The ability to mount protective immune responses depends on the diversity of T cells. T cell diversity may be compromised by the declining thymic output of new T cells. The aging process imposes a threat to diversity, because thymic function deteriorates. In this study we have examined the relationship between thymic production, homeostatic T cell proliferation and TCR β-chain diversity in young (∼25 years), middle-aged (∼60 years), and elderly adults (∼75 years). TCR excision circles (TREC) as a marker of thymic output exponentially decreased by >95% between 25 and 60 years of age. The frequency of Ki67⁺ cycling CD4 T cells remained steady, and surprisingly, the diversity of the naive CD4 T cell repertoire was maintained at ∼2 × 10⁷ different TCR β-chains. After the age of 70 years, TRECs only slightly declined, but homeostatic proliferation doubled. The diversity of the T cell pool drastically contracted to 200,000 TCR β-chains. Also, the phenotypic distinction between naive and memory CD4 T cells became fuzzy. The collapse in CD4 T cell diversity during the seventh and eighth decades indicates substantial T cell loss and implies that therapeutic measures to improve vaccine responses will have to include strategies for T cell replenishment.

Objective: To systematically review the literature to identify interventions that improve minority health related to colorectal cancer care. Data sources: MEDLINE, PsycINFO, CINAHL, and Cochrane databases, from 1950 to 2010. Study eligibility criteria, participants, and interventions: Interventions in US populations eligible for colorectal cancer screening, and composed of ≥50 % racial/ethnic minorities (or that included a specific sub-analysis by race/ethnicity). All included studies were linked to an identifiable healthcare source. The three authors independently reviewed the abstracts of all the articles and a final list was determined by consensus. All papers were independently reviewed and quality scores were calculated and assigned using the Downs and Black checklist. Results: Thirty-three studies were included in our final analysis. Patient education involving phone or in-person contact combined with navigation can lead to modest improvements, on the order of 15 percentage points, in colorectal cancer screening rates in minority populations. Provider-directed multi-modal interventions composed of education sessions and reminders, as well as pure educational interventions were found to be effective in raising colorectal cancer screening rates, also on the order of 10 to 15 percentage points. No relevant interventions focusing on post-screening follow up, treatment adherence and survivorship were identified. Limitations: This review excluded any intervention studies that were not tied to an identifiable healthcare source. The minority populations in most studies reviewed were predominantly Hispanic and African American, limiting generalizability to other ethnic and minority populations. Conclusions and implications of key findings: Tailored patient education combined with patient navigation services, and physician training in communicating with patients of low health literacy, can modestly improve adherence to CRC screening. The onus is now on researchers to continue to evaluate and refine these interventions and begin to expand them to the entire colon cancer care continuum.

Growing physician maldistribution and population demographic shifts have contributed to large geographic variation in healthcare access and the emergence of advanced practice providers as contributors to the healthcare workforce. Current estimates of geographic accessibility of physicians and advanced practice providers rely on outdated “provider per capita” estimates that have shortcomings. To apply state of the art methods to estimate spatial accessibility of physician and non-physician clinician groups and to examine factors associated with higher accessibility. We used a combination of provider location, medical claims, and U.S. Census data to perform a national study of health provider accessibility. The National Plan and Provider Enumeration System was used along with Medicare claims to identify providers actively caring for patients in 2014 including: primary care physicians (i.e., internal medicine and family medicine), specialists, nurse practitioners, and chiropractors. For each U.S. ZIP code tabulation area, we estimated provider accessibility using the Variable-distance Enhanced 2 step Floating Catchment Area method and performed a Getis-Ord Gi* analysis for each provider group. Generalized linear models were used to examine associations between population characteristics and provider accessibility. National spatial patterns of the provider groups differed considerably. Accessibility of internal medicine most resembled specialists with high accessibility in urban locales, whereas relative higher accessibility of family medicine physicians was concentrated in the upper Midwest. In our adjusted analyses independent factors associated with higher accessibility were very similar between internal medicine physicians and specialists–presence of a medical school in the county was associated with approximately 70% higher accessibility and higher accessibility was associated with urban locales. Nurse practitioners were similar to family medicine physicians with both having higher accessibility in rural locales. The Variable-distance Enhanced 2 step Floating Catchment Area method is a viable approach to measure spatial accessibility at the national scale.

Activation of the complement system contributes to the tissue destruction associated with myocardial ischemia/reperfusion. Pentosan polysulfate (PPS), a negatively charged sulfated glycosaminoglycan (GAG) and an effective inhibitor of complement activation, was studied for its potential to decrease infarct size in an experimental model of myocardial ischemia/reperfusion injury. Open-chest rabbits were subjected to 30-min occlusion of the left coronary artery followed by 5 h of reperfusion. Vehicle (saline) or PPS (30 mg/kg/h) was administered intravenously immediately before the onset of reperfusion and every hour during the reperfusion period. Treatment with PPS significantly (p < 0.05) reduced infarct size as compared with vehicle-treated animals (27.5 ± 2.9% vs. 13.34 ± 2.6%). Analysis of tissue demonstrated decreased deposition of membrane-attack complex and neutrophil accumulation in the area at risk. The results indicate that, like heparin and related GAGs, PPS possesses the ability to decrease infarct size after an acute period of myocardial ischemia and reperfusion. The observations are consistent with the suggestion that PPS may mediate its cytoprotective effect through modulation of the complement cascade.