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Background: tumor-infiltrating lymphocytes are prognostic in many human cancers. However, the prognostic value of lymphocytes infiltrating glioblastoma (GBM), and roles in tumor control or progression are unclear. We hypothesized that B and T cell density, and markers of their activity, proliferation, differentiation, or function, would have favorable prognostic significance for patients with GBM. Methods: initial resection specimens from 77 patients with IDH1/2 wild type GBM who received standard-of-care treatment were evaluated with multiplex immunofluorescence histology (mIFH), for the distribution, density, differentiation, and proliferation of T cells and B cells, as well as for the presence of tertiary lymphoid structures (TLS), and IFNγ expression. Immune infiltrates were evaluated for associations with overall survival (OS) by univariate and multivariate Cox proportional hazards modeling. Results: in univariate analyses, improved OS was associated with high densities of proliferating (Ki67+) CD8+ cells (HR 0.36, p = 0.001) and CD20+ cells (HR 0.51, p = 0.008), as well as CD8+Tbet+ cells (HR 0.46, p = 0.004), and RORγt+ cells (HR 0.56, p = 0.04). Conversely, IFNγ intensity was associated with diminished OS (HR 0.59, p = 0.036). In multivariable analyses, adjusting for clinical variables, including age, resection extent, Karnofsky Performance Status (KPS), and MGMT methylation status, improved OS was associated with high densities of proliferating (Ki67+) CD8+ cells (HR 0.15, p < 0.001), and higher ratios of CD8+ cells to CD4+ cells (HR 0.31, p = 0.005). Diminished OS was associated with increases in patient age (HR 1.21, p = 0.005) and higher mean intensities of IFNγ (HR 2.13, p = 0.027). Conclusions: intratumoral densities of proliferating CD8 T cells and higher CD8/CD4 ratios are independent predictors of OS in patients with GBM. Paradoxically, higher mean intensities of IFNγ in the tumors were associated with shorter OS. These findings suggest that survival may be enhanced by increasing proliferation of tumor-reactive CD8+ T cells and that approaches may be needed to promote CD8+ T cell dominance in GBM, and to interfere with the immunoregulatory effects of IFNγ in the tumor microenvironment.

Background The hippocampus is important for memory processing. Several neuropsychiatric diseases including Alzheimer’s disease are associated with reduced hippocampal volume, and further the hippocampus appears vulnerable to environmental insult. Air pollution has been associated with cardiovascular disease, abnormal brain structure, and cognitive deficits. Objective Because of hippocampal vulnerability to environmental insults and based on the association between exposure to air pollution and cognitive function and brain structure, we evaluated the association between exposure to toxins in air pollution and left and right hippocampal volume using brain-imaging and air-pollution data from the UK Biobank, a large community-based dataset. Methods We used regression modelling to evaluate the association between exposure to nitrogen dioxide, nitrogen oxides, PM 2.5 , PM 2.5-10 , and PM 10. and left and right hippocampal volume controlling for age, sex, body-mass index, overall health, alcohol use, smoking, educational attainment, socioeconomic status, inverse distance from the nearest major road, and a measure of total brain volume. Results In these models, PM 2.5 concentration was associated with smaller left hippocampal volume. None of the other measures of air pollution was associated with either left or right hippocampal volume, although interaction models provided some evidence that sex might moderate the relationship between air pollution and hippocampal volume. In adjusted models, age, sex, educational attainment, income, overall health, current smoking, alcohol intake, and body-mass index were associated with hippocampal volume. Conclusions PM 2.5 at levels found in the United Kingdom was associated with smaller left hippocampal volume. Additional associations between several covariates and hippocampal volumes indicate that hippocampal volume might be associated with several potentially modifiable variables.

Infecting approximately one-third of the world’s human population, Toxoplasma gondii has been associated with cognitive function. Here, we sought to further characterize the association between Toxoplasma gondii and cognitive function in a community sample of adults aged approximately 40 to70 years. Using adjusted linear regression models, we found associations of Toxoplasma gondii seropositivity with worse reasoning (b = -.192, p < .05) and matrix pattern completion (b = -.681, p < .01), of higher anti-Toxoplasma gondii p22 antibody levels with worse reasoning (b = -.078, p < .01) and slower Trails (numeric) performance (b = 5.962, p < .05), of higher anti-Toxoplasma gondii sag1 levels with worse reasoning (b = -.081, p < .05) and worse matrix pattern completion (b = -.217, p < .05), and of higher mean of the anti-Toxoplasma gondii p22 and sag1 levels with worse reasoning (b = -.112, p < .05), slower Trails (numeric) performance (b = 9.195, p < .05), and worse matrix pattern completion (b = -.245, p < .05). Neither age nor educational attainment moderated associations between the measures of Toxoplasma gondii seropositivity or serointensity. Sex, however, moderated the association between the sag1 titer and digit-symbol substitution and the association between the mean of the p22 and sag1 levels and digit-symbol substitution, and income moderated the association between Toxoplasma gondii seropositivity and numeric memory and the association between the p22 level and symbol-digit substitution. Based on the available neuropsychological tasks in this study, Toxoplasma gondii seropositivity and serointensity were associated with some aspects of poorer executive function in adults., Author summary Toxoplasma gondii is a parasite that reproduces in cats but that can infect other animals and humans. Toxoplasma gondii has an affinity for the brain and infection results in a long-term immune response that may have negative effects. Animal models have shown that Toxoplasma gondii can affect behavior and cognition (thinking). In humans, the association is less clear, but there are associations between infection and variety of psychiatric and neurological conditions such as schizophrenia and epilepsy. Toxoplasma gondii may even increase the risk of dementia. If true, it is possible that the presence of this infection may affect thinking long before the onset of dementia. We sought to determine if the presence of antibodies in the blood to Toxoplasma gondii, which is the immune system’s response to past infections, might be associated with performance on measures of cognition. We analyzed a large dataset, the UK Biobank, which includes measures of cognition and blood test results for antibodies to Toxoplasma gondii. We found that both the presence of antibodies as well as the amount of these antibodies were related to some aspects of cognition, particularly problem solving and reasoning in otherwise healthy adults ages 40 to 69 years.

INTRODUCTION There is growing evidence that moral injury (MI) is related to greater suicide risk among Veterans and Active Duty Military (V/ADM). This study examines the relationship between MI and suicide risk and the moderating effect of religiosity on this relationship in V/ADM with post-traumatic stress disorder (PTSD) symptoms. MATERIALS AND METHODS This was a cross-sectional multi-site study involving 570 V/ADM from across the USA. Inclusion criteria were having served in a combat theater and the presence of PTSD symptoms. Multidimensional measures assessed MI, religiosity, PTSD symptoms, anxiety, and depression. In this secondary data analysis, a suicide risk index was created based on 10 known risk factors. Associations between MI and the suicide risk index were examined, controlling for demographic, religious, and military characteristics, and the moderating effects of religiosity were explored. RESULTS MI overall was correlated strongly with suicide risk (r = 0.54), as were MI subscales (ranging from r = 0.19 for loss of trust to 0.48 for self-condemnation). Controlling for other characteristics had little effect on this relationship (B = 0.016, SE = 0.001, p < 0.0001). Religiosity was unrelated to suicide risk and did not moderate the relationship between suicide risk and MI or any of its subscales. CONCLUSION MI is strongly and independently associated with risk factors for suicide among V/ADM with PTSD symptoms, and religiosity does not mediate or moderate this relationship. Whether interventions that target MI reduce risk of suicide or suicidal ideation remains unknown and needs further study.

