Selective Blocking of TNF Receptor 1 Attenuates Peritoneal Dialysis Fluid Induced Inflammation of the Peritoneum in Mice

Chronic inflammatory conditions during peritoneal dialysis (PD)-treatment lead to the impairment of peritoneal tissue integrity. The resulting structural and functional reorganization of the peritoneal membrane diminishes ultrafiltration rate and thereby enhances mortality by limiting dialysis effectiveness over time. Tumour necrosis factor (TNF) and its receptors TNFR1 and TNFR2 are key players during inflammatory processes. To date, the role of TNFR1 in peritoneal tissue damage during PD-treatment is completely undefined. In this study, we used an acute PD-mouse model to investigate the role of TNFR1 on structural and morphological changes of the peritoneal membrane. TNFR1-mediated TNF signalling in transgenic mice expressing human TNFR1 was specifically blocked by applying a monoclonal antibody (H398) highly selective for human TNFR1 prior to PD-treatment. Cancer antigen-125 (CA125) plasma concentrations were measured by enzyme-linked immunosorbent assay (ELISA). Western blot analyses were applied to determine TNFR2 protein concentrations. Histological staining of peritoneal tissue sections was performed to assess granulocytes within the peritoneal membrane as well as the content of hyaluronic acid and collagen. We show for the first time that the number of granulocytes within the peritoneal membrane is significantly reduced in mice pre-treated with H398. Moreover, we demonstrate that blocking of TNFR1 not only influences CA125 values but also hyaluronic acid and collagen contents of the peritoneal tissue in these mice. These results strongly suggest that TNFR1 inhibition attenuates peritoneal damage caused by peritoneal dialysis fluid (PDF) and therefore may represent a new therapeutic approach in the treatment of PD-related side effects

Nanotube Action between Human Mesothelial Cells Reveals Novel Aspects of Inflammatory Responses

A well-known role of human peritoneal mesothelial cells (HPMCs), the resident cells of the peritoneal cavity, is the generation of an immune response during peritonitis by activation of T-cells via antigen presentation. Recent findings have shown that intercellular nanotubes (NTs) mediate functional connectivity between various cell types including immune cells - such as T-cells, natural killer (NK) cells or macrophages - by facilitating a spectrum of long range cell-cell interactions. Although of medical interest, the relevance of NT-related findings for human medical conditions and treatment, e.g. in relation to inflammatory processes, remains elusive, particularly due to a lack of appropriate in vivo data. Here, we show for the first time that primary cultures of patient derived HPMCs are functionally connected via membranous nanotubes. NT formation appears to be actin cytoskeleton dependent, mediated by the action of filopodia. Importantly, significant variances in NT numbers between different donors as a consequence of pathophysiological alterations were observable. Furthermore, we show that TNF-α induces nanotube formation and demonstrate a strong correlation of NT connectivity in accordance with the cellular cholesterol level and distribution, pointing to a complex involvement of NTs in inflammatory processes with potential impact for clinical treatment

Detecting and responding to a dengue outbreak: evaluation of existing strategies in country outbreak response planning.

Background. Dengue outbreaks are occurring with increasing frequency and intensity. Evidence-based epidemic preparedness and effective response are now a matter of urgency. Therefore, we have analysed national and municipal dengue outbreak response plans. Methods. Thirteen country plans from Asia, Latin America and Australia, and one international plan were obtained from the World Health Organization. The information was transferred to a data analysis matrix where information was extracted according to predefined and emerging themes and analysed for scope, inconsistencies, omissions, and usefulness. Findings. Outbreak response planning currently has a considerable number of flaws. Outbreak governance was weak with a lack of clarity of stakeholder roles. Late timing of responses due to poor surveillance, a lack of combining routine data with additional alerts, and lack of triggers for initiating the response weakened the functionality of plans. Frequently an outbreak was not defined, and early response mechanisms based on alert signals were neglected. There was a distinct lack of consideration of contextual influences which can affect how an outbreak detection and response is managed. Conclusion. A model contingency plan for dengue outbreak prediction, detection, and response may help national disease control authorities to develop their own more detailed and functional context specific plans

Mental health indicators for children and adolescents in OECD countries: a scoping review.

BACKGROUND This scoping review is a further step to build up the Mental Health Surveillance System for Germany. It summarizes and analyzes indicators used or described in Organization for Economic Co-operation and Development (OECD) countries for public mental health monitoring in children and adolescents aged 0-18 years. METHODS We searched PubMed-MEDLINE, PsycINFO, Cochrane Databases, and Google Scholar from 2000 to September 2022. The search used five general keyword categories: 1) "indicators/monitoring/surveillance" at the population level, 2) "mental/psychological," 3) "health/disorders," 4) "children and adolescents," and 5) 38 OECD countries. The search was complemented with an extensive grey literature search, including OECD public health institutions and an internet search using Google. A predefined set of inclusion and exclusion criteria was applied. RESULTS Over 15,500 articles and documents were screened (scientific search N = 10,539, grey literature search more than 5,000). More than 700 articles and documents have been full-text assessed, with 382 being ultimately included. Out of 7,477 indicators extracted, an initial set of 6,426 indicators met our inclusion criteria for indicators. After consolidating duplicates and similar content, this initial set was categorized into 19 topics, resulting in a final set of 210 different indicators. The analysis highlighted an increasing interest in the topic since 2008, but indicators for the younger age, particularly those aged 0 to 2 years, were less readily available. CONCLUSION Our research provides a comprehensive understanding of the current state of mental health indicators for children and adolescents, identifying both (1) indicators of public mental health noted in a previous scoping review on adults and (2) new indicators specific to this age group. These findings contribute to the development of effective public health surveillance strategies for children and adolescents and inform future research in this field

