Effect of Mycobacterium bovis BCG vaccination on Mycobacterium-specific cellular proliferation and tumor necrosis factor alpha production from distinct guinea pig leukocyte populations

In this study, we focused on three leukocyte-rich guinea pig cell populations, bronchoalveolar lavage (BAL) cells, resident peritoneal cells (PC), and splenocytes (SPC). BAL cells, SPC, and PC were stimulated either with live attenuated Mycobacterium tuberculosis H37Ra or with live or heat-killed virulent M. tuberculosis H37Rv (multiplicity of infection of 1:100). Each cell population was determined to proliferate in response to heat-killed virulent H37Rv, whereas no measurable proliferative response could be detected upon stimulation with live mycobacteria. Additionally, this proliferative capacity (in SPC and PC populations) was significantly enhanced upon prior vaccination with Mycobacterium bovis BCG. Accordingly, in a parallel set of experiments we found a strong positive correlation between production of antigen-specific bioactive tumor necrosis factor alpha (TNF-alpha) and prior vaccination with BCG. A nonspecific stimulus, lipopolysaccharide, failed to induce this effect on BAL cells, SPC, and PC. These results showed that production of bioactive TNF-alpha from mycobacterium-stimulated guinea pig cell cultures positively correlates with the vaccination status of the host and with the virulence of the mycobacterial strain.     

Comparison of once-daily atazanavir with efavirenz, each in combination with fixed-dose zidovudine and lamivudine, as initial therapy for patients infected with HIV

BACKGROUND: Atazanavir, an azapeptide protease inhibitor (PI), has pharmacokinetics that allow once-daily dosing, and it is not associated with significant PI-associated dyslipidemia. METHODS: A randomized, double-blind, double-dummy, active-controlled, 2-arm study comparing the antiviral efficacy and safety of atazanavir 400 mg administered once daily with efavirenz 600 mg administered once daily in combination with open-label fixed-dose zidovudine plus lamivudine twice daily. The 810 treatment-naive patients were stratified by HIV RNA level. The primary efficacy end point was the proportion of treated patients with HIV RNA levels <400 copies/mL through week 48. RESULTS: At week 48, HIV RNA levels were <400 copies/mL in 70% of patients receiving atazanavir and 64% of patients receiving efavirenz (intent-to-treat, difference; 95% confidence interval: 5.2%; -1.2%, 11.7%). Median CD4 cell counts increased at comparable magnitudes and rates in the 2 treatment arms (mean change at week 48: 176 cells/mm with atazanavir, 160 cells/mm with efavirenz). Atazanavir-treated patients relative to comparator-treated patients did not demonstrate significant increases in total cholesterol, fasting low-density lipoprotein cholesterol, or fasting triglycerides over 48 weeks of therapy. Atazanavir-linked bilirubin elevations infrequently resulted in treatment discontinuation (<1%). Atazanavir treatment did not increase fasting glucose or insulin levels. CONCLUSIONS: For initial HIV treatment, a highly active antiretroviral therapy regimen of atazanavir/zidovudine/lamivudine is as efficacious and well tolerated as the combination of efavirenz/zidovudine/lamivudine.     

Depressive symptoms and close relationships during the transition to adulthood: perspectives from dysphoric women, their best friends, and their romantic partners

Late adolescent women's depressive symptoms and interpersonal functioning were assessed using reports from participants, their best friends, and their romantic partners. As predicted, the associations between relationship dysfunction and dysphoria were stronger in romantic relationships than in friendships. Unlike friends, romantic partners perceived dysphoric women as having poorer social skills. Romantic partners also reported providing less emotional support to dysphoric women, whereas friends reported providing more. Finally, romantic partners of dysphoric women had more Cluster A (odd-eccentric) personality disorder symptoms; these symptoms mediated the relation between women's depression and partners' nonsupportiveness. The findings suggest that dysphoric women may find themselves in emotionally nonsupportive romantic relationships because they have paired (through assortative pairing or mutual influence) with symptomatic partners.     

Universal Mindfulness Training in Schools for Adolescents: a Scoping Review and Conceptual Model of Moderators,Mediators, and Implementation Factors

Prevention Science - There is evidence that universal school-based mindfulness training (SBMT) can have positive effects for young people. However, it is unknown who benefits most from such...     

Acceptability and Feasibility of a 13-Week Pilot Randomised Controlled Trial Testing the Effects of Incremental Doses of Beetroot Juice in Overweight and Obese Older Adults

Nitrate-rich food can increase nitric oxide production and improve vascular and brain functions. This study examines the feasibility of a randomised controlled trial (RCT) testing the effects of prolonged consumption of different doses of dietary nitrate (NO₃⁻) in the form of beetroot juice (BJ) in overweight and obese older participants. A single-blind, four-arm parallel pilot RCT was conducted in 62 overweight and obese (30.4 ± 4 kg/m²) older participants (mean ± standard deviation (SD), 66 ± 4 years). Participants were randomized to: (1) high-NO₃⁻ (HN: 2 × 70 mL BJ/day) (2) medium-NO₃⁻ (MN: 70 mL BJ/day), (3) low-NO₃⁻ (LN: 70 mL BJ on alternate days) or (4) Placebo (PL: 70 mL of NO₃⁻-depleted BJ on alternate days), for 13 weeks. Compliance was checked by a daily log of consumed BJ, NO₃⁻ intake, and by measuring NO₃⁻ and NO₂⁻ concentrations in plasma, saliva, and urine samples. Fifty participants completed the study. Self-reported compliance to the interventions was >90%. There were significant positive linear relationships between NO₃⁻ dose and the increase in plasma and urinary NO₃⁻ concentration (R² = 0.71, p < 0.001 and R² = 0.46 p < 0.001, respectively), but relationships between NO₃⁻ dose and changes in salivary NO₃⁻ and NO₂⁻ were non-linear (R² = 0.35, p = 0.002 and R² = 0.23, p = 0.007, respectively). The results confirm the feasibility of prolonged BJ supplementation in older overweight and obese adults.     

The Potential Roles of Blood–Brain Barrier and Blood–Cerebrospinal Fluid Barrier in Maintaining Brain Manganese Homeostasis

Manganese (Mn) is a trace nutrient necessary for life but becomes neurotoxic at high concentrations in the brain. The brain is a “privileged” organ that is separated from systemic blood circulation mainly by two barriers. Endothelial cells within the brain form tight junctions and act as the blood–brain barrier (BBB), which physically separates circulating blood from the brain parenchyma. Between the blood and the cerebrospinal fluid (CSF) is the choroid plexus (CP), which is a tissue that acts as the blood–CSF barrier (BCB). Pharmaceuticals, proteins, and metals in the systemic circulation are unable to reach the brain and spinal cord unless transported through either of the two brain barriers. The BBB and the BCB consist of tightly connected cells that fulfill the critical role of neuroprotection and control the exchange of materials between the brain environment and blood circulation. Many recent publications provide insights into Mn transport in vivo or in cell models. In this review, we will focus on the current research regarding Mn metabolism in the brain and discuss the potential roles of the BBB and BCB in maintaining brain Mn homeostasis.     

Application of Evidence-Based Treatment in Community Mental Health Settings: Examining EBT Delivery Duration and Client Discharge

The Journal of Behavioral Health Services & Research - Characterizing community mental health (CMH) treatment duration and discharge is an important step toward understanding how to better meet...