Peer- and web-based interventions for risky drinking among US National Guard members: Mission Strong randomized controlled trial.

AIMS: To test separatel the efficacy of a web-based and a peer-based brief intervention (BI), compared with an expanded usual care control (EUC) group, among military reserve component members using alcohoI in a hazardous and harmful manner. DESIGN: In the randomized controlled trial, participants were assigned to: [1] web-based BI with web-based boosters (BI + web), [2] web-based BI with peer-based boosters (BI + peer) or [3] enhanced usual care (EUC). SETTING: Michigan, USA. PARTICIPANTS: A total of 739 Michigan Army National Guard members who reported recent hazardous alcohol use; 84% were male, the mean age was 28 years. INTERVENTION: The BI consisted of an interactive program guided by a personally selected avatar. Boosters were delivered either on the web or personally by a trained veteran peer. A pamphlet, given to all participants, included information on hazardous alcohol use and military-specific community resources and served as the EUC condition. MEASUREMENTS: The primary outcome measure was binge drinking episodes in the past 30 days, measured at 12 months after the BI. FINDINGS: All randomized participants were included in the outcome analyses. In adjusted analyses, BI + peer [beta = -0.43, 95% confidence interval (CI) = -0.56 to -0.31, P < 0.001] and BI + web (beta = -0.34, 95% CI = -0.46 to -0.23, P < 0.001) reduced binge drinking compared with EUC. CONCLUSION: This satudy was a web-based brief intervention for hazardous alcohol use, with either web- or peer-based boosters, reduced binge alcohol use among Army National Guard members.

Predictors of Booster Engagement Following a Web-Based Brief Intervention for Alcohol Misuse Among National Guard Members: Secondary Analysis of a Randomized Controlled Trial.

BACKGROUND: Alcohol misuse is a major health concern among military members. Reserve component members face unique barriers as they live off base with limited access to behavioral health services. Web and app-based brief interventions are a promising means to improve access to treatment for those who misuse alcohol, with the use of booster sessions to enhance effectiveness, solidify gains, and reinforce changes. However, little is known about who will engage in booster sessions. OBJECTIVE: This study aims to evaluate booster engagement across booster delivery modalities (Web and Peer) and identify participant-specific factors associated with booster session engagement. METHODS: Following a brief web-based alcohol misuse intervention in National Guard members (N=739), we examined engagement in a series of three booster sessions. Using unadjusted and adjusted models, demographic and clinical characteristics that may serve as predictors of booster session engagement were examined across the 2 arms of the trial with different types of booster sessions: peer-delivered (N=245) and web-delivered (N=246). RESULTS: Booster session completion was greater for Peer than Web Booster sessions, with 142 (58%) service members in the Peer Booster arm completing all three boosters compared with only 108 (44%) of participants in the Web Booster arm (χ23=10.3; P=.006). In a model in which the 2 groups were combined, socioeconomic factors predicted booster engagement. In separate models, the demographic and clinical predictors of booster engagement varied between the 2 delivery modalities. CONCLUSIONS: The use of peer-delivered boosters, especially among subsets of reserve members at risk of lack of engagement, may foster greater uptake and improve treatment outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT02181283; https://clinicaltrials.gov/ct2/show/NCT02181283.

Prevalence and Severity of Alcohol and Cannabis Use Across the Urban-Rural Continuum in the Michigan National Guard.

PURPOSE: The National Guard provides critical support both domestically and abroad with soldiers dispersed throughout America and spanning the urban-rural continuum. To determine if location-specific interventions may be needed, we compared the prevalence and severity of cannabis and alcohol use among National Guard members across localities. METHODS: Michigan National Guard members were enrolled (N = 2,746) during drill weekends as part of a larger randomized behavioral trial. Cannabis (ASSIST; prevalence = 5%) and alcohol use (AUDIT; prevalence = 82%) were compared using hurdle regression models across locality status after adjusting for covariates. FINDINGS: Prevalence of cannabis and alcohol use was predicted by locality (adjusted odds ratio [AOR] = 0.913, 95% CI: 0.838-0.986, P = .029; AOR = 0.963, 95% CI: 0.929-0.998, P = .038, respectively), with more use in urban localities. Neither severity of cannabis nor alcohol use was predicted by locality status. CONCLUSIONS: Prevalence of cannabis and alcohol use in the National Guard is differentially elevated across localities with higher prevalence in more central, densely populated areas. Findings may inform future work considering accessibility and utilization of prevention and treatment services for Guard members across the urban-rural continuum.

