338 research outputs found

    Job satisfaction of foreign-national physicians working in patient care: a cross-sectional study in Saxony, Germany

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    Background: Physician migration is gaining attention worldwide. Despite increasing numbers of foreign physicians in Germany, their perceptions on working in Germany remain unexplored. Within a large survey on Saxon physicians, the aim of this study was to elucidate whether foreign-national physicians’ job satisfaction differed from German physicians'' job satisfaction. Methods: The study was designed as a comprehensive cross-sectional survey. All physicians ≤40 years and registered with the State Chamber of Physicians of Saxony (n = 5956) were mailed a paper-pencil questionnaire, of which 2357 were returned (response rate = 40 %). Questionnaires addressed socio demographics and assessed job satisfaction by asking participants to rate their satisfaction with the overall job situation and 20 different aspects on a 5-point Likert scale (1 = very dissatisfied to 5 = very satisfied). Results: Ten percent of participants were foreign-national physicians. The three main countries of origin were the Czech Republic, Slovakia, and Poland. Foreign-national physicians were more satisfied with aspects related to patient care, such as "possibility to treat patients as you deem optimal" and "relationship with patients". However, they were less satisfied with aspects related to human relations, such as "work atmosphere", relationship with co-workers, and "social status". Foreign-national physicians were also less satisfied with the aspect "work enjoyment". Conclusions: Further research on determinants promoting foreign-national physicians'' job satisfaction is needed as their professional well-being may influence quality of patient care. Measures teaching cross-cultural competence and awareness may be beneficial for both foreign-national and German physicians

    SOCS2 is part of a highly prognostic 4-gene signature in AML and promotes disease aggressiveness.

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    Acute myeloid leukemia (AML) is a heterogeneous disease with respect to its genetic and molecular basis and to patients´ outcome. Clinical, cytogenetic, and mutational data are used to classify patients into risk groups with different survival, however, within-group heterogeneity is still an issue. Here, we used a robust likelihood-based survival modeling approach and publicly available gene expression data to identify a minimal number of genes whose combined expression values were prognostic of overall survival. The resulting gene expression signature (4-GES) consisted of 4 genes (SOCS2, IL2RA, NPDC1, PHGDH), predicted patient survival as an independent prognostic parameter in several cohorts of AML patients (total, 1272 patients), and further refined prognostication based on the European Leukemia Net classification. An oncogenic role of the top scoring gene in this signature, SOCS2, was investigated using MLL-AF9 and Flt3-ITD/NPM1c driven mouse models of AML. SOCS2 promoted leukemogenesis as well as the abundance, quiescence, and activity of AML stem cells. Overall, the 4-GES represents a highly discriminating prognostic parameter in AML, whose clinical applicability is greatly enhanced by its small number of genes. The newly established role of SOCS2 in leukemia aggressiveness and stemness raises the possibility that the signature might even be exploitable therapeutically

    SOCS2 is part of a highly prognostic 4-gene signature in AML and promotes disease aggressiveness

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    Acute myeloid leukemia (AML) is a heterogeneous disease with respect to its genetic and molecular basis and to patients´ outcome. Clinical, cytogenetic, and mutational data are used to classify patients into risk groups with different survival, however, within-group heterogeneity is still an issue. Here, we used a robust likelihood-based survival modeling approach and publicly available gene expression data to identify a minimal number of genes whose combined expression values were prognostic of overall survival. The resulting gene expression signature (4-GES) consisted of 4 genes (SOCS2, IL2RA, NPDC1, PHGDH), predicted patient survival as an independent prognostic parameter in several cohorts of AML patients (total, 1272 patients), and further refined prognostication based on the European Leukemia Net classification. An oncogenic role of the top scoring gene in this signature, SOCS2, was investigated using MLL-AF9 and Flt3-ITD/NPM1c driven mouse models of AML. SOCS2 promoted leukemogenesis as well as the abundance, quiescence, and activity of AML stem cells. Overall, the 4-GES represents a highly discriminating prognostic parameter in AML, whose clinical applicability is greatly enhanced by its small number of genes. The newly established role of SOCS2 in leukemia aggressiveness and stemness raises the possibility that the signature might even be exploitable therapeutically

    Can Gene Expression Analysis in Zero-Time Biopsies Predict Kidney Transplant Rejection?

