considered OSCAR a valuable tool for enhancing combat and operational stress response and recovery efforts in the Marine Corps. However, this evaluation did not find evidence that OSCAR affected the key mental health outcomes it was designed to address. Thus, the results of this evaluation do not support the continuation of OSCAR in its current form. Based on lessons learned about OSCAR from this evaluation, other research, and best practices for program improvement and implementation, recommendations for improving combat and operational stress training in the Marine Corps are offered.

Placing full-service supermarkets in food deserts--areas with limited access to healthy food--has been promoted as a way to reduce inequalities in access to healthy food, improve diet, and reduce the risk of obesity. However, previous studies provide scant evidence of such impacts. We surveyed households in two Pittsburgh, Pennsylvania, neighborhoods in 2011 and 2014, one of which received a new supermarket in 2013. Comparing trends in the two neighborhoods, we obtained evidence of multiple positive impacts from new supermarket placement. In the new supermarket neighborhood we found net positive changes in overall dietary quality; average daily intakes of kilocalories and added sugars; and percentage of kilocalories from solid fats, added sugars, and alcohol. However, the only positive outcome in the recipient neighborhood specifically associated with regular use of the new supermarket was improved perceived access to healthy food. We did not observe differential improvement between the neighborhoods in fruit and vegetable intake, whole grain consumption, or body mass index. Incentivizing supermarkets to locate in food deserts is appropriate. However, efforts should proceed with caution, until the mechanisms by which the stores affect diet and their ability to influence weight status are better understood., (Project HOPE—The People-to-People Health Foundation, Inc.)

The Marine Corps Operational Stress Control and Readiness (OSCAR) program is designed to provide mental health support to marines by embedding mental health personnel within Marine Corps units and increasing the capability of officers and senior noncommissioned officers to improve the early recognition and intervention of marines exhibiting signs of stress. The Defense Centers of Excellence for Psychological Health and Traumatic Brain Injury have asked RAND to evaluate the OSCAR program. As part of this evaluation, RAND conducted a large survey of marines who were preparing for a deployment to Iraq or Afghanistan in 2010 or 2011. This article describes the methods and findings from this survey. The results are among the first to shed light on the pre-deployment mental health status of marines, as well as the social resources they draw on when coping with stress and their attitudes about seeking help for stress-related problems. The 2,620 marines in the survey sample had high rates of positive screens for current major depressive disorder (12.5 percent) and high-risk drinking (25.7 percent) and reported having experienced more potentially traumatic events over their lifetime than adult males in the general population. Marines in the sample also reported relying on peers for support with stress and perceiving moderate levels of support from the Marine Corps for addressing stress problems.

While much has been written about the role of caregiving for the elderly and chronically ill and for children with special needs, little is known about "military caregivers"-the population of those who care for wounded, ill, and injured military personnel and veterans. These caregivers play an essential role in caring for injured or wounded service members and veterans. This enables those for whom they are caring to live better quality lives, and can result in faster and improved rehabilitation and recovery. Yet playing this role can impose a substantial physical, emotional, and financial toll on caregivers. This article distills a longer report, Hidden Heroes: America's Military Caregivers , which describes the results of a study designed to describe the magnitude of military caregiving in the United States today, as well as to identify gaps in the array of programs, policies, and initiatives designed to support military caregivers. Improving military caregivers' well-being and ensuring their continued ability to provide care will require multifaceted approaches to reducing the current burdens caregiving may impose, and bolstering their ability to serve as caregivers more effectively. Given the systematic differences among military caregiver groups, it is also important that tailored approaches meet the unique needs and characteristics of post-9/11 caregivers.

Objective: Roughly half of veterans who served in Operation Enduring Freedom and Operation Iraqi Freedom (OEF/OIF) have not received services from the Veterans Health Administration (VHA). This study assessed probable posttraumatic stress disorder (PTSD) and depression among OEF/OIF veterans by receipt of VHA services., Methods: In 2010 a mixed-mode survey assessing symptoms and VHA services utilization was fielded in a random sample of 913 New York State OEF/OIF veterans., Results: Probable PTSD and depression were roughly three times more common among veterans who had received VHA services (N=537) (PTSD, 23%; depression, 21%) than those who had not (N=376) (PTSD, 6%; depression, 8%)., Conclusions: Studies of veterans receiving VHA services likely overstate the prevalence of mental health problems among the broader OEF/OIF veteran population. However, many veterans with mental health problems are not receiving VHA services. Policies that improve outreach to this population may improve health outcomes.

