Genetic diversity and population structure of Glossina pallidipes in Uganda and western Kenya

<p>Abstract</p> <p>Background</p> <p><it>Glossina pallidipes </it>has been implicated in the spread of sleeping sickness from southeastern Uganda into Kenya. Recent studies indicated resurgence of <it>G. pallidipes </it>in Lambwe Valley and southeastern Uganda after what were deemed to be effective control efforts. It is unknown whether the <it>G. pallidipes </it>belt in southeastern Uganda extends into western Kenya. We investigated the genetic diversity and population structure of <it>G. pallidipes </it>in Uganda and western Kenya.</p> <p>Results</p> <p>AMOVA indicated that differences among sampling sites explained a significant proportion of the genetic variation. Principal component analysis and Bayesian assignment of microsatellite genotypes identified three distinct clusters: western Uganda, southeastern Uganda/Lambwe Valley, and Nguruman in central-southern Kenya. Analyses of mtDNA confirmed the results of microsatellite analysis, except in western Uganda, where Kabunkanga and Murchison Falls populations exhibited haplotypes that differed despite homogeneous microsatellite signatures. To better understand possible causes of the contrast between mitochondrial and nuclear markers we tested for sex-biased dispersal. Mean pairwise relatedness was significantly higher in females than in males within populations, while mean genetic distance was lower and relatedness higher in males than females in between-population comparisons. Two populations sampled on the Kenya/Uganda border, exhibited the lowest levels of genetic diversity. Microsatellite alleles and mtDNA haplotypes in these two populations were a subset of those found in neighboring Lambwe Valley, suggesting that Lambwe was the source population for flies in southeastern Uganda. The relatively high genetic diversity of <it>G. pallidipes </it>in Lambwe Valley suggest large relict populations remained even after repeated control efforts.</p> <p>Conclusion</p> <p>Our research demonstrated that <it>G. pallidipes </it>populations in Kenya and Uganda do not form a contiguous tsetse belt. While Lambwe Valley appears to be a source population for flies colonizing southeastern Uganda, this dispersal does not extend to western Uganda. The complicated phylogeography of <it>G. pallidipes </it>warrants further efforts to distinguish the role of historical and modern gene flow and possible sex-biased dispersal in structuring populations.</p

The effect of linking community health centers to a state-level smoker's quitline on rates of cessation assistance

<p>Abstract</p> <p>Background</p> <p>Smoking cessation quitlines are an effective yet largely untapped resource for clinician referrals. The aim of this study was to assess the effect of a fax referral system that links community health centers (CHCs) with the New York State Quitline on rates of provider cessation assistance.</p> <p>Methods</p> <p>This study was conducted in four CHCs using a quasi experimental study design. Two comparison sites offered usual care (expanded vital sign chart stamp that prompted providers to ask about tobacco use, advice smokers to quit, assess readiness, and offer assistance (4As)) and two intervention sites received the chart stamp plus an office-based fax referral link to the New York State Quitline. The fax referral system links patients to a free proactive telephone counseling service. Provider adherence to the 4 As was assessed with 263 pre and 165 post cross sectional patient exit interviews at all four sites.</p> <p>Results</p> <p>Adherence to the 4As increased significantly over time in the intervention sites with no change from baseline in the comparison sites. Intervention sites were 2.4 (p < .008) times more likely to provide referrals to the state Quitline over time than the comparison sites and 1.8 (p < .001) times more likely to offer medication counseling and/or a prescription.</p> <p>Conclusions</p> <p>Referral links between CHCs and state level telephone quitlines may facilitate the provision of cessation assistance by offering clinicians a practical method for referring smokers to this effective service. Further studies are needed to confirm the efficacy of fax referral systems and to identify implementation strategies that work to facilitate the utilization of these systems across a wide range of clinical settings.</p

Food systems for delivering nutritious and sustainable diets: Perspectives from the global network of science academies

The triple burden of malnutrition, which encompasses undernutrition, micronutrient deficiencies and obesity, is a global challenge experienced by all nations, albeit in different forms. The Food and Nutrition Security and Agriculture (FNSA) project of the InterAcademy Partnership (IAP), a global network of over 130 academies of science and medicine, sought to determine the key challenges and opportunities for science and innovation to contribute to improved FNSA. Four parallel studies were carried out, one for each region (Africa, Europe, Asia and the Pacific and the Americas), which served as a resource for a fifth study focusing on science and policy issues that require international consideration and coordination. Addressing global food and nutrition security requires a food systems approach that considers issues pertaining both to sustainable production and sustainable consumption, to deliver healthy and nutritious diets with a minimal environmental impact. Developing a broad evidence base and building critical mass in research and innovation (scientific, social and in policy), and mobilising these resources in advising policy is critical. It is also important to integrate analysis at national, regional and global levels and focus on local-global linkages and inter-regional issues. This perspectives article discusses some of the key regional and global findings of the IAP FNSA studies, in the context of more recently available evidence on the topic.The IAP FNSA project was funded by the German Federal Ministry of Education and Research (BMBF) .https://www.elsevier.com/locate/gfshj2019Agricultural Economics, Extension and Rural Developmen

