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Interventions that build upon the natural components of early mother-infant interactions are critical to reversing the sequelae of maternal substance abuse and breaking the cycle of addiction. This paper proposes a theoretical model that blends infant massage (IM) into a planned parenting enhancement program (PEP) to promote improved health outcomes in recovering substance- abusing mothers (SAMs) and their babies. With 4.6 million women of child-bearing age regularly using cocaine in the United States and 750,000 drug-exposed births annually, maternal substance abuse highlights the multigenerational impact of drug use in high-risk populations and its risks to our children. The proposed IMPEP model provides a means to assist recovering SAMs in making cognitive-behavioral changes through new knowledge about parenting and parenting skills, with a special focus on infant stimulation via massage. The goal is to enable recovering SAMs to become confident and responsive mothers, empowering them to become effective parents. Pilot data suggest the Infant Massage Parenting Enhancement Program (IMPEP) is effective for both mother and infant, and merits a controlled systematic study., This paper proposes a model for an innovative intervention program for high-risk mothers, i.e., infant massage (IM) blended into a systematically planned Parenting Enhancement Program (PEP), otherwise known as IMPEP. [...]

Idiopathic CD4 lymphopenia (ICL) is a rare syndrome defined by low CD4 T-cell counts (<300/µL) without evidence of HIV infection or other known cause of immunodeficiency. ICL confers an increased risk of opportunistic infections and has no established treatment. Interleukin-7 (IL-7) is fundamental for thymopoiesis, T-cell homeostasis, and survival of mature T cells, which provides a rationale for its potential use as an immunotherapeutic agent for ICL. We performed an open-label phase 1/2A dose-escalation trial of 3 subcutaneous doses of recombinant human IL-7 (rhIL-7) per week in patients with ICL who were at risk of disease progression. The primary objectives of the study were to assess safety and the immunomodulatory effects of rhIL-7 in ICL patients. Injection site reactions were the most frequently reported adverse events. One patient experienced a hypersensitivity reaction and developed non-neutralizing anti-IL-7 antibodies. Patients with autoimmune diseases that required systemic therapy at screening were excluded from the study; however, 1 participant developed systemic lupus erythematosus while on study and was excluded from further rhIL-7 dosing. Quantitatively, rhIL-7 led to an increase in the number of circulating CD4 and CD8 T cells and tissue-resident CD3 T cells in the gut mucosa and bone marrow. Functionally, these T cells were capable of producing cytokines after mitogenic stimulation. rhIL-7 was well tolerated at biologically active doses and may represent a promising therapeutic intervention in ICL. This trial was registered at www.clinicaltrials.gov as #NCT00839436.

This study aimed to determine whether a blended Infant Massage–Parenting Enhancement Program (IMPEP) improved maternal psychosocial health outcomes (parenting stress, depressive symptoms, self-esteem, maternal attachment) and maternal-infant interaction among substance-addicted mothers (SAMs) actively engaged in outpatient rehabilitation.

IL-7 is essential for T-cell homeostasis. Elevated serum IL-7 levels in lymphopenic states, including HIV infection, are thought to be due to increased production by homeostatic feedback, decreased receptor-mediated clearance, or both. The goal of this study was to understand how immune reconstitution through antiretroviral therapy (ART) in HIV+patients affects IL-7 serum levels, expression of the IL-7 receptor (CD127), and T-cell cycling. Immunophenotypic analysis of T cells from 29 HIV−controls and 43 untreated HIV+patients (30 of whom were followed longitudinally for ≤ 24 months on ART) was performed. Restoration of both CD4+and CD8+T cells was driven by increases in CD127+naive and central memory T cells. CD4+T-cell subsets were not fully restored after 2 years of ART, whereas serum IL-7 levels normalized by 1 year of ART. Mathematical modeling indicated that changes in serum IL-7 levels could be accounted for by changes in the receptor concentration. These data suggest that T-cell restoration after ART in HIV infection is driven predominantly by CD127+cells and that decreases of serum IL-7 can be largely explained by improved CD127-mediated clearance.

Immune reconstitution inflammatory syndrome (IRIS) is a considerable problem in the treatment of HIV-infected patients. To identify immunologic correlates of IRIS, we characterized T-cell phenotypic markers and serum cytokine levels in HIV patients with a range of different AIDS-defining illnesses, before and at regular time points after initiation of antiretroviral therapy. Patients developing IRIS episodes displayed higher frequencies of effector memory, PD-1+, HLA-DR+, and Ki67+ CD4+ T cells than patients without IRIS. Moreover, PD-1+ CD4+ T cells in IRIS patients expressed increased levels of LAG-3, CTLA-4, and ICOS and had a Th1/Th17 skewed cytokine profile upon polyclonal stimulation. Elevated PD-1 and Ki67 expression was also seen in regulatory T cells of IRIS patients. Furthermore, IRIS patients displayed higher serum interferon-γ, compared with non-IRIS patients, near the time of their IRIS events and higher serum interleukin-7 levels, suggesting that the T-cell populations are also exposed to augmented homeostatic signals. In conclusion, our findings indicate that IRIS appears to be a predominantly CD4-mediated phenomenon with reconstituting effector and regulatory T cells showing evidence of increased activation from antigenic exposure. These studies are registered online at http://clinicaltrials.gov as NCT00557570 and NCT00286767.

