Controlling the corrosion and cathodic activation of magnesium via microalloying additions of Ge

The evolution of corrosion morphology and kinetics for magnesium (Mg) have been demonstrated to be influenced by cathodic activation, which implies that the rate of the cathodic partial reaction is enhanced as a result of anodic dissolution. This phenomenon was recently demonstrated to be moderated by the use of arsenic (As) alloying as a poison for the cathodic reaction, leading to significantly improved corrosion resistance. The pursuit of alternatives to toxic As is important as a means to imparting a technologically safe and effective corrosion control method for Mg (and its alloys). In this work, Mg was microalloyed with germanium (Ge), with the aim of improving corrosion resistance by retarding cathodic activation. Based on a combined analysis herein, we report that Ge is potent in supressing the cathodic hydrogen evolution reaction (reduction of water) upon Mg, improving corrosion resistance. With the addition of Ge, cathodic activation of Mg subject to cyclic polarisation was also hindered, with beneficial implications for future Mg electrodes

Crosstalk between HIV and hepatitis C virus during co-infection

An estimated one-third of individuals positive for HIV are also infected with hepatitis C virus (HCV). Chronic infection with HCV can lead to serious liver disease including cirrhosis and hepatocellular carcinoma. Liver-related disease is among the leading causes of death in patients with HIV, and individuals with HIV and HCV co-infection are found to progress more rapidly to serious liver disease than mono-infected individuals. The mechanism by which HIV affects HCV infection in the absence of immunosuppression by HIV is currently unknown. In a recent article published in BMC Immunology, Qu et al. demonstrated that HIV tat is capable of inducing IP-10 expression. Further, they were able to show that HIV tat, when added to cells, was able to enhance the replication of HCV. Importantly, the increase in HCV replication by tat was found to be dependent on IP-10. This work has important implications for understanding the effect HIV has on the outcome of HCV infection in co-infected individuals. The findings of Qu et al. may inform the design of intervention and treatment strategies for co-infected individuals

Quality of Care for HIV Infection Provided by Ryan White Program-Supported versus Non-Ryan White Program-Supported Facilities

BACKGROUND: The Ryan White HIV/AIDS Care Act (now the Treatment Modernization Act; Ryan White Program, or RWP) is a source of federal public funding for HIV care in the United States. The Health Services and Resources Administration requires that facilities or providers who receive RWP funds ensure that HIV health services are accessible and delivered according to established HIV-related treatment guidelines. We used data from population-based samples of persons in care for HIV infection in three states to compare the quality of HIV care in facilities supported by the RWP, with facilities not supported by the RWP. METHODOLOGY/PRINCIPAL FINDINGS: Within each area (King County in Washington State; southern Louisiana; and Michigan), a probability sample of patients receiving care for HIV infection in 1998 was drawn. Based on medical records abstraction, information was collected on prescription of antiretroviral therapy according to treatment recommendations, prescription of prophylactic therapy, and provision of recommended vaccinations and screening tests. We calculated population-level estimates of the extent to which HIV care was provided according to then-current treatment guidelines in RWP-supported and non-RWP-supported facilities. For all treatment outcomes analyzed, the compliance with care guidelines was at least as good for patients who received care at RWP-supported (vs non-RWP supported) facilities. For some outcomes in some states, delivery of recommended care was significantly more common for patients receiving care in RWP-supported facilities: for example, in Louisiana, patients receiving care in RWP-supported facilities were more likely to receive indicated prophylaxis for Pneumocystis jirovecii pneumonia and Mycobacterium avium complex, and in all three states, women receiving care in RWP-supported facilities were more likely to have received an annual Pap smear. CONCLUSIONS/SIGNIFICANCE: The quality of HIV care provided in 1998 to patients in RWP-supported facilities was of equivalent or better quality than in non-RWP supported facilities; however, there were significant opportunities for improvement in all facility types. Data from population-based clinical outcomes surveillance data can be used as part of a broader strategy to evaluate the quality of publicly-supported HIV care

Boundaries of Semantic Distraction: Dominance and Lexicality Act at Retrieval

Three experiments investigated memory for semantic information with the goal of determining boundary conditions for the manifestation of semantic auditory distraction. Irrelevant speech disrupted the free recall of semantic category-exemplars to an equal degree regardless of whether the speech coincided with presentation or test phases of the task (Experiment 1) and occurred regardless of whether it comprised random words or coherent sentences (Experiment 2). The effects of background speech were greater when the irrelevant speech was semantically related to the to-be-remembered material, but only when the irrelevant words were high in output dominance (Experiment 3). The implications of these findings in relation to the processing of task material and the processing of background speech is discussed

A Probability Sample for Monitoring the HIV-infected Population in Care in the U.S. and in Selected States

Epidemiologic and clinical changes in the HIV epidemic over time have presented a challenge to public health surveillance to monitor behavioral and clinical factors that affect disease progression and HIV transmission. The Medical Monitoring Project (MMP) is a supplemental surveillance project designed to provide representative, population-based data on clinical status, care, outcomes, and behaviors of HIV-infected persons receiving care at the national level. We describe a three-stage probability sampling method that provides both nationally and state-level representative estimates. In stage-I, 20 states, which included 6 separately funded cities/counties, were selected using probability proportional to size (PPS) sampling. PPS sampling was also used in stage-II to select facilities for participation in each of the 26 funded areas. In stage-III, patients were randomly selected from sampled facilities in a manner that maximized the possibility of having overall equal selection probabilities for every patient in the state or city/county. The sampling methods for MMP could be adapted to other research projects at national or sub-national levels to monitor populations of interest or evaluate outcomes and care for a range of specific diseases or conditions

