3,161 research outputs found

    Benefits, Facilitators, Barriers, and Strategies to Improve Pesticide Protective Behaviors: Insights from Farmworkers in North Carolina Tobacco Fields

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    Pesticide exposure is associated with deleterious health effects. Prior studies suggest Latino farmworkers perceive little control over their occupational health. Using the Health Belief Model as a theoretical guide, we explored the perceptions of Latino farmworkers working in tobacco in North Carolina (n = 72) about benefits and facilitators of pesticide protective behaviors as well as barriers, and strategies to overcome barriers to their use. Interviews were conducted with participants at farmworker housing during non-work time. Qualitative data were analyzed using ATLAS.ti. Farmworkers recognized pesticide protective behaviors as helping them to not get sick and stay healthy. Farmworkers perceived work experience as facilitating protective behaviors. Wetness in the field was the most commonly cited barrier to protective behavior use. To overcome this barrier, farmworkers suggested use of water-resistant outerwear, as well as packing a change of clothes for mid-day, with space and time to change provided by employers. Examination of the efficacy and feasibility of farmworkers’ suggestions for addressing barriers is warranted. Training and behavior modeling by experienced peers may improve behavior adoption and perceived control

    Apolipoprotein E mediates evasion from hepatitis C virus−neutralizing antibodies

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    Background & Aims Efforts to develop an effective vaccine against hepatitis C virus (HCV) have been hindered by the propensity of the virus to evade host immune responses. HCV particles in serum and in cell culture associate with lipoproteins, which contribute to viral entry. Lipoprotein association has also been proposed to mediate viral evasion of the humoral immune response, though the mechanisms are poorly defined. Methods We used small interfering RNAs to reduce levels of apolipoprotein E (apoE) in cell culture−derived HCV−producing Huh7.5-derived hepatoma cells and confirmed its depletion by immunoblot analyses of purified viral particles. Before infection of naïve hepatoma cells, we exposed cell culture−derived HCV strains of different genotypes, subtypes, and variants to serum and polyclonal and monoclonal antibodies isolated from patients with chronic HCV infection. We analyzed the interaction of apoE with viral envelope glycoprotein E2 and HCV virions by immunoprecipitation. Results Through loss-of-function studies on patient-derived HCV variants of several genotypes and subtypes, we found that the HCV particle apoE allows the virus to avoid neutralization by patient-derived antibodies. Functional studies with human monoclonal antiviral antibodies showed that conformational epitopes of envelope glycoprotein E2 domains B and C were exposed after depletion of apoE. The level and conformation of virion-associated apoE affected the ability of the virus to escape neutralization by antibodies. Conclusions In cell-infection studies, we found that HCV-associated apoE helps the virus avoid neutralization by antibodies against HCV isolated from chronically infected patients. This method of immune evasion poses a challenge for the development of HCV vaccines

    Climate change and postglacial human dispersals in southeast Asia

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    Modern humans have been living in Island Southeast Asia (ISEA) for at least 50,000 years. Largely because of the influence of linguistic studies, however, which have a shallow time depth, the attention of archaeologists and geneticists has usually been focused on the last 6,000 years--in particular, on a proposed Neolithic dispersal from China and Taiwan. Here we use complete mitochondrial DNA (mtDNA) genome sequencing to spotlight some earlier processes that clearly had a major role in the demographic history of the region but have hitherto been unrecognized. We show that haplogroup E, an important component of mtDNA diversity in the region, evolved in situ over the last 35,000 years and expanded dramatically throughout ISEA around the beginning of the Holocene, at the time when the ancient continent of Sundaland was being broken up into the present-day archipelago by rising sea levels. It reached Taiwan and Near Oceania more recently, within the last approximately 8,000 years. This suggests that global warming and sea-level rises at the end of the Ice Age, 15,000-7,000 years ago, were the main forces shaping modern human diversity in the region

    Factors predictive of failure to complete planned intraoperative breast radiation using the intrabeamÂź system

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    Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135241/1/jso24473_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/135241/2/jso24473.pd

    Si–C interactions during degradation of the diatom Skeletonema marinoi

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    International audienceWhile a relationship between ballast and carbon in sedimenting particles has been well-documented, the mechanistic basis of this interaction is still under debate. One hypothesis is that mineral ballast protects sinking organic matter from degradation. To test this idea, we undertook a laboratory experiment using the diatom Skeletonema marinoi to study in parallel the dissolution of one of the most common mineral ballasts, biogenic silica (bSiO2), and the associated degradation of organic matter. Three different models were applied to our results to help elucidate the mechanisms driving bSiO2 dissolution and organic compound degradation. Results of this modeling exercise suggest that the diatom frustule is made up of two bSiO2 phases that dissolve simultaneously, but at different rates. In our experiments, the first phase was more soluble (View the MathML source) and made up 31% of the total bSiO2. In this phase, bSiO2 was mainly associated with membrane lipids and the amino acids glutamic acid, tyrosine, and leucine. The second phase was more refractory (View the MathML source), and contained more neutral lipid alcohols and glycine. Until it dissolved, the first bSiO2 phase effectively protected much of the organic matter from degradation: particulate organic carbon (POC) degradation rate constants increased from 0.025 to 0.082 d−1 after the total dissolution of this phase, and particulate organic nitrogen (PON) degradation rate constants increased from 0.030 to 0.094 d−1. Similar to POC and PON, the total hydrolyzable amino acids (THAA) degradation rate constant increased from 0.054 to 0.139 d−1 after dissolution of the first bSiO2 phase. The higher THAA degradation rate constant is attributed to a pool of amino acids that was produced during silicification and enclosed between the two silica phases. This pool of amino acids might come from the incorporation of silica deposition vesicles into the diatom wall and might not be directly associated with bSiO2. In contrast, most lipid degradation was not prevented by association with the more soluble bSiO2 phase, as the average lipid degradation rate constant decreased from 0.048 to 0.010 d−1 after 17 d of degradation. This suggests that most lipids were associated with rather than protected by silica, except pigments that appeared resistant to degradation, independently from silica dissolution. When the only organic compounds remaining were associated with the second bSiO2 phase, degradation rate constants decreased greatly; concentrations changed only slightly after day 25

