Search

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., (© 2023 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.)

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 (χ 2 3 =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., (©Lara N Coughlin, Frederic C Blow, Maureen Walton, Rosalinda V Ignacio, Heather Walters, Lynn Massey, Kristen L Barry, Richard McCormick. Originally published in JMIR Mental Health (https://mental.jmir.org), 26.10.2021.)

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., (© 2019 National Rural Health Association.)

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.

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.

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, ((c) 2018 APA, all rights reserved).)

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).

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)-β1, and tumor necrosis factor (TNF)-α were increased (P < 0.05), and protein expression of CD-68, TGF-β1, 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.

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.

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.

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.

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., (Copyright © 2015 Elsevier Inc. All rights reserved.)

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.

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., (© The Author(s) 2015.)

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.

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., (Published by Elsevier B.V.)

Escherichia coli (E. coli) O157:H7 remains a major food safety concern associated with meat, especially beef products. Shiga toxins (Stx) are key virulence factors produced by E. coli O157:H7 that are responsible for hemorrhagic colitis and Hemolytic Uremic Syndrome. Stx are heat stable and can be absorbed after oral ingestion. Despite the extensive study of E. coli O157:H7 survival during meat processing, little attention is paid to the production of Stx during meat processing. The objective of this study was to elucidate the effect of salt, an essential additive to processed meat, at concentrations relevant to meat processing (0%, 1%, 2%, 3%, W/V) on Stx2 production and Stx2 prophage induction by E. coli O157:H7 strains. For both E. coli O157:H7 86-24 and EDL933 strains, including 2% salt in LB broth decreased (P<0.05) E. coli O157:H7 population, but increased (P<0.05) Stx2 production (as measured relative to Log(10)CFU) compared to that of the control (1% salt). Supplementing 3% salt decreased (P<0.05) both E. coli O157:H7 number and Stx2 production. Quantitative RT-PCR indicated that stx2 mRNA expression in culture media containing 2% salt was greatly increased (P<0.05) compared to other salt concentrations. Consistent with enhanced Stx2 production and stx2 expression, the 2% salt group had highest lambdoid phage titer and stx2 prophage induction among all salt treatments. RecA is a key mediator of bacterial response to stress, which mediates prophage activation. Quantitative RT-PCR further indicated that recA mRNA expression was higher in both 2% and 3% salt than that of 0% and 1% salt treatments, indicating that stress was involved in enhanced Stx2 production. In conclusion, salt at the concentration used for meat processing enhances Stx production, a process linked to bacterial stress response and lambdoid prophage induction., (Published by Elsevier B.V.)

Purpose: In order to assess the effect of daily exercise on extracellular matrix remodeling in the heart after myocardial infarction (MI), we measured collagen concentration (%COL) and nonreducible collagen cross-linking (hydroxylysylpyridinoline, HP) in the right ventricle (RV), and regionally within the infarcted (INF) and viable left ventricular free wall (LVF) and septum (LVS), using a rodent MI training model., Methods: Infarcts (19%-24% of LV) were surgically induced in adult rats that were assigned to either trained (MI-TR) or sedentary (MI-SED) groups and compared to sham-surgery sedentary controls (SHAM)., Results: In LVF, 10 wk of treadmill running had no effect on the increase (P < 0.001) in %COL seen with MI (MI-SED = 7.14% ± 0.15%, MI-TR = 7.61% ± 0.19%, SHAM = 3.55% ± 0.19%). However, it normalized the increase (P < 0.05) in HP cross-linking (MI-SED = 0.43 ± 0.02, MI-TR = 0.27 ± 0.03, SHAM = 0.30 ± 0.04 mol HP·mol(-1) collagen). The INF scar in MI-SED rats showed a sevenfold increase in %COL (P < 0.001) compared to SHAM LVF myocardium, an increase that was attenuated by training (MI-SED = 26% ± 1% vs MI-TR = 21% ± 2%; P < 0.05). However, training had no effect on MI-induced increases in cross-linking in the INF scar (1.01 ± 0.22 vs 0.84 ± 0.14 mol HP·mol(-1) collagen). In LVS, although a small but significant increase in %COL was seen in both MI groups, HP cross-linking was unaltered compared to SHAM rats. Training also normalized the increase observed in cross-linking in RV after MI., Conclusions: Because increased HP cross-linking in the heart is associated with decreased chamber compliance, these findings may help to explain the improved heart function seen after daily exercise in cardiac rehabilitation patients.

