HIV type 1 Env precursor cleavage state affects recognition by both neutralizing and nonneutralizing gp41 antibodies

HIV-1 is relatively resistant to antibody-mediated neutralization; however, rare antibodies to the exterior envelope glycoprotein, gp120, and the transmembrane glycoprotein, gp41, can neutralize a broad array of isolates. Two antibodies, 2F5 and 4E10, are directed against the gp41 membrane proximal external region (MPER); however, the kinetic neutralization signature of these antibodies remains unresolved. Previously, we reported that the fully cleaved, cell surface envelope glycoproteins (Env) derived from the primary isolate, JR-FL, are well recognized exclusively by gp120-directed neutralizing ligands and not by nonneutralizing gp120 antibodies. However, the gp120 nonneutralizing antibodies can recognize HIV spikes that are rendered fully cleavage defective by site-directed mutagenesis. Here, we extended such analysis to gp41 neutralizing and nonneutralizing antibodies and, relative to the rules of gp120-specific antibody recognition, we observed marked contrasts. Similar to gp120 recognition, the nonneutralizing gp41 cluster 1 or cluster 2 antibodies bound much more efficiently to cleavage-defective spikes when compared to their recognition of cleaved spikes. In contrast to gp120 neutralizing antibody recognition, the broadly neutralizing gp41 antibodies 2F5 and 4E10, like the nonneutralizing gp41 antibodies, did not efficiently recognize the predominantly cleaved, primary isolate JR-FL spikes. However, if the spikes were rendered cleavage defective, recognition by both the neutralizing and nonneutralizing ligand markedly increased. CD4 interaction with the cleaved spikes markedly increased recognition by most nonneutralizing gp41 antibodies, whereas such treatment had a minimal increase of 2F5 and 4E10 recognition. These data indicate again the profound influence that cleavage imposes on the quaternary packing of primary isolate spikes and have important implications for soluble trimer candidate immunogens.     

Longevity and Complication Rates of Ultrasound Guided Versus Traditional Peripheral Intravenous Catheters in a Pediatric Emergency Department

Background

Ultrasound-guided peripheral intravenous lines are frequently used in patients with difficult access. We have previously reported on the longevity and complication rates of ultrasound-guided peripheral intravenous lines, but there are limited data comparing outcomes of ultrasound-guided peripheral intravenous lines to traditionally placed peripheral intravenous lines in children. The aim of this study was to compare the longevity and complication rates of ultrasound-guided peripheral intravenous lines to traditionally placed intravenous lines in a pediatric population.

Validating the food behavior questions from the elementary school SPAN questionnaire

BackgroundThe School Physical Activity and Nutrition (SPAN) questionnaire was developed as a surveillance instrument to measure physical activity, nutrition attitudes, and dietary and physical activity behaviors in children and adolescents. The SPAN questionnaire has 2 versions.ObjectiveThis study was conducted to evaluate the validity of food consumption items from the elementary school version of the SPAN questionnaire.DesignValidity was assessed by comparing food items selected on the questionnaire with food items reported from a single 24-hour recall covering the same reference period.Setting5 elementary schools in Indiana.ParticipantsFourth-grade student volunteers (N = 121) from 5 elementary schools.Main Outcome MeasureAgreement between responses to SPAN questionnaire items and reference values obtained through 24-hour dietary recall.AnalysisThe agreement between the questionnaire and the 24-hour recall was measured using Spearman correlation, percentage agreement, and kappa statistic.ResultsCorrelation between SPAN item responses and recall data ranged from .25 (bread and related products) to .67 (gravy). The percentage agreement ranged from 26% (bread and related products) to 90% (gravy). The kappa statistic varied from .06 (chocolate candy) to .60 (beans).Conclusions and implicationsResults from this study indicate that the SPAN questionnaire can be administered in the classroom quickly and easily to measure many previous day dietary behaviors of fourth graders. However, questions addressing consumption of “vegetables,” “candy,” and “snacks” need further investigation.     

Breadth of cellular and humoral immune responses elicited in rhesus monkeys by multi-valent mosaic and consensus immunogens

To create an HIV-1 vaccine that generates sufficient breadth of immune recognition to protect against the genetically diverse forms of the circulating virus, we have been exploring vaccines based on consensus and mosaic protein designs. Increasing the valency of a mosaic immunogen cocktail increases epitope coverage but with diminishing returns, as increasingly rare epitopes are incorporated into the mosaic proteins. In this study we compared the immunogenicity of 2-valent and 3-valent HIV-1 envelope mosaic immunogens in rhesus monkeys. Immunizations with the 3-valent mosaic immunogens resulted in a modest increase in the breadth of vaccine-elicited T lymphocyte responses compared to the 2-valent mosaic immunogens. However, the 3-valent mosaic immunogens elicited significantly higher neutralizing responses to Tier 1 viruses than the 2-valent mosaic immunogens. These findings underscore the potential utility of polyvalent mosaic immunogens for eliciting both cellular and humoral immune responses to HIV-1.     

Perceived factors influencing hospital-based primary care clinic referrals to community health medical nutrition therapy: An exploratory study

Primary care clinics provide an array of diagnostic and clinical services that assist patients in preventing the onset or managing acute and chronic conditions. Some chronic conditions such as high blood pressure, high cholesterol, and type 2 diabetes require primary care professionals to seek additional medical intervention from registered dieticians. This study explored beliefs, attitudes, and practices of medical and administrative professionals in primary care clinics encountering patients who are potential candidates for ongoing nutrition education or counselling. Five focus groups with primary care providers and clinical staff (n = 24) were conducted to identify perceived intra-organisational factors influencing initiation of community health medical nutrition therapy (MNT) referrals. Lack of clarity regarding community health dieticians’ role in chronic disease management was the primary finding for the absence of MNT referrals. Insurance-imposed constraints, perceived patient readiness to change, and service inaccessibility were revealed as barriers that influence referrals to both community health and specialty care dieticians. This study underscores the importance of identifying organisational and interpersonal barriers that influence the initiation of community health MNT referrals. Understanding these barriers can create stronger interprofessional collaboration between primary care providers and community health dieticians.     

A Neutralizing Antibody Recognizing Primarily N-Linked Glycan Targets the Silent Face of the HIV Envelope

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Impact on Plate Waste of Switching from a Tray to a Trayless Delivery System in a University Dining Hall and Employee Response to the Switch

A potential strategy for decreasing food waste in foodservice operations is trayless dining. The objective of this 2010 study was to compare the impact of using a tray vs a trayless system on plate waste and on employees' attitudes. To test the hypothesis that going trayless would reduce waste, liquid and solid plate waste were measured for 1 week with the then-existing tray system and again after a new trayless system was implemented in a buffet-style university dining hall serving roughly1,000 meals a day. Foodservice staff were invited to participate in a focus group about the impact on their jobs. The investigators calculated plate waste per patron under the two systems and used an independent samples t test to examine the significance of the difference. Comments from the focus group were analyzed for themes. A significant decrease in solid waste per patron (0.81 oz; P=0.001) was observed in switching from the tray to the trayless system (4.39±0.24 oz vs 3.58±0.08 oz per patron). A nonsignificant reduction was observed with liquid waste (49.77±2.62 mL vs 46.36±4.51 mL; P=0.18). Most of the employees preferred the trayless system as long as it did reduce waste, but felt that increased breakage of dishware and increased need to wipe down tables were possible concerns resulting from the switch. This study demonstrates that trayless dining can reduce plate waste, and that employees can be supportive of the change.