Comparative population structure of <i>Plasmodium malariae</i> and <i>Plasmodium falciparum</i> under different transmission settings in Malawi

&lt;b&gt;Background:&lt;/b&gt; Described here is the first population genetic study of Plasmodium malariae, the causative agent of quartan malaria. Although not as deadly as Plasmodium falciparum, P. malariae is more common than previously thought, and is frequently in sympatry and co-infection with P. falciparum, making its study increasingly important. This study compares the population parameters of the two species in two districts of Malawi with different malaria transmission patterns - one seasonal, one perennial - to explore the effects of transmission on population structures. &lt;BR/&gt; &lt;b&gt;Methods:&lt;/b&gt; Six species-specific microsatellite markers were used to analyse 257 P. malariae samples and 257 P. falciparum samples matched for age, gender and village of residence. Allele sizes were scored to within 2 bp for each locus and haplotypes were constructed from dominant alleles in multiple infections. Analysis of multiplicity of infection (MOI), population differentiation, clustering of haplotypes and linkage disequilibrium was performed for both species. Regression analyses were used to determine association of MOI measurements with clinical malaria parameters. &lt;BR/&gt; &lt;b&gt;Results:&lt;/b&gt; Multiple-genotype infections within each species were common in both districts, accounting for 86.0% of P. falciparum and 73.2% of P. malariae infections and did not differ significantly with transmission setting. Mean MOI of P. falciparum was increased under perennial transmission compared with seasonal (3.14 vs 2.59, p = 0.008) and was greater in children compared with adults. In contrast, P. malariae mean MOI was similar between transmission settings (2.12 vs 2.11) and there was no difference between children and adults. Population differentiation showed no significant differences between villages or districts for either species. There was no evidence of geographical clustering of haplotypes. Linkage disequilibrium amongst loci was found only for P. falciparum samples from the seasonal transmission setting. &lt;BR/&gt; &lt;b&gt;Conclusions:&lt;/b&gt; The extent of similarity between P. falciparum and P. malariae population structure described by the high level of multiple infection, the lack of significant population differentiation or haplotype clustering and lack of linkage disequilibrium is surprising given the differences in the biological features of these species that suggest a reduced potential for out-crossing and transmission in P. malariae. The absence of a rise in P. malariae MOI with increased transmission or a reduction in MOI with age could be explained by differences in the duration of infection or degree of immunity compared to P. falciparum

Methamphetamine Use among Newly Diagnosed HIV-Positive Young Men in North Carolina, United States, from 2000 to 2005

Methamphetamine (MA) is a new arrival to the Southeastern United States (US). Incidence of HIV is also increasing regionally, but data are limited regarding any association between this trend and MA use. We examined behavioral data from North Carolina (NC) residents newly diagnosed with HIV, collected by the Department of Health between 2000-2005.Among 1,460 newly diagnosed HIV-positive young men, an increasing trend was seen from 2000-2005 in MA use (p = 0.01, total n = 20). In bivariate analyses, users of MA had significantly greater odds of reporting other substance use, including alcohol, powder or crack cocaine, marijuana, and methylenedioxymethamphetamine (MDMA, "ecstasy"). They were also more likely to have reported sexual activity while traveling outside NC; sex with anonymous partners; and previous HIV testing. In a predictive model, MA use had a negative association with nonwhite race, and strong positive associations with powder cocaine, "ecstasy," or intravenous drug use and being a university student.Similar to trends seen in more urban parts of the US, MA use among newly diagnosed, HIV-positive young men is increasing in NC. These data are among the first to demonstrate this relationship in a region with a burgeoning epidemic of MA use. Opportunities exist for MA-related HIV risk-reduction interventions whenever young men intersect the healthcare system

Relationship Contexts as Sources of Socialization: An Exploration of Intimate Partner Violence Experiences of Economically Disadvantaged African American Adolescents

Intimate partner violence (IPV) among African Americans is a serious public health concern. Research suggest that African Americans adolescents, particularly those from economically disadvantaged communities, are at heightened risk for experiencing and perpetrating dating violence compared to youth from other racial and ethnic groups. In the present study, we examined different relationship contexts that are sources of IPV socialization. Semi-structured interviews were conducted with 22 economically disadvantaged African American adolescents. Content analysis yielded five relationship contexts through which the participants witnessed, experienced, and perpetrated IPV: (a) adolescents’ own dating relationships (64%), (b) siblings and extended family members (e.g., cousins, aunts, uncles) (59%), (c) parent-partners (27%), (d) friends (23%), and (e) neighbors (18%). Adolescents also frequently described IPV in their own dating relationships and in parent-partner relationships as mutual. Moreover, they appeared to minimize the experience of IPV in their own relationships. Efforts to reduce rates of IPV among economically disadvantaged African American adolescents should consider these relational contexts through which adolescents are socialized with regards to IPV and adolescents’ beliefs about mutual violence in relationships. Results highlight the importance of culturally relevant prevention and intervention programs that consider these relationship contexts

