Meningeal B Cell Clusters Correlate with Submeningeal Pathology in a Natural Model of Multiple Sclerosis.

Multiple sclerosis (MS) is an idiopathic demyelinating disease in which meningeal inflammation correlates with accelerated disease progression. The study of meningeal inflammation in MS has been limited because of constrained access to MS brain/spinal cord specimens and the lack of experimental models recapitulating progressive MS. Unlike induced models, a spontaneously occurring model would offer a unique opportunity to understand MS immunopathogenesis and provide a compelling framework for translational research. We propose granulomatous meningoencephalomyelitis (GME) as a natural model to study neuropathological aspects of MS. GME is an idiopathic, progressive neuroinflammatory disease of young dogs with a female bias. In the GME cases examined in this study, the meninges displayed focal and disseminated leptomeningeal enhancement on magnetic resonance imaging, which correlated with heavy leptomeningeal lymphocytic infiltration. These leptomeningeal infiltrates resembled tertiary lymphoid organs containing large B cell clusters that included few proliferating Ki67+ cells, plasma cells, follicular dendritic/reticular cells, and germinal center B cell-like cells. These B cell collections were confined in a specialized network of collagen fibers associated with the expression of the lympho-organogenic chemokines CXCL13 and CCL21. Although neuroparenchymal perivascular infiltrates contained B cells, they lacked the immune signature of aggregates in the meningeal compartment. Finally, meningeal B cell accumulation correlated significantly with cortical demyelination reflecting neuropathological similarities to MS. Hence, during chronic neuroinflammation, the meningeal microenvironment sustains B cell accumulation that is accompanied by underlying neuroparenchymal injury, indicating GME as a novel, naturally occurring model to study compartmentalized neuroinflammation and the associated pathology thought to contribute to progressive MS.

Insurance Enrollment at a Student-Run Free Clinic After the Patient Protection and Affordable Care Act.

The Patient Protection and Affordable Care Act (ACA) aims to increase insurance coverage through government subsidies. Medical student-run free clinics (SRFC) are an important entry point into the healthcare system for the uninsured. SRFCs do not have a standardized approach for navigating the complexities of enrollment. The Weill Cornell Community Clinic (WCCC) developed a unique enrollment model that may inform other SRFCs. Our objective is to describe enrollment processes at SRFCs throughout New York City, and to evaluate enrollment outcomes and persistent barriers to coverage at WCCC. We surveyed SRFC leadership throughout NYC to understand enrollment processes. We evaluated enrollment outcomes at WCCC through chart review and structured phone interviews. Subjects included WCCC patients seen in clinic between October 1, 2013 and September 30, 2015 (N = 140). Demographic information, method of insurance enrollment, and qualitative description of enrollment barriers were collected. SRFCs in New York City have diverse enrollment processes. 48% (N = 42) of WCCC patients obtained health insurance. Immigration status was a barrier to coverage in 21% of patients. Failure to gain coverage was predicted by larger household size (p = 0.02). Gender and employment status were not associated with remaining uninsured. The main barriers to enrollment were inability to afford premiums and lack of interest. Insurance enrollment processes at SRFCs in New York City are mostly ad hoc and outcomes are rarely tracked. Following implementation of the ACA, WCCC stands out for its structured approach, with approximately half of eligible WCCC patients gaining coverage during the study period.

Schistosomiasis and Human Immunodeficiency Virus in Men in Tanzania.

AbstractSchistosomiasis is a parasitic worm infection that affects over 260 million individuals worldwide. Women with schistosome infections have been demonstrated to have a 4-fold increase in the odds of human immunodeficiency virus (HIV) infection compared with women without schistosome infections. A relationship between schistosome and HIV infections has not been clearly defined in men. Among 674 men aged 18-50 years living in rural Tanzania, we identified 429 (63.6%) who had a schistosome infection as defined by serum positivity for schistosome circulating anodic antigen, visualization of parasite eggs in urine or stool, or both. HIV infection was identified in 38 (5.6%). The odds of HIV infection was 1.3 [95% confidence interval = 0.6-2.5] (P = 0.53) among men with any schistosome infection (Schistosoma haematobium or Schistosoma mansoni), and it was 1.4 [0.6-3.3] (P = 0.43) among men with S. haematobium infection. Men with S. haematobium infection were significantly more likely to report the symptom of hemospermia than men without S. haematobium infection. We conclude that schistosome infections appear to have little to no association with HIV infection in men.

Krüppel-like factor 5 protects against murine colitis and activates JAK-STAT signaling in vivo.

Inflammatory bowel disease (IBD), which is characterized by chronic or recurring inflammation of the gastrointestinal tract, affects 1.4 million persons in the United States alone. KLF5, a Krüppel-like factor (KLF) family member, is expressed within the epithelia of the gastrointestinal tract and has been implicated in rapid cell proliferation, migration, and remodeling in a number of tissues. Given these functions, we hypothesized that constitutive Klf5 expression would protect against the development of colitis in vivo. To examine the role of KLF5 in vivo, we used the Villin promoter to target Klf5 to the entire horizontal axis of the small intestine and colon. Villin-Klf5 transgenic mice were born at normal Mendelian ratios and appeared grossly normal to at least 1 year of age. Surprisingly, there were no significant changes in cell proliferation or in the differentiation of any of the intestinal lineages within the duodenum, jejunum, ileum, and colon of Villin-Klf5 mice, compared to littermate controls. However, when Villin-Klf5 mice were treated with dextran sodium sulfate (DSS) to induce colitis, they developed less colonic injury and significantly reduced disease activity scores than littermate controls. The mechanism for this decreased injury may come via JAK-STAT signaling, the activation of which was increased in colonic mucosa of DSS treated Villin-Klf5 mice compared to controls. Thus, KLF5 and its downstream mediators may provide therapeutic targets and disease markers for IBD or other diseases characterized by injury and disruption of intestinal epithelia.