HIV-1 mucosal transmission begins with virus or virus-infected cells moving through mucus across mucosal epithelium to infect CD4+ T cells. Although broadly neutralizing antibodies (bnAbs) are the type of HIV-1 antibodies that are most likely protective, they are not induced with current vaccine candidates. In contrast, antibodies that do not neutralize primary HIV-1 strains in the TZM-bl infection assay are readily induced by current vaccine candidates and have also been implicated as secondary correlates of decreased HIV-1 risk in the RV144 vaccine efficacy trial. Here, we have studied the capacity of anti-Env monoclonal antibodies (mAbs) against either the immunodominant region of gp41 (7B2 IgG1), the first constant region of gp120 (A32 IgG1), or the third variable loop (V3) of gp120 (CH22 IgG1) to modulate in vivo rectal mucosal transmission of a high-dose simian-human immunodeficiency virus (SHIV-BaL) in rhesus macaques. 7B2 IgG1 or A32 IgG1, each containing mutations to enhance Fc function, was administered passively to rhesus macaques but afforded no protection against productive clinical infection while the positive control antibody CH22 IgG1 prevented infection in 4 of 6 animals. Enumeration of transmitted/founder (T/F) viruses revealed that passive infusion of each of the three antibodies significantly reduced the number of T/F genomes. Thus, some antibodies that bind HIV-1 Env but fail to neutralize virus in traditional neutralization assays may limit the number of T/F viruses involved in transmission without leading to enhancement of viral infection. For one of these mAbs, gp41 mAb 7B2, we provide the first co-crystal structure in complex with a common cyclical loop motif demonstrated to be critical for infection by other retroviruses.
Depressive scores decreased significantly in patients with IBD treated with immunosuppressive therapy and the number at risk for moderate to severe depression improved significantly.
The current shortage of primary care physicians (PCPs), particularly as more individuals obtain health insurance and seek primary care services, is a growing national concern. The Crimson Care Collaborative (CCC) is a joint student-faculty initiative in post-health-care-reform Massachusetts that was started with the explicit goal of attracting medical students to primary care careers. It fills a niche for student-run clinics, providing evening access to primary care services for patients without a PCP and urgent care services for patients of a Massachusetts General Hospital-affiliated internal medicine clinic, with the aim of decreasing emergency department use in both groups. Unlike other student-run clinics, CCC is integrated into the mainstream health care structure of an existing primary care clinic and, because of universal health insurance coverage in Massachusetts, can bill for its services. In addition to the clinical services offered, the student-run research team evaluates the quality of care and the patients' experiences at the clinic. This article describes the creation and development of CCC, including a brief overview of clinic operations, social services, research, laboratory services, student and patient education programs, and finance. In the wake of the Patient Protection and Affordable Care Act of 2010, CCC is an example of how students can aid the transition to universal health care in the United States and how medical schools can expose students early in their training to primary care and clinic operations.
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