Explaining psychosocial care among unaccompanied minor refugees: a realist review.

Research on the psychosocial care (PSC) of unaccompanied minor refugees (UMRs) has mainly taken a socioepidemiological approach and has focused on the perspectives of experts in the field. In contrast, the knowledge concerning the differing context factors and the underlying mechanisms of current PSC which could inform policy recommendations is scant. The study aims at unravelling the contexts, mechanisms and outcomes of PSC for UMRs. For a realist review (RR), scientific evidence and gray literature were synthesised consistent with the RAMESES publication standards for realist synthesis. Based on an iterative keyword search in electronic databases (e.g., PubMed) and screening, 34 works from 2005 to 2019 were included in a realist synthesis. Theory-informed context-mechanism-outcome configurations (CMOs) were extracted, to explain underlying processes and mechanisms. Characterised by their interrelatedness, the dominant CMOs included the UMRs' intersections of transitions (e.g., adolescence and migration), their needs for culture-, and gender-sensitive PSC, and the undersupply of PSC. These contexts and outcomes are mediated by pre-, peri- and post-migratory stressors as well as care structures and are moreover influenced by overarching discourses and concepts. They comprise adverse and beneficial mechanisms in the PSC of UMRs. The existing literature grasps the PSC of UMRs by different disciplines and approaches but does not offer a comprehensive overview on micro-macro intersections and included discourses. The inclusion of lay perspectives and an intersectional approach could inform health service research. The reflection of UMR-related categorical constructs of resilience and vulnerability, discourses of othering, as well as restrictive health policies may guide policy recommendations.

Smad7 Deficiency in Myeloid Cells Does Not Affect Liver Injury, Inflammation or Fibrosis after Chronic CCl4 Exposure in Mice.

Myeloid cells play an essential role in the maintenance of liver homeostasis, as well as the initiation and termination of innate and adaptive immune responses. In chronic hepatic inflammation, the production of transforming growth factor beta (TGF-ß) is pivotal for scarring and fibrosis induction and progression. TGF-ß signalling is tightly regulated via the Smad protein family. Smad7 acts as an inhibitor of the TGF-ß-signalling pathway, rendering cells that express high levels of it resistant to TGF-ß-dependent signal transduction. In hepatocytes, the absence of Smad7 promotes liver fibrosis. Here, we examine whether Smad7 expression in myeloid cells affects the extent of liver inflammation, injury and fibrosis induction during chronic liver inflammation. Using the well-established model of chronic carbon tetrachloride (CCl4)-mediated liver injury, we investigated the role of Smad7 in myeloid cells in LysM-Cre Smadfl/fl mice that harbour a myeloid-specific knock-down of Smad7. We found that the chronic application of CCl4 induces severe liver injury, with elevated serum alanine transaminase (ALT)/aspartate transaminase (AST) levels, centrilobular and periportal necrosis and immune-cell infiltration. However, the myeloid-specific knock-down of Smad7 did not influence these and other parameters in the CCl4-treated animals. In summary, our results suggest that, during long-term application of CCl4, Smad7 expression in myeloid cells and its potential effects on the TGF-ß-signalling pathway are dispensable for regulating the extent of chronic liver injury and inflammation.

An Evaluation of T-Cell Functionality After Flow Cytometry Sorting Revealed p38 MAPK Activation.

Cell alterations during isolation and preparation for flow cytometry cell sorting by antibodies, temperature, homogenization, buffer composition and mitogens are well known. In contrast, little is known about cell alteration caused by the instrument or the sorting process itself. We systematically evaluated cellular responses to different sorter-induced physical forces. In summary, flow cytometry cell-sorting induced forces can affect cellular signaling cascades, especially the MAPK p38. Functional assays, related to the p38 MAPK pathway, of human primary T cells after flow cytometry sorting did lead to minor physiological modulation but no functional impairments. © 2020 The Authors. Cytometry Part A published by Wiley Periodicals, Inc. on behalf of International Society for Advancement of Cytometry.

Longitudinal single-cell data informs deterministic modelling of inflammatory bowel disease.