Moral injury (MI) involves feelings of shame, grief, meaninglessness, and remorse from having violated core moral beliefs related to traumatic experiences. This multisite cross-sectional study examined the association between religious involvement (RI) and MI symptoms, mediators of the relationship, and the modifying effects of posttraumatic stress disorder (PTSD) severity in 373 US veterans with PTSD symptoms who served in a combat theater. Assessed were demographic, military, religious, physical, social, behavioral, and psychological characteristics using standard measures of RI, MI symptoms, PTSD, depression, and anxiety. MI was widespread, with over 90% reporting high levels of at least one MI symptom and the majority reporting at least five symptoms or more. In the overall sample, religiosity was inversely related to MI in bivariate analyses (r = -0.25, p < 0.0001) and multivariate analyses (B = -0.40, p = 0.001); however, this relationship was present only among veterans with severe PTSD (B = -0.65, p = 0.0003). These findings have relevance for the care of veterans with PTSD.

Mood disorders are common mental illnesses. Among the factors associated with major depression are exposures to infectious diseases including hepatitis C, influenza, varicella-zoster, and herpes viruses. In this study, we sought to evaluate further associations between viral exposure and depression. From the US Center for Disease Control's National Health and Nutrition Examination Survey, we obtained data about depression status, antidepressant use, exposure to hepatitis A, hepatitis B, herpes simplex virus type 1, herpes simplex virus type 2, human immunodeficiency virus, and cytomegalovirus, and sociodemographic variables and evaluated associations between depression and viral exposure in adjusted multivariable models. Herpes simplex virus type 2 was associated with an increased risk of depression, whereas hepatitis A, hepatitis B, and herpes simplex virus type 1 were not. Higher cytomegalovirus antibody levels were associated with depression in subjects seropositive for cytomegalovirus. In conclusion, exposure to herpes simplex virus type 2 and possibly cytomegalovirus are associated with depression in an adult US sample.

Supportive non-parental adults, particularly non-familial adults, provide critical support during the transition to adulthood, opening doors to educational and career paths. The current study examined whether economic disadvantage shapes access to these relationships. Results showed that low-income adolescents had reduced access to naturally-occurring mentors, and the relationships they did form tended to be close bonds with family and friends, rather than non-familial adults. Their mentors were more likely to focus on practical support, and less likely to serve as role models or provide career advice. These effects of socio-economic status on natural mentoring relationships remained evident, even when accounting for youth race/ethnicity. Findings suggest that networks of support differ depending on a youth’s socio-economic context in ways that could perpetuate social and economic inequalities.

Social support promotes resilience to adverse childhood events, but little is known about the role of natural mentors-caring, nonparental adults-in the lives of childhood abuse survivors. The current study draws from a large, longitudinal, nationally representative sample (Add Health) to examine the prevalence and characteristics of natural mentoring relationships for adolescents with a history of caregiver childhood abuse, and the extent to which these relationships are associated with psychological and health outcomes in adulthood. Among the sample (n = 12,270), 28.82% and 4.86% reported caregiver childhood physical and sexual abuse, respectively. Youth who reported caregiver childhood physical abuse were more likely than those who did not endorse abuse to report having a natural mentor, but their mentoring relationships were characterized by lower interpersonal closeness, shorter duration, and less frequent contact. Exposure to caregiver childhood abuse was associated with adverse outcomes during adulthood, including antisocial behavior, physical health limitations, and suicidality; the presence of a natural mentor did not buffer the negative impact of trauma on adult outcomes. However, longer mentoring relationships during adolescence buffered the strength of the association between both caregiver physical and sexual abuse during childhood and suicidality during early adulthood.

Purpose The purpose of the study was to evaluate a 12-week cooking education class on cooking confidence, dietary habits, weight status, and laboratory data among veterans with prediabetes and diabetes. Methods The sample for this study included 75 veterans within the Overton Brooks Veteran Affairs Medical Center who completed the 12-week class in an in-person group setting in Shreveport, Louisiana, or via Clinical Video Telehealth (CVT) in Longview, Texas. Veterans were referred to the Healthy Teaching Kitchen by their primary care provider or primary care dietitian. Enrollment in the class was on a volunteer basis. The cooking and nutrition education classes included topics such as carbohydrate counting, safety and sanitation, meal planning, and creating budget-friendly recipes. Participants completed 2 questionnaires for assessment of healthy dietary habits and confidence related to cooking. Changes in body weight, lipid panel, and hemoglobin A1C were assessed. Differences in class settings were tested via independent samples t tests. Paired samples t tests were completed to compare changes in mean laboratory results, weight, and questionnaire responses. Results Subjects lost a mean 2.91 ± 5.8 lbs ( P < .001). There was no significant difference in percent change in laboratory data and weight between subjects participating via CVT and subjects in the live class. Overall, there was significant improvement in the confidence questionnaire ratings and Healthy Habits Questionnaire responses. Conclusions Cooking and nutrition education can increase cooking confidence and dietary quality. These results provide support for the need for further research on the long-term effects of nutrition cooking education and for the benefits of using CVT software to provide education to remote facilities.

The intracellular protozoal parasite Toxoplasma gondii has been associated with worsened cognitive function in animal models and in humans. Despite these associations, the mechanisms by which Toxoplasma gondii might affect cognitive function remain unknown, although Toxoplasma gondii does produce physiologically active intraneuronal cysts and appears to affect dopamine synthesis. Using data from the UK Biobank, we sought to determine whether Toxoplasma gondii is associated with decreased prefrontal, hippocampal, and thalamic gray-matter volumes and with decreased total gray-matter and total white-matter volumes in an adult community-based sample. The results from adjusted multivariable regression modelling showed no associations between Toxoplasma gondii and prefrontal, hippocampal, and thalamic brain gray-matter volumes. In contrast, natural-log transformed antibody levels against the Toxoplasma gondii p22 (b = -3960, 95-percent confidence interval, -6536 to -1383, p < .01) and sag1 (b = -4863, 95-percent confidence interval, –8301 to -1425, p < .01) antigens were associated with smaller total gray-matter volume, as was the mean of natural-log transformed p22 and sag1 titers (b = -6141, 95-percent confidence interval, -9886 to -2397, p < .01). There were no associations between any of the measures of Toxoplasma gondii and total white-matter volume. These findings suggest that Toxoplasma gondii might be associated with decreased total gray-matter in middle-aged and older middle-aged adults in a community-based sample from the United Kingdom.

Using a sample of 256 juvenile offenders who were randomly assigned to treatment or control groups, this study evaluates a cognitive-behavioral program that combines cognitive training, goal setting, and a phone-coach follow-up. The training involved six classroom sessions where participants received instruction and help in creating individualized goals. After attending the classes, participants received automated phone calls twice a day for up to a year. During the year following the program, the treatment and control groups were not significantly different in whether or not they were rearrested or in total rearrests. However, the total number of calls received had a significant negative association with whether or not they were rearrested for a felony and with the total number of felony rearrests.

OBJECTIVE To demonstrate the effectiveness of a Diabetes Prevention Program-inspired 12-month behavioral intervention for patients with severe mental illness (SMI) and medication-associated obesity. METHOD This randomized, controlled, parallel, superiority study screened 225 volunteers from November 2005 to August 2008 at the VA Greater Los Angeles Healthcare System. 122 outpatients with DSM-IV-diagnosed SMI taking antipsychotic medications who had ≥ 7% weight gain or body mass index (BMI) > 25 were randomized by computer-generated number to Lifestyle Balance treatment intervention (n = 60) or usual care control (n = 62) groups. Clinical raters were masked to randomization. Treatment intervention included weekly classes and individual counseling for 8 weeks, food and exercise diaries, rewards, caregiver consultations, and monthly booster classes and counseling for 1 year. Controls received self-help materials and visited at equivalent intervals without formal classes or counseling. Outcomes were changes in anthropometric measurements, psychiatric symptoms, health knowledge, and glucose, hemoglobin A1c, and lipid levels. RESULTS Our intention-to-treat analysis found significant differences in predicted trajectory of mean weight change between the groups over 12 months (P < .01), with treatment participants expected to lose an average 4.6 kg, while control participants would gain an average 0.6 kg. BMI and body fat percentage followed the same pattern. Both groups demonstrated statistically significant improvements in health knowledge quiz scores over time (P = .006), without significant difference between groups. CONCLUSIONS Treatment was more effective than usual care control in treating medication-associated obesity, independent of SMI diagnosis, antipsychotic medication, and knowledge gained, suggesting that behavioral interventions are effective in SMI patients. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT00344500.

