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Global Health Problem (global + health_problem)
Kinds of Global Health Problem Selected AbstractsSurprises from the crystal structure of the hepatitis C virus NS2-3 protease,HEPATOLOGY, Issue 6 2006Jerome Gouttenoire Ph.D. Hepatitis C virus is a major global health problem affecting an estimated 170 million people worldwide. Chronic infection is common and can lead to cirrhosis and liver cancer. There is no vaccine available and current therapies have met with limited success. The viral RNA genome encodes a polyprotein that includes 2 proteases essential for virus replication. The NS2-3 protease mediates a single cleavage at the NS2/NS3 junction, whereas the NS3-4A protease cleaves at 4 downstream sites in the polyprotein. NS3-4A is characterized as a serine protease with a chymotrypsin-like fold, but the enzymatic mechanism of the NS2-3 protease remains unresolved. Here, we report the crystal structure of the catalytic domain of the NS2-3 protease at 2.3 Å resolution. The structure reveals a dimeric cysteine protease with 2 composite active sites. For each active site, the catalytic histidine and glutamate residues are contributed by one monomer, and the nucleophilic cysteine by the other. The carboxy-terminal residues remain coordinated in the 2 active sites, predicting an inactive postcleavage form. Proteolysis through formation of a composite active site occurs in the context of the viral polyprotein expressed in mammalian cells. These features offer unexpected insights into polyprotein processing by hepatitis C virus and new opportunities for antiviral drug design. [source] Evaluation of IL10, IL19 and IL20 gene polymorphisms and chronic hepatitis B infection outcomeINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 3 2008Ann L. Truelove Summary Hepatitis B virus (HBV) infection remains a serious global health problem despite the availability of a highly effective vaccine. Approximately 5% of HBV-infected adults develop chronic hepatitis B, which may result in liver cirrhosis or hepatocellular carcinoma. Variants of interleukin-10 (IL10) have been previously associated with chronic hepatitis B infection and progression to hepatocellular carcinoma. Single nucleotide polymorphisms (SNP; n = 42) from the IL10, IL19 and IL20 gene regions were examined for an association with HBV infection outcome, either chronic or recovered, in a nested case,control study of African Americans and European Americans. Among African Americans, three nominally statistically significant SNP associations in IL10, two in IL20, and one haplotype association were observed with different HBV infection outcomes (P = 0.005,0.04). A SNP (rs1518108) in IL20 deviated significantly from Hardy,Weinberg equilibrium in African Americans, with a large excess of heterozygotes in chronic HBV-infected cases (P = 0.0006), which suggests a strong genetic effect. Among European Americans, a nominally statistically significant SNP association in IL20 and an IL20 haplotype were associated with HBV recovery (P = 0.01,0.04). These results suggest that IL10 and IL20 gene variants influence HBV infection outcome and encourage the pursuit of further studies of these cytokines in HBV pathogenesis. [source] Rapid production of a plasmid DNA encoding a malaria vaccine candidate via amino-functionalized poly(GMA- co -EDMA) monolithAICHE JOURNAL, Issue 11 2008Michael K. Danquah Abstract Malaria is a global health problem; an effective vaccine is urgently needed. Due to the relative poverty and lack of infrastructure in malaria endemic areas, DNA-based vaccines that are stable at ambient temperatures and easy to formulate have great potential. While attention has been focused mainly on antigen selection, vector design and efficacy assessment, the development of a rapid and commercially viable process to manufacture DNA is generally overlooked. We report here a continuous purification technique employing an optimized stationary adsorbent to allow high-vaccine recovery, low-processing time, and, hence, high-productivity. A 40.0 mL monolithic stationary phase was synthesized and functionalized with amino groups from 2-Chloro-N,N-diethylethylamine hydrochloride for anion-exchange isolation of a plasmid DNA (pDNA) that encodes a malaria vaccine candidate, VR1020-PyMSP4/5. Physical characterization of the monolithic polymer showed a macroporous material with a modal pore diameter of 750 nm. The final vaccine product isolated after 3 min elution was homogeneous supercoiled plasmid with gDNA, RNA and protein levels in keeping with clinical regulatory standards. Toxicological studies of the pVR1020-PyMSP4/5 showed a minimum endotoxin level of 0.28 EU/mg pDNA. This cost-effective technique is cGMP compatible and highly scalable for the production of DNA-based vaccines