IL-21-IgFc immunotherapy alters transcriptional landscape of lymph node cells leading to enhanced flu vaccine response in aging and SIV infection.

Aging people living with HIV (PWH) frequently manifest impaired antibody (Ab) responses to seasonal flu vaccination which has been attributed to ongoing inflammation and immune activation. We have recently reported a similar scenario in old simian immunodeficiency virus (SIV) infected rhesus macaques (RM) with controlled viremia and have been able to compensate for this deficiency by immunotherapy with interleukin (IL)-21-IgFc. To understand the underlying mechanisms of IL-21-induced immunomodulation leading to enhanced flu vaccine response in aging and SIV, we have investigated draining lymph node (LN) cells of IL-21-treated and -untreated animals at postvaccination. We observed IL-21-induced proliferation of flu-specific LN memory CD4 T cells, expansion of B cells expressing IL-21 receptor (IL-21R), and modest expansion of T follicular helper cells (Tfh) co-expressing T-cell immunoreceptor with Ig and ITIM domains (TIGIT) and DNAX accessory molecule (DNAM-1). Transcriptional analysis of LN cells of IL-21-treated animals revealed significant inhibition of germinal center (GC) Tfh and B-cell interferon signaling pathways along with enhanced B-cell development and antigen presentation pathways. We conclude that IL-21 treatment at the time of flu vaccination in aging SIV-infected animals modulates the inductive LN GC activity, to reverse SIV-associated LN Tfh and B-cell dysfunction. IL-21 is a potential candidate molecule for immunotherapy to enhance flu vaccine responses in aging PWH who have deficient antibody responses.

Analysis of Hormone-Protein Binding in Solution by Ultrafast Affinity Extraction: Interactions of Testosterone with Human Serum Albumin and Sex Hormone Binding Globulin.

Ultrafast affinity extraction was used to study hormone-protein interactions in solution, using testosterone and its transport proteins human serum albumin (HSA) and sex hormone binding globulin (SHBG) as models. Both single column and two-dimensional systems based on HSA microcolumns were utilized to measure the free fraction of testosterone in hormone/protein mixtures at equilibrium or that were allowed to dissociate for various lengths of time. These data were used to determine the association equilibrium constants (Ka) or global affinities (nKa') and dissociation rate constants (kd) for testosterone with soluble HSA and SHBG. This method was also used to measure simultaneously the free fraction of testosterone and its equilibrium constants with both these proteins in physiological mixtures of these agents. The kd and Ka values obtained for HSA were 2.1-2.2 s(-1) and 3.2-3.5 × 10(4) M(-1) at pH 7.4 and 37 °C. The corresponding constants for SHBG were 0.053-0.058 s(-1) and 0.7-1.2 × 10(9) M(-1). All of these results gave good agreement with literature values, indicating that this approach could provide information on a wide range of rate constants and binding strengths for hormone-protein interactions in solution and at clinically relevant concentrations. The same method could be extended to alternative hormone-protein systems or other solutes and binding agents.

Community Health Worker Home Visits for Medicaid-Enrolled Children With Asthma: Effects on Asthma Outcomes and Costs.

OBJECTIVES: We sought to estimate the return on investment of a streamlined version of an evidence-based community health worker (CHW) asthma home visit program. METHODS: We used a randomized parallel group trial of home visits by CHWs to Medicaid-enrolled children with uncontrolled asthma versus usual care. RESULTS: A total of 373 participants enrolled in the study (182 in the intervention group and 191 in the control group, of whom 154 and 179, respectively, completed the study). The intervention group had greater improvements in asthma symptom-free days (2.10 days more over 2 weeks; 95% CI = 1.17, 3.05; P < .001) and caretakers' quality of life (0.43 units more; 95% CI = 0.20, 0.66; P < .001) and a larger reduction in urgent health care utilization events (1.31 events fewer over 12 months; 95% CI = -2.10, -0.52; P = .001). The intervention arm compared with the control arm saved $1340.92 for the $707.04 additional costs invested for the average participant. The return on investment was 1.90. CONCLUSIONS: A streamlined CHW asthma home visit program for children with uncontrolled asthma improved health outcomes and yielded a return on investment of 1.90.

Implementation and acceptability of Mindful Awareness in Body-oriented Therapy in women's substance use disorder treatment.

