Association between frequency of telephonic contact and clinical testing for a large, geographically diverse diabetes disease management population

Diabetes disease management (DM) programs strive to promote healthy behaviors, including obtaining hemoglobin A1c (A1c) and low-density lipoprotein (LDL) tests as part of standards of care. The purpose of this study was to examine the relationship between frequency of telephonic contact and A1c and LDL testing rates. A total of 245,668 members continuously enrolled in diabetes DM programs were evaluated for performance of an A1c or LDL test during their first 12 months in the programs. The association between the number of calls a member received and clinical testing rates was examined. Members who received four calls demonstrated a 24.1% and 21.5% relative increase in A1c and LDL testing rates, respectively, compared to members who received DM mailings alone. Response to the telephonic intervention as part of the diabetes DM programs was influenced by member characteristics including gender, age, and disease burden. For example, females who received four calls achieved a 27.7% and 23.6% increase in A1c and LDL testing, respectively, compared to females who received mailings alone; by comparison, males who were called achieved 21.2% and 19.9% relative increase in A1c and LDL testing, respectively, compared to those who received mailings alone. This study demonstrates a positive association between frequency of telephonic contact and increased performance of an A1c or LDL test in a large, diverse diabetes population participating in DM programs. The impact of member characteristics on the responsiveness to these programs provides DM program designers with knowledge for developing strategies to promote healthy behaviors and improve diabetes outcomes

HIV-1 activates macrophages independent of Toll-like receptors.

Macrophages provide an interface between innate and adaptive immunity and are important long-lived reservoirs for Human Immunodeficiency Virus Type-1 (HIV-1). Multiple genetic networks involved in regulating signal transduction cascades and immune responses in macrophages are coordinately modulated by HIV-1 infection.To evaluate complex interrelated processes and to assemble an integrated view of activated signaling networks, a systems biology strategy was applied to genomic and proteomic responses by primary human macrophages over the course of HIV-1 infection. Macrophage responses, including cell cycle, calcium, apoptosis, mitogen-activated protein kinases (MAPK), and cytokines/chemokines, to HIV-1 were temporally regulated, in the absence of cell proliferation. In contrast, Toll-like receptor (TLR) pathways remained unaltered by HIV-1, although TLRs 3, 4, 7, and 8 were expressed and responded to ligand stimulation in macrophages. HIV-1 failed to activate phosphorylation of IRAK-1 or IRF-3, modulate intracellular protein levels of Mx1, an interferon-stimulated gene, or stimulate secretion of TNF, IL-1beta, or IL-6. Activation of pathways other than TLR was inadequate to stimulate, via cross-talk mechanisms through molecular hubs, the production of proinflammatory cytokines typical of a TLR response. HIV-1 sensitized macrophage responses to TLR ligands, and the magnitude of viral priming was related to virus replication.HIV-1 induced a primed, proinflammatory state, M1(HIV), which increased the responsiveness of macrophages to TLR ligands. HIV-1 might passively evade pattern recognition, actively inhibit or suppress recognition and signaling, or require dynamic interactions between macrophages and other cells, such as lymphocytes or endothelial cells. HIV-1 evasion of TLR recognition and simultaneous priming of macrophages may represent a strategy for viral survival, contribute to immune pathogenesis, and provide important targets for therapeutic approaches

Macrophages fail to produce Mx1 in response to HIV-1.

<p>Whole cell lysates derived from macrophages treated with media, HIV-1, LPS, Poly(I:C), or CL075 for 24 hours were immunoblotted for Mx1 or actin protein expression.</p

Macrophage activation by virus is independent of cell proliferation.

<p>Macrophage cellular proliferation over 10 days (A) in the absence or (B) presence of HIV-1. Cellular proliferation of PBMC in 4 days (C) in the absence of stimulation or (D) the presence of PHA.</p

TLR pathway is unaltered by HIV-1.

<p>TLR signaling pathway. Factors increased in expression by HIV-1 treatment are red and factors expressed at lower levels by virus are green. Ovals represent factors detected at the RNA level. Signaling hubs are depicted with a yellow border.</p

HIV-1 treatment affects expression patterns of members of the apoptotic pathway in primary macrophages.

<p>(A) Diagram of the apoptotic signaling pathway depicting factors altered in expression within macrophages upon treatment with HIV-1 within 2 days. Factors increased in expression by HIV-1 treatment are red and factors expressed at lower levels by virus are green. Ovals represent factors altered at the RNA level and diamonds are factors modulated at the protein level. Signaling hubs are depicted with a yellow border. The orange pentagon represents virus-encoded Nef. (B) Heat map representing expression of genes whose protein products are involved in apoptosis. The heat map includes the Entrez Gene identification number and the expression cluster that the gene belongs to. Red indicates expression profiles above the mean, black are equal to the mean, and green represents values below the level of the mean. (C) Median Log₂ differences of pro-apoptotic genes (blue) and anti-apoptotic genes (orange) in the HIV-treated samples versus mock plotted over 7 days. (D) PowerBlot of apoptotic proteins altered in macrophages by HIV-1 treatment. The signal intensity ratio of HIV-treated to mock-treated is indicated for each protein above the blot.</p

Temporal program of gene expression modulated in HIV-1-treated macrophages.

<p>(A) Gene expression values from HIV-1-treated macrophage cultures were divided by expression values from mock-treated cultures to derive fold-change ratios. Median values were calculated for all four donors and hierarchical agglomerative clustering with absolute correlation (un-centered) of approximately 900 genes was based on expression patterns over time. Median increase (red) or decrease (green) of expression ranged between +4 and −4 for each gene. Genes were distributed into nine cluster patterns designated A-I (color coded on right Y axis of the dendrogram) Major branches in the dendrogram were defined by correlation coefficients of greater than 0.75 (mean 0.85, range 0.75 to 0.96). (B) Six cluster patterns were selected for further analysis based on their unique temporal expression patterns. Two patterns of temporal gene expression were observed: early day 2 (clusters B, C, D, and G), and late day 7 (clusters E and I).</p

Summary of signaling pathways altered or evaded by virus.

<p>Factors expressed at higher levels in HIV-treated than mock are red and factors expressed at lower levels in HIV-treated than mock are green. Ovals represent factors detected at the RNA level, diamonds are factors detected at the protein level, and hexagons are factors detected at both RNA and protein. Signaling hubs are depicted with a yellow border.</p