Publications

Prior evidence suggests that the health and longevity benefits of antiretroviral therapy (ART) for persons living with AIDS (PLWAs) have not been equally distributed across racial/ethnic groups in the United States. Notably, black PLWAs tend to fare worse than their counterparts. We examine the role of neighborhood socioeconomic context on racial/ethnic differences in AIDS treatment and survival in San Francisco. The study population encompassed 4211 San Francisco residents diagnosed with AIDS between 1996 and 2001. Vital status was reported through 2006. Census data were used to define neighborhood-level indicators of income, housing, demographics, employment and education. Cox proportional hazards models were employed in multivariate analyses of survival times. Compared to whites, blacks had a significant 1.4 greater mortality hazard ratio (HR), which decreased after accounting for ART initiation. PLWAs in the lowest socioeconomic neighborhoods had a significant HR of 1.4 relative to those in higher socioeconomic neighborhoods, independent of race/ethnicity. The neighborhood association decreased after accounting for ART initiation. Path analysis was used to explore causal pathways to ART initiation. Racial/ethnic differences in neighborhood residence accounted for 19-22% of the 1.6-1.8 black-white relative odds ratio (ROR) and 14-15% of the 1.3-1.4 Latino-white ROR for delayed or no treatment. Our findings illuminate the independent and synergistic contributions of race and place on treatment disparities and highlight the need for future studies and interventions to address treatment initiation as well as neighborhood effects on treatment differences.

The transient receptor potential vanilloid 4 (TRPV4) contributes to mechanical hyperalgesia of diverse etiologies, presumably as part of a mechanoreceptor signaling complex (Alessandri-Haber et al., 2008). To investigate the hypothesis that a functional interaction between TRPV4 and stretch-activated ion channels (SACs) is involved in this mechanical transduction mechanism, we used a selective SACs inhibitor, GsMTx-4. Intradermal injection of GsMTx-4 in the rat hindpaw reversed the mechanical hyperalgesia induced by intradermal injection of inflammatory mediators. In vivo single fiber recordings showed that GsMTx-4 reversed inflammatory mediator-induced decrease in mechanical threshold in half of sensitized C-fibers. Furthermore, GsMTx-4 reduced hyperalgesia to both mechanical and hypotonic stimuli in different models of inflammatory and neuropathic pain, although it had no effect on baseline mechanical nociceptive thresholds. TRPC1 and TRPC6, two GsMTx-4-sensitive SACs, are expressed in dorsal root ganglion (DRG) neurons. Single-cell reverse transcription-PCR showed that messenger RNAs for TRPV4, TRPC1, and TRPC6 are frequently coexpressed in DRG neurons. Spinal intrathecal administration of oligodeoxynucleotides antisense to TRPC1 and TRPC6, like that to TRPV4, reversed the hyperalgesia to mechanical and hypotonic stimuli induced by inflammatory mediators without affecting baseline mechanical nociceptive threshold. However, antisense to TRPC6, but not to TRPC1, reversed the mechanical hyperalgesia induced by a thermal injury or the TRPV4-selective agonist 4alpha-PDD (4 alpha-phorbol 12,13-didecanoate). We conclude that TRPC1 and TRPC6 channels cooperate with TRPV4 channels to mediate mechanical hyperalgesia and primary afferent nociceptor sensitization, although they may have distinctive roles.

RATIONALE AND OBJECTIVES

Research on communication between radiologists and women undergoing screening and diagnostic mammography is limited. We describe community radiologists' communication practices with patients regarding screening and diagnostic mammogram results and factors associated with frequency of communication.

MATERIALS AND METHODS

We received surveys from 257 radiologists (70% of those eligible) about the extent to which they talk to women as part of their health care visit for either screening or diagnostic mammograms, whether this occurs if the exam assessment is positive or negative, and how they use estimates of patient risk to convey information about an abnormal exam where the specific finding of cancer is not yet known. We also assessed characteristics of the radiologists to identify associations with more or less frequent communication at the time of the mammogram.

RESULTS

Two hundred and forty-three radiologists provided complete data (95%). Very few (<6%) reported routinely communicating with women when screening mammograms were either normal or abnormal. Fewer than half (47%) routinely communicated with women when their diagnostic mammograms were normal, whereas 77% often or always communicated with women when their diagnostic exams were abnormal. For positive diagnostic exams, female radiologists were more likely to be frequent communicators compared to males (87.1%-72.8%; P=.02) and those who spend 40%-79% of their time in breast imaging (94.6%) were more likely to be frequent communicators compared to those who spend less time (67.2%-78.9%; P=.02). Most radiologists convey risk information using general rather than numeric statements (57.7% vs. 28.5%).