Maternal obesity (MO) has harmful effects on both fetal development and subsequent offspring health. We previously demonstrated that MO enhances collagen accumulation in fetal skeletal muscle, but its impact on mature offspring muscle collagen accumulation is unknown. Ewes were fed either a control diet (Con, fed 100% of NRC nutrient recommendations) or obesogenic diet (OB, fed 150% of NRC nutrient recommendations) from 60 days before conception to birth. All ewes received the Con diet during lactation. Male offspring were euthanized at 2.5 years (mean) and the left Longissimus dorsi (LD) muscle and semitendinosus (ST) muscle were sampled. Collagen concentration increased by 37.8 ± 19.0% (P<0.05) in LD and 31.2 ± 16.0% (P<0.05) in ST muscle of OB compared to Con offspring muscle. Mature collagen cross-linking (pyridinoline concentration) was increased for 22.3 ± 7.4% and 36.3 ± 9.9% (P<0.05) in LD and ST muscle of OB group respectively. Expression of lysyl oxidase, lysyl hydroxylase-2b (LH2b) and prolyl 4-hydroxylase (P4HA) was higher in OB LD and ST muscle. In addition, the expression of metalloproteinases (MMPs) was lower but tissue inhibitor of metalloproteinases (TIMPs) was higher in OB offspring muscle, indicating reduced collagen remodeling. MO enhanced collagen content and cross-linking in offspring muscle, which might be partially due to reduced collagen remodeling. Our observation that the collagen content and cross-linking are enhanced in MO offspring muscle is significant, because fibrosis is known to impair muscle functions and is a hallmark of muscle aging.

Objective: Patients with hepatitis C virus (HCV) are advised to refrain from alcohol consumption. A questionnaire was developed to measure concepts associated with alcohol use for individuals with HCV., Method: Subjects with HCV (N = 527) completed a telephone survey. Eligible respondents had screened negative for current abuse/dependence disorders (Alcohol Use Disorders Identification Test [AUDIT] ≤ 10). Measures of personality, self-efficacy, knowledge, readiness, coping styles, stigma, and symptoms were examined for associations with alcohol use., Results: Factor analysis supported a measurement structure of 105 items in 35 subdomains. A total of 26 subdomains had significant bivariate associations with alcohol use. Higher self-efficacy for resisting drinking in social situations was associated with lower alcohol use (r = -.68, p < .001), as was knowledge of alcohol and HCV (r = -.27, p < .001). Although agreeableness and marital status are typically associated with lower current drinking in samples of those with alcohol use problems, in our study agreeableness (β = .13, p < .01) and marital status (β = .08, p < .05) were modestly associated with higher current drinking. The final multivariate R² was .55., Conclusions: The pattern of associations suggests the importance of the social aspects of drinking for drinking decisions. Existing brief interventions will need to be tailored to a contextualized psychosocial model for medical patients with HCV and AUDIT scores ≤ 10 to optimize effectiveness. Such future interventions should emphasize the potential medical hazards of drinking for persons with HCV, the maintenance of social relationships in the absence of alcohol use, and strategies for building confidence for resisting drinking in specific situations.

Maternal obesity (MO) has harmful effects on both fetal development and subsequent offspring health. The impact of MO on fetal myocardium development has received little attention. Fibrogenesis is regulated by the transforming growth factor-β (TGF-β)/p38 signaling pathway. Using the well-established model of MO in pregnant sheep, we evaluated the effect of MO on TGF-β/p38 and collagen accumulation in fetal myocardium. Nonpregnant ewes were assigned to a control diet [Con, fed 100% of National Research Council (NRC) nutrient recommendations] or obesogenic diet (OB, fed 150% of NRC recommendations) from 60 days before conception. Fetal ventricular muscle was sampled at 75 and 135 days of gestation (dG). At 75 dG, the expression of precursor TGF-β was 39.9 ± 9.9% higher (P < 0.05) in OB than Con fetal myocardium, consistent with the higher content of phosphorylated Smad3 in OB myocardium. The phosphorylation of p38 tended to be higher in OB myocardium (P = 0.08). In addition, enhanced Smad complexes were bound to Smad-binding elements in 75 dG OB fetal myocardium measured by DNA mobility shift assay (130.2 ± 26.0% higher, P < 0.05). Similar elevation of TGF-β signaling was observed in OB fetal myocardium at 135 dG. Total collagen concentration in OB was greater than Con fetal myocardium (2.42 ± 0.16 vs. 1.87 ± 0.04%, P < 0.05). Matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-3 were higher in the Con group compared with OB sheep (43.86 ± 16.01 and 37.23 ± 7.97% respectively, P < 0.05). In summary, MO results in greater fetal heart connective tissue accumulation associated with an upregulated TGF-β/p38 signaling pathway at late gestation; such changes would be expected to negatively impact offspring heart function.