The 5-factor client-report Dimensions of Change in Therapeutic Communities Treatment Instrument-Adolescent (DCI-A) was developed to assess adolescent substance abuse treatment process in the therapeutic community (TC). The goal of this study was to use bifactor modeling to derive a unidimensional DCI-A short-form (DCI-A-SF) that would represent content from the original DCI-A factors. Data are from 442 adolescents receiving treatment at one of seven residential TC programs. Bifactor analyses suggested selection of seven DCI-A items to comprise the short form. Three items are from the treatment motivation factor, and one item was selected from each of the remaining four factors. Confirmatory factor analysis suggested that the 7-item DCI-A-SF is strongly unidimensional, and unidimensional IRT analysis of the items indicated good internal consistency. A structural equation model that demonstrates the mediating relationship of DCI-A-SF with other measures, including demographic and pre-treatment characteristics, and subsequent treatment completion, provides preliminary evidence of internal validity., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Gain-of-function mutant p53 is thought to induce gene expression in part by binding transcription factors bound to promoters for genes that mediate oncogenesis. We investigated the mechanism of mutant p53 binding by mapping the human genomic binding sites for p53 R273H using ChIP-Seq and showed them to localize to ETS DNA sequence motifs and locations with ETS1 and GABPA binding, both within promoters and distal to promoters. Strikingly, p53 R273H showed statistically significant and substantial binding to bidirectional promoters, which are enriched for inverted repeated ETS DNA sequence motifs. p53 R273H exhibited an exponential increase in probability of binding promoters with a higher number of ETS motifs. Both ETS1 and GABPA also showed an increase in the probability of binding to promoters with a higher number of ETS motifs. However, despite this increase in probability of binding by p53 R273H and ETS1, there was no increase in the binding signal, suggesting that the number of ETS1 and p53 R273H proteins bound per promoter is being limited. In contrast, GABPA did exhibit an increase in binding signal with higher numbers of ETS motifs per promoter. Analysis of the distance between inverted pairs of ETS motifs within promoters and binding by p53 R273H, ETS1 and GABPA, showed a novel coordination of binding for the three proteins. Both ETS1 and p53 R273H exhibited preference for binding promoters with distantly spaced ETS motifs in face-to-face and back-to-back orientations, and low binding preference to promoters with closely spaced ETS motifs. GABPA exhibited the inverse pattern of binding by preferring to bind promoters with closely spaced ETS motifs. Analysis of the helical phase between ETS motifs showed that ETS1 and p53 R273H exhibited a low preference for binding promoters with ETS motifs on the same face of the DNA helix. We propose a model for the binding of ETS1 and p53 R273H in which two inverted ETS motifs on a looped DNA helix are juxtaposed for ETS1 binding as a homodimer, with p53 R273H bound to ETS1. We propose that the formation of this DNA loop and protein-bound complex prevents additional binding of ETS1 and p53 R273H proteins to other proximal binding sites.

Objective: This article describes the characteristics and early implementation experiences of community behavioral health agencies that received Primary and Behavioral Health Care Integration (PBHCI) grants from the Substance Abuse and Mental Health Services Administration to integrate primary care into programs for adults with serious mental illness., Methods: Data were collected from 56 programs, across 26 states, that received PBHCI grants in 2009 (N=13) or 2010 (N=43). The authors systematically extracted quantitative and qualitative information about program characteristics from grantee proposals and semistructured telephone interviews with core program staff. Quarterly reports submitted by grantees were coded to identify barriers to implementing integrated care., Results: Grantees shared core features required by the grant but varied widely in terms of characteristics of the organization, such as size and location, and in the way services were integrated, such as through partnerships with a primary care agency. Barriers to program implementation at start-up included difficulty recruiting and retaining qualified staff and issues related to data collection and use of electronic health records, licensing and approvals, and physical space. By the end of the first year, some problems, such as space issues, were largely resolved, but other issues, including problems with staffing and data collection, remained. New challenges, such as patient recruitment, had emerged., Conclusions: Early implementation experiences of PBHCI grantees may inform other programs that seek to integrate primary care into behavioral health settings as part of new, large-scale government initiatives, such as specialty mental health homes.

