A systematic review of current knowledge of HIV epidemiology and of sexual behaviour in Nepal

OBJECTIVE: To systematically review information on HIV epidemiology and on sexual behaviour in Nepal with a view to identifying gaps in current knowledge. METHODS: Systematic review covering electronic databases, web-based information, personal contact with experts and hand searching of key journals. RESULTS: HIV-1 seroprevalence has been rising rapidly in association with high-risk behaviours, with current levels of 40% amongst the nation's injecting drug users and approaching 20% amongst Kathmandu's female commercial sex workers (FCSWs). HIV seroprevalence remains low in the general population (0.29% of 15–49 year olds). There are significant methodological limitations in many of the seroprevalence studies identified, and these estimates need to be treated with caution. There are extensive migration patterns both within the country and internationally which provide the potential for considerable sexual networking. However, studies of sexual behaviour have focused on FCSWs and the extent of sexual networks within the general population is largely unknown. CONCLUSIONS: Whilst some of the ingredients are present for an explosive HIV epidemic in Nepal, crucial knowledge on sexual behaviour in the general population is missing. Research on sexual networking is urgently required to guide HIV control in Nepal. There is also a need for further good-quality epidemiological studies of HIV seroprevalence

Punica granatum (Pomegranate) juice provides an HIV-1 entry inhibitor and candidate topical microbicide

BACKGROUND: For ≈ 24 years the AIDS pandemic has claimed ≈ 30 million lives, causing ≈ 14,000 new HIV-1 infections daily worldwide in 2003. About 80% of infections occur by heterosexual transmission. In the absence of vaccines, topical microbicides, expected to block virus transmission, offer hope for controlling the pandemic. Antiretroviral chemotherapeutics have decreased AIDS mortality in industrialized countries, but only minimally in developing countries. To prevent an analogous dichotomy, microbicides should be: acceptable; accessible; affordable; and accelerative in transition from development to marketing. Already marketed pharmaceutical excipients or foods, with established safety records and adequate anti-HIV-1 activity, may provide this option. METHODS: Fruit juices were screened for inhibitory activity against HIV-1 IIIB using CD4 and CXCR4 as cell receptors. The best juice was tested for inhibition of: (1) infection by HIV-1 BaL, utilizing CCR5 as the cellular coreceptor; and (2) binding of gp120 IIIB and gp120 BaL, respectively, to CXCR4 and CCR5. To remove most colored juice components, the adsorption of the effective ingredient(s) to dispersible excipients and other foods was investigated. A selected complex was assayed for inhibition of infection by primary HIV-1 isolates. RESULTS: HIV-1 entry inhibitors from pomegranate juice adsorb onto corn starch. The resulting complex blocks virus binding to CD4 and CXCR4/CCR5 and inhibits infection by primary virus clades A to G and group O. CONCLUSION: These results suggest the possibility of producing an anti-HIV-1 microbicide from inexpensive, widely available sources, whose safety has been established throughout centuries, provided that its quality is adequately standardized and monitored

Designing an automated clinical decision support system to match clinical practice guidelines for opioid therapy for chronic pain

Abstract Background Opioid prescribing for chronic pain is common and controversial, but recommended clinical practices are followed inconsistently in many clinical settings. Strategies for increasing adherence to clinical practice guideline recommendations are needed to increase effectiveness and reduce negative consequences of opioid prescribing in chronic pain patients. Methods Here we describe the process and outcomes of a project to operationalize the 2003 VA/DOD Clinical Practice Guideline for Opioid Therapy for Chronic Non-Cancer Pain into a computerized decision support system (DSS) to encourage good opioid prescribing practices during primary care visits. We based the DSS on the existing ATHENA-DSS. We used an iterative process of design, testing, and revision of the DSS by a diverse team including guideline authors, medical informatics experts, clinical content experts, and end-users to convert the written clinical practice guideline into a computable algorithm to generate patient-specific recommendations for care based upon existing information in the electronic medical record (EMR), and a set of clinical tools. Results The iterative revision process identified numerous and varied problems with the initially designed system despite diverse expert participation in the design process. The process of operationalizing the guideline identified areas in which the guideline was vague, left decisions to clinical judgment, or required clarification of detail to insure safe clinical implementation. The revisions led to workable solutions to problems, defined the limits of the DSS and its utility in clinical practice, improved integration into clinical workflow, and improved the clarity and accuracy of system recommendations and tools. Conclusions Use of this iterative process led to development of a multifunctional DSS that met the approval of the clinical practice guideline authors, content experts, and clinicians involved in testing. The process and experiences described provide a model for development of other DSSs that translate written guidelines into actionable, real-time clinical recommendations.http://deepblue.lib.umich.edu/bitstream/2027.42/78267/1/1748-5908-5-26.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78267/2/1748-5908-5-26.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/78267/3/1748-5908-5-26-S3.TIFFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78267/4/1748-5908-5-26-S2.TIFFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78267/5/1748-5908-5-26-S1.TIFFPeer Reviewe

Significance of Postprandial Insulin and Triglycerides to Evaluate the Metabolic Response of Composite Meals Differing in Nutrient Composition - A Randomized Cross-Over Trial.

