175 research outputs found

    Middle Columbia River Aquatic Nuisance Species Survey

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    Aquatic nonindigenous species (ANS) in the middle Columbia and lower Snake rivers were surveyed during the summer of 2006. The project area included eight reservoirs and the free-flowing, Hanford Reach on the Columbia River. We also conducted a literature review to create a complete list of ANS for the study area

    Chocolate, Air Pollution and Children's Neuroprotection: What Cognition Tools should be at Hand to Evaluate Interventions?

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    Indexación: Web of ScienceMillions of children across the world are exposed to multiple sources of indoor and outdoor air pollutants, including high concentrations of fine particulate matter (PM2.5) and ozone (O-3). The established link between exposure to PM2.5, brain structural, volumetric and metabolic changes, severe cognitive deficits (1.5-2 SD from average IQ) in APOE 4 heterozygous females with >75 - <94% BMI percentiles, and the presence of Alzheimer's disease (AD) hallmarks in urban children and young adults necessitates exploration of ways to protect these individuals from the deleterious neural effects of pollution exposure. Emerging research suggests that cocoa interventions may be a viable option for neuroprotection, with evidence suggesting that early cocoa interventions could limit the risk of cognitive and developmental concerns including: endothelial dysfunction, cerebral hypoperfusion, neuroinflammation, and metabolic detrimental brain effects. Currently, however, it is not clear how early we should implement consumption of cocoa to optimize its neuroprotective effects. Moreover, we have yet to identify suitable instruments for evaluating cognitive responses to these interventions in clinically healthy children, teens, and young adults. An approach to guide the selection of cognitive tools should take into account neuropsychological markers of cognitive declines in patients with Alzheimer's neuropathology, the distinct patterns of memory impairment between early and late onset AD, and the key literature associating white matter integrity and poor memory binding performance in cases of asymptomatic familial AD. We highlight potential systemic and neural benefits of cocoa consumption. We also highlight Working Memory Capacity (WMC) and attention control tasks as opened avenues for exploration in the air pollution scenario. Exposures to air pollutants during brain development have serious brain consequences in the short and long term and reliable cognition tools should be at hand to evaluate interventions.http://journal.frontiersin.org/article/10.3389/fphar.2016.00232/ful

    Simultaneous evaluation of treatment efficacy and toxicity for bispecific T-cell engager therapeutics in a humanized mouse model.

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    Immuno-oncology (IO)-based therapies such as checkpoint inhibitors, bi-specific antibodies, and CAR-T-cell therapies have shown significant success in the treat- ment of several cancer indications. However, these therapies can result in the de- velopment of severe adverse events, including cytokine release syndrome (CRS). Currently, there is a paucity of in vivo models that can evaluate dose-response relationships for both tumor control and CRS-related safety issues. We tested an in vivo PBMC humanized mouse model to assess both treatment efficacy against specific tumors and the concurrent cytokine release profiles for individual human donors after treatment with a CD19xCD3 bispecific T-cell engager (BiTE). Using this model, we evaluated tumor burden, T-cell activation, and cytokine release in response to bispecific T-cell-engaging antibody in humanized mice generated with different PBMC donors. The results show that PBMC engrafted NOD-scid Il2rgnull mice lacking expression of mouse MHC class I and II (NSG-MHC-DKO mice) and implanted with a tumor xenograft predict both efficacy for tumor control by CD19xCD3 BiTE and stimulated cytokine release. Moreover, our find- ings indicate that this PBMC-engrafted model captures variability among donors for tumor control and cytokine release following treatment. Tumor control and cytokine release were reproducible for the same PBMC donor in separate experi- ments. The PBMC humanized mouse model described here is a sensitive and re- producible platform that identifies specific patient/cancer/therapy combinations for treatment efficacy and development of complications

    Walk well:a randomised controlled trial of a walking intervention for adults with intellectual disabilities: study protocol

