Zobrazení zdroje stránky Mayobuur7596

Neonicotinoid pesticides, originally developed to target the insect nervous system, have been reported to interact with human receptors and to activate rodent neurons. Therefore, we evaluated in how far these compounds may trigger signaling in human neurons, and thus, affect the human adult or developing nervous system. We used SH-SY5Y neuroblastoma cells as established model of nicotinic acetylcholine receptor (nAChR) signaling. In parallel, we profiled dopaminergic neurons, generated from LUHMES neuronal precursor cells, as novel system to study nAChR activation in human post-mitotic neurons. Changes of the free intracellular Ca2+ concentration ([Ca2+]i) were used as readout, and key findings were confirmed by patch clamp recordings. Nicotine triggered typical neuronal signaling responses that were blocked by antagonists, such as tubocurarine and mecamylamine. Pharmacological approaches suggested a functional expression of α7 and non-α7 nAChRs on LUHMES cells. In this novel test system, the neonicotinoids acetamiprid, imidacloprid, clothianidin and thiacloprid, but not thiamethoxam and dinotefuran, triggered [Ca2+]i signaling at 10-100 µM. Strong synergy of the active neonicotinoids (at low micromolar concentrations) with the α7 nAChR-positive allosteric modulator PNU-120596 was observed in LUHMES and SH-SY5Y cells, and specific antagonists fully inhibited such signaling. To provide a third line of evidence for neonicotinoid signaling via nAChR, we studied cross-desensitization pretreatment of LUHMES and SH-SY5Y cells with active neonicotinoids (at 1-10 µM) blunted the signaling response of nicotine. The pesticides (at 3-30 µM) also blunted the response to the non-α7 agonist ABT 594 in LUHMES cells. These data show that human neuronal cells are functionally affected by low micromolar concentrations of several neonicotinoids. An effect of such signals on nervous system development is a toxicological concern.Environmental stress influences the cellular physiology in multiple ways. Transcription by all the three RNA polymerases (Pols I, II, or III) in eukaryotes is a highly regulated process. With latest advances in technology, which have made many extensive genome-wide studies possible, it is increasingly recognized that all the cellular processes may be interconnected. [https://www.selleckchem.com/products/pf-04691502.html https://www.selleckchem.com/products/pf-04691502.html] A comprehensive view of the current research observations brings forward an interesting possibility that Pol II-associated factors may be directly involved in the regulation of expression from the Pol III-transcribed genes and vice versa, thus enabling a cross-talk between the two polymerases. An equally important cross-talk between the Pol I and Pol II/III has also been documented. Collectively, these observations lead to a change in the current perception that looks at the transcription of a set of genes transcribed by the three Pols in isolation. Emergence of an inclusive perspective underscores that all stress signals may converge on common mechanisms of transcription regulation, requiring an extensive cross-talk between the regulatory partners. Of the three RNA polymerases, Pol III turns out as the hub of these cross-talks, an essential component of the cellular stress-response under which the majority of the cellular transcriptional activity is shut down or re-aligned.<br /><br /> To perform a European survey of the evidence needs and training demands of insurance medicine professionals related to professional tasks and evidence-based practice.<br /><br /> International survey.<br /><br /> Professionals working in insurance medicine.<br /><br /> Experts designed an online questionnaire including 26 questions related to 4 themes evidence needs; training demands; evidence-seeking behaviour; and attitudes towards evidence-based medicine. Descriptive statistics were presented by country/conference and the total sample.<br /><br /> A total of 782 participants responded. Three-quarter of participants experienced evidence needs at least once a week, related to mental disorders (79%), musculoskeletal disorders (67%) and occupational health (65%). Guidelines (76%) and systematic reviews (60%) were the preferred types of evidence and were requested for assessment of work capacity (64%) and prognosis of return-to-work (51%). Evidence-based medicine was thought to facilitate decision-making in insurance medicine (95%). Fifty-two percent of participants felt comfortable finding, reading, interpreting, and applying evidence. Countries expressed similar needs for reviews on typical topics.<br /><br /> This study reveals evidence gaps in key areas of insurance medicine, supporting the need for further research, guidelines and training in evidence-based insurance medicine. Importantly, insurance medicine professionals should recognize that evidence-based practice is crucial in producing high-quality assessments.<br /><br />This study reveals evidence gaps in key areas of insurance medicine, supporting the need for further research, guidelines and training in evidence-based insurance medicine. Importantly, insurance medicine professionals should recognize that evidence-based practice is crucial in producing high-quality assessments.<br /><br /> To explore perspectives, including social and psychological aspects, of patients seeking manual care for low back pain, in order to understand constructs of functioning that are important across different cultural contexts. The International Classification of Functioning, Disability and Health (ICF) emphasizes the importance of these aspects to describe health-related functioning.<br /><br /> Focus group interviews.<br /><br /> Patients from Botswana, Canada and Norway seeking manual care for their low back pain.<br /><br /> Interviews were conducted in the 3 countries, transcribed verbatim, translated into English, and linked to the ICF according to established rules.