Background B cells play a critical role in the development and maintenance of food allergy by producing allergen-specific IgE. Despite the importance of B cells in IgE-mediated food allergy, the identity of sIgE-producing human B cells and how IgE is regulated are poorly understood. Objective To identify the immunophenotypes of circulating B cells associated with the production of galactose-alpha-1,3-galactose-specific IgE production in patients with red meat allergy. Methods B cells in PBMC samples obtained from 19 adults with physician-diagnosed red meat allergy and 20 non-meat allergic healthy controls were assessed by mass cytometry along with a bioinformatics analysis pipeline to identify discrete B cell phenotypes that associated with serum sIgE. Fluorescent flow cytometry was then applied to sort purify discrete B cell subsets, and B cells were functionally evaluated on an individual cell level for the production of sIgE by ELISPOT. Results Discrete B cell phenotypes abundant in meat allergic subjects compared to non-meat allergic controls were found in peripheral blood that do not share typical characteristics of classical isotype-switched memory B cells that express high levels of CD27. These B cell subsets shared higher IgD and lower IgM expression levels coupled with CXCR4, CCR6 and CD25 expression. In vitro polyclonal stimulation of purified B cell subsets from meat allergic subjects demonstrated that these subsets were enriched for cells induced to secrete sIgE. Conclusions and clinical relevance Circulating B cells display increased abundance of discrete B cell subsets in meat allergic subjects. This observation, coupled with the capacity of individual B cell subsets to produce sIgE following activation, implicates these novel B cell phenotypes in promoting IgE in meat allergy.

The rate of telemedicine adoption using interactive video between patient and provider has not met expectations. Technology, regulations, and physician buy-in are cited reasons, but patient acceptance has not received much consideration. We examine attitudes regarding telemedicine to better understand the subjective definitions of its acceptability and utility that shape patients' willingness to use telemedicine.Using the Montana Health Matters study (a random, statewide survey [n=3,512]), we use latent class analysis to identify groups with similar patterns of attitudes toward telemedicine followed by multinomial logistic regression to estimate predictors of group membership.Although only 5% are amenable to telemedicine regardless of circumstance, 23% would be comfortable if it could be convenient, whereas 29% would be situationally amenable but uncomfortable using telemedicine. Still, a substantial percentage (43%) is unequivocally averse to telemedicine despite the inconvenience of in-person visits. Educational attainment, prior Internet use, and rural residence are main predictors that increase the likelihood of being in an amenable group.From the patient's perspective, the advantages of reduced travel and convenience are recognized, but questions remain about the equivalence to physician visits. Many people are averse to telemedicine, indicating a perceived incompatibility with patient needs. Only 1.7% of the respondents reported using telemedicine in the previous year; about half were veterans. Hence, few have used telemedicine, and key innovation adoption criteria-trialability and observability-are low. Increased attention to public awareness in the adoption process is needed to increase willingness to embrace telemedicine as a convenient way to obtain quality healthcare services.

Introduction To develop a short form (SF) of the 45-item multidimensional Moral Injury Symptom Scale - Military Version (MISS-M) to use when screening for moral injury and monitoring treatment response in veterans and active duty military with PTSD. Methods A total of 427 veterans and active duty military with PTSD symptoms were recruited from VA Medical Centers in Augusta, GA; Los Angeles, CA; Durham, NC; Houston, TX; and San Antonio, TX; and from Liberty University, Lynchburg, Virginia. The sample was randomly split in two. In the first half (n = 214), exploratory factor analysis identified the highest loading item on each of the 10 MISS scales (guilt, shame, moral concerns, loss of meaning, difficulty forgiving, loss of trust, self-condemnation, religious struggle, and loss of religious faith) to form the 10-item MISS-M-SF; confirmatory factor analysis was then performed to replicate results in the second half of the sample (n = 213). Internal reliability, test-retest reliability, and convergent, discriminant, and concurrent validity were examined in the overall sample. The study was approved by the institutional review boards and the Research & Development (R&D) Committees at Veterans Administration medical centers in Durham, Los Angeles, Augusta, Houston, and San Antonio, and the Liberty University and Duke University Medical Center institutional review boards. Findings The 10-item MISS-M-SF had a median of 50 and a range of 12-91 (possible range 10-100). Over 70% scored a 9 or 10 (highest possible) on at least one item. Cronbach's alpha was 0.73 (95% CI 0.69-0.76), and test-retest reliability was 0.87 (95% CI 0.79-0.92). Convergent validity with the 45-item MISS-M was r = 0.92. Discriminant validity was demonstrated by relatively weak correlations with social, religious, and physical health constructs (r = 0.21-0.35), and concurrent validity was indicated by strong correlations with PTSD, depression, and anxiety symptoms (r = 0.54-0.58). Discussion The MISS-M-SF is a reliable and valid measure of MI symptoms that can be used to screen for MI and monitor response to treatment in veterans and active duty military with PTSD.

Veterans with mental illness tend to have shorter life spans and suboptimal physical health because of a variety of factors. These factors include poor nutrition, being overweight, and smoking cigarettes. Nonphysical contributors that may affect quality of life are the stigma associated with mental illness, social difficulties, and spiritual crises. Current mental health treatment focuses primarily on the delivery of medication and evidence-based psychotherapies, which may not affect all the above areas of a Veteran's life as they focus primarily on improving psychological symptoms. Clinicians may find greater success using integrative, comprehensive, multifaceted programs to treat these problems spanning the biological, psychological, social, and spiritual domains. These pilot studies test an adjunctive, holistic, behavioral approach to treat mental illness. This pilot work explores the hypotheses that engagement in a greater number of therapeutic lifestyle changes (TLCs) leads to improvement in quality of life, reduction of psychiatric symptoms, and weight loss.Institutional Review Boards for human subjects at the Veterans Affairs (VA) Greater Los Angeles and Long Beach Healthcare Systems approved pilot study activities at their sites. Pilot Study 1 was a prospective survey study of Veterans with mental illness, who gained weight on an atypical antipsychotic medication regimen, participating in a weight management study. At each session of the 1-year study, researchers asked a convenience sample of 55 Veterans in the treatment arm whether they engaged in each of the eight TLCs: exercise, nutrition/diet, stress management and relaxation, time in nature, relationships, service to others, religious or spiritual involvement, and recreation. Pilot Study 2 applied the TLC behavioral intervention and examined 19 Veterans with mental illness, who attended four classes about TLCs, received individual counseling over 9 weeks, and maintained journals to track TLC practice. Besides weekly journals, researchers also collected prospective data on quality of life, psychiatric symptoms, vitals, and anthropometric measurements. In both studies, investigators tested for main effects of the total number of TLCs practiced and study week using mixed-effects linear models with independent intercepts by participant.In Study 1, engagement in more TLC behaviors was significantly associated with higher ratings of quality of life, as well as greater weight loss for each additional type of TLC practiced. In Study 2, TLC practice increased significantly over 9 weeks, and was significantly associated with improvements in quality of life and diastolic blood pressure.Counseling Veterans to practice TLCs provides a holistic adjunct to current treatments for mental illness. TLCs may confer multiple benefits upon Veterans with mental illness, enhancing quality of life and well-being along with weight management efforts. As these were pilot studies, the samples sizes were relatively small and a control group was lacking. Our findings may have broader implications supporting a holistic approach in both primary and mental health care settings. Future research will expand this work to address its weaknesses and examine the cost differential between this holistic approach and traditional mental health treatment.