in commercial quantities, when such vaccines prove to be effective against malaria. © 2008 American Institute of Chemical Engineers AIChE J, 2008 [source] How to use virological tools for optimal management of chronic hepatitis CLIVER INTERNATIONAL, Issue 2009Stéphane Chevaliez Abstract Chronic hepatitis C is a global health problem that may cause cirrhosis and progression to hepatocellular carcinoma. Currently available antiviral treatments are moderately effective. Several virological assays are available to help diagnose and manage patients infected with the hepatitis C virus (HCV). These include the anti-HCV antibody assays, measurement of HCV RNA viral load and HCV genotyping. HCV RNA can be assayed by two types of molecular biology-based techniques: target amplification as in polymerase chain reaction methods and signal amplification such as the branched DNA assay. Monitoring of viral kinetics during the early phases of antiviral treatment is crucial in making treatment decisions such as early stopping rules and also in optimizing the length of treatment. The HCV genotype can be determined by several methods. Whatever the method, pretreatment determination allows treatment length and ribavirin dose to be optimized and also offers prognostic information on treatment outcomes as certain genotypes respond more favourably to treatment. Thus, virological assays are indispensable in the diagnosis and management of individuals infected with the HCV. [source] Allergic rhinitis and the common cold , high cost to societyALLERGY, Issue 6 2010J. Hellgren To cite this article: Hellgren J, Cervin A, Nordling S, Bergman A, Cardell LO. Allergic rhinitis and the common cold , high cost to society. Allergy 2010; 65: 776,783. Abstract Background:, The common cold and allergic rhinitis constitute a global health problem that affects social life, sleep, school and work performance and is likely to impose a substantial economic burden on society because of absence from work and reduced working capacity. This study assesses the loss of productivity as a result of both allergic rhinitis and the common cold in the Swedish working population. Methods:, Four thousand questionnaires were sent to a randomized adult population, aged 18,65 years, in Sweden, stratified by gender and area of residence (metropolitan area vs rest of the country). The human capital approach was used to assign monetary value to lost productivity in terms of absenteeism (absence from work), presenteeism (reduced working capacity while at work) and caregiver absenteeism (absence from work to take care of a sick child). Results:, Thousand two hundred and thirteen individuals responded, response rate 32%. The mean productivity loss was estimated at 5.1 days or , 653 per worker and year, yielding a total productivity loss in Sweden of , 2.7 billion a year. Of the total costs, absenteeism (44%) was the dominant factor, followed by presenteeism (37%) and caregiver absenteeism (19%). Poisson regression analyses revealed that women, people in the 18,29 year age group, and respondents with ,doctor-diagnosed asthma' reported more lost days than the rest of the group. Conclusion:, In Sweden, the cost of rhinitis is , 2.7 billion a year in terms of lost productivity. A reduction in lost productivity of 1 day per individual and year would potentially save , 528 million. [source] Recommendations for assessing Patient-Reported Outcomes and Health-Related quality of life in clinical trials on allergy: a GA2LEN taskforce position paperALLERGY, Issue 3 2010I. Baiardini To cite this article: Baiardini I, Bousquet PJ, Brzoza Z, Canonica GW, Compalati E, Fiocchi A, Fokkens W, van Wijk RG, La Grutta S, Lombardi C, Maurer M, Pinto AM, Ridolo E, Senna GE, Terreehorst I, Todo Bom A, Bousquet J, Zuberbier T, Braido F. Recommendations for assessing Patient-Reported Outcomes and Health-Related quality of life in clinical trials on allergy: a GA2LEN taskforce position paper. Allergy 2010; 65: 290,295. Abstract The aim of this Global Allergy and Asthma European Network (GA2LEN) consensus report is to provide recommendations for patient-reported outcomes (PROs) evaluation in clinical trials for allergic diseases, which constitute a global health problem in terms of physical, psychological economic and social impact. During the last 40 years, PROs have gained large consideration and use in the scientific community, to gain a better understanding of patients' subjective assessment with respect to elements concerning their health condition. They include all health-related reports coming from the patient, without involvement or interpretation by physician or others. PROs assessment should be performed by validated tools (disease-specific tools when available or generic ones) selected taking into account the aim of the study, the expected