Angiotensin II Influences Pre-mRNA Splicing Regulation by Enhancing RBM20 Transcription Through Activation of the MAPK/ELK1 Signaling Pathway.

RNA binding motif 20 (RBM20) is a key regulator of pre-mRNA splicing of titin and other genes that are associated with cardiac diseases. Hormones, like insulin, triiodothyronine (T3), and angiotensin II (Ang II), can regulate gene-splicing through RBM20, but the detailed mechanism remains unclear. This study was aimed at investigating the signaling mechanism by which hormones regulate pre-mRNA splicing through RBM20. We first examined the role of RBM20 in Z-, I-, and M-band titin splicing at different ages in wild type (WT) and RBM20 knockout (KO) rats using RT-PCR; we found that RBM20 is the predominant regulator of I-band titin splicing at all ages. Then we treated rats with propylthiouracil (PTU), T3, streptozotocin (STZ), and Ang II and evaluated the impact of these hormones on the splicing of titin, LIM domain binding 3 (Ldb3), calcium/calmodulin-dependent protein kinase II gamma (Camk2g), and triadin (Trdn). We determined the activation of mitogen-activated protein kinase (MAPK) signaling in primary cardiomyocytes treated with insulin, T3, and Ang II using western blotting; MAPK signaling was activated and RBM20 expression increased after treatment. Two downstream transcriptional factors c-jun and ETS Transcription Factor (ELK1) can bind the promoter of RBM20. A dual-luciferase activity assay revealed that Ang II, but not insulin and T3, can trigger ELK1 and thus promote transcription of RBM20. This study revealed that Ang II can trigger ELK1 through activation of MAPK signaling by enhancing RBM20 expression which regulates pre-mRNA splicing. Our study provides a potential therapeutic target for the treatment of cardiac diseases in RBM20-mediated pre-mRNA splicing.

Functional health status of adults with serious mental illness and diabetes mellitus: A latent profile analysis.

OBJECTIVE: Adults with serious mental illness are at increased risk for diabetes mellitus and diabetes-related complications. This article classifies subgroups among people with serious mental illness and comorbid diabetes with respect to functional status and examines differences among those groups. METHODS: This analysis used a baseline sample of 157 adults with serious mental illness and diabetes mellitus enrolled in a National Institute of Health-funded research study. Latent profile analysis was used to distinguish health status profiles and investigate how these subgroups differed across assessment domains. RESULTS: Participants with depression, schizophrenia, and bipolar disorder (n = 157) were included in the study. Mean age was 52.9 years (standard deviation = 9.8), and 62 (40%) were African American. From the latent profile analysis, a three-class model appeared to provide the best fit. Class 1 (34.9%) had a very low functional health status approximately two standard deviations below the general population mean. Class 2 (43.7%) had a low functional status approximately one standard deviation below the general mean. Class 3 (21.4%) had moderate functional status with scores near population mean. Groups differed on measures of personal characteristics, clinical status and symptom severity, self-care behaviors, and environmental characteristics. CONCLUSIONS: Although individuals with schizophrenia generally have poor prognosis once they develop diabetes, latent profile analysis identified distinct health status subgroups. Although all three groups demonstrated illness burden, the pattern of differences between these groups across measures may suggest the need for different interventions for highly diverse adults who received care within safety-net primary care.

Race analysis in an African American sample with serious mental illness and comorbid diabetes.