The intracellular parasite Toxoplasma gondii (Nicolle et Manceaux, 1908) infects humans resulting in acute toxoplasmosis, an infection that in immunocompetent people is typically mild but results in persistent latent toxoplasmosis. In that T. gondii appears to affect dopamine synthesis and because addicting drugs affect midbrain dopamine transmission, latent toxoplasmosis could influence substance use. Using both the third and continuous National Health and Nutrition Examination Surveys from the US Centers for Disease Control and Prevention, we used logistic regression to test for associations between T. gondii seropositivity and subject self-report of having ever used tobacco, alcohol, marijuana, cocaine, heroin, or methamphetamine. In the third NHANES dataset, which included data for tobacco, alcohol, marijuana and cocaine, T. gondii seropositivity was associated with a reduced likelihood of self-reported marijuana (OR = 0.71 [95% CI: 0.58; 0.87]; p = 0.001) and cocaine use (OR = 0.72 [95% CI: 0.56; 0.91]; p = 0.006). In the continuous National Health and Nutrition Examination Surveys dataset, which included data for all six substances, T. gondii seropositivity was associated with a reduced likelihood of self-reported tobacco (OR = 0.87 [95% CI: 0.76; 1.00]; p = 0.044), marijuana (OR = 0.60 [95% CI: 0.50; 0.72]; p < 0.001), heroin (OR = 0.60 [95% CI: 0.42; 0.85]; p = 0.005) and methamphetamine use (OR = 0.54 [95% CI: 0.38; 0.77]; p = 0.001). We observed interactions between sex and T. gondii seropositivity in the prediction of self-reported use of tobacco and alcohol. Further, T. gondii seropositivity appeared to remove the protective effect of education and economic status against self-reported cigarette smoking. These findings suggest that T. gondii seropositivity may be inversely associated with some but not all types of substance use in US adults.

Weight gain and other metabolic sequelae of antipsychotic medications can lead to medication non-adherence, reduced quality of life, increased costs, and premature mortality. Of the approaches to address this, behavioral interventions are less invasive, cost less, and can result in sustained long-term benefits. We investigated behavioral weight management interventions for veterans with mental illness across four medical centers within the Veterans Affairs (VA) Healthcare System. We conducted a 12-month, multi-site extension of our previous randomized, controlled study, comparing treatment and control groups. Veterans (and some non-veteran women) diagnosed with mental illness, overweight (defined as having a BMI over 25), and required ongoing antipsychotic therapy. One group received “Lifestyle Balance” (LB; modified from the Diabetes Prevention Program) consisting of classes and individual nutritional counseling with a dietitian. A second group received less intensive “Usual Care” (UC) consisting of weight monitoring and provision of self-help. Participants completed anthropometric and nutrition assessments weekly for 8 weeks, then monthly. Psychiatric, behavioral, and physical assessments were conducted at baseline and months 2, 6, and 12. Metabolic and lipid laboratory tests were performed quarterly. Participants in both groups lost weight. LB participants had a greater decrease in average waist circumference [F(1,1244) = 11.9, p

BackgroundInfectious diseases might affect cognitive aging and dementia risk, possibly via neuroinflammation. Similarly, risk factors for cardiovascular and cerebrovascular diseases are associated with cognitive function and dementia. We hypothesized that cardiovascular risk factors moderate the association of exposure to infectious diseases with cognitive function.MethodsWe studied 5662 participants aged 20 to 59 years from the third National Health and Nutrition Examination Survey (1988-1994) in the United States. We used linear regression to investigate whether the Framingham general cardiovascular risk index moderated the association of infection burden based on exposure to eight different infectious diseases with cognitive functioning as measured by the Symbol Digit Substitution, Serial Digit Learning, and Reaction Time tests.ResultsThe multiplicative interaction between the infection-burden index and the cardiovascular-risk index was associated with performance on the Symbol Digit Substitution (B = .019 [95% CI: .008, .031], p < .001) but not on the Serial Digit Learning (B = .034 [95% CI: -.025, .094]) or for Reaction Time (B = -.030 [95% CI: -.848, .787]). Participants with a lower cardiovascular risk appeared to be more resilient against the potential adverse effects of higher infection burden on the Symbol Digit Substitution task.ConclusionsParticipants at zero risk for a cardiovascular event in the next 10 years had no differences in processing speed with increasing exposure to infectious disease, whereas participants with higher risk for a cardiovascular event had worse processing speed with increased exposure to infectious disease.

Although highly heritable, adult height is also associated with numerous environmental factors, including exposure to infection. Particularly in developing regions of the world, infection burden appears to slow growth during childhood. Using a large database representative of the US population, we examined associations between adult height and leg length and an infection-burden index based on past exposure to Toxocara species, Toxoplasmosis gondii, cytomegalovirus, hepatitis A, hepatitis B, hepatitis C, herpes simplex virus 1, and herpes simplex virus 2. In models controlled for age, sex, educational attainment, socioeconomic status, and race-ethnicity, we found that the infection-burden index predicted height (β=-0.10 [95% CI: -0.15, -0.05], p .0010.001) but not leg length (β=-0.04 [95% CI: -0.12, 0.04], p=0.357). Both sex and race-ethnicity moderated this association. In addition, exposures to Toxocara species, cytomegalovirus, and hepatitis A were each individually associated with reduced height and reduced leg length. While associations between growth and infection have been found principally in children in developing regions of the world, our findings suggest that the effects of infection on height may persist into adulthood even in developed nations.

Toxoplasma gondii (T. gondii) seropositivity may be associated with decreased memory in older adults. To further investigate the association between T. gondii seropositivity and memory in non-demented older adults, we obtained serum samples from 114 non-demented older adults evaluated by the Alzheimer’s Disease and Research Center at Washington University in St. Louis Missouri, USA. We determined T. gondii seropositivity and anti-T. gondii IgG antibody titer and examined associations with memory function while controlling for socioeconomic status, education level, age, and apolipoprotein E4 status. There were few associations between T. gondii seropositivity or anti-T. gondii IgG antibodies and memory, although there was some support suggesting an interaction between anti-T. gondii and sex. In the seropositive-only sample, there was an inverse relationship between anti-T. gondii titer and performance on the selective reminding test. Overall, we found little evidence of an association between impaired memory function and T. gondii seropositivity and anti-T gondii IgG antibodies in this sample of non-demented older adults.

Toxoplasma gondii (Nicolle et Manceaux, 1908) is an intracellular parasite that can cause ongoing latent infection persisting for the duration of a non-definitive host's life. Affecting approximately one-third of the world's population, latent toxoplasmosis has been associated with neuropsychological outcomes and a previous report suggested an association between latent toxoplasmosis and adult height. Given the large number of people with latent toxoplasmosis and its potential associations with human height, we sought to better understand the association between latent toxoplasmosis and human morphology by evaluating seropositivity for T. gondii and multiple body measures reported in the National Health and Nutrition Examination Survey III (NHANES III) and in the more recent continuous NHANES data sets from the United States Centers for Disease Control and Prevention for which data on T. gondii are available. In these analyses, latent toxoplasmosis was not associated with any of the body measures assessed in the NHANES datasets even after taking into account interactions between latent toxoplasmosis and testosterone suggesting that in these samples, latent toxoplasmosis is not associated with adult morphology including height.

SAMP1/YitFcs mice serve as a model of Crohn's disease, and we have used them to assess gastritis. Gastritis was compared in SAMP1/YitFcs, AKR, and C57BL/6 mice by histology, immunohistochemistry, and flow cytometry. Gastric acid secretion was measured in ligated stomachs, while anti-parietal cell antibodies were assayed by immunofluorescence and enzyme-linked immunosorbent spot assay. SAMP1/YitFcs mice display a corpus-dominant, chronic gastritis with multifocal aggregates of mononuclear cells consisting of T and B lymphocytes. Relatively few aggregates were observed elsewhere in the stomach. The infiltrates in the oxyntic mucosa were associated with the loss of parietal cell mass. AKR mice, the founder strain of the SAMP1/YitFcs, also have gastritis, although they do not develop ileitis. Genetic studies using SAMP1/YitFcs-C57BL/6 congenic mice showed that the genetic regions regulating ileitis had comparable effects on gastritis. The majority of the cells in the aggregates expressed the T cell marker CD3 or the B cell marker B220. Adoptive transfer of SAMP1/YitFcs CD4+ T helper cells, with or without B cells, into immunodeficient recipients induced a pangastritis and duodenitis. SAMP1/YitFcs and AKR mice manifest hypochlorhydria and anti-parietal cell antibodies. These data suggest that common genetic factors controlling gastroenteric disease in SAMP1/YitFcs mice regulate distinct pathogenic mechanisms causing inflammation in separate sites within the digestive tract.