intervention effects and the determinant and confounding factors or patient-related factors which could influence PROs. Moreover, each tool should be used exclusively in the patient population following the authors' indications without modification and performing a cross-cultural validation if the tool must be used in a language that differs from the original. The result analysis also suggests that the relevance of PROs results in any interventional study should include a pre,post assessment providing information concerning statistical differences within or among groups, rates of response for the PROs and a minimal important difference for the population. The report underlines the importance of further investigation on some topics, such as the quality assessment of existing PROs tools, the definition of inclusion and exclusion criteria and a more extensive evaluation of the correlation between PROs, besides health-related quality of life, and clinical data. [source] Trans Fatty Acids, Insulin Resistance, and Type 2 DiabetesNUTRITION REVIEWS, Issue 8 2006Andrew O. Odegaard BA Type 2 diabetes, a growing global health problem, has a complex etiology involving many interactions between genetic and environmental factors. Essential to the development of the disease is insulin resistance of the peripheral tissues. Insulin resistance may be partly modified by the specific types of dietary fatty acids. Trans fatty acids (TFAs), created through the transformation of polyunsaturated fatty acids from their natural cis form to the trans form, are abundant in the Western diet. TFAs take on similar properties as saturated fats, and appear to be more atherogenic. High intakes of saturated fats may promote insulin resistance. It is therefore reasonable to hypothesize that high intakes of TFAs would have similar, or stronger, effects. In this review, all current evidence on the topic of TFAs, insulin resistance, and type 2 diabetes is summarized and interpreted. Although there is some support from observational and experimental studies for the hypothesis that high intakes of TFAs may increase the risk for type 2 diabetes, inconsistencies across studies and methodological problems make it premature to draw definitive conclusions at this time. More experimental research in humans is needed to further address this question. [source] Functional ability in female leg ulcer patients , a challenge for physiotherapyPHYSIOTHERAPY RESEARCH INTERNATIONAL, Issue 4 2006Kirsti Skavberg Roaldsen Abstract Background and Purpose.,Venous leg ulceration represents a global health problem affecting predominantly elderly women. Traditionally, functional problems in this group of patients have attracted modest attention from wound care providers and physiotherapists. The aim of the present study was to describe and quantify disease consequences in female leg ulcer patients as a background for future physiotherapy interventions, using the nomenclature of the WHO International Classification of Functioning, Disability and Health (ICF).,Method.,A prospective study was conducted in 34 women aged 60,85 years with current or previous venous leg ulcer as compared to 27 age-matched non-ulcer subjects. The outcome variables were pain, ankle range of motion, walking speed, walking endurance, self-perceived exertion, mobility, activities of daily living (ADL), physical activity, general health, life satisfaction and use of walking aids and community services. Established instruments were utilized and categorized within ICF domains to provide a conceptual framework and basis for physiotherapeutic research.,Results.,Leg ulcer patients showed significantly reduced values of ankle range of motion, walking speed and endurance, self-perceived exertion, mobility, ADL and physical activity level as compared to control subjects. Patients suffering from active ulceration were more negatively affected, and more of them had pain than post-ulcer fellows. By contrast, general health and life satisfaction were similarly rated by the two study groups.,Conclusions.,Elderly females in our study with chronic leg ulcer of venous aetiology had significant mobility impairments, but the reasons and consequences of these impairments remain to be elucidated. The potential of preventive measures and physical rehabilitation to aid functioning and prospects of leg ulcer repair need to be investigated in future studies. Copyright © 2006 John Wiley & Sons, Ltd. [source] Synthesis and Antimycobacterial Activity of Azetidine-, Quinazoline-, and Triazolo-thiadiazole-containing PyrazinesARCHIV DER PHARMAZIE, Issue 4 2010Chandrakant G. Bonde Abstract The re-emergence of tuberculosis (TB) as a global health problem over the past few decades, accompanied by the rise of drug-resistant strains of Mycobacterium tuberculosis, emphasizes the need