OBJECTIVES: The purpose of this study was to examine the implementation and acceptability of Mindful Awareness in Body-oriented Therapy (MABT), a novel adjunctive approach to substance use disorder (SUD) treatment. The primary aims of the study were to examine implementation of MABT as an adjunct to addiction treatment, and MABT acceptability to study participants and treatment staff. METHODS: MABT was delivered to participants randomly assigned to the intervention in a larger ongoing trial. This study focuses only on the implementation and acceptability of the intervention, as outcomes are not yet available. MABT was delivered once weekly for 8 weeks (1.5-hour sessions) and spanned inpatient and outpatient programs at a women-only treatment facility. Descriptive statistics were used to examine participant recruitment and retention to the intervention. To measure MABT acceptability, survey and written questionnaires were administered; analysis involved descriptive statistics and content analysis using Atlas.ti software. RESULTS: Thirty-one (31) of the women enrolled in the study were randomized to MABT. Eighteen (18) participants completed 75%-100% of the MABT sessions. Intervention implementation required flexibility on the part of both the researchers and the clinic staff, and minor changes were made to successfully implement MABT as an adjunct to usual care. MABT was perceived to increase emotional awareness and provide new tools to cope with stress, and to positively influence SUD treatment by facilitating emotion regulation. CONCLUSIONS: It was feasible to implement MABT and to recruit and retain women to MABT in women's chemical-dependency treatment. MABT acceptability and perceived benefit was high.

Effectiveness of therapeutic massage for generalized anxiety disorder: a randomized controlled trial.

BACKGROUND: Although massage is one of the most popular complementary and alternative medical (CAM) treatments for anxiety, its effectiveness has never been rigorously evaluated for a diagnosed anxiety disorder. This study evaluates the effectiveness of therapeutic massage for persons with generalized anxiety disorder (GAD). METHODS: Sixty-eight persons with GAD were randomized to therapeutic massage (n=23), thermotherapy (n=22), or relaxing room therapy (n=23) for a total of 10 sessions over 12 weeks. Mean reduction in anxiety was measured by the Hamilton Anxiety Rating Scale (HARS). Secondary outcomes included 50% reduction in HARS and symptom resolution of GAD, changes in depressive symptoms (Patient Health Questionnaire (PHQ-8)), worry and GAD-related disability. We compared changes in these outcomes in the massage and control groups posttreatment and at 6 months using generalized estimating equation (GEE) regression. RESULTS: All groups had improved by the end of treatment (adjusted mean change scores for the HARS ranged from -10.0 to -13.0; P<.001) and maintained their gains at the 26-week followup. No differences were seen between groups (P=.39). Symptom reduction and resolution of GAD, depressive symptoms, worry and disability showed similar patterns. CONCLUSIONS: Massage was not superior to the control treatments, and all showed some clinically important improvements, likely due to some beneficial but generalized relaxation response. Because the relaxing room treatment is substantially less expensive than the other treatments, a similar treatment packaged in a clinically credible manner might be the most cost effective option for persons with GAD who want to try relaxation-oriented CAM therapies.

Physiological adjustments to stress measures following massage therapy: a review of the literature.

Use of massage therapy by the general public has increased substantially in recent years. In light of the popularity of massage therapy for stress reduction, a comprehensive review of the peer-reviewed literature is important to summarize the effectiveness of this modality on stress-reactive physiological measures. On-line databases were searched for articles relevant to both massage therapy and stress. Articles were included in this review if (i) the massage therapy account consisted of manipulation of soft tissues and was conducted by a trained therapist, and (ii) a dependent measure to evaluate physiological stress was reported. Hormonal and physical parameters are reviewed. A total of 25 studies met all inclusion criteria. A majority of studies employed a 20-30 min massage administered twice-weekly over 5 weeks with evaluations conducted pre-post an individual session (single treatment) or following a series of sessions (multiple treatments). Single treatment reductions in salivary cortisol and heart rate were consistently noted. A sustained reduction for these measures was not supported in the literature, although the single-treatment effect was repeatable within a study. To date, the research data is insufficient to make definitive statements regarding the multiple treatment effect of massage therapy on urinary cortisol or catecholamines, but some evidence for a positive effect on diastolic blood pressure has been documented. While significant improvement has been demonstrated following massage therapy, the general research body on this topic lacks the necessary scientific rigor to provide a definitive understanding of the effect massage therapy has on many physiological variables associated with stress.