Maternal obesity (MO) is increasing at an alarming rate. The objective of this study was to evaluate the effect of MO on fibrogenesis in fetal skeletal muscle during maturation in late gestation. Nonpregnant ewes were assigned to a control diet (Con; fed 100% of NRC nutrient recommendations, n = 6) or obesogenic diet (OB; fed 150% of NRC recommendations, n = 6) from 60 days before conception, and fetal semitendenosus (St) muscle was sampled at 135 days of gestation (term 148 days). Total concentration and area of collagen in cross-sections of muscle increased by 27.0 +/- 6.0 (P < 0.05) and 105.1 +/- 5.9% (P = 0.05) in OB compared with Con fetuses. The expression of precursor TGF-beta was 177.3 +/- 47.6% higher, and concentration of phospho-p38 74.7 +/- 23.6% was higher (P < 0.05) in OB than in CON fetal muscle. Increases of 327.9 +/- 168.0 (P < 0.05) and 188.9 +/- 82.1% (P < 0.05), respectively, were observed for mRNA expression of Smad7 and fibronectin in OB compared with Con muscles. In addition, enzymes involved in collagen synthesis, including lysyl oxidase, lysyl hydroxylase 2b, and prolyl 4-hydroxylase-alpha1, were increased by 350.2 +/- 90.0 (P < 0.05), 236.5 +/- 25.2 (P < 0.05), and 82.0 +/- 36.2% (P = 0.05), respectively, in OB muscle. In conclusion, MO-enhanced fibrogenesis in fetal muscle in late gestation was associated with upregulation of the TGF-beta/p38 signaling pathway. Enhanced fibrogenesis at such an early stage of development is expected to negatively affect the properties of offspring muscle because muscle fibrosis is a hallmark of aging.

Objectives: To examine management strategies and goals reported by people diagnosed with chronic hepatitis C., Methods: We analyzed data from semistructured interviews (N = 42) and from electronic sources [illness narratives (N = 79) and Internet threaded discussions (N = 264)]. Line-by-line coding, comparisons, and team discussions generated catalogs of lay management strategies and goals. We analyzed code-based files to identify informants' selection of specific strategies for each goal., Results: We classified lay management strategies into 3 categories: medical self-care, behavior change, and coping. These strategies were used selectively in addressing multiple goals, categorized as fighting the virus, strengthening the body, and managing consequences., Conclusions: Results underscore the diversity of strategies for living with a disease characterized by uncertain prognosis and variable expression of symptoms.

Most studies of decisions to curtail alcohol consumption reflect experiences of abusing drinkers. We employ an exploratory sequential research design to explore the applicability of this research to the experience of nonabusing drinkers advised to curtail alcohol consumption after a Hepatitis C diagnosis. A qualitative component identified 17 new decision factors not reflected in an inventory of factors based on synthesis of existing scales. We triangulated qualitative data by supplementing semi-structured interviews with Internet postings. A quantitative component estimated prevalence and association with current drinking of these new decision factors. Patients who quit drinking tended to attribute post-diagnosis drinking to occasional triggers, whereas patients who were still drinking were more likely to endorse rationales not tied to specific triggers.

Background: Abstaining from alcohol consumption is generally recommended for patients with Hepatitis C(HCV). However, mixed research findings coupled with a lack of consistent guidelines on alcohol consumption and HCV may influence what healthcare providers tell their HCV patients about drinking. This may be more problematic when advising nonharmful drinkers with HCV, a population for whom consumption would not bea problem in the absence of their HCV diagnosis., Objective: This study explores what healthcare providers advise their HCV patients who are drinking alcohol at nonharmful levels about alcohol use and what these patients actually hear., Design: We conducted separate focus groups and interviews about alcohol use and HCV with nonharmful drinkers with HCV (N=50) and healthcare providers (N=14) at a metropolitan teaching hospital. All focus groups and interviews were audio-taped, transcribed, and analyzed using NVivo, a qualitative data management and analysis program., Results: We found similar themes about HCV and alcohol consumption (stop completely, occasional drink is ok, cut down, and provision of mixed/ambiguous messages), reported by both providers and patients.Patient respondents who reported hearing “stop completely”were more likely to have had their last medical visit at the gastroenterology (GI) clinic as opposed to the internal medicine (IM) clinic. Furthermore, IM providers were more likely to give their recommendations in“medical language” than were GI providers., Conclusions: To make the best health-related decisions about their disease, HCV patients need consistent information about alcohol consumption. Departments of Internal Medicine can increase provider knowledge about HCV and alcohol use by providing more education and training on HCV.