Single-cell-based methods such as flow cytometry or single-cell mRNA sequencing (scRNA-seq) allow deep molecular and cellular profiling of immunological processes. Despite their high throughput, however, these measurements represent only a snapshot in time. Here, we explore how longitudinal single-cell-based datasets can be used for deterministic ordinary differential equation (ODE)-based modelling to mechanistically describe immune dynamics. We derived longitudinal changes in cell numbers of colonic cell types during inflammatory bowel disease (IBD) from flow cytometry and scRNA-seq data of murine colitis using ODE-based models. Our mathematical model generalised well across different protocols and experimental techniques, and we hypothesised that the estimated model parameters reflect biological processes. We validated this prediction of cellular turnover rates with KI-67 staining and with gene expression information from the scRNA-seq data not used for model fitting. Finally, we tested the translational relevance of the mathematical model by deconvolution of longitudinal bulk mRNA-sequencing data from a cohort of human IBD patients treated with olamkicept. We found that neutrophil depletion may contribute to IBD patients entering remission. The predictive power of IBD deterministic modelling highlights its potential to advance our understanding of immune dynamics in health and disease.

The ADP-Ribosylation Factor 4d Restricts Regulatory T-Cell Induction via Control of IL-2 Availability.

Interleukin-2 is central to the induction and maintenance of both natural (nTreg) and induced Foxp3-expressing regulatory T cells (iTreg). Thus, signals that modulate IL-2 availability may, in turn, also influence Treg homeostasis. Using global knockout and cell-specific knockout mouse models, we evaluated the role of the small GTPase ADP-ribosylation factor 4d (Arl4d) in regulatory T-cell biology. We show that the expression of Arl4d in T cells restricts both IL-2 production and responsiveness to IL-2, as measured by the phosphorylation of STAT5. Arl4d-deficient CD4 T cells converted more efficiently into Foxp3+ iTreg in vitro in the presence of αCD3ε and TGFß, which was associated with their enhanced IL-2 secretion. As such, Arl4d-/- CD4 T cells induced significantly less colonic inflammation and lymphocytic infiltration in a model of transfer colitis. Thus, our data reveal a negative regulatory role for Arl4d in CD4 T-cell biology, limiting iTreg conversion via the restriction of IL-2 production, leading to reduced induction of Treg from conventional CD4 T cells.

Healthcare needs among unaccompanied minor refugees: a study protocol of a qualitative study explaining access and utilisation across place and gender.

INTRODUCTION: Several studies have identified that unaccompanied minor refugees (UMRs) are allegedly 'vulnerable' and belong to a high-risk group in terms of psychological distress and post-traumatic stress disorder due to their preflight, periflight and postflight experiences. Psychosocial care (PSC) is of high importance for UMRs, but little is known about barriers to access and utilisation of PSC across place and gender. The aims of this gender-sensitive qualitative study will be to build on the existing body of literature and to provide qualitative evidence on the contexts and mechanisms of PSC for male and female UMRs in Germany by comparing two German regions. METHODS AND ANALYSIS: Following the study preparing realist review, a qualitative study will be undertaken in Berlin and Central German cities. Approximately 24 experts from the field of PSC and 12 lay UMRs will participate in face-to-face, semistructured interviews. Data will be transcribed and analysed based on the grounded theory research paradigm. ETHICS AND DISSEMINATION: Only participants who have been informed in both German and their native tongue and who have signed a declaration of consent will be included in the study. The study will comply rigorously with German data protection standards. Approval from the Ethical Review Committee at Martin Luther University Halle-Wittenberg, Germany has been obtained and granted. The results of the study will be presented at several conferences and will be published in high-quality, peer-reviewed international journals. The results will display a differentiated picture of the PSC of UMRs in Germany. Such knowledge is a precondition for a 'science of change' that translates explanations into practical recommendations on how to improve healthcare policies. TRIAL REGISTRATION NUMBER: DRKS00018080.

Getting on with persistent pollutants: Decreasing trends of perfluoroalkyl acids (PFAAs) in sewage sludge.