Antiviral Abs, for example those produced in response to influenza virus infection, are critical for virus neutralization and defense against secondary infection. While the half-life of Abs is short, Ab titers can last a lifetime due to a subset of the Ab-secreting cells (ASCs) that is long lived. However, the mechanisms governing ASC longevity are poorly understood. Here, we have identified a critical role for extrinsic cytokine signals in the survival of respiratory tract ASCs in a mouse model of influenza infection. Irradiation of mice at various time points after influenza virus infection markedly diminished numbers of lung ASCs, suggesting that they are short-lived and require extrinsic factors in order to persist. Neutralization of the TNF superfamily cytokines B lymphocyte stimulator (BLyS; also known as BAFF) and a proliferation-inducing ligand (APRIL) reduced numbers of antiviral ASCs in the lungs and bone marrow, whereas ASCs in the spleen and lung-draining lymph node were surprisingly unaffected. Mice deficient in transmembrane activator and calcium-modulator and cyclophilin ligand interactor (TACI), a receptor for BLyS and APRIL, mounted an initial antiviral B cell response similar to that generated in WT mice but failed to sustain protective Ab titers in the airways and serum, leading to increased susceptibility to secondary viral challenge. These studies highlight the importance of TACI signaling for the maintenance of ASCs and protection against influenza virus infection.

Previous observational and quasi-experimental studies in sub-Saharan Africa have suggested the effectiveness of youth-targeted HIV prevention interventions using sport as an educational tool. No studies have yet assessed the effect of similar programs in the Caribbean. A quasi-experimental trial was conducted to assess the effectiveness of a sports-based intervention in six migrant settlements in the Puerto Plata Province of the Dominican Republic. A total of 397 structured interviews were conducted with 140 adolescents prior to, immediately following, and four months following 10-hour interventions using the Grassroot Soccer curriculum. Interview responses were coded, aggregated into composite scores, and analyzed using logistic regression, adjusting for baseline differences as well as age, sex, community, and descent. At post-intervention, significant differences were observed between groups in HIV-related knowledge (adjOR = 13.02, 95% CI = 8.26, 20.52), reported attitudes (adjOR = 12.01, 95% CI = 7.61, 18.94), and reported communication (adjOR = 3.13, 95% CI = 1.91, 5.12). These differences remained significant at four-month follow-up, though declines in post-intervention knowledge were observed in the Intervention group while gains in knowledge and reported attitudes were observed in the Control group. Results suggest that this sports-based intervention could play a valuable role in HIV prevention efforts in the Caribbean, particularly those targeting early adolescents. Further evaluation of sports-based interventions should include indicators assessing behavioral and biological outcomes, longer-term follow-up, a larger sample, randomization of study participants, and strenuous efforts to minimize loss-to-follow-up.

The aim of this study was to determine how laser in situkeratomileusis (LASIK) affects quality of life (QOL) and to identify factors that may affect satisfaction after LASIK. A total of 104 patients with a mean age of 29±6, treated with LASIK for myopia and astigmatism, were enrolled in a prospective study. High (90%) and low (10%) contrast visual acuity (CVA) were measured under photopic and scotopic conditions before surgery and at 3 months later. A multidimensional QOL scale (Institute for Eye Research multidimensional QOL scale), which assesses psychological characteristics, personality traits, cosmesis, frequency, and tolerance to disturbing visual and ocular symptoms, and overall satisfaction with vision correction, was also used. Paired rank tests were used to compare preoperative and postoperative vision and QOL scores. Correlations and a multiple linear regression were used to describe the relationship between CVA, QOL, and satisfaction after LASIK. Significant postoperative changes included increased satisfaction following LASIK (P

Several lines of evidence suggest that suicide may have, in part, a genetic predisposition. In this study, we identified a family with high rates of suicidal behavior and assessed brain gene expression levels in the proband. A neuronally-expressed solute carrier for glutamine (Sodium-coupled neutral amino acid transporter 1 (SNAT1), also known as solute carrier family 38, member 1 (SLC38A1)) was identified as severely decreased across all brain regions. Follow-up analysis by semi-quantitative polymerase chain reaction (qPCR) and Western blot confirmed the reduction of SNAT1. We categorized the SNAT1 gene in human brain, cloned the gene promoter and assessed in silico the expression pattern of SNAT1 in >25 tissues from human. Complete DNA sequencing of the SNAT1 gene was performed in the family and 276 controls. The family was homozygous for rare alleles which suggests a possible association between low expression of SNAT1 and suicidal behavior.

To assess pre-operative visual function, psychological factors, personality traits and satisfaction in myopic patients seeking laser-assisted in situkeratomileusis (LASIK). Eligible patients seeking LASIK (n=183) and successful contact lens wearers (n=23) not interested in LASIK completed the Institute for Eye Research Quality of Life (QOL) Scale. Of the 183 patients seeking LASIK who completed the QOL instrument before LASIK, 30 declined the procedure and 153 underwent LASIK. One hundred and two patients who underwent LASIK attended their 3-month post-operative follow-up appointment and 51 patients failed to present for their post-operative follow-up appointment. Multiple comparisons (One-way Analysis of Variance (ANOVA)) were conducted to determine differences in visual function, psychological factors, personality traits and satisfaction between patient groups. Successful soft contact lens (SCL) wearers reported better functional vision (P=0.001), felt more attractive (P=0.007), had a lower frequency of disturbing visual and ocular symptoms (P=0.027) and higher overall satisfaction with their current optical correction (P

Utah's Gold Medal Schools program supports the adoption of school policies that provide opportunities for nutritious food choices and regular physical activity. The effectiveness of Gold Medal Schools was evaluated via anthropometric measurements and dietary and physical activity surveys. The study population included first-, third-, and fifth-grade elementary school students and parents from four schools in Tooele County, UT. Two schools implemented Gold Medal Schools (intervention) and two did not (comparison). Data were collected at baseline (June 2005) and 1 year (May 2006). Body mass index (calculated as kg/m(2)) z scores increased significantly in the comparison group (0.53+/-0.38; P0.05), but not in the intervention group (0.21+/-0.47; P=0.484), from baseline to 1 year. Children in the Gold Medal Schools cohort reported drinking fewer soft drinks per day (excluding diet drinks) at 1 year (P=0.008) and walking or biking to school more often at baseline and 1 year (P0.001) than non-Gold Medal Schools children. While children in both groups increased the days per week they walked or biked to school, a substantial improvement was observed for the non-Gold Medal Schools students only (P0.001). Overall, this pilot study suggests that Gold Medal Schools positively impacted body mass index z scores and health behaviors among elementary-aged students.

Studies of gene-environment interplay typically focus on one environmental factor at a time, resulting in a constrained view of social context. The concept of environmental contingency is introduced as a corrective. Drawing on the National Longitudinal Study of Adolescent Health and qualitative comparative analysis, the authors focus on an example involving social capital, a gene associated with a dopamine receptor (DRD2), and educational continuation beyond secondary school. For boys, (1) DRD2 risk is associated with a decreased likelihood of school continuation; (2) one configuration of social capital -- high parental socioeconomic status, high parental involvement in school, and a high-quality school -- compensates for this negative relationship, consistent with environmental contingency; but (3) boys with DRD2 risk are less commonly observed in settings that are rich in social capital.