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    Background - Walking interventions have been shown to have a positive impact on physical activity (PA) levels, health and wellbeing for adult and older adult populations. There has been very little work carried out to explore the effectiveness of walking interventions for adults with intellectual disabilities. This paper will provide details of the Walk Well intervention, designed for adults with intellectual disabilities, and a randomised controlled trial (RCT) to test its effectiveness. Methods/design - This study will adopt a RCT design, with participants allocated to the walking intervention group or a waiting list control group. The intervention consists of three PA consultations (baseline, six weeks and 12 weeks) and an individualised 12 week walking programme. A range of measures will be completed by participants at baseline, post intervention (three months from baseline) and at follow up (three months post intervention and six months from baseline). All outcome measures will be collected by a researcher who will be blinded to the study groups. The primary outcome will be steps walked per day, measured using accelerometers. Secondary outcome measures will include time spent in PA per day (across various intensity levels), time spent in sedentary behaviour per day, quality of life, self-efficacy and anthropometric measures to monitor weight change. Discussion - Since there are currently no published RCTs of walking interventions for adults with intellectual disabilities, this RCT will examine if a walking intervention can successfully increase PA, health and wellbeing of adults with intellectual disabilities

    Calcium and Vitamin D increase mRNA levels for the growth control hIK1 channel in human epidermal keratinocytes but functional channels are not observed

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    BACKGROUND: Intermediate-conductance, calcium-activated potassium channels (IKs) modulate proliferation and differentiation in mesodermal cells by enhancing calcium influx, and they contribute to the physiology of fluid movement in certain epithelia. Previous reports suggest that IK channels stimulate proliferative growth in a keratinocyte cell line; however, because these channels indirectly promote calcium influx, a critically unique component of the keratinocyte differentiation program, an alternative hypothesis is that they would be anti-proliferative and pro-differentiating. This study addresses these hypotheses. METHODS: Real-time PCR, patch clamp electrophysiology, and proliferation assays were used to determine if human IK1 (hIK1) expression and function are correlated with either proliferation or differentiation in cultured human skin epidermal keratinocytes, and skin biopsies grown in explant culture. RESULTS: hIK1 mRNA expression in human keratinocytes and skin was increased in response to anti-proliferative/pro-differentiating stimuli (elevated calcium and Vitamin D). Correspondingly, the hIK1 agonist 1-EBIO inhibited keratinocyte proliferation suggesting that the channel could be anti-proliferative and pro-differentiating. However, this proliferative inhibition by 1-EBIO was not reversed by a panel of hIK1 blockers, calling into question the mechanism of 1-EBIO action. Subsequent patch clamp electrophysiological analysis failed to detect hIK1 channel currents in keratinocytes, even those expressing substantial hIK1 mRNA in response to calcium and Vitamin D induced differentiation. Identical electrophysiological recording conditions were then used to observe robust IK1 currents in fibroblasts which express IK1 mRNA levels comparable to those of keratinocytes. Thus, the absence of observable hIK1 currents in keratinocytes was not a function of the electrophysiological techniques. CONCLUSION: Human keratinocyte differentiation is stimulated by calcium mobilization and influx, and differentiation stimuli coordinately upregulate mRNA levels of the calcium-activated hIK1 channel. This upregulation is paradoxical in that functional hIK1 channels are not observed in cultured keratinocytes. It appears, therefore, that hIK1 does not contribute to the functional electrophysiology of primary human keratinocytes, nor intact human skin. Further, the results indicate caution is required when interpreting experiments utilizing pharmacological hIK1 modulators in human keratinocytes

    Assessment of Objectively Measured Physical Activity Levels in Individuals with Intellectual Disabilities with and without Down's Syndrome

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    Objective: To investigate, using accelerometers, the levels of physical activity being undertaken by individuals with intellectual disabilities with and without Down’s syndrome. Methods: One hundred and fifty two individuals with intellectual disabilities aged 12–70 years from East and South-East England. Physical activity levels in counts per minute (counts/min), steps per day (steps/day), and minutes of sedentary, light, moderate, vigorous, and moderate to vigorous physical activity (MVPA) measured with a uni-axial accelerometer (Actigraph GT1M) for seven days. Results: No individuals with intellectual disabilities met current physical activity recommendations. Males were more active than females. There was a trend for physical activity to decline and sedentary behaviour to increase with age, and for those with more severe levels of intellectual disability to be more sedentary and less physically active, however any relationship was not significant when adjusted for confounding variables. Participants with Down’s syndrome engaged in significantly less physical activity than those with intellectual disabilities without Down’s syndrome and levels of activity declined significantly with age. Conclusions: Individuals with intellectual disabilities, especially those with Down’s syndrome may be at risk of developing diseases associated with physical inactivity. There is a need for well-designed, accessible, preventive health promotio
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