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    Zero-time biopsies are taken to determine the quality of the donor organ at the time of transplantation. Histological analyses alone have so far not been able to identify parameters that allow the prediction of subsequent rejection episodes or graft survival. This study investigated whether gene expression analyses of zero-time biopsies might support this prediction. Using a well-characterized cohort of 26 zero-time biopsies from renal transplant patients that include 4 living donor (LD) and 22 deceased donor (DD) biopsies that later developed no rejection (Ctrl, n = 7), delayed graft function (DGF, n = 4), cellular (T-cell mediated rejection; TCMR, n = 8), or antibody-mediated rejection (ABMR, n = 7), we analyzed gene expression profiles for different types of subsequent renal transplant complication. To this end, RNA was isolated from formalin-fixed, paraffin-embedded (FFPE) sections and gene expression profiles were quantified. Results were correlated with transplant data and B-cell, and plasma cell infiltration was assessed by immunofluorescence microscopy. Both principal component analysis and clustering analysis of gene expression data revealed marked separation between LDs and DDs. Differential expression analysis identified 185 significant differentially expressed genes (adjusted p < 0.05). The expression of 68% of these genes significantly correlated with cold ischemia time (CIT). Furthermore, immunoglobulins were differentially expressed in zero-time biopsies from transplants later developing rejection (TCMR + ABMR) compared to non-rejected (Ctrl + DGF) transplants. In addition, immunoglobulin expression did not correlate with CIT but was increased in transplants with previous acute renal failure (ARF). In conclusion, gene expression profiles in zero-time biopsies derived from LDs are markedly different from those of DDs. Pre-transplant ARF increased immunoglobulin expression, which might be involved in triggering later rejection events. However, these findings must be confirmed in larger cohorts and the role of early immunoglobulin upregulation in zero-biopsies needs further clarification

    Barriers and opportunities of soil knowledge to address soil challenges: Stakeholders? perspectives across Europe

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    Climate-smart sustainable management of agricultural soil is critical to improve soil health, enhance food and water security, contribute to climate change mitigation and adaptation, biodiversity preservation, and improve human health and wellbeing. The European Joint Programme for Soil (EJP SOIL) started in 2020 with the aim to significantly improve soil management knowledge and create a sustainable and integrated European soil research system. EJP SOIL involves more than 350 scientists across 24 Countries and has been addressing multiple aspects associated with soil management across different European agroecosystems. This study summarizes the key findings of stakeholder consultations conducted at the national level across 20 countries with the aim to identify important barriers and challenges currently affecting soil knowledge but also assess opportunities to overcome these obstacles. Our findings demonstrate that there is significant room for improvement in terms of knowledge production, dissemination and adoption. Among the most important barriers identified by consulted stakeholders are technical, political, social and economic obstacles, which strongly limit the development and full exploitation of the outcomes of soil research. The main soil challenge across consulted member states remains to improve soil organic matter and peat soil conservation while soil water storage capacity is a key challenge in Southern Europe. Findings from this study clearly suggest that going forward climate-smart sustainable soil management will benefit from (1) increases in research funding, (2) the maintenance and valorisation of long-term (field) ex-periments, (3) the creation of knowledge sharing networks and interlinked national and European in-frastructures, and (4) the development of regionally-tailored soil management strategies. All the above -mentioned interventions can contribute to the creation of healthy, resilient and sustainable soil ecosystems across Europe

    Ambulatory Multi-Drug Resistant Tuberculosis Treatment Outcomes in a Cohort of HIV-Infected Patients in a Slum Setting in Mumbai, India

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    Background: India carries one quarter of the global burden of multi-drug resistant TB (MDR-TB) and has an estimated 2.5 million people living with HIV. Despite this reality, provision of treatment for MDR-TB is extremely limited, particularly for HIV-infected individuals. Médecins Sans Frontières (MSF) has been treating HIV-infected MDR-TB patients in Mumbai since May 2007. This is the first report of treatment outcomes among HIV-infected MDR-TB patients in India. Methods: HIV-infected patients with suspected MDR-TB were referred to the MSF-clinic by public Antiretroviral Therapy (ART) Centers or by a network of community non-governmental organizations. Patients were initiated on either empiric or individualized second-line TB-treatment as per WHO recommendations. MDR-TB treatment was given on an ambulatory basis and under directly observed therapy using a decentralized network of providers. Patients not already receiving ART were started on treatment within two months of initiating MDR-TB treatment. Results: Between May 2007 and May 2011, 71 HIV-infected patients were suspected to have MDR-TB, and 58 were initiated on treatment. MDR-TB was confirmed in 45 (78%), of which 18 (40%) were resistant to ofloxacin. Final treatment outcomes were available for 23 patients; 11 (48%) were successfully treated, 4 (17%) died, 6 (26%) defaulted, and 2 (9%) failed treatment. Overall, among 58 patients on treatment, 13 (22%) were successfully treated, 13 (22%) died, 7 (12%) defaulted, two (3%) failed treatment, and 23 (40%) were alive and still on treatment at the end of the observation period. Twenty-six patients (45%) experienced moderate to severe adverse events, requiring modification of the regimen in 12 (20%). Overall, 20 (28%) of the 71 patients with MDR-TB died, including 7 not initiated on treatment. Conclusions: Despite high fluoroquinolone resistance and extensive prior second-line treatment, encouraging results are being achieved in an ambulatory MDR-T- program in a slum setting in India. Rapid scale-up of both ART and second-line treatment for MDR-TB is needed to ensure survival of co-infected patients and mitigate this growing epidemic.</br