Background: Abstaining from alcohol consumption is generally recommended for patients with Hepatitis C (HCV). However, mixed research findings coupled with a lack of consistent guidelines on alcohol consumption and HCV may influence what healthcare providers tell their HCV patients about drinking. This may be more problematic when advising nonharmful drinkers with HCV, a population for whom consumption would not be a problem in the absence of their HCV diagnosis., Objective: This study explores what healthcare providers advise their HCV patients who are drinking alcohol at nonharmful levels about alcohol use and what these patients actually hear., Design: We conducted separate focus groups and interviews about alcohol use and HCV with nonharmful drinkers with HCV (N = 50) and healthcare providers (N = 14) at a metropolitan teaching hospital. All focus groups and interviews were audio-taped, transcribed, and analyzed using NVivo, a qualitative data management and analysis program., Results: We found similar themes about HCV and alcohol consumption (stop completely, occasional drink is ok, cut down, and provision of mixed/ambiguous messages), reported by both providers and patients. Patient respondents who reported hearing "stop completely" were more likely to have had their last medical visit at the gastroenterology (GI) clinic as opposed to the internal medicine (IM) clinic. Furthermore, IM providers were more likely to give their recommendations in "medical language" than were GI providers., Conclusions: To make the best health-related decisions about their disease, HCV patients need consistent information about alcohol consumption. Departments of Internal Medicine can increase provider knowledge about HCV and alcohol use by providing more education and training on HCV.

Collagen accumulates disproportionately in cardiac remodeling induced by hypertension and associated with advancing age. Spironolactone (Spiro), an aldosterone antagonist, attenuates the accumulation of collagen induced by hypertension. It was hypothesized that Spiro would attenuate the age-associated increase in percent collagen in the heart. Female Fisher 344 rats at 3 months (Y), 12 months (M), and 21 months (O) of age were treated with Spiro (30 mg/kg/d) or vehicle (Veh) for 2 months, yielding six groups: Y-Veh, Y-Spiro, M-Veh, M-Spiro, O-Veh, and O-Spiro. Hearts were harvested for immunoblotting, RNA blotting, and biochemical analysis. Percent collagen in the left ventricle and septum was greatest in the oldest rats. Spiro did not significantly attenuate the age-associated increase in collagen fraction or the age-associated increases in expression of atrial natriuretic factor and beta-myosin heavy chain messenger RNA. Chronic aldosterone antagonism does not attenuate the age-associated increase in collagen fraction in the female Fisher 344 rat heart.

Aims: Little is known about how non-problematic drinkers respond to advice to reduce alcohol consumption as part of disease management. In this article, we examine patient reports of drinking behaviour after being diagnosed with chronic hepatitis C, a condition for which alcohol consumption is contraindicated., Methods: In this qualitative study, we analyzed transcripts of semi-structured interviews with hepatitis C virus+ (HCV+) patients whose level of alcohol consumption would not be considered problematic in the absence of their diagnosis., Results: Most respondents reported some instances of adherence, but only half adhered to the advice to limit drinking consistently over time. Respondents who did not stop drinking often modified their behaviour by changing the type of alcohol consumed or limiting drinking to particular occasions., Conclusion: Most informants understood the risks of drinking after HCV infection, particularly in the presence of symptoms, with the onset of complications, or when undergoing treatment. But some believed they could monitor their bodies for evidence of disease progression or that drinking was acceptable during early, asymptomatic stages of infection. Our results also identified situations in which patients need support in adhering to intentions not to drink, including social pressures, stressful situations, or environmental triggers.