p53 mutations are mostly single amino acid changes resulting in expression of a stable mutant protein with "gain of function" (GOF) activity having a dominant oncogenic role rather than simple loss of function of wild-type p53. Knock-down of mutant p53 in human lung cancer cell lines with different endogenous p53 mutants results in loss of GOF activity as shown by lowering of cell growth rate. Two lung cancer cell lines, ABC1 and H1437, carrying endogenous mutants p53-P278S and -R267P, show reduction in growth rate on knock-down on p53 levels. However, whereas reduction of the p53 level induces loss of tumorigenicity in nude mice for ABC1 cells, it escalates tumorigenicity for H1437 cells. We have tested their transactivation potential on p53 target gene promoters by performing transient transcriptional assays in the p53-null H1299 lung cancer cell line. Interestingly, while the mutant p53 target promoter Axl was activated by both the mutants, the p21 promoter was activated by p53-R267P and wild-type p53 but not by p53-P278S; showing a clear difference in transcriptional activity between the two mutants. Our results demonstrate allele specificity between GOF p53 mutants and attempt to show that the specificity is dependent on the transactivation property of GOF p53; it also suggests importance of p21 activation in tumor suppression by p53., (Copyright © 2012 Elsevier Inc. All rights reserved.)

p53 mutations are present in up to 70% of lung cancer. Cancer cells with p53 mutations, in general, grow more aggressively than those with wild-type p53 or no p53. Expression of tumor-derived mutant p53 in cells leads to up-regulated expression of genes that may affect cell growth and oncogenesis. In our study of this aggressive phenotype, we have investigated the receptor protein tyrosine kinase Axl, which is up-regulated by p53 mutants at both RNA and protein levels in H1299 lung cancer cells expressing mutants p53-R175H, -R273H, and -D281G. Knockdown of endogenous mutant p53 levels in human lung cancer cells H1048 (p53-R273C) and H1437 (p53-R267P) led to a reduction in the level of Axl as well. This effect on Axl expression is refractory to the mutations at positions 22 and 23 of p53, suggesting that p53's transactivation domain may not play a critical role in the up-regulation of Axl gene expression. Chromatin immunoprecipitation (ChIP) assays carried out with acetylated histone antibodies demonstrated induced histone acetylation on the Axl promoter region by mutant p53. Direct mutant p53 nucleation on the Axl promoter was demonstrated by ChIP assays using antibodies against p53. The Axl promoter has a p53/p63 binding site, which however is not required for mutant p53-mediated transactivation. Knockdown of Axl by Axl-specific RNAi caused a reduction of gain-of-function (GOF) activities, reducing the cell growth rate and motility rate in lung cancer cells expressing mutant p53. This indicates that for lung cancer cell lines with mutant p53, GOF activities are mediated in part through Axl.

The role of dominant transforming p53 in carcinogenesis is poorly understood. Our previous data suggested that aberrant p53 proteins can enhance tumorigenesis and metastasis. Here, we examined potential mechanisms through which gain-of-function (GOF) p53 proteins can induce motility. Cells expressing GOF p53 -R175H, -R273H and -D281G showed enhanced migration, which was reversed by RNA interference (RNAi) or transactivation-deficient mutants. In cells with engineered or endogenous p53 mutants, enhanced migration was reduced by downregulation of nuclear factor-kappaB2, a GOF p53 target. We found that GOF p53 proteins upregulate CXC-chemokine expression, the inflammatory mediators that contribute to multiple aspects of tumorigenesis. Elevated expression of CXCL5, CXCL8 and CXCL12 was found in cells expressing oncogenic p53. Transcription was elevated as CXCL5 and CXCL8 promoter activity was higher in cells expressing GOF p53, whereas wild-type p53 repressed promoter activity. Chromatin immunoprecipitation assays revealed enhanced presence of acetylated histone H3 on the CXCL5 promoter in H1299/R273H cells, in agreement with increased transcriptional activity of the promoter, whereas RNAi-mediated repression of CXCL5 inhibited cell migration. Consistent with this, knockdown of the endogenous mutant p53 in lung cancer or melanoma cells reduced CXCL5 expression and cell migration. Furthermore, short hairpin RNA knockdown of mutant p53 in MDA-MB-231 cells reduced expression of a number of key targets, including several chemokines and other inflammatory mediators. Finally, CXCL5 expression was also elevated in lung tumor samples containing GOF p53, indicating relevance to human cancer. The data suggest a mechanistic link between GOF p53 proteins and chemokines in enhanced cell motility.