Abstract. The objective of the present study was to investigate factors that affect sugar sweetened beverage (SSB) intake in rural, southern college students in the US. The majority of the participants were male (58 %) and Caucasian (63 %). The average total SSB consumption was 79.4 fl oz/day (2.35 L/d). Results of binary logistic regression analyses of total SSB intake greater than 57.4 fl oz/day (1.8 L/d) versus less than 57.4 fl oz/day showed that factors associated with greater odds for high SSB intake were age greater than 20 years old (odds ratio [OR] = 3.551, 95 % confidence interval [CI] = 1.385 - 9.104, p = 0.008) and being African American (OR = 3.477, 95 % CI = 1.291 - 9.363, p = 0.013). Results of binary logistic regression analyses of total bottled water intake greater than 39.4 fl oz/day (median) versus less than 39.4 fl oz/day showed that consuming alcohol was significantly related to an increased probability of drinking more than 39.4 fl oz (1.17 L/d) of bottled water per day (median; OR = 2.914, 95 % CI = 1.223 - 6.943, p = 0.016). Culturally sensitive strategies are needed to raise awareness for making healthy beverage choices when dining on campus to effectively reduce college student’s SSB consumption.

INTRODUCTION Latent infection with Toxoplasma gondii has been associated with behavioral and cognitive changes in animal models and in humans. Early findings have suggested an association between latent toxoplasmosis and Alzheimer disease (AD). On the basis of these factors, we sought to determine whether there is an association between latent toxoplasmosis and AD using a large, well-characterized sample of subjects with AD and age-matched and sex-matched controls without dementia. METHODS Using ELISA, we determined anti-T. gondii IgG antibody titers in 114 control subjects and in 105 subjects diagnosed with AD through an Alzheimer's Disease Research Center. RESULTS There were no group differences between groups in age, ethnicity, or sex. Education and socioeconomic status was slightly higher in the control group. Neither the prevalence of anti-T. gondii IgG antibodies (33% in the nondemented control group compared with 41% in the AD group, P=0.25) nor log-transformed antibody concentration (106.6 IU/mL in the control group compared with 140.9 IU/mL in the AD group, P=0.85) differed between the control and AD groups. DISCUSSION In this sample, we found neither a higher prevalence of latent toxoplasmosis in the AD group compared with the control group nor differences in serum anti-T. gondii IgG titers between groups.

This study assesses the prevalence of primary-care physician (PCP) bypass among rural middle-aged and older adults. Bypass is a behavior where people travel beyond local providers to obtain health care. This article applies a precise Geographic Information System (GIS)-based measure of bypass and examines the role of community and non-health-care-related characteristics on bypass. Our results indicate that bypass behavior among rural middle-aged and older adults is multifaceted. In addition to the perceived quality of local primary care, dissatisfaction with local services, such as shopping, creates an effect that increases the likelihood of bypass, whereas strong community ties decrease the likelihood of bypass. The results suggest that the "outshopping theory," where respondents select services in larger regional economic centers rather than local "mom and pop" providers, now extends to older adult health care selection.

Prior research has suggested an association between exposure to infectious disease and neurocognitive function in humans. While most of these studies have explored individual viral, bacterial, and even parasitic sources of infection, few have considered the potential neurocognitive burden associated with multiple infections. In this study, we utilized publically available data from a large dataset produced by the Centers for Disease Control and Prevention that included measures of neurocognitive function, sociodemographic variables, and serum antibody data for several infectious diseases. Specifically, immunoglobulin G antibodies for toxocariasis, toxoplasmosis, hepatitis A, hepatitis B, and hepatitis C, cytomegalovirus, and herpes 1 and 2 were available in 5662 subjects. We calculated an overall index of infectious-disease burden to determine if an aggregate measure of exposure to infectious disease would be associated with neurocognitive function in adults aged 20-59 years. The index predicted processing speed and learning and memory but not reaction time after controlling for age, sex, race-ethnicity, immigration status, education, and the poverty-to-income ratio. Interactions between the infectious-disease index and some sociodemographic variables were also associated with neurocognitive function. In summary, an index aggregating exposure to several infectious diseases was associated with neurocognitive function in young- to middle-aged adults.

Summary Background and objective: The objective of this research was to determine the effects of the dietary supplement Echinacea purpurea on aerobic and anaerobic bacteria common to the human gastrointestinal (GI) tract. Botanical extracts have shown in vitro antimicrobial effects against certain pathogenic bacteria. It is uncertain if medicinal herbs have any effect against pathogenic bacteria or on the native GI microbiota. Methods: Fifteen human subjects consumed 1000 mg of standardized E. purpurea for 10 days. Faecal samples were collected at baseline, 10 days and 17–18 days following supplementation. Samples were tested for select aerobic and anaerobic bacteria using plate culture microbiological methods. Results and discussion: Significant increases were found for total aerobic bacteria, Bacteroides group and Bacteroides fragilis after E. purpurea exposure. Supplementation did not significantly alter the number of enteric bacteria, enterococci, lactobacilli, bifidobacteria or total anaerobic bacteria. Conclusion: Echinacea supplementation has altered the GI microbiota. The health consequences associated with this change are unknown but previous research has shown increased Bacteroides concentrations associated with diarrhoea, inflammatory bowel disease and increased risk of colon cancer. Additional research should delineate the role of Echinacea in the stimulation of Bacteroides and describe the effects of other botanical supplements to the GI microbiota.

We studied the distribution and cellular localization of Na + -coupled neutral amino acid transporter 2, a member of the system A family of amino acid transporters, in the rat and human cerebral cortex using immunocytochemical methods. Na + -coupled neutral amino acid transporter 2-positive neurons were pyramidal and non-pyramidal, and Na + -coupled neutral amino acid transporter 2/GABA double-labeling studies revealed that Na + -coupled neutral amino acid transporter 2 was highly expressed by GABAergic neurons. Double-labeling studies with the synaptophysin indicated that rare axon terminals express Na + -coupled neutral amino acid transporter 2. Na + -coupled neutral amino acid transporter 2-immunoreactivity was also found in astrocytes, leptomeninges, ependymal cells and choroid plexus. Electron microscopy showed robust Na + -coupled neutral amino acid transporter 2-immunoreactivity in the somato-dendritic compartment of neurons and in glial processes, but, as in the case of double-labeling studies, failed to reveal Na + -coupled neutral amino acid transporter 2-immunoreactivity in terminals. To rule out the possibility that the absence of Na + -coupled neutral amino acid transporter 1-[Melone M, Quagliano F, Barbaresi P, Varoqui H, Erickson JD, Conti F (2004) Localization of the glutamine transporter SNAT1 in rat cerebral cortex and neighboring structures, with a note on its localization in human cortex. Cereb Cortex 14:562–574] and Na + -coupled neutral amino acid transporter 2-positive terminals was due to insufficient antigen detection, we evaluated Na + -coupled neutral amino acid transporter 1/synaptophysin and Na + -coupled neutral amino acid transporter 2/synaptophysin coexpression using non-standard immunocytochemical procedures and found that Na + -coupled neutral amino acid transporter 1 and Na + -coupled neutral amino acid transporter 2+ terminals were rare in all conditions. These findings indicate that Na + -coupled neutral amino acid transporter 1 and Na + -coupled neutral amino acid transporter 2 are virtually absent in cortical terminals, and suggest that they do not contribute significantly to replenishing the Glu and GABA transmitter pools through the glutamate–glutamine cycle. The strong expression of Na + -coupled neutral amino acid transporter 2 in the somato-dendritic compartment and in non-neuronal elements that are integral parts of the blood–brain and brain–cerebrospinal fluid barrier suggests that Na + -coupled neutral amino acid transporter 2 plays a role in regulating the levels of Gln and other amino acids in the metabolic compartment of cortical neurons.

