Living Smart, Living Fit

Background: Depression and obesity/overweight during pregnancy are important public health concerns, as they are frequently associated with poor birth outcomes. The Living Smart, Living Fit® (LSLF) program was an intervention program initiated in 2008 to provide comprehensive care to low-income pregnant and postpartum women with elevated body mass index (BMI) and depressive symptoms. It linked patients to clinical care coordinators trained in motivational interviewing who promoted participation in a portfolio of mental and physical wellness activities. Objective: The objective of this study was to evaluate the effectiveness of LSLF in improving depression, BMI, birth weight, and smoking status among low-income perinatal patients. Methods: Women with Patient Health Questionnaire (PHQ-9) depression scores ≥10 and/or BMI >25 kg/m 2 at their prenatal intake visit were eligible for enrollment into the LSLF program. Enrolled participants met with clinical care coordinators who encouraged engagement in a portfolio of LSLF activities that included pregnancy/family, physical health, and mental health interventions. Outcomes were measured at the 6-week postpartum visit and included change in PHQ-9 scores, change in BMI, birth weight, and change in smoking status. Results: Of the 107 enrollees, 86% participated in some LSLF activity. Participation in pregnancy/family related activities was significantly associated with decreased PHQ-9 scores. Participation in mental health services was significantly associated with increased birth weight. No changes in BMI or smoking status were associated with LSLF involvement. Conclusions: The findings of this pilot study indicate that pregnant women with depression or obesity/overweight can benefit from care coordination and a portfolio of activities for mental and physical wellness. The LSLF program provides a model for delivering this patient-centered comprehensive support. Further research should include more controlled trials to better evaluate the effectiveness of LSLF intervention

Commensal bacteria contribute to insulin resistance in aging by activating innate B1a cells

Aging in humans is associated with increased hyperglycemia and insulin resistance (collectively termed IR) and dysregulation of the immune system. However, the causative factors underlying their association remain unknown. Here, using "healthy" aged mice and macaques, we found that IR was induced by activated innate 4-1BBL + B1a cells. These cells (also known as 4BL cells) accumulated in aging in response to changes in gut commensals and a decrease in beneficial metabolites such as butyrate. We found evidence suggesting that loss of the commensal bacterium Akkermansia muciniphila impaired intestinal integrity, causing leakage of bacterial products such as endotoxin, which activated CCR2(+) monocytes when butyrate was decreased. Upon infiltration into the omentum, CCR2(+) monocytes converted B1a cells into 4BL cells, which, in turn, induced IR by expressing 4-1BBL, presumably to trigger 4-1BB receptor signaling as in obesity-induced metabolic disorders. This pathway and IR were reversible, as supplementation with either A. muciniphila or the antibiotic enrofloxacin, which increased the abundance of A. muciniphila, restored normal insulin response in aged mice and macaques. In addition, treatment with butyrate or antibodies that depleted CCR2(+) monocytes or 4BL cells had the same effect on IR. These results underscore the pathological function of B1a cells and suggest that the microbiome-monocyte-B cell axis could potentially be targeted to reverse age-associated IR

Discovering naturally processed antigenic determinants that confer protective T cell immunity

CD8(+) T cells (TCD8) confer protective immunity against many infectious diseases, suggesting that microbial TCD8 determinants are promising vaccine targets. Nevertheless, current T cell antigen identification approaches do not discern which epitopes drive protective immunity during active infection — information that is critical for the rational design of TCD8-targeted vaccines. We employed a proteomics-based approach for large-scale discovery of naturally processed determinants derived from a complex pathogen, vaccinia virus (VACV), that are presented by the most frequent representatives of four major HLA class I supertypes. Immunologic characterization revealed that many previously unidentified VACV determinants were recognized by smallpox-vaccinated human peripheral blood cells in a variegated manner. Many such determinants were recognized by HLA class I–transgenic mouse immune TCD8 too and elicited protective TCD8 immunity against lethal intranasal VACV infection. Notably, efficient processing and stable presentation of immune determinants as well as the availability of naive TCD8 precursors were sufficient to drive a multifunctional, protective TCD8 response. Our approach uses fundamental insights into T cell epitope processing and presentation to define targets of protective TCD8 immunity within human pathogens that have complex proteomes, suggesting that this approach has general applicability in vaccine sciences

V1V2-specific complement activating serum IgG as a correlate of reduced HIV-1 infection risk in RV144

<div><p>Non-neutralizing IgG to the V1V2 loop of HIV-1 gp120 correlates with a decreased risk of HIV-1 infection but the mechanism of protection remains unknown. This V1V2 IgG correlate was identified in RV144 Thai trial vaccine recipients, who were primed with a canarypox vector expressing membrane-bound gp120 (vCP1521) and boosted with vCP1521 plus a mixture gp120 proteins from clade B and clade CRF01_AE (B/E gp120). We sought to determine whether the mechanism of vaccine protection might involve antibody-dependent complement activation. Complement activation was measured as a function of complement component C3d deposition on V1V2-coated beads in the presence of RV144 sera. Variable levels of complement activation were detected two weeks post final boosting in RV144, which is when the V1V2 IgG correlate was identified. The magnitude of complement activation correlated with V1V2-specific serum IgG and was stronger and more common in RV144 than in HIV-1 infected individuals and two related HIV-1 vaccine trials, VAX003 and VAX004, where no protection was seen. After adjusting for gp120 IgA, V1V2 IgG, gender, and risk score, complement activation by case-control plasmas from RV144 correlated inversely with a reduced risk of HIV-1 infection, with odds ratio for positive versus negative response to TH023-V1V2 0.42 (95% CI 0.18 to 0.99, p = 0.048) and to A244-V1V2 0.49 (95% CI 0.21 to 1.10, p = 0.085). These results suggest that complement activity may have contributed in part to modest protection against the acquisition of HIV-1 infection seen in the RV144 trial.</p></div

Results testing the correlation of quantitative complement activity readouts with HIV-1 infection.

<p>Results testing the correlation of quantitative complement activity readouts with HIV-1 infection.</p