Genetic polymorphisms of angiotensin-2 type 1 receptor and angiotensinogen and risk of renal dysfunction and coronary heart disease in type 2 diabetes mellitus

<p>Abstract</p> <p>Background</p> <p>Increased activation of the renin-angiotensin system (RAS) may be important in promoting coronary heart disease (CHD) and renal dysfunction, but limited data are available on associations between angiotensin type 1 receptor (<it>AGT1R</it>) and angiotensinogen (<it>AGT</it>) genotypes in type 2 diabetes.</p> <p>Methods</p> <p>Study participants were diabetics from the Health Professionals Follow-Up Study (HPFS) and the Nurses' Health Study (NHS). We analyzed single nucleotide polymorphisms (SNPs) associated with cardiovascular pathophysiology (including <it>AGT1R </it>T573C, <it>AGT1R </it>A1166C, and <it>AGT </it>M235T) and presence of renal dysfunction (eGFR<60 ml/min/1.73 m²) or history of CHD.</p> <p>Results</p> <p>The <it>AGT1R </it>1166 C-allele was associated with eGFR<60 ml/min/1.73 m²(multivariable OR 1.63 [1.01, 2.65]) in the HPFS men (n = 733) and in the combined dataset (n = 1566) (OR 1.42 [1.02, 1.98]). The <it>AGT1R </it>1166 C-allele was also associated with CHD in men (OR 1.57 [1.10, 2.24]). In NHS women (n = 833), <it>AGT </it>235T-allele was associated with CHD (OR 1.72 [1.20, 2.47]). Removal of hypertension from the fully adjusted models did not influence results, suggesting that the associations may not be mediated by hypertension. There were significant interactions between sex and <it>AGT1R </it>1166 C-allele (p = 0.008) and <it>AGT </it>M235T (p = 0.03) in models for CHD. No significant associations were seen between <it>AGT1R </it>T573 C-allele and renal dysfunction or CHD.</p> <p>Conclusion</p> <p>Polymorphisms in <it>AGT1R </it>and <it>AGT </it>genes are associated with renal dysfunction and CHD in type 2 diabetes and further support the important role of the RAS in these complications. Sex may modify associations between <it>AGT1R </it>1166 C-allele and <it>AGT </it>235T and CHD in type 2 diabetes.</p

Saturated Fatty Acids and Risk of Coronary Heart Disease: Modulation by Replacement Nutrients

Despite the well-established observation that substitution of saturated fats for carbohydrates or unsaturated fats increases low-density lipoprotein (LDL) cholesterol in humans and animal models, the relationship of saturated fat intake to risk for atherosclerotic cardiovascular disease in humans remains controversial. A critical question is what macronutrient should be used to replace saturated fat. Substituting polyunsaturated fat for saturated fat reduces LDL cholesterol and the total cholesterol to high-density lipoprotein cholesterol ratio. However, replacement of saturated fat by carbohydrates, particularly refined carbohydrates and added sugars, increases levels of triglyceride and small LDL particles and reduces high-density lipoprotein cholesterol, effects that are of particular concern in the context of the increased prevalence of obesity and insulin resistance. Epidemiologic studies and randomized clinical trials have provided consistent evidence that replacing saturated fat with polyunsaturated fat, but not carbohydrates, is beneficial for coronary heart disease. Therefore, dietary recommendations should emphasize substitution of polyunsaturated fat and minimally processed grains for saturated fat

Sleeping sickness and its relationship with development and biodiversity conservation in the Luangwa valley, Zambia

The Luangwa Valley has a long historical association with Human African trypanosomiasis (HAT) and is a recognised geographical focus of this disease. It is also internationally acclaimed for its high biodiversity and contains many valuable habitats. Local inhabitants of the valley have developed sustainable land use systems in co-existence with wildlife over centuries, based on non-livestock keeping practices largely due to the threat from African Animal Trypanosomiasis. Historical epidemics of human sleeping sickness have influenced how and where communities have settled and have had a profound impact on development in the Valley. Historical attempts to control trypanosomiasis have also had a negative impact on conservation of biodiversity. Centralised control over wildlife utilisation has marginalised local communities from managing the wildlife resource. To some extent this has been reversed by the implementation of community based natural resource management programmes in the latter half of the 20th century and the Luangwa Valley provides some of the earliest examples of such programmes. More recently, there has been significant uncontrolled migration of people into the mid-Luangwa Valley driven by pressure on resources in the eastern plateau region, encouragement from local chiefs and economic development in the tourist centre of Mfuwe. This has brought changing land-use patterns, most notably agricultural development through livestock keeping and cotton production. These changes threaten to alter the endemically stable patterns of HAT transmission and could have significant impacts on ecosystem health and ecosystem services. In this paper we review the history of HAT in the context of conservation and development and consider the impacts current changes may have on this complex social-ecological system. We conclude that improved understanding is required to identify specific circumstances where win-win trade-offs can be achieved between the conservation of biodiversity and the reduction of disease in the human population.Ecosystem Services for Poverty Alleviation (ESPA