OBJECTIVES: Targeted Training in Illness Management (TTIM) focuses on enhancing care engagement for people living with serious mental illness and diabetes. This secondary analysis from a 60-week, randomized controlled trial of TTIM versus treatment as usual evaluated racial subgroup outcomes. METHOD: Demographics, clinical characteristics, and diabetes status were evaluated for those self-identifying as non-Hispanic White, African American, and Hispanic. Longitudinal response to TTIM was evaluated using a multiple domain risk index. Due to their small sample size; those identifying as Hispanic were excluded from this analysis. RESULTS: Non-Hispanic White participants had greater baseline socioeconomic advantages. Baseline risk scores, glycosylated hemoglobin (HbA1c) values, and HbA1c differences over time were similar for African American and non-Hispanic White participants. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: African American participants living with serious mental illness and diabetes receiving TTIM did as well as non-Hispanic White participants. Inclusive approaches that feature peer support and are situated in safety-net health care settings need to be further investigated with respect to potentially impacting health disparities. (PsycINFO Database Record

Associations among comorbid anxiety, psychiatric symptomatology, and diabetic control in a population with serious mental illness and diabetes: Findings from an interventional randomized controlled trial.

Objective Serious mental illness and type II diabetes mellitus have a high comorbidity, and both have a higher prevalence of anxiety disorders compared to the general population. Targeted Training in Illness Management is a group-based self-management training approach which targets serious mental illness and type II diabetes mellitus concurrently. This analysis examines data from a randomized controlled trial of Targeted Training in Illness Management intervention to examine the impact of comorbid anxiety on baseline psychiatric symptomatology and diabetic control, and on longitudinal treatment outcomes. Methods We conducted secondary analyses on data from a prospective, 60-week, randomized controlled trial testing Targeted Training in Illness Management versus treatment as usual in 200 individuals with serious mental illness and diabetes. Primary outcomes included measures related to serious mental illness symptoms, functional status, general health status, and diabetes control. Measures were compared between those participants with anxiety disorders versus those without anxiety at baseline as well as over time using linear mixed effects analyses. Results Forty seven percent of the participants had one or more anxiety disorders. At baseline, those with an anxiety diagnosis had higher illness severity, depressive, and other psychiatric symptomatology and disability. Diabetic control (HbA1c) was not significantly different at baseline. In the longitudinal analyses, no significant mean slope differences over time (group-by-time interaction effect) between those with anxiety diagnoses and those without in treatment as usual group were found for primary outcomes. Within the Targeted Training in Illness Management arm, those with anxiety disorders had significantly greater improvement in mental health functioning. Those with anxiety comorbidity in the Targeted Training in Illness Management group demonstrated significantly lower HbA1c levels compared to no anxiety comorbidity and also demonstrated a greater improvement in HbA1c over the first 30 weeks compared to those without anxiety comorbidity. Conclusion Comorbid anxiety in serious mental illness and type II diabetes mellitus population is associated with increased psychiatric symptomatology and greater disability. Individuals from this population appear to experience greater improvement in functioning from baseline with the Targeted Training in Illness Management intervention. Anxiety comorbidity in the serious mental illness and type II diabetes mellitus population does not appear to have a negative impact on diabetic control. These complex relationships need further study. Clinical Trials Registration ClinicalTrials.gov: Improving outcomes for individuals with serious mental illness and diabetes (NCT01410357).

Maternal obesity in the ewe increases cardiac ventricular expression of glucocorticoid receptors, proinflammatory cytokines and fibrosis in adult male offspring.