Immune reconstitution inflammatory syndrome (IRIS) is a considerable problem in the treatment of HIV-infected patients. To identify immunologic correlates of IRIS, we characterized T-cell phenotypic markers and serum cytokine levels in HIV patients with a range of different AIDS-defining illnesses, before and at regular time points after initiation of antiretroviral therapy. Patients developing IRIS episodes displayed higher frequencies of effector memory, PD-1+, HLA-DR+, and Ki67+CD4+T cells than patients without IRIS. Moreover, PD-1+CD4+T cells in IRIS patients expressed increased levels of LAG-3, CTLA-4, and ICOS and had a Th1/Th17 skewed cytokine profile upon polyclonal stimulation. Elevated PD-1 and Ki67 expression was also seen in regulatory T cells of IRIS patients. Furthermore, IRIS patients displayed higher serum interferon-γ, compared with non-IRIS patients, near the time of their IRIS events and higher serum interleukin-7 levels, suggesting that the T-cell populations are also exposed to augmented homeostatic signals. In conclusion, our findings indicate that IRIS appears to be a predominantly CD4-mediated phenomenon with reconstituting effector and regulatory T cells showing evidence of increased activation from antigenic exposure. These studies are registered online at http://clinicaltrials.govas NCT00557570 and NCT00286767.

Background: To investigate the efficacy of secukinumab in patients with active non-radiographic axial spondyloarthritis (nr-axSpA) grouped by disease activity as assessed by C-reactive protein (CRP) levels and/or magnetic resonance imaging (MRI) scores, human leukocyte antigen (HLA)-B27 status, and sex. Methods: The phase III PREVENT study randomized (1:1:1) 555 patients to receive subcutaneous secukinumab 150 mg with (LD) or without (NL) loading dose or placebo weekly, followed by every 4 weeks starting at week 4. Here, we report the results of a post hoc analysis reporting the efficacy outcomes (pooled secukinumab) to 16 weeks by CRP, MRI, HLA-B27, and sex. Results: Efficacy differences between the secukinumab and the placebo groups were highest in the CRP+, MRI+, HLA-B27+, and male subgroups, particularly for Ankylosing Spondylitis Disease Activity Score-CRP inactive disease and Assessment of SpondyloArthritis international Society (ASAS) partial remission outcomes. ASAS40 response rates in the CRP+/MRI+ subgroup was 52.3% (secukinumab) versus 21.8% (placebo; P&lt; 0.0001) at week 16. ASAS40 response rates (secukinumab versus placebo) were 43.9% versus 32.6% in HLA-B27+, 32.7% versus 16.4% in HLA-B27− subgroups, 51.2% versus 30.8% in male, and 31.7% versus 25.3% in female patients, respectively. Conclusions: Secukinumab improved the signs and symptoms of nr-axSpA across patients grouped by CRP (+/−) and/or MRI (+/−) status, HLA-B27 (+/−) status, and sex. The highest treatment differences between secukinumab and placebo were observed in patients with both elevated CRP and evidence of sacroiliitis on MRI. Treatment difference was minimal between HLA-B27 (+) and (−) subgroups. Male patients had higher relative responses than female patients. Trial registration: ClinicalTrials.gov, NCT02696031. Registered on 02 March 2016

Both thymic and extrathymic T lineage development are characterized by cytokine-dependent regulation of complex proliferative, differentiative, and anti-apoptotic processes. The role of the γc-dependent cytokines in this program has been interpreted as limited to the activity of IL-7. However, through the analysis of double knock-out mice, which lack signaling through the IL-7R and other γc-dependent cytokines, we revealed a role for IL-15 in the production of early thymic pro-T cells. Although IL-2 does not function in the production of thymocytes, thymic restoration of IL-2R expression prevented fatal autoimmunity associated with IL-2- or IL-2R-deficient mice, suggesting that IL-2R functions non-redundantly at the level of the thymus to regulate self-reactivity. Moreover, IL-2, IL-7, and IL-15 also extend their developmental effects beyond the thymus to other sites of T lymphocyte production, including the gut. Here, their redundant and non-redundant activities are directly correlated to the development of phenotypically diverse subsets of intestinal intraepithelial lymphocytes.

Prostanoids exhibit both pro-apoptotic and anti-apoptotic functions depending on the maturation stage and tissue localization of target cells. Prostaglandin (PG) E2 has been shown to protect T lymphocytes from TCR-mediated activation-induced cell death, but the mechanism by which PGE2 inhibits apoptosis of T cells has not been established. We show that this protection involves the down-regulation of Fas-ligand (Fas-L) mRNA levels in T cells. Modulation of cell surface Fas-L expressin by physiological concentrations of PGE2 was shown to be both anti-apoptotic as well as capable of inhibiting Fas-L-mediated cytotoxicity of Fas-transfected P815 target cells. Thus, this study provides direct evidence of the likely biological means by which PGE2 down-regulates T cell apoptosis.

The article discusses research on the benefits of the Infant Massage-Parenting Enhancement Program (IMPEP) and Parenting Enhancement Program (PEP) to recovering substance-addicted mothers, conducted by Luz S. Porter and colleagues, published in the December 2015 issue of "Asian Nursing Research" journal. Topics explored include the infant massage techniques taught to participants, the stress evaluation conducted following the IMPEP and PEP classes, and the reduction in parenting stress noted.