Imaging cell surface glycosylation in vivo using "double click" chemistry.

Dynamic alterations in cell surface glycosylation occur in numerous biological processes that involve cell-cell communication and cell migration. We report here imaging of cell surface glycosylation in live mice using double click chemistry. Cell surface glycans were metabolically labeled using peracetylated azido-labeled N-acetylgalactosamine and then reacted, in the first click reaction, with either a cyclooctyne, in a Huisgen [3 + 2] cycloaddition, or with a Staudinger phosphine, via Staudinger ligation. The second click reaction was a [4 + 2] inverse electron demand Diels-Alder reaction between a trans-cyclooctene and a tetrazine, where the latter reagent had been fluorescently labeled with a far-red fluorophore. After administration of the fluorescent tetrazine, the bifunctional cyclooctyne-cyclooctene produced significant azido sugar-dependent fluorescence labeling of tumor, kidney, liver, spleen, and small intestine in vivo, where the kidney and tumor could be imaged noninvasively in the live mouse

Preliminary outcomes of a paediatric highly active antiretroviral therapy cohort from KwaZulu-Natal, South Africa

BACKGROUND: Few studies address the use of paediatric highly active antiretroviral therapy (HAART) in Africa. METHODS: We performed a retrospective cohort study to investigate preliminary outcomes of all children eligible for HAART at Sinikithemba HIV/AIDS clinic in KwaZulu-Natal, South Africa. Immunologic, virologic, clinical, mortality, primary caregiver, and psychosocial variables were collected and analyzed. RESULTS: From August 31, 2003 until October 31, 2005, 151 children initiated HAART. The median age at HAART initiation was 5.7 years (range 0.3–15.4). Median follow-up time of the cohort after HAART initiation was 8 months (IQR 3.5–13.5). The median change in CD4% from baseline (p < 0.001) was 10.2 (IQR 5.0–13.8) at 6 months (n = 90), and 16.2 (IQR 9.6–20.3) at 12 months (n = 59). Viral loads (VLs) were available for 100 children at 6 months of which 84% had HIV-1 RNA levels ≤ 50 copies/mL. At 12 months, 80.3% (n = 61) had undetectable VLs. Sixty-five out of 88 children (73.8%) reported a significant increase (p < 0.001) in weight after the first month. Eighty-nine percent of the cohort (n = 132) reported ≤ 2 missed doses during any given treatment month (> 95%adherence). Seventeen patients (11.3%) had a regimen change; two (1.3%) were due to antiretroviral toxicity. The Kaplan-Meier one year survival estimate was 90.9% (95%confidence interval (CI) 84.8–94.6). Thirteen children died during follow-up (8.6%), one changed service provider, and no children were lost to follow-up. All 13 deaths occurred in children with advanced HIV disease within 5 months of treatment initiation. In multivariate analysis of baseline variables against mortality using Cox proportional-hazards model, chronic gastroenteritis was associated with death [hazard ratio (HR), 12.34; 95%CI, 1.27–119.71) and an HIV-positive primary caregiver was found to be protective against mortality [HR, 0.12; 95%CI, 0.02–0.88). Age, orphanhood, baseline CD4%, and hemoglobin were not predicators of mortality in our cohort. Fifty-two percent of the cohort had at least one HIV-positive primary caregiver, and 38.4% had at least one primary caregiver also on HAART at Sinikithemba clinic. CONCLUSION: This report suggests that paediatric HAART can be effective despite the challenges of a resource-limited setting

Lessons learned from family-centred models of treatment for children living with HIV: current approaches and future directions

BACKGROUND: Despite strong global interest in family-centred HIV care models, no reviews exist that detail the current approaches to family-centred care and their impact on the health of children with HIV. A systematic review of family-centred HIV care programmes was conducted in order to describe both programme components and paediatric cohort characteristics. METHODS: We searched online databases, including PubMed and the International AIDS Society abstract database, using systematic criteria. Data were extracted regarding programme setting, staffing, services available and enrolment methods, as well as cohort demographics and paediatric outcomes. RESULTS: The search yielded 25 publications and abstracts describing 22 separate cohorts. These contained between 43 and 657 children, and varied widely in terms of staffing, services provided, enrolment methods and cohort demographics. Data on clinical outcomes was limited, but generally positive. Excellent adherence, retention in care, and low mortality and/or loss to follow up were documented. CONCLUSIONS: The family-centred model of care addresses many needs of infected patients and other household members. Major reported obstacles involved recruiting one or more types of family members into care, early diagnosis and treatment of infected children, preventing mortality during children's first six months of highly active antiretroviral therapy, and staffing and infrastructural limitations. Recommendations include: developing interventions to enrol hard-to-reach populations; identifying high-risk patients at treatment initiation and providing specialized care; and designing and implementing evidence-based care packages. Increased research on family-centred care, and better documentation of interventions and outcomes is also critical

Imaging Cell Surface Glycosylation in Vivo Using “Double Click” Chemistry

Dynamic alterations in cell surface glycosylation occur in numerous biological processes that involve cell–cell communication and cell migration. We report here imaging of cell surface glycosylation in live mice using double click chemistry. Cell surface glycans were metabolically labeled using peracetylated azido-labeled <i>N</i>-acetylgalactosamine and then reacted, in the first click reaction, with either a cyclooctyne, in a Huisgen [3 + 2] cycloaddition, or with a Staudinger phosphine, via Staudinger ligation. The second click reaction was a [4 + 2] inverse electron demand Diels–Alder reaction between a <i>trans</i>-cyclooctene and a tetrazine, where the latter reagent had been fluorescently labeled with a far-red fluorophore. After administration of the fluorescent tetrazine, the bifunctional cyclooctyne-cyclooctene produced significant azido sugar-dependent fluorescence labeling of tumor, kidney, liver, spleen, and small intestine in vivo, where the kidney and tumor could be imaged noninvasively in the live mouse

Beyond Women, Children, and Families: Gender, Representation, and Public Funding for the Arts

Research on the impact of female legislators has found that in their voting records women in elective office tend to be more liberal and more supportive of issues of concern to women, children, and families than are men, differences that conform to gender stereotypes held by voters. This article examines another well-established gender stereotype that is not linked to the traditional concerns of women as conventionally defined by scholars: that women in public office will be more supportive of the arts. Copyright (c) 2007 Southwestern Social Science Association.