Obesity during human pregnancy predisposes offspring to obesity and cardiovascular disease in postnatal life. In a sheep model of maternal overnutrition/obesity we have previously reported myocardial inflammation and fibrosis, as well as cardiac dysfunction in late term fetuses, in association with chronically elevated blood cortisol. Significant research has suggested a link between elevated glucocorticoid exposure in utero and hypertension and cardiovascular disease postnatally. Here we examined the effects of maternal obesity on myocardial inflammation and fibrosis of their adult offspring. Adult male offspring from control (CON) mothers fed 100% of National Research Council (NRC) recommendations (n = 6) and male offspring from obese mothers (MO) fed 150% NRC (n = 6), were put on a 12-week ad libitum feeding challenge then necropsied. At necropsy, plasma cortisol and left and right ventricular thickness were markedly increased (P<0.05) in adult male MO offspring. Myocardial collagen content and collagen-crosslinking were greater (P<0.05) in MO offspring compared to CON offspring in association with increased mRNA and protein expression of glucocorticoid receptors (GR). No group difference was found in myocardial mineralocorticoids receptor (MR) protein expression. Further, mRNA expression for the proinflammatory cytokines: cluster of differentiation (CD)-68, transforming growth factor (TGF)-ß1, and tumor necrosis factor (TNF)-α were increased (P < 0.05), and protein expression of CD-68, TGF-ß1, and TNF-α tended to increase (P<0.10) in MO vs. CON offspring. These data provide evidence for MO-induced programming of elevated plasma cortisol and myocardial inflammation and fibrosis in adult offspring potentially through increased GR.

Clinic Appointment Attendance in Adults with Serious Mental Illness and Diabetes.

OBJECTIVES: We assessed characteristics that may predict outpatient appointment attendance in outpatient medical clinics among patients comorbid for serious mental illness (SMI) and type 2 diabetes (DM). METHODS: Baseline covariate data from 200 individuals with SMI-DM enrolled in a randomized controlled trial (RCT) were used to examine characteristics associated with electronic health record-identified clinic appointment attendance using a generalized estimating equations approach. The analyses evaluated the relationship between clinic attendance and potentially modifiable factors including disease knowledge, self-efficacy, social support, physical health, and mental health, as well as demographic information. RESULTS: Demographic and mental health characteristics were most associated with clinic attendance in adults with SMI-DM. Physical health was not associated with clinic attendance. CONCLUSIONS: Information on clinical and demographic characteristics and factors potentially modifiable by psychological interventions may be useful in improving adherence to treatment among SMI-DM patients. It is our hope that clinicians and researchers will use these results to help tailor adherence-facilitating interventions among people at particular risk for poor engagement in care.

A 60-Week Prospective RCT of a Self-Management Intervention for Individuals With Serious Mental Illness and Diabetes Mellitus.

OBJECTIVES: A 60-week randomized controlled trial assessed the effects of targeted training in illness management (TTIM) versus treatment as usual among 200 individuals with serious mental illness and diabetes mellitus. METHODS: The study used the Clinical Global Impression (CGI), the Montgomery-Asberg Depression Rating Scale (MADRS), and the Brief Psychiatric Rating Scale (BPRS) to assess psychiatric symptoms; the Global Assessment of Functioning (GAF) and the Sheehan Disability Scale (SDS) to assess functioning; the 36-Item Short-Form Health Survey (SF-36) to assess general health, and serum glycosylated hemoglobin (HbA1c) to assess diabetes control. RESULTS: Participants' mean±SD age was 52.7±9.5 years, and 54% were African American. They were diagnosed as having depression (48%), schizophrenia (25%), and bipolar disorder (28%). At baseline, depression severity was substantial but psychosis severity was modest. At 60 weeks, there was greater improvement among TTIM participants versus treatment-as-usual recipients on the CGI (p<.001), the MADRS (p=.016), and the GAF (p=.003). Diabetes knowledge was significantly improved among TTIM participants but not in the treatment-as-usual group. In post hoc analyses among participants whose HbA1c levels at baseline met recommendations set by the American Diabetes Association for persons with high comorbidity (53%), TTIM participants had minimal change in HbA1c over the 60-week follow-up, whereas HbA1c levels worsened in the treatment-as-usual group. CONCLUSIONS: TTIM was associated with improved psychiatric symptoms, functioning, and diabetes knowledge compared with treatment as usual. Among participants with better diabetes control at baseline, TTIM participants had better diabetes control at 60 weeks compared with recipients of treatment as usual.

Psychosocial Features of Clinically Relevant Patient Subgroups With Serious Mental Illness and Comorbid Diabetes.

