Citations

Abstract Allergic asthma is commonly thought to result from dysregulated airway inflammatory responses to ubiquitous environmental antigens mediated by CD4+ T cells polarized to a Th2 or Th17 cell. However, the mechanisms involved in the development of these T-cell responses remain unknown. This study examines the effects of IL-1 family cytokines, such as IL-33 and IL-1β, on the development of antigen-specific Th2 and Th17 cells in the airway. We administered IL-1 family cytokines and model antigens, such as ovalbumin, into the airways of naive BALB/c mice, and examined the cellular and humoral immune responses. To investigate the immunologic mechanisms, we used IL-4 green fluorescent protein reporter mice and mice deficient in the Il4 gene. Innocuous antigens, such as endotoxin-free ovalbumin and short ragweed extract, did not sensitize naive mice when administered through the airways. However, when mice were exposed to the same antigens with IL-1β or IL-33, they developed IgE antibodies. In particular, IL-33 induced robust and long-lasting Th2 cells that produced a large quantity of IL-5 and IL-13 and asthma-like airway pathology. IL-1β induced Th17 cells. In naive, nonsensitized animals, IL-33 stimulated endogenous IL-4 expression by CD4+ T cells, which was critical for the polarization of CD4+ T cells to the Th2 type. In the absence of IL-4, mice developed Th17 cells and neutrophilic airway inflammation. In conclusion, IL-1 family cytokines possess a potent adjuvant activity to promote both Th2 and Th17 cells to innocuous airborne antigens, and they may play fundamental roles in the immunopathology of asthma.

AbstractWe previously reported an increased risk of monoclonal gammopathy of undetermined significance (MGUS) in first‐degree relatives of MGUS and multiple myeloma patients. Here, we examine whether primary cytogenetic categories of myeloma differ between patients with and without a family history of MGUS or myeloma. We studied 201 myeloma patients with available data on family history and molecular cytogenetic classification. Myeloma with trisomies was more common in probands who had an affected first‐degree relative with MGUS or myeloma compared with those without a family history (46.9% vs. 33.5%, P = 0.125); however, the difference was not statistically significant. Additional studies on the cytogenetic types of myeloma associated with familial tendency are needed.

Controlling the overall cost of medical care requires controlling the number of physician visits. Nurse practitioners and physician assistants (NPs/PAs) may function as lower-cost substitutes for physicians or they may complement physician services. The association between NP/PA and physician visits when NPs/PAs are not working as primary care providers (PCPs) has not been thoroughly studied. A sample of 400 family medicine patients drawn from 1 large multisite practice was studied using multiple logistic regression analysis. NPs/PAs did not function as PCPs during the study period. Patients were defined as outliers if they visited physicians more than 5 times in a year. Patients who visited NPs/PAs in non-retail clinics were significantly more likely to be physician visit outliers. Visits to NPs/PAs in retail clinics were not related to physician visits. NP/PA visits in standard medical office settings complement physician visits when the NPs/PAs were not working as PCPs in this large multisite practice. Health care reform proposals relying on increased use of NPs/PAs may be more cost-efficient if NPs/PAs are located in retail settings or function as PCPs. ( Population Health Management 2013;16:242–245)

Recently, the concept of ligand-directed signaling—the ability of different ligands of an individual receptor to promote distinct patterns of cellular response—has gained much traction in the field of drug discovery, with the potential to sculpt biological response to favor therapeutically beneficial signaling pathways over those leading to harmful effects. However, there is limited understanding of the mechanistic basis underlying biased signaling. The glucagon-like peptide-1 receptor is a major target for treatment of type-2 diabetes and is subject to ligand-directed signaling. Here, we demonstrate the importance of polar transmembrane residues conserved within family B G protein-coupled receptors, not only for protein folding and expression, but also in controlling activation transition, ligand-biased, and pathway-biased signaling. Distinct clusters of polar residues were important for receptor activation and signal preference, globally changing the profile of receptor response to distinct peptide ligands, including endogenous ligands glucagon-like peptide-1, oxyntomodulin, and the clinically used mimetic exendin-4.

Despite advances in evidence‐based treatments (EBTs), research suggests these interventions are not utilized in practice settings. This study examined implementation of multi‐family psychoeducational psychotherapy (MF‐PEP), an EBT for childhood mood disorders, in two outpatient community clinics. Fifteen community therapists facilitated MF‐PEP. Twenty community clinicians referred 40 children ages 8–12 with mood disorders and their parents who participated in MF‐PEP. Preliminary descriptive findings based on observations and self‐report questionnaires demonstrated implementation outcomes of acceptability, adoption, appropriateness, feasibility, implementation cost, penetration, and sustainability of MF‐PEP at these clinics. Parents also demonstrated significant improvement in knowledge of mood disorders posttreatment. Preliminary results support implementation of MF‐PEP in practice settings and suggest community‐based MF‐PEP may be associated with improvement in clinical outcomes.