    Beneficial effects of reconstituted high-density lipoprotein (rHDL) on circulating CD34+ cells in patients after an acute coronary syndrome

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    Background: High-density lipoproteins (HDL) favorably affect endothelial progenitor cells (EPC). Circulating progenitor cell level and function are impaired in patients with acute coronary syndrome (ACS). This study investigates the short-term effects of reconstituted HDL (rHDL) on circulating progenitor cells in patients with ACS. Methods and Findings: The study population consisted of 33 patients with recent ACS: 20 patients from the ERASE trial (randomized to receive 4 weekly intravenous infusions of CSL-111 40 mg/kg or placebo) and 13 additional patients recruited as controls using the same enrolment criteria. Blood was collected from 16 rHDL (CSL-111)-treated patients and 17 controls at baseline and at 6–7 weeks (i.e. 2–3 weeks after the fourth infusion of CSL-111 in ERASE). CD34+ and CD34+/kinase insert domain receptor (KDR+) progenitor cell counts were analyzed by flow cytometry. We found preserved CD34+ cell counts in CSL-111-treated subjects at follow-up (change of 1.6%), while the number of CD34+ cells was reduced (-32.9%) in controls (p = 0.017 between groups). The level of circulating SDF-1 (stromal cell-derived factor-1), a chemokine involved in progenitor cell recruitment, increased significantly (change of 21.5%) in controls, while it remained unchanged in CSL-111-treated patients (p = 0.031 between groups). In vitro exposure to CSL-111 of early EPC isolated from healthy volunteers significantly increased CD34+ cells, reduced early EPC apoptosis and enhanced their migration capacity towards SDF-1. Conclusions: The relative increase in circulating CD34+ cells and the low SDF-1 levels observed following rHDL infusions in ACS patients point towards a role of rHDL in cardiovascular repair mechanisms

    End of life care:A qualitative study comparing the views of people with dementia and family carers

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    Background: In recent years, UK policy has increasingly recognised the importance of end-of-life care in dementia. While professional consensus on optimal palliative care in dementia has been reported, little is known about the perspectives of people with dementia and family carers. Aim: To compare the views of people with dementia and family carers of people with dementia (current and recently bereaved) on optimal end-of-life care. Design: Qualitative interviews (32) and a focus group were conducted. Data were thematically analysed. Setting/participants: Participants comprised people with early stage dementia, living at home in the north-east of England (n = 11); and current and bereaved carers (n = 25) from six services providing end-of-life care in England. Findings: Seven areas were identified as important to end-of-life care for people with dementia and/or family carers. People with dementia and carers expressed the need for receiving care in place, ensuring comfort and a skilled care team. However, they disagreed about the importance of planning for the future and the role of families in organising care and future decision-making. Conclusion: Further comparison of our findings with expert consensus views highlighted key areas of divergence and agreement. Discordant views concerning perceptions of dementia as a palliative condition, responsibility for future decision-making and the practical co-ordination of end-of-life care may undermine the provision of optimal palliative care. Professionals must explore and recognise the individual perspectives of people with dementia and family carers

    Analysis of clinically relevant somatic mutations in high-risk head and neck cutaneous squamous cell carcinoma

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    Cutaneous squamous cell carcinoma is the second most prevalent malignancy, most frequently occurring in the head and neck (head and neck cutaneous squamous cell carcinoma). Treatment of locally advanced or metastatic disease is associated with functional morbidity and disfigurement. Underlying genetic mechanisms are poorly understood. Targeted sequencing of 48 clinically relevant genes was performed on DNA extracted from formalinfixed and paraffin-embedded high-risk primary head and neck cutaneous squamous cell carcinomas that remained non-metastatic at minimum follow-up of 24 months. Associations of somatic mutations with clinicopathologic characteristics were evaluated and compared with those described in the literature for metastatic disease. Alterations in 44 cancer-associated genes were identified. TP53 was mutated in 100% of cases; APC, ATM, ERBB4, GNAQ, KIT, RB1 and ABL1 were altered in 60% of cases. FGFR2 mutations (40%) were exclusively seen in patients with perineural invasion. MLH1 mutations were exclusively seen in the two younger patients (\u3c45 \u3eyears). Lower incidences of NOTCH1 mutations were observed compared with that described in metastatic head and neck cutaneous squamous cell carcinoma in the literature. Somatic mutations susceptible to EGFR inhibitors, and other small molecular targeted therapeutics were seen in 60% of cases. This study provides insights into somatic mutations in non-metastatic, high-risk head and neck cutaneous squamous cell carcinoma and identifies potential therapeutic targets. Alterations in FGFR2 and NOTCH1 may have roles in local and distant disease progression
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