OBJECTIVE The purpose of this project was to educate inpatients with psychotic disorders, many of whom were taking second-generation antipsychotics, about lifestyle changes they can make to combat weight gain. METHOD All inpatients on a Veterans Affairs acute inpatient schizophrenia treatment unit were invited to a 30-minute, didactic presentation given by a medical student and a psychology student under the supervision of the primary investigator. The topics covered included the health benefits of maintaining an ideal body weight by selecting foods according to the USDA Food Pyramid, determining adequate food portions, choosing healthy meals outside the home, and beginning and adhering to an exercise program. Subjects completed a 13-item quiz concerning their knowledge of food and nutrition before and after the presentation to determine its efficacy in teaching patients the material. RESULTS Fifty patients completed both the pre- and post-presentation tests. The mean percentage of correct answers on the pre-test was 85.6%, which rose to 89.3% on the post-test. This difference of 3.7% was statistically significant (t = 2.43, df = 49, p < 0.02), and the mean percent of improvement was 6.1%. CONCLUSIONS This study demonstrates that psychotic individuals are able to benefit from educational presentations about nutrition and a healthy lifestyle. A statistically significant improvement in test scores suggests that subjects gained an understanding of basic concepts related to food choices and fitness.

Background: Male DNA or cells are often used to measure microchimerism in a woman. In studies of autoimmune diseases male microchimerism is most often attributed to the previous birth of a son. Objective: To determine the frequency of male microchimerism in healthy women or women with systemic sclerosis who had never given birth to a son. Methods: Real time quantitative polymerase chain reaction targeting the Y chromosome specific sequence DYS14 was employed to test DNA extracted from peripheral blood mononuclear cells of 26 women with systemic sclerosis and 23 healthy women who had never given birth to a son. Results are expressed as the genome equivalent number of male cells per million host cells (gEq/mil). Results: Male DNA was found in 15% of women with systemic sclerosis (range 0 to 23.7 gEq/mil) and in 13% of healthy women (range 0 to 5.1 gEq/mil). Although two women with male DNA had an induced abortion, most had no history of spontaneous or induced abortion (either systemic sclerosis or healthy). Conclusions: Microchimerism with male DNA can be found in the circulation of women who have never given birth to a son. Thus sources other than a male birth must be considered when male DNA is used to measure microchimerism. Although other studies are needed, there was no apparent difference in women with systemic sclerosis and healthy women. Possible sources of male DNA include unrecognised male pregnancy or unrecognised male twin, an older male sibling with transfer through the maternal circulation, or sexual intercourse alone.

Cortical regions of the brain stand out for their high content in synaptic zinc, which may thus be involved in synaptic function. The relative number, chemical nature and transmitter receptor profile of synapses that sequester vesicular zinc are largely unknown. To address this, we combined pre-embedding zinc histochemistry and post-embedding immunogold electron microscopy in rat hippocampus. All giant mossy fibre (MF) terminals in the CA3 region and approximately 45% of boutons making axospinous synapses in stratum radiatum in CA1 contained synaptic vesicles that stained for zinc. Both types of zinc-positive boutons selectively expressed the vesicular zinc transporter ZnT-3. Zinc-positive boutons further immunoreacted to the vesicular glutamate transporter VGLUT-1, but not to the transmitter gamma-aminobutyric acid. Most dendritic spines in CA1 immunoreacted to alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor (AMPAR) subunits GluR1-3 (approximately 80%) and to N-methyl-D-aspartate receptor (NMDAR) subunits NR1 + NR2A/B (approximately 90%). Synapses made by zinc-positive boutons contained 40% less AMPAR particles than those made by zinc-negative boutons, whereas NMDAR counts were similar. Further analysis indicated that this was due to the reduced synaptic expression of both GluR1 and GluR2 subunits. Hence, the levels of postsynaptic AMPARs may vary according to the presence of vesicular zinc in excitatory afferents to CA1. Zinc-positive and zinc-negative synapses may represent two glutamatergic subpopulations with distinct synaptic signalling.

Objective To explore potential interactions between folate-cycle factors and Helicobacter pylori seropositivity in the prediction of cognitive function. Methods We used data obtained from the 1999–2000 continuous National Health and Nutrition Examination Survey produced by the United States’ Centers for Disease Control and Prevention. Using Ordinary Least Squares regression, we tested for associations between multiple folate-cycle factors, Helicobacter pylori seropositivity, and cognitive function assessed by the digit symbol coding subtest of the Wechsler Adult Intelligence Scale-III. We then tested for interactions between each of the folate-cycle factors and Helicobacter pylori in the prediction of cognitive function. Results Although Helicobacter pylori seropositivity, 5-methyltetrahydrofolate, vitamin B-12, and homocysteine were not associated with performance on the digit symbol coding task, Helicobacter pylori seropositivity interacted with 5-methyltetrahydrofolate concentration to predict performance on the digit symbol coding task. The Helicobacter pylori seropositive group performed worse on the digit symbol coding task as 5-methyltetrahydrofolate concentration decreased. Conclusion The interaction between Helicobacter pylori seropositivity and reduced folate-cycle factor 5-methyltetrahydrofolate might impair aspects of cognitive function.

Cognitive function may be influenced by education, socioeconomic status, sex, and health status. Furthermore, aging interacts with these factors to influence cognition and dementia risk in late life. Factors that may increase or decrease successful cognitive aging are of critical importance, particularly if they are modifiable. The purpose of this study was to determine if economic status in late life is associated with cognition independent of socioeconomic status in early life. Cross-sectional demographic, socioeconomic, and cognitive function data were obtained in 2592 older adults (average age 71.6 years) from the Center for Disease Control's National Health and Nutrition Examination Survey (NHANES) and analyzed with linear regression modeling. Cognitive function, as measured with a test of processing speed, was significantly associated with poverty index scores after adjusting for educational attainment as an estimate of childhood socioeconomic status, ethnic background, age, health status, and sex (P0.001). Our findings suggest that current economic status is independently associated with cognitive function in adults over age 60 years.

Male DNA, of presumed fetal origin, can be detected in the maternal circulation decades after delivery and is referred to as fetal microchimerism (FM). We previously found quantitatively greater FM in the circulation of women with the autoimmune disease scleroderma (SSc) than of healthy women. However, it is unknown whether this difference is due to intact circulating cells or free DNA released from breakdown in disease-affected tissues. To distinguish the origin of FM, we developed a real-time quantitative polymerase chain reaction (PCR) assay for the Y-chromosome–specific sequenceDYS14, and tested 114 women in peripheral blood mononuclear cells (PBMCs) and/or plasma. Fifty-seven controls and 57 SSc patients were studied, 48 and 43 of whom, respectively, had given birth to at least one son. Circulating FM was quantitatively greater in PBMCs from SSc patients (n = 39; range, 0.0-12.5 male genome–equivalent cells per million maternal cells), compared with healthy women (n = 39; range, 0.0-4.4; P = .03). In contrast, there was no difference between patients (n = 25) and controls (n = 22) in plasma, and no evidence of free DNA. FM was enriched among T lymphocytes compared with PBMCs (P = .01) in controls (n = 14), but not in SSc patients (n = 14); the latter finding was most likely due to immunosuppressive medications. In conclusion, this real-time quantitative assay showed that quantitative differences in the circulation of women with SSc are due to cells and not to free DNA. As FM was not uncommon in healthy women, including among T cells, and because graft-versus-host disease has similarities to SSc, these results also suggest that FM merits investigation in pheresis products used for stem cell transplantation.

The transport of alanine by system A is an important source of carbons for the synthesis of glucose in the liver. Here, we show that the mRNA encoding the ubiquitously expressed isoform of the rat system A transporter (SAT2) is dramatically increased in liver following streptozotocin-induced diabetes. This increase in SAT2 mRNA is intensified in the gluconeogenic periportal hepatocytes and also in hepatocytes surrounding the central vein. SAT3, the more abundant system A mRNA isoform present in liver, is restricted to perivenous hepatocytes and is also increased following this treatment but to a much lesser extent than SAT2 mRNA. SN1, an abundant system N mRNA isoform expressed in both perivenous and periportal hepatocytes, is not affected by streptozotocin treatment. A pharmacological dose of glucagon also increased both SAT2 and SAT3 mRNA levels in liver while SN1 mRNA levels remained unaffected. These results indicate that the increase in system A activity observed in liver following experimentally induced diabetes or glucagon treatment is due to the selective increase in mRNAs encoding system A transporters.