Establishment of Protein Delivery Systems Targeting Podocytes

Podocytes are uniquely structured cells that are critical to the kidney filtration barrier. Their anatomic location on the outer side of the glomerular capillaries expose podocytes to large quantities of both plasma and urinary components and thus are reachable for drug delivery. Recent years have made clear that interference with podocyte-specific disease pathways can modulate glomerular function and influence severity and progression of glomerular disease.Here, we describe studies that show efficient transport of proteins into the mammalian cells mouse 3T3 fibroblasts and podocytes, utilizing an approach termed profection. We are using synthetic lipid structures that allow the safe packing of proteins or antibodies resulting in the subsequent delivery of protein into the cell. The uptake of lipid coated protein is facilitated by the intrinsic characteristic of cells such as podocytes to engulf particles that are physiologically retained in the extracellular matrix. Profection of the restriction enzyme MunI in 3T3 mouse fibroblasts caused an increase in DNA degradation. Moreover, purified proteins such as beta-galactosidase and the large GTPase dynamin could be profected into podocytes using two different profection reagents with the success rate of 95-100%. The delivered beta-galactosidase enzyme was properly folded and able to cleave its substrate X-gal in podocytes. Diseased podocytes are also potential recipients of protein cargo as we also delivered fluorophore labeled IgG into puromycin treated podocytes. We are currently optimizing our protocol for in vivo profection.Protein transfer is developing as an exciting tool to study and target highly differentiated cells such as podocytes

Backbone rigidity and static presentation of guanidinium groups increases cellular uptake of arginine-rich cell-penetrating peptides

In addition to endocytosis-mediated cellular uptake, hydrophilic cell-penetrating peptides are able to traverse biological membranes in a non-endocytic mode termed transduction, resulting in immediate bioavailability. Here we analysed structural requirements for the non-endocytic uptake mode of arginine-rich cell-penetrating peptides, by a combination of live-cell microscopy, molecular dynamics simulations and analytical ultracentrifugation. We demonstrate that the transduction efficiency of arginine-rich peptides increases with higher peptide structural rigidity. Consequently, cyclic arginine-rich cell-penetrating peptides showed enhanced cellular uptake kinetics relative to their linear and more flexible counterpart. We propose that guanidinium groups are forced into maximally distant positions by cyclization. This orientation increases membrane contacts leading to enhanced cell penetration

Analytic philosophy for biomedical research: the imperative of applying yesterday's timeless messages to today's impasses

The mantra that "the best way to predict the future is to invent it" (attributed to the computer scientist Alan Kay) exemplifies some of the expectations from the technical and innovative sides of biomedical research at present. However, for technical advancements to make real impacts both on patient health and genuine scientific understanding, quite a number of lingering challenges facing the entire spectrum from protein biology all the way to randomized controlled trials should start to be overcome. The proposal in this chapter is that philosophy is essential in this process. By reviewing select examples from the history of science and philosophy, disciplines which were indistinguishable until the mid-nineteenth century, I argue that progress toward the many impasses in biomedicine can be achieved by emphasizing theoretical work (in the true sense of the word 'theory') as a vital foundation for experimental biology. Furthermore, a philosophical biology program that could provide a framework for theoretical investigations is outlined

Can teaching agenda-setting skills to physicians improve clinical interaction quality? A controlled intervention

<p>Abstract</p> <p>Background</p> <p>Physicians and medical educators have repeatedly acknowledged the inadequacy of communication skills training in the medical school curriculum and opportunities to improve these skills in practice. This study of a controlled intervention evaluates the effect of teaching practicing physicians the skill of "agenda-setting" on patients' experiences with care. The agenda-setting intervention aimed to engage clinicians in the practice of initiating patient encounters by eliciting the full set of concerns from the patient's perspective and using that information to prioritize and negotiate which clinical issues should most appropriately be dealt with and which (if any) should be deferred to a subsequent visit.</p> <p>Methods</p> <p>Ten physicians from a large physician organization in California with baseline patient survey scores below the statewide 25th percentile participated in the agenda-setting intervention. Eleven physicians matched on baseline scores, geography, specialty, and practice size were selected as controls. Changes in survey summary scores from pre- and post-intervention surveys were compared between the two groups. Multilevel regression models that accounted for the clustering of patients within physicians and controlled for respondent characteristics were used to examine the effect of the intervention on survey scale scores.</p> <p>Results</p> <p>There was statistically significant improvement in intervention physicians' ability to "explain things in a way that was easy to understand" (p = 0.02) and marginally significant improvement in the overall quality of physician-patient interactions (p = 0.08) compared to control group physicians. Changes in patients' experiences with organizational access, care coordination, and office staff interactions did not differ by experimental group.</p> <p>Conclusion</p> <p>A simple and modest behavioral training for practicing physicians has potential to positively affect physician-patient relationship interaction quality. It will be important to evaluate the effect of more extensive trainings, including those that work with physicians on a broader set of communication techniques.</p