Sewage sludge can be a relevant source of perfluoroalkyl acids (PFAAs) for the environment. In order to reduce emissions from this source, Bavarian authorities enforced in 2008 an analysis of PFAAs from sewage sludge derived from municipal wastewater treatment plants (WWTPs). 4981 sludge samples from 1165 different WWTPs were analyzed between 2008 and 2013 for 11 PFAAs compounds. During this period, 71 WWTPs exceeded the precautionary limit of 125 µg kg(-1) dm of total PFAAs in sludge samples at least once with a decreasing tendency. The yearly exceedances of the investigated WWTPs decreased from 6% in 2008 to 0.8% in 2013. At the same time, the percentage of uncontaminated WWTPs increased from 33% to 65%. Perfluorooctane sulfonic acid (PFOS) was the predominant compound found in 41% of all sludge samples. Perfluorodecanoic acid (PFDA) was detected in 19% and Perfluorooctanoic acid (PFOA) in 7%. Very high PFAAs concentrations (>500 µg kg(-1) dm) in sewage sludge were generally caused by firefighting foams containing PFAAs or emissions from PFAAs-using industries including metal plating, textile, leather or paper industries. Trend analyses of the six year period show that PFAAs contamination in sewage sludge clearly decreased for 47% of the WWTPs. However, for 16% of the WWTPs an increasing trend was detected, even though the concentration levels were below the precautionary limit. During the six years of investigation the load of total PFAAs in sewage sludge was reduced by more than 90%, from 17 t a(-1) in 2008 to 1.5 t a(-1) in 2013.

Detection of Intracellular Gene Expression in Live Cells of Murine, Human and Porcine Origin Using Fluorescence-labeled Nanoparticles.

The reprogramming of somatic cells to induced pluripotent stem cells (iPS) has successfully been performed in different mammalian species including mouse, rat, human, pig and others. The verification of iPS clones mainly relies on the detection of the endogenous expression of different pluripotency genes. These genes mostly represent transcription factors which are located in the cell nucleus. Traditionally, the proof of their endogenous expression is supplied by immunohistochemical staining after fixation of the cells. This approach requires replicate cultures of each clone at this early stage to preserve validated clones for further experiments. The present protocol describes an approach with gene-specific nanoparticles which allows the evaluation of intracellular gene expression directly in live cells by fluorescence. The nanoparticles consist of a central gold particle coupled to a capture strand carrying a sequence complementary to the target mRNA as well as a quenched reporter strand. These nanoparticles are actively endocytosed and the target mRNA displaces the reporter strand which then start to fluoresce. Therefore, specific target gene expression can be detected directly under the microscope. In addition, the emitted fluorescence allows the identification, isolation and enrichment of cells expressing a specific gene by flow cytometry. This method can be applied directly to live cells in culture without any manipulation of the target cells.

Dynamics and attenuation of acidic pharmaceuticals along a river stretch.

While substantial knowledge on the occurrence of pharmaceuticals in the environment is available, their behavior and fate in surface waters is still poorly understood. Therefore, the aims of this study were to analyze the short-term dynamics of selected pharmaceuticals along a 13.6 km long river stretch downstream of a wastewater treatment plant (WWTP), and to quantify their attenuation by a mass balance approach. Four acidic pharmaceuticals (bezafibrate, clofibric acid, diclofenac, naproxen) with different attenuation properties were measured over a period of three weeks at high temporal resolution, and in situ photolysis experiments were carried out. The average concentrations of pharmaceuticals were between 9 +/- 4 and 339 +/- 133 ng L(-1), corresponding to loads between 1.9 +/- 1.2 and 63 +/- 37 g d(-1) (n = 134). The temporal dynamics of pharmaceuticals was closely related to discharge of the WWTP and precipitation, and highest concentrations were observed at the beginning of a discharge event. During a dry period, naproxen was eliminated along the river stretch with a dissipation time (DT(50)) of 3.6 +/- 2.1 days while the other compounds did not exhibit significant attenuation. As photolysis and other abiotic processes were of limited quantitative relevance, the attenuation of naproxen can most likely be attributed to biotransformation.