Cancer cells with p53 mutations, in general, grow more aggressively than those with wild-type p53 and show "gain of function" (GOF) phenotypes such as increased growth rate, enhanced resistance to chemotherapeutic drugs, increased cell motility and tumorigenicity; although the mechanism for this function remains unknown. In this communication we report that p53-mediated NF-κB2 up-regulation significantly contributes to the aggressive oncogenic behavior of cancer cells. Lowering the level of mutant p53 in a number of cancer cell lines resulted in a loss of GOF phenotypes directly implicating p53 mutants in the process. RNAi against NF-κB2 in naturally occurring cancer cell lines also lowers GOF activities. In H1299 cells expressing mutant p53, chromatin immunoprecipitation (ChIP) assays indicate that mutant p53 induces histone acetylation at specific sites on the regulatory regions of its target genes. ChIP assays using antibodies against transcription factors putatively capable of interacting with the NF-κB2 promoter show increased interaction of CBP and STAT2 in the presence of mutant p53. Thus, we propose that in H1299 cells, mutant p53 elevates expression of genes capable of enhancing cell proliferation, motility, and tumorigenicity by inducing acetylation of histones via recruitment of CBP and STAT2 on the promoters causing CBP-mediated histone acetylation., (Copyright © 2011. Published by Elsevier Inc.)

Mental health disorders and other types of impairments resulting from deployment experiences are beginning to emerge, but fundamental gaps remain in our knowledge about the needs of veterans returning from Iraq and Afghanistan, the services available to meet those needs, and the experiences of veterans who have tried to use these services. This article highlights the findings of a study focused directly on the veterans living in New York state. The study included veterans who currently use U.S. Department of Veterans Affairs (VA) services as well as those who do not; and it looked at needs across a broad range of domains. The authors collected information and advice from a series of qualitative interviews with veterans of Operation Iraqi Freedom (OIF)/Operation Enduring Freedom (OEF) residing in New York, as well as their family members. In addition, they conducted a quantitative assessment of the needs of veterans and their spouses from a sample that is broadly representative of OEF/OIF veterans in New York state. Finally, they conducted a review the services currently available in New York state for veterans. The study found substantially elevated rates of post-traumatic stress disorder (PTSD) and major depression among veterans. It also found that both VA and non-VA services are critically important for addressing veterans' needs, and that the health care systems that serve veterans are extremely complicated. Addressing veterans' mental health needs will require a multipronged approach: reducing barriers to seeking treatment; improving the sustainment of, or adherence to, treatment; and improving the quality of the services being delivered. Finally, veterans have other serious needs besides mental health care and would benefit from a broad range of services.

A theoretical model of gender differences in depressive symptoms during adolescence was evaluated using data from Waves I and II of the National Longitudinal Study of Adolescent Health. The theoretical model under examination was primarily informed by the gender-additive model of gender differences in depressive symptoms during adolescence proposed by Stice and Bearman (2001). In the model, it was posited that BMI would be associated with perceiving oneself as overweight, which would then lead to a higher probability of dieting, which would be associated with greater depressive symptoms. Participants were 10,864 male and female adolescents. Gender did not moderate any of the model pathways, but mediation analysis indicated that gender differences in changes in depressive symptoms were mediated by perceived weight status and dieting. Findings suggest that one explanation for girls' higher depressive symptoms in adolescence relative to boys is girls' greater tendencies to perceive themselves as overweight and to diet.

The current study examined the contributions of maternal and peer support to depressive symptoms in early to mid-adolescence and variation in these contributions across age, gender, and race. Five waves of data on maternal support, peer support, and depressive symptoms were collected on rural youth (N = 3,444) at 6 month intervals. Multilevel modeling was used to evaluate within and between-person effects of maternal and peer support on depressive symptoms. Within-person effects of peer support did not vary by age, gender, or race. At the between-person level, peer support predicted levels of depressive symptoms at age 12, but this effect became nonsignificant after controlling for maternal support. Within-person effects of maternal support did not vary with age but were qualified by gender and race. Between-person effects of maternal support on depressive symptom levels at age 12 and slopes varied across race and gender, respectively. Findings highlight the robustness of the protective effects of maternal and peer support during adolescence among girls and white youth.

