Primary care physicians and their HIV prevention practices

A national random-sample survey of 4011 primary care physicians was conducted to determine the extent to which they are providing HIV prevention and clinical services, and to learn what characteristics and attitudes might impede the provision of such services. Physicians were asked about their history-taking practices for new adult and adolescent patients, including asking about the use of illicit drugs (injection and noninjection), the number of sexual partners, use of condoms and contraceptives, past episodes of sexually transmitted diseases (STDs), sexual orientation, and sexual contact with partner(s) at high risk for HIV. A preliminary analysis was conducted and reported earlier by the Centers for Disease Control and Prevention (CDC), focusing on the HIV-prevention services being provided by primary care physicians. This report provides additional analyses from this study, focusing on characteristics and attitudes that may prevent physicians from providing these services. Male physicians and the physicians' belief that patients would be offended if asked questions about their sex behaviors were strongly predictive of not asking new patients about their sex and drug behaviors. The physician's specialty was also a strong predictor-OB/GYNs were predictive of asking these questions and GP/FPs were predictive of not asking the questions. Physicians who indicated that a majority of their patients were white were less likely to report asking patients about their sex and drug behaviors. The authors conclude that a substantial number of primary care physicians are missing important opportunities to prevent HIV transmission by not adequately assessing patients' risks and not providing necessary risk-reduction counseling during their physician-patient encounters. Physician's attitudes and beliefs about their patients, as well as their level of experience with HIV, may help to explain these observations.     

Troponin I protein kinase C phosphorylation sites and ventricular function

OBJECTIVE: Cardiac Troponin I (cTnI) phosphorylation by protein kinase C (PKC) results in a reduction of maximal actomyosin ATPase activity, an effect that is more marked at higher levels of calcium (Ca2+) and is likely to reduce active force development. We postulated that there would be greater Ca2+-dependent changes in ventricular function in hearts of cTnI transgenic (TG) mice expressing mutant troponin I lacking PKC sites compared to wild-type (WT). METHODS: We studied left ventricular function in isolated perfused hearts over a wide range of left ventricular volumes (Frank-Starling relationships) and mechanical restitution at three levels of perfusate Ca2+ (1.5, 2.5, and 3.5 mM). Manganese-enhanced magnetic resonance imaging (MRI) was used to study in-vivo sarcolemmal Ca2+ influx. The phosphorylation status of cTnI was examined by western blot analysis. RESULTS: Systolic contractile function in TG mice was altered in a calcium-dependent manner such that ventricular contractility was significantly greater in TG mice only at 3.5 mM perfusate Ca2+. The relaxation process and passive mechanical properties were unaltered in TG mice. Mechanical restitution parameters were abnormal in TG mice only at 1.5 mM perfusate Ca2+. In-vivo MRI data demonstrated up to 48% reduction in Mn2+-induced contrast enhancement, indicating reduced sarcolemmal Ca2+ influx. Western blot analysis indicated increased cTnI phosphorylation in TG mice. CONCLUSIONS: (1) TG mice exhibit calcium-dependent positive inotropy without slowed relaxation and this phenotype is mitigated by concomitant (compensatory) changes of reduced intracellular Ca2+ and increased phosphorylation of remaining cTnI sites. (2) The contractile phenotype in TG mice can be interpreted as an amplification of the normal response to changes in cellular Ca2+ observed in WT mice. Thus, PKC phosphorylation sites on cTnI play a role in attenuating contractile responses to changes in intracellular Ca2+.     

Pilot Evaluation of the Ability of Men Who Have Sex with Men to Self-Administer Rapid HIV Tests,Prepare Dried Blood Spot Cards,and Interpret Test Results,Atlanta, Georgia, 2013

In the United States, an estimated 67% of new HIV diagnoses are among men who have sex with men (MSM), however 25% of HIV-positive MSM in the 2014 National HIV Behavioral Surveillance Survey were unaware of their infection. HIV self-testing (HIVST) with rapid diagnostic tests (RDTs) may facilitate access to HIV testing. We evaluated the ability of 22 MSM to conduct two HIV RDTs (OraQuick ^® In-Home HIV Test and a home-use prototype of Sure Check ^® HIV 1/2 Assay), interpret sample images of test results, and collect a dried blood spot (DBS) specimen. While some participants did not follow every direction, most participants were able to conduct HIVST and correctly interpret their results. Interpretation of panels of RDT images was especially difficult when the “control” line was missing, and 27% of DBS cards produced were rated as of bad quality. Modifications to the DBS instructions were necessary prior to evaluating the performance of these tests in real-world settings.     

Nanoparticle-mediated Gene Silencing Confers Radioprotection to Salivary Glands In Vivo

Radiation treatment of head and neck cancers causes irreversible damage of the salivary glands (SG). Here, we introduce a preclinical mouse model for small-interfering RNA (siRNA)-based gene silencing to provide protection of SG from radiation-induced apoptosis. Novel, pH-responsive nanoparticles complexed with siRNAs were introduced into mouse submandibular glands (SMG) by retroductal injection to modulate gene expression in vivo. To validate this approach, we first targeted Nkcc1, an ion transporter that is essential for saliva secretion. Nkcc1 siRNA delivery resulted in efficient knockdown, as quantified at the mRNA and the protein levels, and the functional result of Nkcc1 knockdown phenocopied the severe decrease in saliva secretion, characteristic of the systemic Nkcc1 gene knockout. To establish a strategy to prevent apoptotic cell loss due to radiation damage, siRNAs targeting the proapoptotic Pkcδ gene were administered into SMG before ionizing radiation. Knockdown of Pkcδ not only reduced the number of apoptotic cells during the acute phase of radiation damage, but also markedly improved saliva secretion at 3 months in irradiated animals, indicating that this treatment confers protection from hyposalivation. These results demonstrate that nanoparticle delivery of siRNAs targeting a proapoptotic gene is a localized, nonviral, and effective means of conferring radioprotection to the SGs.     

ACE抑制剂卡托普利对实验性围手术期心肌缺血的影响

目的:图手术期心肌缺血主要是因为应激引起冠状动脉内皮功能障碍所致,所以观察卡托普利对其影响。方法:杂种犬20只均分为4组:Ⅰ组(对照组),Ⅱ组(心肌梗塞模型组),Ⅲ组(心梗 胃大部切除术)和Ⅳ组(心梗 卡托普利 胃大部切除术)。心梗2周后行胃大部分切除术,测定Ⅲ、Ⅳ两组的基础状态、术前和术后的血流动力学指标、血浆内皮素(ET)及一氧化氮(NO)。用组织原位杂交方法观察4组非梗塞区冠脉内皮-氧化氮合酶(NOS)mRNA表达水平。结果:在Ⅲ组,手术使LV dP/dt_(max)、心脏指数(CI)及NO下降,引起LVEDP、PCWP、总外周阻力(TPR)、左室舒张压力下降时间常数(T值)和ET升高。在Ⅳ组,用卡托普利后40min,TPR下降,T值升高;手术使血流动力学指标回降,不影响其它指标。组织原位杂交示,NOS mRNA在Ⅰ组高度表达,Ⅱ组和Ⅳ组次之,Ⅲ组最低。结论:卡托普利能预防胃大部切除术引起的左室舒缩障碍和冠脉内皮功能障碍。