OBJECTIVE: Care for people with serious mental illness and diabetes is complicated by clinical heterogeneity. This cross-sectional analysis of 200 individuals with comorbid serious mental illness and diabetes explored differentiation between patient subgroups that were characterized on the basis of selected dimensions within a biopsychosocial framework. METHODS: Relationships between self-efficacy, treatment expectation, social support, and depression were first assessed via bivariate Spearman correlations among 200 individuals participating in a randomized controlled trial who had diabetes along with major depression, bipolar disorder, or schizophrenia. Next, latent profile analyses were conducted to determine underlying subgroups on the basis of these variables. The resultant groups were compared on diabetes control, function, and symptoms. RESULTS: Two subgroups emerged. One had more severe psychiatric symptoms, low scores on other psychosocial variables, and worse diabetes control. The other had low levels of psychiatric symptoms, better scores on other variables, and better diabetes control. CONCLUSIONS: Symptom presentation and internal and external resources appeared to be related to diabetes control for people with comorbid diabetes and serious mental illness. Care approaches need to go beyond standard education and consider biopsychosocial variables.

Rethinking A1C targets for patients with mental illness?

The American Diabetes Association (ADA)'s "Standards of Medical Care in Diabetes" recognizes that hemoglobin A1C targets for patients should be individualized.² We consider it important to discuss challenges and limitations with each patient.

A Preliminary Analysis of Individuals With Serious Mental Illness and Comorbid Diabetes.

OBJECTIVE: To understand factors related to managing illness in older individuals with serious mental illness (SMI). METHODS: Baseline data from 200 individuals with SMI and diabetes enrolled in a study were used to compare characteristics between older (age >55) vs. younger (age ≤55) individuals. RESULTS: Older individuals had better diabetes control compared to younger individuals, those with major depressive disorder had diabetes for a longer duration, worse diabetic control, and more emergency department encounters. CONCLUSIONS: Helping younger individuals with SMI learn to manage their mental and physical health early-on might minimize the negative and cumulative effect of diabetes.

Associations between comorbid anxiety, diabetes control, and overall medical burden in patients with serious mental illness and diabetes.

OBJECTIVE: While previous work has demonstrated elevation of both comorbid anxiety disorders and diabetes mellitus type II in individuals with serious mental illness, little is known regarding the impact of comorbid anxiety on diabetes mellitus type II outcomes in serious mental illness populations. We analyzed baseline data from patients with serious mental illness and diabetes mellitus type II to examine relationships between comorbid anxiety, glucose control as measured by hemoglobin A1c score, and overall illness burden. METHODS: Using baseline data from an ongoing prospective treatment study involving 157 individuals with serious mental illness and diabetes mellitus type II, we compared individuals with and without a comorbid anxiety disorder and compared hemoglobin A1c levels between these groups to assess the relationship between anxiety and management of diabetes mellitus type II. We conducted a similar analysis using cumulative number of anxiety diagnoses as a proxy for anxiety load. Finally, we searched for associations between anxiety and overall medical illness burden as measured by Charlson score. RESULTS: Anxiety disorders were seen in 33.1% (N=52) of individuals with serious mental illness and diabetes mellitus type II and were associated with increased severity of depressive symptoms and decreased function. Hemoglobin A1c levels were not significantly different in those with or without anxiety, and having multiple anxiety disorders was not associated with differences in diabetes mellitus type II control. However, depressive symptoms were significantly associated with higher hemoglobin A1c levels. Neither comorbid anxiety nor anxiety load was significantly associated with overall medical burden. CONCLUSION: One in three people with serious mental illness and diabetes mellitus type II had anxiety. Depressive symptoms were significantly associated with Hb1Ac levels while anxiety symptoms had no relation to hemoglobin A1c; this is consistent with previously published work. More studies are needed to better understand the relationship between depression, anxiety, and health management in people with serious mental illness and diabetes mellitus type II.

Clinical characteristics of individuals with serious mental illness and type 2 diabetes.

