Multilocus genotyping of microbial pathogens has revealed a range of population structures, with some bacteria showing extensive recombination and others showing almost complete clonality. The population structure of the protozoan parasite Plasmodium falciparum has been harder to evaluate, since most studies have used a limited number of antigen-encoding loci that are known to be under strong selection. We describe length variation at 12 microsatellite loci in 465 infections collected from 9 locations worldwide. These data reveal dramatic differences in parasite population structure in different locations. Strong linkage disequilibrium (LD) was observed in six of nine populations. Significant LD occurred in all locations with prevalence <1% and in only two of five of the populations from regions with higher transmission intensities. Where present, LD results largely from the presence of identical multilocus genotypes within populations, suggesting high levels of self-fertilization in populations with low levels of transmission. We also observed dramatic variation in diversity and geographical differentiation in different regions. Mean heterozygosities in South American countries (0.3-0.4) were less than half those observed in African locations (0. 76-0.8), with intermediate heterozygosities in the Southeast Asia/Pacific samples (0.51-0.65). Furthermore, variation was distributed among locations in South America (F:(ST) = 0.364) and within locations in Africa (F:(ST) = 0.007). The intraspecific patterns of diversity and genetic differentiation observed in P. falciparum are strikingly similar to those seen in interspecific comparisons of plants and animals with differing levels of outcrossing, suggesting that similar processes may be involved. The differences observed may also reflect the recent colonization of non-African populations from an African source, and the relative influences of epidemiology and population history are difficult to disentangle. These data reveal a range of population structures within a single pathogen species and suggest intimate links between patterns of epidemiology and genetic structure in this organism.
S_rThe effect of insulhn-like growth factor II (IGF-II) on
ObjectiveTo assess the association between the employment status of human immunodeficiency virus (HIV)-infected individuals and adherence to antiretroviral therapy (ART).MethodsWe searched the Medline, Embase and Cochrane Central Register of Controlled Trials databases for studies reporting ART adherence and employment status published between January 1980 and September 2014. Information from a wide range of other sources, including the grey literature, was also analysed. Two independent reviewers extracted data on treatment adherence and study characteristics. Study data on the association between being employed and adhering to ART were pooled using a random-effects model. Between-study heterogeneity and sources of bias were evaluated.FindingsThe meta-analysis included 28 studies published between 1996 and 2014 that together involved 8743 HIV-infected individuals from 14 countries. The overall pooled odds ratio (OR) for the association between being employed and adhering to ART was 1.27 (95% confidence interval, CI: 1.04–1.55). The association was significant for studies from low-income countries (OR: 1.85, 95% CI: 1.58–2.18) and high-income countries (OR: 1.33, 95% CI: 1.02–1.74) but not middle-income countries (OR: 0.94, 95% CI: 0.62–1.42). In addition, studies published after 2011 and larger studies showed less association between employment and adherence than earlier and small studies, respectively.ConclusionEmployed HIV-infected individuals, particularly those in low- and high-income countries, were more likely to adhere to ART than unemployed individuals. Further research is needed on the mechanisms by which employment and ART adherence affect each other and on whether employment-creation interventions can positively influence ART adherence, HIV disease progression and quality of life.
Injection tnseness was used to study the long-term effects of excess Insulin-like growth factor I on mouse growth and diferaeatio. By using a construct in which the coding region the mouse Insulin like growth factor I gene (Igf-2) was placed under the control of a keratin gene promoter, four lie were esablhed, al of which displayed overgrowth f the skin as judged by wrinkling. In addition to high levels of expression in the skin, transgene transcripts were lo present in the alimentary canal and uterus. At most of the site of tagene expression the cell number (DNA content) wasgreaty Increased, indicating a local action of the excess insulin-like growth factor U on cell multiplication. Adult total live weight was slightly increased and there was no macroscopic evidence of tumor formation. The characteristics of these t -ic mice indicate distinct local and systemic actions for iuli-like growth factor U.
Background: Socioeconomic marginalization (SEM) is an important but under-explored determinant of opioid overdose with important implications for health equity and associated public policy initiatives. This systematic review synthesizes evidence on the role of SEM in both fatal and non-fatal overdose among people who use opioids. Methods: Studies published between January 1, 2000 and March 31, 2018 were identified through searching electronic databases, citations, and by contacting experts. The titles, abstracts, citation information, and descriptor terms of citations were screened by two team members. Data were synthesized using the lumping technique. Results: A total of 37 studies met inclusion criteria and were included in the review, with 34 of 37 finding a significant association between at least one socioeconomic factor and overdose. The included studies contained variables related to eight socioeconomic factors: criminal justice system involvement, income, employment, social support, health insurance, housing/homelessness, education, and composite measures of socio-economic status. Most studies found associations in the hypothesized direction, whereby increased SEM was associated with a higher rate or increased likelihood of the overdose outcome measured. The review revealed an underdeveloped evidence base. Conclusions: Nearly all reviewed studies found a connection between a socioeconomic variable and overdose, but more research is needed with an explicit focus on SEM, using robust and nuanced measures that capture multiple dimensions of disadvantage, and collect data over time to better inform decision making around opioid overdose.
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