BACKGROUND AND AIMS: GlucoTRIG, based on postprandial plasma insulin and triglyceride concentrations, has been recently developed as a novel index to determine the postprandial metabolic response to the meals. This study aimed to test GlucoTRIG as a measure for ranking composite meals for their metabolic effects. METHODS: In a randomized cross-over trial, healthy adult volunteers (both males and females; n = 10 for each meal) consumed three is caloric (2000 kj) test meals (meal 1, meal 2, meal 3) of varying macronutrient composition. Postmeal consumption, venous blood samples were collected to determine plasma insulin and plasma triglycerides for estimating the GlucoTRIG value using (Triglycerides180min × Insulin180min) - (Triglycerides0min × Insulin0min). RESULTS: The GlucoTRIG values differed significantly (p = 0.0085) across meals. The statistical significance remains even after adjusting for confounding variables such as baseline diet, insulin, and triglycerides. The meal (M3) with a high fiber, low total fat content and containing less refined foods (fruits, beans, vegetables, plain yogurt) exhibited a significantly (p = 0.007) lower GlucoTRIG value (10 ± 7.7) compared to the other two meals, M1 (77 ± 19.8) and M2 (38 ± 12.1) which contained low processed foods, and were relatively high in fat and low in fiber meals. No statistically significant differences were observed between M1 and M2 meal. CONCLUSIONS: GlucoTRIG is a physiologically based index that may be useful to rank composite meals for reducing the risk of metabolic diseases. Further research focusing on the application of GlucoTRIG to foods, meals, and diets is warranted. ACTRN12619000973112 (Australian New Zealand Clinical Trials Registry, ANZCTR).fals

Scheduling algorithms for efficient execution of stream workflow applications in multicloud environments

Big data processing applications are becoming more and more complex. They are no more monolithic in nature but instead they are composed of decoupled analytical processes in the form of a workflow. One type of such workflow applications is stream workflow application, which integrates multiple streaming big data applications to support decision making. Each analytical component of these applications runs continuously and processes data streams whose velocity will depend on several factors such as network bandwidth and processing rate of parent analytical component. As a consequence, the execution of these applications on cloud environments requires advanced scheduling techniques that adhere to end user's requirements in terms of data processing and deadline for decision making. In this paper, we propose two Multicloud scheduling and resource allocation techniques for efficient execution of stream workflow applications on Multicloud environments while adhering to workflow application and user performance requirements and reducing execution cost. Results showed that the proposed genetic algorithm is an adequate and effective for all experiments

IoTSim-Stream: Modeling stream graph application in cloud simulation

In the era of big data, the high velocity of data imposes the demand for processing such data in real-time to gain real-time insights. Various real-time big data platforms/services (i.e. Apache Storm, Amazon Kinesis) allow to develop real-time big data applications to process continuous data to get incremental results. Composing those applications to form a workflow that is designed to accomplish certain goal is the becoming more important nowadays. However, given the current need of composing those applications into data pipelines forming stream workflow applications (aka stream graph applications) to support decision making, a simulation toolkit is required to simulate the behaviour of this graph application in Cloud computing environment. Therefore, in this paper, we propose an IoT Simulator for Stream processing on the big data (named IoTSim-Stream) that offers an environment to model complex stream graph applications in Multicloud environment, where the large-scale simulation-based studies can be conducted to evaluate and analyse these applications. The experimental results show that IoTSim-Stream is effective in modelling and simulating different structures of complex stream graph applications with excellent performance and scalability

Therapeutic Potential of Mitophagy-Inducing Microflora Metabolite, Urolithin A for Alzheimer's Disease

Mitochondrial dysfunction including deficits of mitophagy is seen in aging and neurodegenerative disorders including Alzheimer's disease (AD). Apart from traditionally targeting amyloid beta (Aβ), the main culprit in AD brains, other approaches include investigating impaired mitochondrial pathways for potential therapeutic benefits against AD. Thus, a future therapy for AD may focus on novel candidates that enhance optimal mitochondrial integrity and turnover. Bioactive food components, known as nutraceuticals, may serve as such agents to combat AD. Urolithin A is an intestinal microbe-derived metabolite of a class of polyphenols, ellagitannins (ETs). Urolithin A is known to exert many health benefits. Its antioxidant, anti-inflammatory, anti-atherogenic, anti-Aβ, and pro-mitophagy properties are increasingly recognized. However, the underlying mechanisms of urolithin A in inducing mitophagy is poorly understood. This review discusses the mitophagy deficits in AD and examines potential molecular mechanisms of its activation. Moreover, the current knowledge of urolithin A is discussed, focusing on its neuroprotective properties and its potential to induce mitophagy. Specifically, this review proposes potential mechanisms by which urolithin A may activate and promote mitophagy.fals

The Major Roles of DNA Polymerases Epsilon and Delta at the Eukaryotic Replication Fork Are Evolutionarily Conserved