Gout. Epidemiology of gout

Gout is the most prevalent form of inflammatory arthropathy. Several studies suggest that its prevalence and incidence have risen in recent decades. Numerous risk factors for the development of gout have been established, including hyperuricaemia, genetic factors, dietary factors, alcohol consumption, metabolic syndrome, hypertension, obesity, diuretic use and chronic renal disease. Osteoarthritis predisposes to local crystal deposition. Gout appears to be an independent risk factor for all-cause mortality and cardiovascular mortality and morbidity, additional to the risk conferred by its association with traditional cardiovascular risk factors

Systematic Analysis of Cis-Elements in Unstable mRNAs Demonstrates that CUGBP1 Is a Key Regulator of mRNA Decay in Muscle Cells

BACKGROUND: Dramatic changes in gene expression occur in response to extracellular stimuli and during differentiation. Although transcriptional effects are important, alterations in mRNA decay also play a major role in achieving rapid and massive changes in mRNA abundance. Moreover, just as transcription factor activity varies between different cell types, the factors influencing mRNA decay are also cell-type specific. PRINCIPAL FINDINGS: We have established the rates of decay for over 7000 transcripts expressed in mouse C2C12 myoblasts. We found that GU-rich (GRE) and AU-rich (ARE) elements are over-represented in the 3'UTRs of short-lived mRNAs and that these mRNAs tend to encode factors involved in cell cycle and transcription regulation. Stabilizing elements were also identified. By comparing mRNA decay rates in C2C12 cells with those previously measured for pluripotent and differentiating embryonic stem (ES) cells, we identified several groups of transcripts that exhibit cell-type specific decay rates. Further, whereas in C2C12 cells the impact of GREs on mRNA decay appears to be greater than that of AREs, AREs are more significant in ES cells, supporting the idea that cis elements make a cell-specific contribution to mRNA stability. GREs are recognized by CUGBP1, an RNA-binding protein and instability factor whose function is affected in several neuromuscular diseases. We therefore utilized RNA immunoprecipitation followed by microarray (RIP-Chip) to identify CUGBP1-associated transcripts. These mRNAs also showed dramatic enrichment of GREs in their 3'UTRs and encode proteins linked with cell cycle, and intracellular transport. Interestingly several CUGBP1 substrate mRNAs, including those encoding the myogenic transcription factors Myod1 and Myog, are also bound by the stabilizing factor HuR in C2C12 cells. Finally, we show that several CUGBP1-associated mRNAs containing 3'UTR GREs, including Myod1, are stabilized in cells depleted of CUGBP1, consistent with the role of CUGBP1 as a destabilizing factor. CONCLUSIONS: Taken together, our results systematically establish cis-acting determinants of mRNA decay rates in C2C12 myoblast cells and demonstrate that CUGBP1 associates with GREs to regulate decay of a wide range of mRNAs including several that are critical for muscle development

Antiangiogenic agents in the treatment of recurrent or newly diagnosed glioblastoma: Analysis of single-agent and combined modality approaches

Surgical resection followed by radiotherapy and temozolomide in newly diagnosed glioblastoma can prolong survival, but it is not curative. For patients with disease progression after frontline therapy, there is no standard of care, although further surgery, chemotherapy, and radiotherapy may be used. Antiangiogenic therapies may be appropriate for treating glioblastomas because angiogenesis is critical to tumor growth. In a large, noncomparative phase II trial, bevacizumab was evaluated alone and with irinotecan in patients with recurrent glioblastoma; combination treatment was associated with an estimated 6-month progression-free survival (PFS) rate of 50.3%, a median overall survival of 8.9 months, and a response rate of 37.8%. Single-agent bevacizumab also exceeded the predetermined threshold of activity for salvage chemotherapy (6-month PFS rate, 15%), achieving a 6-month PFS rate of 42.6% (p < 0.0001). On the basis of these results and those from another phase II trial, the US Food and Drug Administration granted accelerated approval of single-agent bevacizumab for the treatment of glioblastoma that has progressed following prior therapy. Potential antiangiogenic agents-such as cilengitide and XL184-also show evidence of single-agent activity in recurrent glioblastoma. Moreover, the use of antiangiogenic agents with radiation at disease progression may improve the therapeutic ratio of single-modality approaches. Overall, these agents appear to be well tolerated, with adverse event profiles similar to those reported in studies of other solid tumors. Further research is needed to determine the role of antiangiogenic therapy in frontline treatment and to identify the optimal schedule and partnering agents for use in combination therapy