Hepatic histologic response (HR) to combination therapy among HCV/HIV-coinfected individuals: interferon induces HR independent of sustained virologic response (SVR).

Most HIV/HCV-coinfected patients fail to achieve a sustained virologic response (SVR) to peginterferon-ribavirin therapy. We examined the hepatic histologic response (HR), defined as an improvement in hepatic inflammation scores of two points or more, to combination therapy among HIV/HCV-coinfected subjects. An open label prospective trial treated 32 HIV/HCV-coinfected patients with peginterferon alpha-2b and ribavirin for 48 weeks. Liver biopsies, scored by a single pathologist using the Histology Activity Index (HAI, range 0-18) and Ishak fibrosis scores (range 0-6), were performed before and after treatment. Gene expression profiles of PBMCs were performed using Affymetrix U133A gene chips. A total of 87% of SVR subjects and 88% of nonresponders (NR) had an HR, but no significant change in the liver fibrosis scores was observed (p > 0.05). For genotype 1 patients, a baseline fibrosis score 2 (p = 0.012). Combination therapy for HCV among HIV-coinfected subjects resulted in a modest SVR rate. Persons with mild liver disease had a better SVR rate, suggesting early treatment may be beneficial. Combination therapy resulted in an HR for most of the patients, however, further follow-up of these patients will determine the durability of such an HR.

Long-term health implications of school quality.

OBJECTIVE: Individual academic achievement is a well-known predictor of adult health, and addressing education inequities may be critical to reducing health disparities. Disparities in school quality are well documented. However, we lack nationally representative studies evaluating the impact of school quality on adult health. We aim to determine whether high school quality predicts adult health outcomes after controlling for baseline health, socio-demographics and individual academic achievement. METHODS: We analyzed data from 7037 adolescents who attended one of 77 high schools in the Unites States and were followed into adulthood from the National Longitudinal Study of Adolescent to Adult Health. Selected school-level quality measures-average daily attendance, school promotion rate, parental involvement, and teacher experience-were validated based on ability to predict high school graduation and college attendance. Individual adult health outcomes included self-rated health, diagnosis of depression, and having a measured BMI in the obese range. RESULTS: Logistic regressions controlling for socio-demographics, baseline health, health insurance, and individual academic performance demonstrated that school quality significantly predicted all health outcomes. As hypothesized, attending a school with lower average daily attendance predicted lower self-rated health (Adjusted Odds Ratio (AOR) 1.59, p = 0.003) and higher odds of depression diagnosis (AOR 1.35, p = 0.03); and attending a school with higher parent involvement predicted lower odds of obesity (AOR 0.69, p = 0.001). However, attending a school with higher promotion rate also predicted lower self-rated health (AOR1.20, p < 0.001). CONCLUSIONS: High school quality may be an important, but complex, social determinant of health. These findings highlight the potential inter-dependence of education and health policy.

Osteopenia in X-linked hyper-IgM syndrome reveals a regulatory role for CD40 ligand in osteoclastogenesis.

We report that osteopenia is a prominent and previously unappreciated clinical feature of patients with X-linked hyper-IgM syndrome, an inherited immune deficiency disorder caused by mutations in the gene encoding CD40 ligand (CD40L). We therefore conducted studies to determine the relationship between CD40L and osteoclastogenesis. Recognizing that activated T cells express surface receptor activator of NF-kappaB ligand (RANKL) and can induce osteoclast differentiation of myeloid cells expressing RANK, we assessed the capacity of wild-type T cells and CD40L(-/-) T cells to induce osteoclastogenesis in vitro. Relative to wild-type T cells, activated CD40L(-/-) T cells from both humans and mice promoted robust osteoclast differentiation of myeloid cells. Whereas activated CD40L(-/-) T cells had normal expression of RANKL, they were deficient in IFN-gamma production. In subsequent studies, we cultured activated CD40L(-/-) T cells in the presence of IFN-gamma, and we found that the osteoclastic capacity of CD40L(-/-) T cells could be greatly diminished. These results show that CD40L can influence RANKL signaling through T cell priming, and thus they demonstrate a regulatory role for CD40L in bone mineralization that is absent in patients with X-linked hyper-IgM syndrome.