for the discovery of new therapeutic drugs against this disease. The emerging serious problem both in terms of TB control and clinical management prompted us to synthesize a novel series of N -[2-(substituted aryl)-3-chloro-4-oxoazetidin-1-yl]-2-(pyrazin-2-yloxy)acetamide, 6-(substituted aryl)-3-[(pyrazin-2-yloxy)methyl][1,2,4]triazolo[3,4- b][1,3,4]thiadiazole, and N -[6-({2-[(pyrazin-2-yloxy)acetyl] hydrazino}sulfonyl)-2-methyl-4-oxo-1,4-dihydroquinazolin-3(2H)yl]-substituted aryl sulfonamides. The compounds were synthesized using the appropriate synthetic route. All synthesized compounds were assayed in vitro for antimycobacterial activity against the H37 Rv strain of Mycobacterium tuberculosis. The minimum inhibitory concentration (MIC) was determined for the test compounds as well as for the reference standards. The compound which exhibited good antimycobacterial activity contains the substituents fluorine and methoxy. These electron-withdrawing or -donating substituents amend the lipophilicity of the test compounds which, in turn, alter the permeability across the bacterial cell membrane. Compounds 28, 37, and 43 showed good antimycobacterial activity while compound 51 showed a promising antimycobacterial activity. [source] Biosecurity and the international response to HIV/AIDS: governmentality, globalisation and securityAREA, Issue 3 2010Alan Ingram A growing critical literature examines the rise of biosecurity. HIV/AIDS has been mentioned in this literature as a biosecurity issue, but despite its importance as a major global health problem, the ways in which HIV/AIDS might be considered a matter of biosecurity have not been explored in depth. This article addresses this issue, particularly in relation to the international response to HIV/AIDS, through the conceptual prism of governmentality and in relation to concerns about globalisation and security. Following a discussion of the relevance of governmentality to research on the intersections between globalisation and security, the article considers biosecurity and the international response to HIV/AIDS in terms of modes of problematisation and institutionalisation. In terms of problematisation, it argues that while some biosecurity issues and HIV/AIDS have been addressed as emergencies, the characteristics of anticipation, preparedness, emergence and pre-emption, which are central to the dominant formation of biosecurity, are less relevant to HIV/AIDS. As the article shows, the two fields have also been institutionalised in rather distinct ways. It therefore cautions against regarding the international response to HIV/AIDS as a biosecurity intervention. In conclusion, the article identifies three broad avenues for further research: unpacking the politics of global health and security during recession; engaging with theoretical debates around governmentality; and engaging with problems of space. [source] Screening programmes for the early detection and prevention of oral cancerAUSTRALIAN DENTAL JOURNAL, Issue 2 2009O Kujan Background:, Screening programmes for major cancers, such as breast and cervical cancer have effectively decreased the mortality rate and helped to reduce the incidence of these cancers. Although oral cancer is a global health problem with increasing incidence and mortality rates, no national population-based screening programmes for oral cancer have been implemented. To date there is debate on whether to employ screening methods for oral cancer in the daily routine work of health providers. Objectives:, To assess the effectiveness of current screening methods in decreasing oral cancer mortality. Search strategy:, Electronic databases (MEDLINE, CANCERLIT, EMBASE (1966 to July 2005) and CENTRAL (The Cochrane Library 2005, Issue 3), bibliographies, handsearching of specific journals and contact authors were used to identify published and unpublished data. Selection criteria:, Randomized controlled trials of screening for oral cancer or precursor oral lesions using visual examination, toluidine blue, fluorescence imaging or brush biopsy. Data collection and analysis:, The search found 112 citations and these have been reviewed. One randomized controlled trial of screening strategies for oral cancer was identified as meeting the review's inclusion criteria. Validity assessment, data extraction and statistics evaluation were undertaken by two independent review authors. Main results:, One 10-year randomized controlled trial has been included (n = 13 clusters: 191 873 participants). There was no difference in the age-standardized oral cancer mortality rates for the screened group (16.4/100 000 person-years) and the control group (20.7/100 000 person-years). Interestingly, a significant 34% reduction in mortality was recorded in high-risk subjects between the intervention cohort (29.9/100 000 