<br /><br /> Seven focus groups yielded 1,863 meaningful concepts that were linked to ICF categories. The largest proportion of responses linked to the Activities and Participation domain. The most frequently mentioned chapters related to pain and its mental aspects, suggesting that the psychological impact of living with low back pain is important to patients.<br /><br /> Despite cultural differences, patients seeking manual care for low back pain in Botswana, Canada and Norway reported similar experiences of disability across ICF domains. The relatively high ranking of psychosocial factors highlights their importance for patients, in addition to factors of biological origin, and indicates that the contextual nature of the lived experience of low back pain may not be covered in standard examinations used in manual medicine.<br /><br />Despite cultural differences, patients seeking manual care for low back pain in Botswana, Canada and Norway reported similar experiences of disability across ICF domains. The relatively high ranking of psychosocial factors highlights their importance for patients, in addition to factors of biological origin, and indicates that the contextual nature of the lived experience of low back pain may not be covered in standard examinations used in manual medicine.<br /><br /> This study aimed to explore the development of working conditions within and between occupations in the Swedish labor market from 1997 to 2015 and whether any polarization in working conditions concurrently occurred between occupations.<br /><br /> Cross-sectional data from ten waves of the Swedish Work Environment Surveys (1997-2015) were used and an aggregated occupational-level dataset was created using the Swedish Standard Classification of Occupations. To capture the patterns of change in working conditions over time (ie, growth), growth curve modeling was used to identify the starting points for 89 occupations (intercepts) as well as both the shape (functional form) and rate of growth (slope) over time.<br /><br /> The Swedish labor market was stable overall, with some small, mainly positive, changes in job demands and resources. Different occupations developed in divergent directions, but there was no evidence of polarization.<br /><br /> The findings indicate that macro-level stability can hide highly heterogeneous patterns of change among different occupational groups. This type of analysis, taking context into account, could be valuable for decision makers intending to improve the work environment.<br /><br />The findings indicate that macro-level stability can hide highly heterogeneous patterns of change among different occupational groups. This type of analysis, taking context into account, could be valuable for decision makers intending to improve the work environment.<br /><br /> The coronavirus disease 2019 (COVID-19) pandemic led to a near-total cessation of mammography services in the United States in mid-March 2020. It is unclear if screening and diagnostic mammography volumes have recovered to pre-pandemic levels and whether utilization has varied by women's characteristics.<br /><br /> We collected data on 461,083 screening mammograms and 112,207 diagnostic mammograms conducted during January 2019 through July 2020 at 62 radiology facilities in the Breast Cancer Surveillance Consortium. We compared monthly screening and diagnostic mammography volumes before and during the pandemic, stratified by age, race/ethnicity, breast density, and family history of breast cancer.<br /><br /> Screening and diagnostic mammography volumes in April 2020 were 1.1% (95% confidence interval [CI] = 0.5% to 2.4%) and 21.4% (95% CI = 18.7% to 24.4%) of April 2019 pre-pandemic volumes, respectively, but by July 2020 rebounded to 89.7% (95% CI = 79.6% to 101.1%) and 101.6% (95% CI = 93.8% to 110.1%) of July 2019 pre-panmulative deficit in missed mammograms accumulated, which may have important health consequences.Traditional filtered back projection (FBP) reconstruction methods have served the computed tomography (CT) community well for over 40 years. With the increased use of CT during the last decades, efforts to minimise patient exposure, while maintaining sufficient or improved image quality, have led to the development of model-based iterative reconstruction (MBIR) algorithms from several vendors. The usefulness of the advanced modeled iterative reconstruction (ADMIRE) (Siemens Healthineers) MBIR in abdominal CT is reviewed and its noise suppression and/or dose reduction possibilities explored. Quantitative and qualitative methods with phantom and human subjects were used. Assessment of the quality of phantom images will not always correlate positively with those of patient images, particularly at the higher strength of the ADMIRE algorithm. With few exceptions, ADMIRE Strength 3 typically allows for substantial noise reduction compared to FBP and hence to significant (≈30%) patient dose reductions. The size of the dose reductions depends on the diagnostic task.Over the past 25 years, there has been significant progress in increasing the recognition of, resources for, and action on adolescent health, and adolescent sexual and reproductive health (ASRH) in particular. As with numerous other health areas, however, many of the projects that aim to improve ASRH are implemented without well-thought-out plans for evaluation. As a result, the lessons that projects learn as they encounter and address policy and programmatic challenges are often not extracted and placed in the public arena. In such cases, post-project evaluation (PPE) offers the possibility to generate learnings about what works (and does not work), to complement prospective studies of new or follow-on projects. To fill the gap in the literature and guidance on PPE, the World Health Organization developed The project has ended, but we can still learn from it! Practical guidance for conducting post-project evaluations of adolescent sexual and reproductive health projects. This article provides an overview of the guidance by outlining key methodological and contextual challenges in conducting PPE, as well as illustrative solutions for responding to them.