OBJECTIVE: Data from 157 individuals with serious mental illness and comorbid diabetes enrolled in an ongoing treatment study were used to examine clinical correlates of diabetes control. METHODS: Factors assessed included depressive symptoms (Montgomery-Åsberg Depression Rating Scale), global psychopathology severity (Brief Psychiatric Rating Scale), and glycosylated hemoglobin (HbA1c), a biomarker of diabetes control. RESULTS: Seventy-seven participants had depression, 40 had schizophrenia, and 40 had bipolar disorder. Most were moderately to severely depressed with poor diabetes control. No correlation between diagnosis and diabetes control was found after adjustment for gender, race, health literacy, diabetes duration, and diabetes knowledge. Greater depression severity and longer diabetes duration were related to poorer diabetes control. Lower severity of global psychopathology was related to poorer diabetes control, perhaps because of overall low levels of psychosis and mania. CONCLUSIONS: People with serious mental illness and diabetes face multiple challenges, which, along with severe depression, may impede diabetes self-management.

Polynucleotide phosphorylase is required for Escherichia coli O157:H7 growth above refrigerated temperature.

BACKGROUND: The growth of Escherichia coli O157:H7 in contaminated dairy and other refrigerated food products due to temperature fluctuation poses a major food safety threat. Effective control or inhibition of E. coli O157:H7 growth depends on our understanding of mechanisms that regulate its growth at low temperature. We hypothesized that polynucleotide phosphorylase (PNPase) plays a critical role in E. coli O157:H7 low-temperature growth. METHODS: To test this hypothesis, the pnp deletion mutant of E. coli O157:H7 was generated using the λ Red recombinase system, and the growth and survival of wild-type and pnp deletion mutant strains were compared at low temperatures. RESULTS: The growth of pnp deletion mutant strains in Luria Broth (LB) and agar plate at 37°C was similar to their corresponding wild-type strains, while the deletion of pnp impaired E. coli O157:H7 growth in LB at 10°C and 22°C; growth impairment could be partially recovered in the mutant strains by ectopic expression of the pnp complementation plasmid, demonstrating that growth impairment was PNPase-specific. During 14 days of 10°C storage in both LB and milk, wild type strain EDL933 grew and reached >8 log10 colony-forming units per milliliter after 4 days of 10°C storage, while EDL933Δpnp gradually died off with effects more pronounced in milk, which were again mitigated by pnp overexpression. In addition, pnp deletion impaired the motility of E. coli O157:H7 but did not affect its susceptibility to H2O2. CONCLUSION: PNPase is required for the growth of E. coli O157:H7 at low temperature; PNPase thus provides a molecular target to control the growth of E. coli O157:H7, which may have important practical applications in dairy and other food industry.

c-di-GMP signaling regulates E. coli O157:H7 adhesion to colonic epithelium.

Escherichia coli O157:H7 is an important foodborne pathogen that causes serious illness in humans at low infectious doses. The main source of infections is beef or greens contaminated with E. coli O157:H7 shed by cattle. Here we investigated the role of c-di-GMP-dependent signal transduction in cattle gut colonization of E. coli O157:H7. To manipulate intracellular c-di-GMP levels, we introduced into E. coli O157:H7 a c-di-GMP specific phosphodiesterase (PDE). Liquid chromatography tandem mass spectrometry analysis confirmed that in E. coli O157:H7, over-expression of PDE decreased c-di-GMP level. Consistent with the altered c-di-GMP level, PDE overexpression resulted in decreased biofilm formation in E. coli O157:H7. Furthermore, this diminished c-di-GMP levels reduced adhesion of E. coli O157:H7 to both cultured HT-29 cells and cattle colon explants. Consistently, mRNA levels of genes involved in adhesion were down-regulated including genes encoding E. coli common pili, long polar fimbriae 1, hemorrhagic coli pilus, as well as intimin and tir. We further observed decreased curli fimbriae synthesis in the strain with decreased c-di-GMP levels, which was supported by the reduction in the transcription of curli large subunit gene csgA and the curli expression regulator gene csgD. Genes for enterocyte effacement encoded regulator (Ler) and type III secretion system effectors, EspA and EspB, were also down-regulated. Collectively, data indicated that c-di-GMP signaling positively regulates E. coli O157:H7 intestinal epithelial cell and tissue colonization and expression of associated adhesion factors.