Publications

Damaged cardiac valves attract blood-borne bacteria, and infective endocarditis is often caused by viridans group streptococci. While such bacteria use multiple adhesins to maintain their normal oral commensal state, recognition of platelet sialoglycans provides an intermediary for binding to damaged valvular endocardium. We use a customized sialoglycan microarray to explore the varied binding properties of phylogenetically related serine-rich repeat adhesins, the GspB, Hsa, and SrpA homologs from Streptococcus gordonii and Streptococcus sanguinis species, which belong to a highly conserved family of glycoproteins that contribute to virulence for a broad range of Gram-positive pathogens. Binding profiles of recombinant soluble homologs containing novel sialic acid-recognizing Siglec-like domains correlate well with binding of corresponding whole bacteria to arrays. These bacteria show multiple modes of glycan, protein, or divalent cation-dependent binding to synthetic glycoconjugates and isolated glycoproteins in vitro. However, endogenous asialoglycan-recognizing clearance receptors are known to ensure that only fully sialylated glycans dominate in the endovascular system, wherein we find these particular streptococci become primarily dependent on their Siglec-like adhesins for glycan-mediated recognition events. Remarkably, despite an excess of alternate sialoglycan ligands in cellular and soluble blood components, these adhesins selectively target intact bacteria to sialylated ligands on platelets, within human whole blood. These preferred interactions are inhibited by corresponding recombinant soluble adhesins, which also preferentially recognize platelets. Our data indicate that circulating platelets may act as inadvertent Trojan horse carriers of oral streptococci to the site of damaged endocardium, and provide an explanation why it is that among innumerable microbes that gain occasional access to the bloodstream, certain viridans group streptococci have a selective advantage in colonizing damaged cardiac valves and cause infective endocarditis.

PURPOSE

Health-related quality of life (HRQL) domains vary across disease conditions and are determined by standards, values, and priorities internal to patients. Although the clinical goals of lung transplantation are to improve patient survival and HRQL, what defines HRQL in lung transplantation is unknown. Employing a qualitative approach, we aimed to identify HRQL domains important in lung transplantation.

METHODS

We conducted semi-structured interviews in purposefully sampled lung transplant recipients (n = 8) representing a spectrum of ages, gender, indications for transplantation, and time since transplantation as well as healthcare practitioners representing a spectrum of practitioner types (n = 9). Grounded theory was used to identify HRQL domains important in lung transplantation, building on but going beyond domains already defined in the SF-36, the most commonly used instrument in this population.

RESULTS

In addition to confirming the relevance of the eight SF-36 domains, we identified 11 novel HRQL domains. Palliation of respiratory symptoms was identified as important. After transplant surgery, new HRQL domains emerged including: distressing symptoms spanning multiple organ systems, worry about infection and acute rejection, treatment burden, and depression. Further, patients identified challenges to intimacy, changes in social relationships, and problems with cognitive functioning. Saliently, worry about limited life expectancy was pervasive and impaired life planning.

CONCLUSIONS

We found that HRQL in lung transplantation is defined by both generic and transplant-specific domains. Delineating and refining these domains can inform efforts to improve clinical outcomes and HRQL measurement in lung transplantation.

BACKGROUND

While studies have suggested that depression and HIV-related stigma may impede access to care, a growing body of literature also suggests that access to HIV care itself may help to decrease internalized HIV-related stigma and symptoms of depression in the general population of persons living with HIV. However, this has not been investigated in postpartum women living with HIV. Furthermore, linkage to care itself may have additional impacts on postpartum depression beyond the effects of antiretroviral therapy. We examined associations between linkage to HIV care, postpartum depression, and internalized stigma in a population with a high risk of depression: newly diagnosed HIV-positive pregnant women.

METHODS

In this prospective observational study, data were obtained from 135 HIV-positive women from eight antenatal clinics in the rural Nyanza Province of Kenya at their first antenatal visit (prior to testing HIV-positive for the first time) and subsequently at 6 weeks after giving birth.

RESULTS

At 6 weeks postpartum, women who had not linked to HIV care after testing positive at their first antenatal visit had higher levels of depression and internalized stigma, compared to women who had linked to care. Internalized stigma mediated the effect of linkage to care on depression. Furthermore, participants who had both linked to HIV care and initiated antiretroviral therapy reported the lowest levels of depressive symptoms.

CONCLUSIONS

These results provide further support for current efforts to ensure that women who are newly diagnosed with HIV during pregnancy become linked to HIV care as early as possible, with important benefits for both physical and mental health.