A novel spontaneous model of epithelial-mesenchymal transition (EMT) using a primary prostate cancer derived cell line demonstrating distinct stem-like characteristics

Cells acquire the invasive and migratory properties necessary for the invasion-metastasis cascade and the establishment of aggressive, metastatic disease by reactivating a latent embryonic programme: epithelial-to-mesenchymal transition (EMT). Herein, we report the development of a new, spontaneous model of EMT which involves four phenotypically distinct clones derived from a primary tumour-derived human prostate cancer cell line (OPCT-1), and its use to explore relationships between EMT and the generation of cancer stem cells (CSCs) in prostate cancer. Expression of epithelial (E-cadherin) and mesenchymal markers (vimentin, fibronectin) revealed that two of the four clones were incapable of spontaneously activating EMT, whereas the others contained large populations of EMT-derived, vimentin-positive cells having spindle-like morphology. One of the two EMT-positive clones exhibited aggressive and stem cell-like characteristics, whereas the other was non-aggressive and showed no stem cell phenotype. One of the two EMT-negative clones exhibited aggressive stem cell-like properties, whereas the other was the least aggressive of all clones. These findings demonstrate the existence of distinct, aggressive CSC-like populations in prostate cancer, but, importantly, that not all cells having a potential for EMT exhibit stem cell-like properties. This unique model can be used to further interrogate the biology of EMT in prostate cancer

Effectiveness of smoking cessation therapies: a systematic review and meta-analysis

BACKGROUND: Smoking remains the leading preventable cause of premature deaths. Several pharmacological interventions now exist to aid smokers in cessation. These include Nicotine Replacement Therapy [NRT], bupropion, and varenicline. We aimed to assess their relative efficacy in smoking cessation by conducting a systematic review and meta-analysis. METHODS: We searched 10 electronic medical databases (inception to Sept. 2006) and bibliographies of published reviews. We selected randomized controlled trials [RCTs] evaluating interventions for smoking cessation at 1 year, through chemical confirmation. Our primary endpoint was smoking cessation at 1 year. Secondary endpoints included short-term smoking cessation (~3 months) and adverse events. We conducted random-effects meta-analysis and meta-regression. We compared treatment effects across interventions using head-to-head trials and when these did not exist, we calculated indirect comparisons. RESULTS: We identified 70 trials of NRT versus control at 1 year, Odds Ratio [OR] 1.71, 95% Confidence Interval [CI], 1.55–1.88, P =< 0.0001). This was consistent when examining all placebo-controlled trials (49 RCTs, OR 1.78, 95% CI, 1.60–1.99), NRT gum (OR 1.60, 95% CI, 1.37–1.86) or patch (OR 1.63, 95% CI, 1.41–1.89). NRT also reduced smoking at 3 months (OR 1.98, 95% CI, 1.77–2.21). Bupropion trials were superior to controls at 1 year (12 RCTs, OR1.56, 95% CI, 1.10–2.21, P = 0.01) and at 3 months (OR 2.13, 95% CI, 1.72–2.64). Two RCTs evaluated the superiority of bupropion versus NRT at 1 year (OR 1.14, 95% CI, 0.20–6.42). Varenicline was superior to placebo at 1 year (4 RCTs, OR 2.96, 95% CI, 2.12–4.12, P =< 0.0001) and also at approximately 3 months (OR 3.75, 95% CI, 2.65–5.30). Three RCTs evaluated the effectiveness of varenicline versus bupropion at 1 year (OR 1.58, 95% CI, 1.22–2.05) and at approximately 3 months (OR 1.61, 95% CI, 1.16–2.21). Using indirect comparisons, varenicline was superior to NRT when compared to placebo controls (OR 1.66, 95% CI 1.17–2.36, P = 0.004) or to all controls at 1 year (OR 1.73, 95% CI 1.22–2.45, P = 0.001). This was also the case for 3-month data. Adverse events were not systematically different across studies. CONCLUSION: NRT, bupropion and varenicline all provide therapeutic effects in assisting with smoking cessation. Direct and indirect comparisons identify a hierarchy of effectiveness