    Motor, cognitive and mobility deficits in 1000 geriatric patients : protocol of a quantitative observational study before and after routine clinical geriatric treatment – the ComOn-study

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    © The Author(s). 2020 Open Access. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background: Motor and cognitive deficits and consequently mobility problems are common in geriatric patients. The currently available methods for diagnosis and for the evaluation of treatment in this vulnerable cohort are limited. The aims of the ComOn (COgnitive and Motor interactions in the Older populatioN) study are (i) to define quantitative markers with clinical relevance for motor and cognitive deficits, (ii) to investigate the interaction between both motor and cognitive deficits and (iii) to assess health status as well as treatment outcome of 1000 geriatric inpatients in hospitals of Kiel (Germany), Brescia (Italy), Porto (Portugal), Curitiba (Brazil) and Bochum (Germany). Methods: This is a prospective, explorative observational multi-center study. In addition to the comprehensive geriatric assessment, quantitative measures of reduced mobility and motor and cognitive deficits are performed before and after a two week's inpatient stay. Components of the assessment are mobile technology-based assessments of gait, balance and transfer performance, neuropsychological tests, frailty, sarcopenia, autonomic dysfunction and sensation, and questionnaires to assess behavioral deficits, activities of daily living, quality of life, fear of falling and dysphagia. Structural MRI and an unsupervised 24/7 home assessment of mobility are performed in a subgroup of participants. The study will also investigate the minimal clinically relevant change of the investigated parameters. Discussion: This study will help form a better understanding of symptoms and their complex interactions and treatment effects in a large geriatric cohort.info:eu-repo/semantics/publishedVersio

    mTORC1 is essential for early steps during Schwann cell differentiation of amniotic fluid stem cells and regulates lipogenic gene expression.

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    Schwann cell development is hallmarked by the induction of a lipogenic profile. Here we used amniotic fluid stem (AFS) cells and focused on the mechanisms occurring during early steps of differentiation along the Schwann cell lineage. Therefore, we initiated Schwann cell differentiation in AFS cells and monitored as well as modulated the activity of the mechanistic target of rapamycin (mTOR) pathway, the major regulator of anabolic processes. Our results show that mTOR complex 1 (mTORC1) activity is essential for glial marker expression and expression of Sterol Regulatory Element-Binding Protein (SREBP) target genes. Moreover, SREBP target gene activation by statin treatment promoted lipogenic gene expression, induced mTORC1 activation and stimulated Schwann cell differentiation. To investigate mTORC1 downstream signaling we expressed a mutant S6K1, which subsequently induced the expression of the Schwann cell marker S100b, but did not affect lipogenic gene expression. This suggests that S6K1 dependent and independent pathways downstream of mTORC1 drive AFS cells to early Schwann cell differentiation and lipogenic gene expression. In conclusion our results propose that future strategies for peripheral nervous system regeneration will depend on ways to efficiently induce the mTORC1 pathway

    Genome-wide meta-analyses reveal novel loci for verbal short-term memory and learning

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    Understanding the genomic basis of memory processes may help in combating neurodegenerative disorders. Hence, we examined the associations of common genetic variants with verbal short-term memory and verbal learning in adults without dementia or stroke (N = 53,637). We identified novel loci in the intronic region of CDH18, and at 13q21 and 3p21.1, as well as an expected signal in the APOE/APOC1/TOMM40 region. These results replicated in an independent sample. Functional and bioinformatic analyses supported many of these loci and further implicated POC1. We showed that polygenic score for verbal learning associated with brain activation in right parieto-occipital region during working memory task. Finally, we showed genetic correlations of these memory traits with several neurocognitive and health outcomes. Our findings suggest a role of several genomic loci in verbal memory processes.Peer reviewe
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