CONCLUSIONS

Radiologists are most likely to convey information about diagnostic mammographic findings when results are abnormal. Most radiologists convey risk information using general rather than numeric statements.

Mouse models have shown the importance of acidic mammalian chitinase activity in settings of chitin exposure and allergic inflammation. However, little is known regarding genetic regulation of AMCase enzymatic activity in human allergic diseases. Resequencing the AMCase gene exons we identified 8 non-synonymous single nucleotide polymorphisms including three novel variants (A290G, G296A, G339T) near the gene area coding for the enzyme active site, all in linkage disequilibrium. AMCase protein isoforms, encoded by two gene-wide haplotypes, and differentiated by these three single nucleotide polymorphisms, were recombinantly expressed and purified. Biochemical analysis revealed the isoform encoded by the variant haplotype displayed a distinct pH profile exhibiting greater retention of chitinase activity at acidic and basic pH values. Determination of absolute kinetic activity found the variant isoform encoded by the variant haplotype was 4-, 2.5-, and 10-fold more active than the wild type AMCase isoform at pH 2.2, 4.6, and 7.0, respectively. Modeling of the AMCase isoforms revealed positional changes in amino acids critical for both pH specificity and substrate binding. Genetic association analyses of AMCase haplotypes for asthma revealed significant protective associations between the variant haplotype in several asthma cohorts. The structural, kinetic, and genetic data regarding the AMCase isoforms are consistent with the Th2-priming effects of environmental chitin and a role for AMCase in negatively regulating this stimulus.

OBJECTIVE

To examine whether the effect of health literacy (HL) on patient-physician communication varies with patient-physician language concordance and communication type.

METHODS

771 outpatients rated three types of patient-physician communication: receptive communication (physician to patient); proactive communication (patient to physician); and interactive, bidirectional communication. We assessed HL and language categories including: English-speakers, Spanish-speakers with Spanish-speaking physicians (Spanish-concordant), and Spanish-speakers without Spanish-speaking physicians (Spanish-discordant).

RESULTS

Overall, the mean age of participants was 56 years, 58% were women, 53% were English-speakers, 23% Spanish-concordant, 24% Spanish-discordant, and 51% had limited HL. Thirty percent reported poor receptive, 28% poor proactive, and 56% poor interactive communication. In multivariable analyses, limited HL was associated with poor receptive and proactive communication. Spanish-concordance and discordance was associated with poor interactive communication. In stratified analyses, among English-speakers, limited HL was associated with poor receptive and proactive, but not interactive communication. Among Spanish-concordant participants, limited HL was associated with poor proactive and interactive, but not receptive communication. Spanish-discordant participants reported the worst communication for all types, independent of HL.

CONCLUSION

Limited health literacy impedes patient-physician communication, but its effects vary with language concordance and communication type. For language discordant dyads, language barriers may supersede limited HL in impeding interactive communication.

PRACTICE IMPLICATIONS

Patient-physician communication interventions for diverse populations need to consider HL, language concordance, and communication type.

In various mammalian species, including humans, water restriction leads to an acute increase in urinary sodium excretion. This process, known as dehydration natriuresis, helps prevent further accentuation of hypernatremia and the accompanying rise in extracellular tonicity. Serum- and glucocorticoid-inducible kinase (Sgk1), which is expressed in the renal medulla, is regulated by extracellular tonicity. However, the mechanism of its regulation and the physiological role of hypertonicity-induced SGK1 gene expression remain unclear. Here, we identified a tonicity-responsive enhancer (TonE) upstream of the rat Sgk1 transcriptional start site. The transcription factor NFAT5 associated with TonE in a tonicity-dependent fashion in cultured rat renal medullary cells, and selective blockade of NFAT5 activity resulted in suppression of the osmotic induction of the Sgk1 promoter. In vivo, water restriction of rats or mice led to increased urine osmolality, increased Sgk1 expression, increased expression of the type A natriuretic peptide receptor (NPR-A), and dehydration natriuresis. In cultured rat renal medullary cells, siRNA-mediated Sgk1 knockdown blocked the osmotic induction of natriuretic peptide receptor 1 (Npr1) gene expression. Furthermore, Npr1-/- mice were resistant to dehydration natriuresis, which suggests that Sgk1-dependent activation of the NPR-A pathway may contribute to this response. Collectively, these findings define a specific mechanistic pathway for the osmotic regulation of Sgk1 gene expression and suggest that Sgk1 may play an important role in promoting the physiological response of the kidney to elevations in extracellular tonicity.