Evolving uses of oral reverse transcriptase inhibitors in the HIV-1 epidemic: From treatment to prevention

The HIV epidemic continues unabated, with no highly effective vaccine and no cure. Each new infection has significant economic, social and human costs and prevention efforts are now as great a priority as global antiretroviral therapy (ART) scale up. Reverse transcriptase inhibitors, the first licensed class of ART, have been at the forefront of treatment and prevention of mother to child transmission over the past two decades. Now, their use in adult prevention is being

The Policy Dystopia Model:an interpretive analysis of tobacco industry political activity

BACKGROUND: Tobacco industry interference has been identified as the greatest obstacle to the implementation of evidence-based measures to reduce tobacco use. Understanding and addressing industry interference in public health policy-making is therefore crucial. Existing conceptualisations of corporate political activity (CPA) are embedded in a business perspective and do not attend to CPA's social and public health costs; most have not drawn on the unique resource represented by internal tobacco industry documents. Building on this literature, including systematic reviews, we develop a critically informed conceptual model of tobacco industry political activity. METHODS AND FINDINGS: We thematically analysed published papers included in two systematic reviews examining tobacco industry influence on taxation and marketing of tobacco; we included 45 of 46 papers in the former category and 20 of 48 papers in the latter (n = 65). We used a grounded theory approach to build taxonomies of "discursive" (argument-based) and "instrumental" (action-based) industry strategies and from these devised the Policy Dystopia Model, which shows that the industry, working through different constituencies, constructs a metanarrative to argue that proposed policies will lead to a dysfunctional future of policy failure and widely dispersed adverse social and economic consequences. Simultaneously, it uses diverse, interlocking insider and outsider instrumental strategies to disseminate this narrative and enhance its persuasiveness in order to secure its preferred policy outcomes. Limitations are that many papers were historical (some dating back to the 1970s) and focused on high-income regions. CONCLUSIONS: The model provides an evidence-based, accessible way of understanding diverse corporate political strategies. It should enable public health actors and officials to preempt these strategies and develop realistic assessments of the industry's claims

The human capital transition and the role of policy

Along with information and communication technology, infrastructure, and the innovation system, human capital is a key pillar of the knowledge economy with its scope for increasing returns. With this in mind, the purpose of this chapter is to investigate how industrialized economies managed to achieve the transition from low to high levels of human capital. The first phase of the human capital transition was the result of the interaction of supply and demand, triggered by technological change and boosted by the demands for (immaterial) services. The second phase of the human capital transition (i.e., mass education) resulted from enforced legislation and major public investment. The state’s aim to influence children’s beliefs appears to have been a key driver in public investment. Nevertheless, the roles governments played differed according to the developmental status and inherent socioeconomic and political characteristics of their countries. These features of the human capital transition highlight the importance of understanding governments’ incentives and roles in transitions

Exploring consensus on how to measure smoking cessation. A Delphi study

Background Different criteria regarding outcome measures in smoking research are used, which can lead to confusion about study results. Consensus in outcome criteria may enhance the comparability of future studies. This study aims (1) to provide an overview of tobacco researchers’ considered preferences regarding outcome criteria in randomized controlled smoking cessation trials, and (2) to identify the extent to which researchers can reach consensus on the importance of these outcome criteria. Methods A three-round online Delphi study was conducted among smoking cessation experts. In the first round, the most important smoking cessation outcome measures were collected by means of open-ended questions, which were categorized around self-reported and biochemical validation measures. Experts (n = 17) were asked to name the outcome measures (as well as their assessment method and ideal follow-up period) that they thought were important when assessing smoking-related outcomes. In the second (n = 48) and third rounds (n = 37), a list of outcome measures—identified in the first round—was presented to experts. Asking them to rate the importance of each measure on a seven-point scale. Results Experts reached consensus on several items. For self-reports, experts agreed that prolonged abstinence (6 or/and 12 months), point prevalence abstinence (7 days), continuous abstinence (6 months), and the number of cigarettes smoked (7 days) are important outcome measures. Experts reached consensus that biochemical validation methods should not always be used. The preferred biochemical validation methods were carbon monoxide (expired air) and cotinine (saliva). Preferred follow-ups included 6 and/or 12 months, with or without intermediate measurements. Conclusions Findings suggest only partial compliance with the Russell standard and that more outcome measures may be important (including seven-day point-prevalence abstinence, number of cigarettes smoked, and cotinine when using biochemical validation). This study showed where there is and is not consensus, reflecting the need to develop a more comprehensive standard. For these purposes we provided suggestions for the Russell 2.0 standard