Data_Sheet_2_Mental health indicators for children and adolescents in OECD countries: a scoping review.docx

BackgroundThis scoping review is a further step to build up the Mental Health Surveillance System for Germany. It summarizes and analyzes indicators used or described in Organization for Economic Co-operation and Development (OECD) countries for public mental health monitoring in children and adolescents aged 0–18 years.MethodsWe searched PubMed-MEDLINE, PsycINFO, Cochrane Databases, and Google Scholar from 2000 to September 2022. The search used five general keyword categories: 1) “indicators/monitoring/surveillance” at the population level, 2) “mental/psychological,” 3) “health/disorders,” 4) “children and adolescents,” and 5) 38 OECD countries. The search was complemented with an extensive grey literature search, including OECD public health institutions and an internet search using Google. A predefined set of inclusion and exclusion criteria was applied.ResultsOver 15,500 articles and documents were screened (scientific search N = 10,539, grey literature search more than 5,000). More than 700 articles and documents have been full-text assessed, with 382 being ultimately included. Out of 7,477 indicators extracted, an initial set of 6,426 indicators met our inclusion criteria for indicators. After consolidating duplicates and similar content, this initial set was categorized into 19 topics, resulting in a final set of 210 different indicators. The analysis highlighted an increasing interest in the topic since 2008, but indicators for the younger age, particularly those aged 0 to 2 years, were less readily available.ConclusionOur research provides a comprehensive understanding of the current state of mental health indicators for children and adolescents, identifying both (1) indicators of public mental health noted in a previous scoping review on adults and (2) new indicators specific to this age group. These findings contribute to the development of effective public health surveillance strategies for children and adolescents and inform future research in this field.</p

Data_Sheet_1_Mental health indicators for children and adolescents in OECD countries: a scoping review.docx

BackgroundThis scoping review is a further step to build up the Mental Health Surveillance System for Germany. It summarizes and analyzes indicators used or described in Organization for Economic Co-operation and Development (OECD) countries for public mental health monitoring in children and adolescents aged 0–18 years.MethodsWe searched PubMed-MEDLINE, PsycINFO, Cochrane Databases, and Google Scholar from 2000 to September 2022. The search used five general keyword categories: 1) “indicators/monitoring/surveillance” at the population level, 2) “mental/psychological,” 3) “health/disorders,” 4) “children and adolescents,” and 5) 38 OECD countries. The search was complemented with an extensive grey literature search, including OECD public health institutions and an internet search using Google. A predefined set of inclusion and exclusion criteria was applied.ResultsOver 15,500 articles and documents were screened (scientific search N = 10,539, grey literature search more than 5,000). More than 700 articles and documents have been full-text assessed, with 382 being ultimately included. Out of 7,477 indicators extracted, an initial set of 6,426 indicators met our inclusion criteria for indicators. After consolidating duplicates and similar content, this initial set was categorized into 19 topics, resulting in a final set of 210 different indicators. The analysis highlighted an increasing interest in the topic since 2008, but indicators for the younger age, particularly those aged 0 to 2 years, were less readily available.ConclusionOur research provides a comprehensive understanding of the current state of mental health indicators for children and adolescents, identifying both (1) indicators of public mental health noted in a previous scoping review on adults and (2) new indicators specific to this age group. These findings contribute to the development of effective public health surveillance strategies for children and adolescents and inform future research in this field.</p

Impact of TNFR1 blockage on hyaluronic acid (HA) content in the peritoneum.

<p>Representative immunohistochemical staining of parietal peritoneum tissue sections displaying HA in brown color (A-D). HA is dramatically reduced in the peritoneum from mice treated with PDF (B) compared to tissue from untreated mice (A) and mice pretreated with H398 2 hours before application of PDF (C) or PBS (D) (Scale bar: 100μm).</p

Inhibition of TNFR1 signalling by H398 reduces PDF caused gain of collagen in the peritoneum.

<p>Representative histological staining of collagen in parietal peritoneum. Compared to tissue from untreated mice (A), collagen is highly expressed in the submesothelial layer of mice treated with PDF (B, arrow). An increased accumulation of collagen is also displayed along the mesothelial cell layer (B´, arrow) in comparison to the control (A´, arrow). In mice pre-treated with H398 2 hours before application of PDF or PBS, collagen is less expressed in both the submesothelial layer (C and D) and along the mesothelial cell layer (C´ and D´) (Scale bar: 100μm).</p

Selective inhibition of TNFR1 reduces the number of granulocytes within the peritoneum during PD-treatment in mice.

<p>Representative histological staining of parietal peritoneum showing granulocytes in large numbers in tissue from mice treated with PDF (B, arrow) compared to tissue from untreated mice (A) or mice pretreated with H398 2 hours before application of PDF (C) or PBS (D) (Scale bar: 100 μm). (E) Quantitative analyses of the number of granulocytes in the parietal peritoneum. Data are shown as means ± SEM, *p<0.05, **p<0.01.</p