Pale, soft, and exudative (PSE) meat has been recognized for decades. Fast glycolysis during early post-mortem stage while the muscle temperature is still high is the cause of PSE meat. To elucidate the molecular mechanism underlying this fast glycolysis in muscle to become PSE meat, post-mortem ATP metabolism, fructose-2,6-diphosphate content, and the activities of AMPK, glycogen phosphorylase, and pyruvate kinase were examined in post-mortem muscle. Earlier and faster post-mortem AMPK activation was responsible for the significantly lower pH and higher lactic acid accumulation (p<0.05) seen in PSE muscle, which resulted in the occurrence of PSE meat. In muscle that became PSE meat, AMPK was activated at 0 h post-mortem and reached maximal activation at 0.5 h post-mortem, whereas AMPK reached maximal activation at 1 h post-mortem in the normal pork loin. Higher fructose-2,6-diphosphate content (p<0.05) was detected in PSE muscle compared to normal muscle at early post-mortem stage. However, no difference in the activities of glycogen phosphorylase and pyruvate kinase, rate-controlling enzymes in glycogenolysis and glycolysis, respectively, was detected between PSE and normal pork loins. Because fructose-2,6-diphosphate is a product of phosphofructokinase-2 (PFK-2), these data suggest that AMPK regulates post-mortem glycolysis through its phosphorylation and activation of PFK-2, which then up-regulates the activity of phosphofructokinase-1 (PFK-1), a key rate-controlling enzyme in glycolysis. Early AMPK activation in PSE muscle is associated with early consumption of ATP, because higher AMP and IMP contents and lower ATP content were detected in PSE meat compared to normal meat. Other mechanisms causing early AMPK activation in PSE meat may exist, which warrants further investigation.

We report a genome-wide survey of early responses of the mouse heart transcriptome to acute myocardial infarction (AMI). For three regions of the left ventricle (LV), namely, ischemic/infarcted tissue (IF), the surviving LV free wall (FW), and the interventricular septum (IVS), 36,899 transcripts were assayed at six time points from 15 min to 48 h post-AMI in both AMI and sham surgery mice. For each transcript, temporal expression patterns were systematically compared between AMI and sham groups, which identified 515 AMI-responsive genes in IF tissue, 35 in the FW, 7 in the IVS, with three genes induced in all three regions. Using the literature, we assigned functional annotations to all 519 nonredundant AMI-induced genes and present two testable models for central signaling pathways induced early post-AMI. First, the early induction of 15 genes involved in assembly and activation of the activator protein-1 (AP-1) family of transcription factors implicates AP-1 as a dominant regulator of earliest post-ischemic molecular events. Second, dramatic increases in transcripts for arginase 1 (ARG1), the enzymes of polyamine biosynthesis, and protein inhibitor of nitric oxide synthase (NOS) activity indicate that NO production may be regulated, in part, by inhibition of NOS and coordinate depletion of the NOS substrate, L: -arginine. ARG1: was the single-most highly induced transcript in the database (121-fold in IF region) and its induction in heart has not been previously reported.

This study examined the long-term relationship of changes in the motivation to remedy alcohol abuse to alcohol use severity among patients with a dual diagnosis of substance abuse disorder and severe and persistent mental illness. Linear regression analyses showed that patients who increasingly recognized alcohol use problems over a 9-month period exhibited significantly greater alcohol use severity at 9 months and a significant increase in alcohol use severity over time. Moreover, patients who became increasingly determined to take actions against alcohol use over a 9-month period exhibited significantly lower alcohol use severity at 9 months and a significant decrease in alcohol use severity over time. The findings support Prochaska et al.'s transtheoretical model of the motivation for change. They suggest that the recognition of alcohol use problems comes along with learning adverse consequences of alcohol use and that increased determination to take actions is critical to the long-term behavioral changes in alcohol use.

Objective: This study examined the effect of motivation for change, measured by the Stages of Change Readiness and Treatment Eagerness Scale (SOCRATES), on alcohol use severity among alcoholic patients with severe and persistent mental illness., Method: At a Veterans Affairs hospital, 390 dually diagnosed patients were recruited and assessed for motivation for change, alcohol use severity, psychotic symptoms and global functioning at baseline and 9-month follow-up., Results: Regression analyses showed that patients who were highly ambivalent about their alcohol use at baseline consumed significantly more alcohol 9 months later, on the basis of Addiction Severity Index ratings (p < or = .01), than patients who felt less ambivalent., Conclusions: The findings suggest that increased awareness of alcohol-related problems is essential to reducing alcohol use severity for alcoholic patients with severe and persistent mental illness. The implications and limitations of the findings are discussed.

