Publications

Hepatic steatosis (HS) is common in individuals with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) infections, but the independent contributions of HCV and HIV to HS are unclear. Magnetic resonance imaging and spectroscopy were used to measure visceral adipose tissue (VAT) and liver fat fraction (LFF) (total lipids/[total lipids + water]) in 356 adults: 57 with HCV monoinfection, 70 with HIV/HCV coinfection, 122 with HIV monoinfection, and 107 with neither infection. Participants who were infected with HCV genotype 3 were excluded because of the genotype's reported steatogenic effects. For prevalence estimates, HS was defined as LFF ≥ 0.05. We estimated the association of HIV and HCV status with LFF using multivariable linear regression, adjusting for demographics, lifestyle, and metabolic factors including the homeostasis model assessment estimate of insulin resistance (HOMA-IR) and liver fibrosis defined using the aspartate aminotransferase-to-platelet ratio index (APRI). The prevalence of HS was highest in the uninfected (33%) and HIV-monoinfected (28%), followed by the HCV-monoinfected (19%) and HIV/HCV-coinfected (11%) (P = 0.003 across groups). Compared with uninfected participants-and after adjusting for demographics, lifestyle, and metabolic factors-HIV monoinfection, HCV monoinfection, and HIV/HCV coinfection were associated with 19% (95% confidence interval [CI], -39% to 6%), 38% (95% CI, -55% to -12%), and 42% (95% CI, -59% to -18%) lower LFF, respectively. HCV monoinfection and HIV/HCV coinfection remained strongly associated with lower LFF after further adjusting for APRI, and results were unchanged after excluding subjects with suspected cirrhosis. Among the entire cohort, Hispanic ethnicity, male sex, VAT, and HOMA-IR were independently associated with greater LFF.

CONCLUSION

Contrary to expectations, HIV/HCV-coinfected and HCV-monoinfected adults had significantly less liver fat than uninfected adults, even after adjusting for demographics, lifestyle, metabolic factors, and hepatic fibrosis. Our findings suggest that non-genotype 3 HCV infection may be protective against HS. The mechanisms by which this occurs and the impact of HCV treatment on HS requires further investigation. (Hepatology 2017;65:853-863).

Lymphocytes integrate Ag and cytokine receptor signals to make cell fate decisions. Using a specific reporter of TCR signaling that is insensitive to cytokine signaling, Nur77-eGFP, we identify a sharp, minimal threshold of cumulative TCR signaling required for proliferation in CD4 and CD8 T cells that is independent of both Ag concentration and affinity. Unexpectedly, IL-2 reduces this threshold in CD8 but not CD4 T cells, suggesting that integration of multiple mitogenic inputs may alter the minimal requirement for TCR signaling in CD8 T cells. Neither naive CD4 nor naive CD8 T cells are responsive to low doses of IL-2. We show that activated CD8 T cells become responsive to low doses of IL-2 more quickly than CD4 T cells, and propose that this relative delay in turn accounts for the differential effects of IL-2 on the minimal TCR signaling threshold for proliferation in these populations. In contrast to Nur77-eGFP, c-Myc protein expression integrates mitogenic signals downstream of both IL-2 and the TCR, yet marks an invariant minimal threshold of cumulative mitogenic stimulation required for cell division. Our work provides a conceptual framework for understanding the regulation of clonal expansion of CD8 T cells by subthreshold TCR signaling in the context of mitogenic IL-2 signals, thereby rendering CD8 T cells exquisitely dependent upon environmental cues. Conversely, CD4 T cell proliferation requires an invariant minimal intensity of TCR signaling that is not modulated by IL-2, thereby restricting responses to low-affinity or low-abundance self-antigens even in the context of an inflammatory milieu.

PURPOSE

To compare remote myocardium native T in patients with chronic myocardial infarction (MI) and controls without MI and to elucidate the relationship of infarct size and native T in the remote myocardium for the prediction of left ventricular (LV) systolic dysfunction after MI.

MATERIALS AND METHODS

A total of 41 chronic MI (18 anterior MI) patients and 15 age-matched volunteers with normal LV systolic function and no history of MI underwent cardiac magnetic resonance imaging (MRI) at 1.5T. Native T map was performed using a slice interleaved T mapping and late gadolinium enhancement (LGE) imaging. Cine MR was acquired to assess LV function and mass.

RESULTS

The remote myocardium native T time was significantly elevated in patients with prior MI, compared to controls, for both anterior MI and nonanterior MI (anterior MI: 1099 ± 30, nonanterior MI: 1097 ± 39, controls: 1068 ± 25 msec, P < 0.05). Remote myocardium native T moderately correlated with LV volume, mass index, and ejection fraction (r = 0.38, 0.50, -0.49, respectively, all P < 0.05). LGE infarct size had a moderate correlation with reduced LV ejection fraction (r = -0.33, P < 0.05), but there was no significant association between native T and infarct size. Native T time in the remote myocardium was independently associated with reduced LV ejection fraction, after adjusting for age, gender, infarct size, and comorbidity (β = -0.34, P = 0.03).

CONCLUSION

In chronic MI, the severity of LV systolic dysfunction after MI is independently associated with native T in the remote myocardium. Diffuse myocardial fibrosis in the remote myocardium may play an important pathophysiological role of post-MI LV dysfunction.

LEVEL OF EVIDENCE

1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017;46:1073-1081.

OBJECTIVES

To examine 6-month change in life-space mobility as a predictor of subsequent 6-month mortality in community-dwelling older adults.

DESIGN

Prospective cohort study.

SETTING

Community-dwelling older adults from five Alabama counties in the University of Alabama at Birmingham (UAB) Study of Aging.

PARTICIPANTS

A random sample of 1,000 Medicare beneficiaries, stratified according to sex, race, and rural or urban residence, recruited between November 1999 and February 2001, followed by a telephone interview every 6 months for the subsequent 8.5 years.

MEASUREMENTS

Mortality data were determined from informant contacts and confirmed using the National Death Index and Social Security Death Index. Life-space was measured at each interview using the UAB Life-Space Assessment, a validated instrument for assessing community mobility. Eleven thousand eight hundred seventeen 6-month life-space change scores were calculated over 8.5 years of follow-up. Generalized linear mixed models were used to test predictors of mortality at subsequent 6-month intervals.

RESULTS

Three hundred fifty-four deaths occurred within 6 months of two sequential life-space assessments. Controlling for age, sex, race, rural or urban residence, and comorbidity, life-space score and life-space decline over the preceding 6-month interval predicted mortality. A 10-point decrease in life-space resulted in a 72% increase in odds of dying over the subsequent 6 months (odds ratio = 1.723, P < .001).

CONCLUSIONS

Life-space score at the beginning of a 6-month interval and change in life-space over 6 months were each associated with significant differences in subsequent 6-month mortality. Life-space assessment may assist clinicians in identifying older adults at risk of short-term mortality.