person-years) and the control arm (45.4/100 000). However, this study has some methodological weaknesses. Additionally, the study did not provide any information related to costs, quality of life or even harms of screening from false-positive or false-negative findings. Authors' conclusions:, Given the limitation of evidence (only one included randomized controlled trial) and the potential methodological weakness of the included study, it is valid to say that there is insufficient evidence to support or refute the use of a visual examination as a method of screening for oral cancer using a visual examination in the general population. Furthermore, no robust evidence exists to suggest that other methods of screening, toluidine blue, fluorescence imaging or brush biopsy, are either beneficial or harmful. Future high quality studies to assess the efficacy, effectiveness and costs of screening are required for the best use of public health resources. In addition, studies to elucidate the natural history of oral cancer, prevention methods and the effectiveness of opportunistic screening in high risk groups are needed. Future studies on improved treatment modalities for oral cancer and precancer are also required. Plain language summary:, Screening programmes for the early detection and prevention of oral cancer. More evidence needed to find out whether screening programmes could detect oral cancer earlier and reduce the number of deaths from this disease. Cancer of the mouth and back of the throat (oral cancer) has a low survival rate, largely because the disease is often not diagnosed until it is advanced. Screening the general population for oral cancer might make it possible to detect cases of the disease earlier. The most common method is visual inspection by a clinician, but other techniques include the use of a special blue "dye" and an imaging technique. The review found that there is not enough evidence to decide whether screening by visual inspection reduces the death rate for oral cancer, and no evidence for other screening methods. [source] Genetic variation and susceptibility to infection: the red cell and malariaBRITISH JOURNAL OF HAEMATOLOGY, Issue 3 2008D. J. Weatherall Summary There is now convincing evidence that the extremely high frequencies of certain genetic disorders of the red cell involving haemoglobin, the red-cell membrane, or its metabolic pathways reflect relative resistance to malaria over thousands of years. At least some progress has been made towards an understanding of the cellular mechanisms involved, although much remains to be learnt. As well as the extremely valuable information that this field is providing about how exposure to infection has moulded the current structure of the human genome, recent research in this field is starting to provide some valuable new approaches to the better control of parasitic and other infections that remain a major global health problem. [source] Reduced fat oxidation and obesity risks among the Buryat of Southern Siberia,AMERICAN JOURNAL OF HUMAN BIOLOGY, Issue 5 2009William R. Leonard Over the last 20 years, obesity and associated metabolic diseases have emerged as major global health problems. Among urbanizing populations of developing regions of the world, childhood undernutrition often coexists with adult overnutrition, a phenomenon known as the "dual nutritional burden". A recent work (Frisancho 2003: Am J Hum Biol 15:522,532) suggests that linear growth stunting in early childhood may contribute to adult obesity by reducing the body's ability to oxidize fat. We test central aspects of this model drawing on data from 112 adult Buryat herders (53 males; 59 females) from Southern Siberia. The results are consistent with the predictions of the model, but only for women. Shorter Buryat women (height-for-age Z -scores , ,1) have significantly lower fasting fat oxidation levels compared to their taller counterparts. Shorter women are also significantly heavier and fatter, and have higher serum lipid levels. Among all Buryat women, reduced fat oxidation is significantly correlated with percent body fatness, serum triglyceride levels, and serum leptin levels, after controlling for relevant covariates. Additionally, Buryat women with high dietary fat intakes and low fat oxidation are significantly fatter and have higher lipid and leptin levels than those with low fat intakes and high fat oxidation. These results suggest that developmental changes in fat oxidation may play a role in the origins of obesity among populations with high rates of linear growth stunting. Further longitudinal research is necessary to elucidate the pathways through which early-life undernutrition may increase risks for adulthood obesity and cardiovascular disease. Am. J. Hum. Biol. 2009. © 2009 Wiley-Liss, Inc. [source] |