Although evidence indicates that brief alcohol screening and interventions are effective across primary care settings, implementation of these techniques has been problematic. The primary objective of this study was to determine current practices and barriers for screening and interventions with primary care patients across randomly selected clinics in a large health care system, the Veterans Health Administration. Focus groups and mailed structured surveys were used. Results from providers indicated that 85% of patients treated in primary care received some screening for alcohol use disorders. The CAGE was the predominant screening tool. The primary clinical focus was on treatment referrals for patients who met abuse/dependence criteria. Lack of time was the most important perceived barrier to implementing screening and brief alcohol interventions for at-risk and problem drinkers. Implications for implementation of screening and intervention programs for a range of drinkers (at-risk use, problem use, abuse, dependence) are discussed.

Early gestation is critical for placentomal growth, differentiation, and vascularization, as well as fetal organogenesis. The fetal origins of adult disease hypothesis proposes that alterations in fetal nutrition and endocrine status result in developmental adaptations that permanently change structure, physiology, and metabolism, thereby predisposing individuals to cardiovascular, metabolic, and endocrine disease in adult life. Multiparous ewes were fed to 50% (nutrient restricted) or 100% (control fed) of total digestible nutrients from Days 28 to 78 of gestation. All ewes were weighed weekly and diets adjusted for individual weight loss or gain. Ewes were killed on Day 78 of gestation and gravid uteri recovered. Fetal body and organ weights were determined, and numbers, morphologies, diameters, and weights of all placentomes were obtained. From Day 28 to Day 78, restricted ewes lost 7.4% of body weight, while control ewes gained 7.5%. Maternal and fetal blood glucose concentrations were reduced in restricted versus control pregnancies. Fetuses were markedly smaller in the restricted group than in the control group. Further, restricted fetuses exhibited greater right- and left-ventricular and liver weights per unit fetal weight than control fetuses. No treatment differences were observed in any gross placentomal measurement. However, caruncular vascularity was enhanced in conceptuses from nutrient-restricted ewes but only in twin pregnancies. While these alterations in fetal/placental development may be beneficial to early fetal survival in the face of a nutrient restriction, their effects later in gestation as well as in postnatal life need further investigation.

To date, no study has assessed the degree of similarity between left ventricular (LV) reverse remodeling and atrophic remodeling. Stable LV hypertrophy was induced by creation of an arteriovenous fistula (AVF) in Lewis rats (32 days). LV unloading was induced by heterotopic transplantation of normal (NL-HT) and/or hypertrophic (AVF-HT) hearts (7 days). We compared indexes of remodeling in AVF, NL-HT, and AVF-HT groups with those of normal controls. LV unloading induced decreases in cardiomyocyte size in NL-HT and AVF-HT hearts. NL-HT and AVF-HT LV were both characterized by relative increases in collagen concentration that were largely a reflection of decreases in myocyte volume. NL-HT and AVF-HT LV were associated with similar increases in matrix metalloproteinase (MMP-2 and -9) zymographic activity, without change in the abundance of the tissue inhibitors of the MMPs. In contrast, AVF-HT, but not NL-HT, was associated with a dramatic increase in collagen cross-linking. Our findings suggest an overall similarity in the response of the normal and hypertrophic LV to surgical unloading. However, the dramatic increase in collagen cross-linking after just 1 wk of unloading suggests a potential difference in the dynamics of collagen metabolism between the two models. Further studies will be required to determine the precise molecular mechanisms responsible for these differences in extracellular matrix regulation. However, with respect to these and related issues, heterotopic transplantation of hypertrophied hearts will be a useful small animal model for defining mechanisms of myocyte-matrix interactions during decreased loading conditions.

Completed suicides over a one year period of time were reported from a nationwide survey of Department of Veteran Affairs medical centers. Of a total of 248 completed suicides, 11 occurred in outpatient substance abuse programs, and an additional 5 occurred among patients receiving combined outpatient substance abuse and psychiatric treatment. There were no inpatient suicides. During this time, there were 7 suicide attempts on inpatient units and 37 suicide attempts in outpatient chemical dependency treatment. The majority of suicides were committed by males who had a primary alcohol addiction (63%). Thirty-eight percent of the sample had a comorbid mood disorder and 38% had a comorbid personality disorder. Risk factors relating to the potential for suicide in chemical dependency programs are discussed.

The general struggle throughout Christian history has been to seek the proper balance between dominion and limits, intervention and nonintervention, givenness, and creativity. This struggle has worked itself out in six areas that touch human life. In this essay, I will revisit the Catholic tradition's treatment of these in terms of dominion and limits to see whether we can discern developmental patterns that might suggest an approach to issues pertaining to the sources of life (reproductive ethics) as we move into the next century.