The greater BMI of African American relative to Caucasian women is implicated in racial/ethnic disparities in health outcomes. The principal aim of the current study was to evaluate a theoretical account of racial/ethnic differences in BMI. Thin-ideal internalization, the perceived romantic appeal of thinness, dietary restriction, weight, and height were assessed via self-report measures on a sample of female undergraduates of African American (n=140) and Caucasian (n=676) race/ethnicity. Using structural equation modeling, support was obtained for the primary hypothesis that racial/ethnic differences in BMI are explained by Caucasian women's greater thin-ideal internalization and perceived romantic appeal of thinness, thereby resulting in greater levels of dietary restriction. Current findings illustrate the potential for racial/ethnic differences in sociocultural standards of appearance to influence racial/ethnic disparities in physical health, of which BMI is a marker, via effects on weight control behavior.

Objective: Evidence indicates that depression is linked to the development and worsening of diabetes, but the mechanisms underlying this link are not well understood. The authors examined the hypothesis that diabetes-related symptoms mediate the effect of both behavioral adherence and body mass index (BMI) on depression. In addition, they examined whether a prior finding that self-efficacy mediates the effect of behavioral adherence and BMI on depression would replicate with a larger sample size (W. P. Sacco, K. J. Wells, C. A. Vaughan, A. Friedman, S. Perez, & R. Morales, 2005). Also, the relative contributions of diabetes-related symptoms and self-efficacy to depression were evaluated., Design and Participants: Cross-sectional design involving adults diagnosed with Type 2 diabetes (N = 99)., Main Outcome Measures: The primary outcome measure was depression (Patient Health Questionnaire: Nine Symptom Depression Checklist). Predictors of depression were diet and exercise adherence (Summary of Diabetes Self-Care Activities Questionnaire), diet and exercise self-efficacy (Multidimensional Diabetes Questionnaire), diabetes symptoms (Diabetes Symptom Checklist), and BMI (based on height and weight data from medical records)., Results: Path and mediation analyses indicated that adherence and BMI each contributed to depression indirectly, via their effects on self-efficacy and diabetes-related medical symptoms., Conclusion: Results provide evidence consistent with two independent pathways by which BMI and adherence could increase depression in people with Type 2 diabetes. The first pathway indicates that the effects of higher BMI and poor adherence on depression are mediated by lower self-efficacy perceptions. The second pathway indicates that the effect of higher BMI on depression is mediated by increased diabetes symptoms., ((PsycINFO Database Record (c) 2007 APA, all rights reserved).)

Considerable evidence links depression with the development and worsening of diabetes, but the factors contributing to this link have not been established. The authors examined the role of adherence, body mass index (BMI), and self-efficacy. Adult patients with Type 2 diabetes (N = 56) completed self-report measures of diet and exercise adherence, diet and exercise self-efficacy, and depression. BMI was obtained from medical records. Path and mediation analyses indicated that both adherence and BMI independently contributed to self-efficacy. Self-efficacy mediated both the association between adherence and depression and the association between BMI and depression. These findings are consistent with the proposal that lower self-efficacy in reaction to adherence failure and higher BMI contributes to depression in adults with diabetes.

Experiments were done to determine whether there is a maturational increase in production of guanosine 3',5'-cyclic monophosphate (cGMP) by glomeruli or in eggression of cGMP out of glomerular cells. Both preweaned and adult isolated rat glomeruli responded with an acute rise in intracellular cGMP after 0.5-min exposure to 0.1 microM ANP. However, at 4 h extracellular cGMP was significantly greater in ANP-treated adult compared with preweaned glomeruli (P less than 0.005). In the absence of 3-isobutyl-1-methylxanthine (IBMX) intracellular cGMP was significantly higher in preweaned glomeruli (P less than 0.05). Moreover, the specific activity of phosphodiesterases for cGMP hydrolysis was twofold less in preweaned glomerular membranes (P less than 0.004). Finally, probenecid decreased export of adult glomerular cGMP by 60 +/- 4%, whereas preweaned glomerular cGMP export decreased by only 27 +/- 4% (P less than 0.05). In conclusion, compared with adult, ANP-treated preweaned glomeruli export less cGMP out of glomerular cells, have a higher concentration of intracellular cGMP, and have lower cGMP-specific phosphodiesterase activity, and the organic ion transporter in preweaned glomerular cells exports cGMP less effectively. The limited transport of cGMP out of preweaned glomeruli may account for the blunted natriuretic and diuretic response following ANP stimulation of young rats.