Coordinated replication of eukaryotic genomes is intrinsically asymmetric, with continuous leading strand synthesis preceding discontinuous lagging strand synthesis. Here we provide two types of evidence indicating that, in fission yeast, these two biosynthetic tasks are performed by two different replicases. First, in Schizosaccharomyces pombe strains encoding a polδ-L591M mutator allele, base substitutions in reporter genes placed in opposite orientations relative to a well-characterized replication origin are strand-specific and distributed in patterns implying that Polδ is primarily involved in lagging strand replication. Second, in strains encoding a polε-M630F allele and lacking the ability to repair rNMPs in DNA due to a defect in RNase H2, rNMPs are selectively observed in nascent leading strand DNA. The latter observation demonstrates that abundant rNMP incorporation during replication can be tolerated and that they are normally removed in an RNase H2-dependent manner. This provides strong physical evidence that Polε is the primary leading strand replicase. Collectively, these data and earlier results in budding yeast indicate that the major roles of Polδ and Polε at the eukaryotic replication fork are evolutionarily conserved

The AUstralian multidomain Approach to Reduce dementia Risk by prOtecting brain health With lifestyle intervention study (AU-ARROW): A study protocol for a single-blind, multi-site, randomized controlled trial

INTRODUCTION: The Finnish Geriatric Intervention Study (FINGER) led to the global dementia risk reduction initiative: World-Wide FINGERS (WW-FINGERS). As part of WW-FINGERS, the Australian AU-ARROW study mirrors aspects of FINGER, as well as US-POINTER. METHOD: AU-ARROW is a randomized, single-blind, multisite, 2-year clinical trial (n = 600; aged 55–79). The multimodal lifestyle intervention group will engage in aerobic exercise, resistance training and stretching, dietary advice to encourage MIND diet adherence, BrainHQ cognitive training, and medical monitoring and health education. The Health Education and Coaching group will receive occasional health education sessions. The primary outcome measure is the change in a global composite cognitive score. Extra value will emanate from blood biomarker analysis, positron emission tomography (PET) imaging, brain magnetic resonance imaging (MRI), and retinal biomarker tests. DISCUSSION: The finalized AU-ARROW protocol is expected to allow development of an evidence-based innovative treatment plan to reduce cognitive decline and dementia risk, and effective transfer of research outcomes into Australian health policy. Highlights: Study protocol for a single-blind, randomized controlled trial, the AU-ARROW Study. The AU-ARROW Study is a member of the World-Wide FINGERS (WW-FINGERS) initiative. AU-ARROW's primary outcome measure is change in a global composite cognitive score. Extra significance from amyloid PET imaging, brain MRI, and retinal biomarker tests. Leading to development of an innovative treatment plan to reduce cognitive decline

Effects of automated alerts on unnecessarily repeated serology tests in a cardiovascular surgery department: a time series analysis

<p>Abstract</p> <p>Background</p> <p>Laboratory testing is frequently unnecessary, particularly repetitive testing. Among the interventions proposed to reduce unnecessary testing, Computerized Decision Support Systems (CDSS) have been shown to be effective, but their impact depends on their technical characteristics. The objective of the study was to evaluate the impact of a Serology-CDSS providing point of care reminders of previous existing serology results, embedded in a Computerized Physician Order Entry at a university teaching hospital in Paris, France.</p> <p>Methods</p> <p>A CDSS was implemented in the Cardiovascular Surgery department of the hospital in order to decrease inappropriate repetitions of viral serology tests (HBV).</p> <p>A time series analysis was performed to assess the impact of the alert on physicians' practices. The study took place between January 2004 and December 2007. The primary outcome was the proportion of unnecessarily repeated HBs antigen tests over the periods of the study. A test was considered unnecessary when it was ordered within 90 days after a previous test for the same patient. A secondary outcome was the proportion of potentially unnecessary HBs antigen test orders cancelled after an alert display.</p> <p>Results</p> <p>In the pre-intervention period, 3,480 viral serology tests were ordered, of which 538 (15.5%) were unnecessarily repeated. During the intervention period, of the 2,095 HBs antigen tests performed, 330 unnecessary repetitions (15.8%) were observed. Before the intervention, the mean proportion of unnecessarily repeated HBs antigen tests increased by 0.4% per month (absolute increase, 95% CI 0.2% to 0.6%, <it>p </it>< 0.001). After the intervention, a significant trend change occurred, with a monthly difference estimated at -0.4% (95% CI -0.7% to -0.1%, <it>p </it>= 0.02) resulting in a stable proportion of unnecessarily repeated HBs antigen tests. A total of 380 unnecessary tests were ordered among 500 alerts displayed (compliance rate 24%).</p> <p>Conclusions</p> <p>The proportion of unnecessarily repeated tests immediately dropped after CDSS implementation and remained stable, contrasting with the significant continuous increase observed before. The compliance rate confirmed the effect of the alerts. It is necessary to continue experimentation with dedicated systems in order to improve understanding of the diversity of CDSS and their impact on clinical practice.</p