Toxoplasma gondii (T. gondii) is a microscopic, apicomplexan parasite that can infect muscle or neural tissue, including the brain, in humans. While T. gondii infection has been associated with changes in mood, behavior, and cognition, the mechanism remains unclear. Recent evidence suggests that T. gondii may harvest folate from host neural cells. Reduced folate availability is associated with an increased risk of neurodevelopmental disorders, neurodegenerative diseases, and cognitive decline. We hypothesized that impairment in cognitive functioning in subjects seropositive for T. gondii might be associated with a reduction of folate availability in neural cells. We analyzed data from the third National Health and Nutrition Examination Survey to determine the associations between T. gondii infection, multiple folate-cycle factors, and three tests of cognitive functioning in U.S. adults aged 20 to 59 years. In these analyses, T. gondii moderated the associations of folate, vitamin B-12, and homocysteine with performance on the Serial Digit Learning task, a measure of learning and memory, as well as the association of folate with reaction time. The results of this study suggest that T. gondii might affect brain levels of folate and/or vitamin B-12 enough to affect cognitive functioning.

Weight gain and worsening metabolic parameters are often side effects of antipsychotic medications used by individuals with severe mental illness. To address this, a randomized, controlled research study of a behavioral weight management program for individuals with severe mental illness was undertaken to assess its efficacy. Patients unable to meet weight loss goals during the first portion of the year-long study were given the option of using meal replacement shakes in an effort to assist with weight loss. Specific requirements for use of meal replacement shakes were specified in the study protocol; only five patients were able to use the shakes in accordance with the protocol and lose weight while improving metabolic parameters. Case studies of two subjects are presented, illustrating the challenges and obstacles they faced, as well as their successes. Taking responsibility for their own weight loss, remaining motivated through the end of the study, and incorporating the meal replacement shakes into a daily routine were factors found in common with these patients. Use of meal replacements shakes with this population may be effective.

(1) To assess the prevalence of rural primary care physician (PCP) bypass, a behavior in which residents travel farther than necessary to obtain health care, (2) To examine the role of community and non-health-care-related characteristics on bypass behavior, and (3) To analyze spatial bypass patterns to determine which rural communities are most affected by bypass.Data came from the Montana Health Matters survey, which gathered self-reported information from Montana residents on their health care utilization, satisfaction with health care services, and community and demographic characteristics. Logistic regression and spatial analysis were used to examine the probability and spatial patterns of bypass.Overall, 39% of respondents bypass local health care. Similar to previous studies, dissatisfaction with local health care was found to increase the likelihood of bypass. Dissatisfaction with local shopping also increases the likelihood of bypass, while the number of friends in a community, and commonality with community reduce the likelihood of bypass. Other significant factors associated with bypass include age, income, health, and living in a highly rural community or one with high commuting flows.Our results suggest that outshopping theory, in which patients bundle services and shopping for added convenience, extends to primary health care selection. This implies that rural health care selection is multifaceted, and that in addition to perceived satisfaction with local health care, the quality of local shopping and levels of community attachment also influence bypass behavior.

Latent infection with the apicomplexan Toxoplasma gondii (Nicolle et Manceaux, 1908) has been associated with schizophrenia, bipolar disorder and self-harm behaviour. However, the potential relationship between T. gondii immunoglobulin G antibody (IgG) seropositivity and generalised-anxiety disorder (GAD) and panic disorder (PD) has not been investigated. The associations between serum reactivity to T. gondii and major depressive disorder (MDD), GAD and PD were evaluated in a total sample of 1 846 adult participants between the ages of 20 and 39 years from the United States Center for Disease Control's National Health and Nutrition Examination Survey (NHANES). Approximately 16% of the overall sample was seropositive for T. gondii and 7% of the sample met criteria for MDD, 2% for GAD and 2% for PD. There were no significant associations between T. gondii IgG seroprevalence and MDD (OR = 0.484, 95% CI = 0.186-1.258), GAD (OR = 0.737, 95% CI = 0.218-2.490) or PD (OR = 0.683, 95% CI = 0.206-2.270) controlling for sex, ethnicity, poverty-to-income ratio and educational attainment. However, limited evidence suggested a possible association between absolute antibody titres for T. gondii and GAD and PD but not MDD. Toxoplasma gondii seroprevalence was not associated with MDD, GAD or PD within the context of the limitations of this study, although there may be an association of T. gondii serointensity with and GAD and PD, which requires further study.

A 67-year-old man who was treated with oxacillin for one week because of Staphylococcus aureus bacteremia, developed renal failure and diffuse, symmetric, palpable purpuric lesions on his feet. Necrotic blisters were noted on his fingers. Skin biopsies showed findings diagnostic of leucocytoclastic vasculitis. Oxacillin was discontinued and patient was treated with corticosteroids. The rash disappeared after three weeks and renal function returned to normal. Leucocytoclastic vasculitis presents as palpable purpura of the lower extremities often accompanied by abdominal pain, arthralgia, and renal involvement. Etiologic factors or associated disorders include infections, medications, collagen vascular disease and neoplasia. However, in half of the cases no etiologic factor is identified. Usually it is a self-limited disorder, but corticosteroid therapy may be needed in life-threatening cases since early treatment with corticosteroids in severe cases can prevent complications. Oxacillin should be included among the drugs that can cause leucocytoclastic vasculitis.

Objective. Hypospadias is a common congenital anomaly, the cause of which is unknown. Unexplained increases in the rates of hypospadias occurred in five European countries in the 1970s and 1980s. We examined data from two birth defects surveillance systems in the United States for evidence of similar trends. Methodology. The Metropolitan Atlanta Congenital Defects Program (MACDP) provided birth prevalence rates from 1968 to 1993. The nationwide Birth Defects Monitoring Program (BDMP) provided rates from 1970 to 1993. MACDP data are population-based and could be categorized by the severity of the hypospadias. BDMP data allowed analysis of rate trends for the four census regions of the United States. Results. Data from both surveillance systems showed an approximate doubling of hypospadias rates in the 1970s and 1980s. MACDP data showed that the rate of severe cases increased while the ratio of mild to severe cases decreased. BDMP data showed that hypospadias rates increased markedly in all four regions of the United States. Conclusions. The observed increases are unlikely to be attributable to increased sensitivity of the surveillance systems or the identification of more mild cases by physicians over time, because either trend would have increased rather than decreased the ratio of mild to severe cases. If real, these trends represent the largest number of cases and the first report of an increase in hypospadias rates outside of Europe. Additional investigation of a possible increase in hypospadias rates is warranted.

The nucleolus is implicated in sensing and responding to cellular stress by stabilizing p53. The pro-apoptotic effect of p53 is associated with several neurodegenerative disorders, including Huntington's disease (HD), which is characterized by the progressive loss of medium spiny neurons (MSNs) in the striatum. Here we show that disruption of nucleolar integrity and function causes nucleolar stress and is an early event in MSNs of R6/2 mice, a transgenic model of HD. Targeted perturbation of nucleolar function in MSNs by conditional knockout of the RNA polymerase I-specific transcription initiation factor IA (TIF-IA) leads to late progressive striatal degeneration, HD-like motor abnormalities and molecular signatures. Significantly, p53 prolongs neuronal survival in TIF-IA-deficient MSNs by transient upregulation of phosphatase and tensin homolog deleted on chromosome 10 (PTEN), a tumor suppressor that inhibits mammalian target of rapamycin signaling and induces autophagy. The results emphasize the initial role of nucleolar stress in neurodegeneration and uncover a p53/PTEN-dependent neuroprotective response.