Multi-zone & multi-compartment model for dynamic simulation of horizontal fluidized bed granulator

[EN] Due to the ongoing development and implementation of process control and observation techniques in production processes of particulate products, the research on complexly designed process apparatuses has become of great interest. The work presented in this paper is focused on a model-based study on a multi-chamber horizontal fluidized bed apparatus for fluidized bed layering granulation. The model for the solid phase is extended by a new drying model. Because of the great variety of parameters that influence this complex system a preliminary model-based study on a simplified setup shall show which construction or process parameters influence the product quality.Financial support for this research from German Research Foundation (DFG) as part of the SPP project DynSim 1679 is gratefully acknowledged.Mielke, L.; Bück, A.; Tsotsas, E. (2018). Multi-zone & multi-compartment model for dynamic simulation of horizontal fluidized bed granulator. En IDS 2018. 21st International Drying Symposium Proceedings. Editorial Universitat Politècnica de València. 123-130. https://doi.org/10.4995/IDS2018.2018.7474OCS12313

Innate immunodeficiency following genetic ablation of Mcl1 in natural killer cells

The cytokine IL-15 is required for natural killer (NK) cell homeostasis; however, the intrinsic mechanism governing this requirement remains unexplored. Here we identify the absolute requirement for myeloid cell leukaemia sequence-1 (Mcl1) in the sustained survival of NK cells in vivo. Mcl1 is highly expressed in NK cells and regulated by IL-15 in a dose-dependent manner via STAT5 phosphorylation and subsequent binding to the 3'-UTR of Mcl1. Specific deletion of Mcl1 in NK cells results in the absolute loss of NK cells from all tissues owing to a failure to antagonize pro-apoptotic proteins in the outer mitochondrial membrane. This NK lymphopenia results in mice succumbing to multiorgan melanoma metastases, being permissive to allogeneic transplantation and being resistant to toxic shock following polymicrobial sepsis challenge. These results clearly demonstrate a non-redundant pathway linking IL-15 to Mcl1 in the maintenance of NK cells and innate immune responses in vivo

Tpl2 kinase regulates T cell interferon-γ production and host resistance to Toxoplasma gondii

Tpl2 (Tumor progression locus 2), also known as Cot/MAP3K8, is a hematopoietically expressed serine-threonine kinase. Tpl2 is known to have critical functions in innate immunity in regulating tumor necrosis factor–α, Toll-like receptor, and G protein–coupled receptor signaling; however, our understanding of its physiological role in T cells is limited. We investigated the potential roles of Tpl2 in T cells and found that it was induced by interleukin-12 in human and mouse T cells in a Stat4-dependent manner. Deficiency of Tpl2 was associated with impaired interferon (IFN)-γ production. Accordingly, Tpl2−/− mice had impaired host defense against Toxoplasma gondii with reduced parasite clearance and decreased IFN-γ production. Furthermore, reconstitution of Rag2−/− mice with Tpl2-deficient T cells followed by T. gondii infection recapitulated the IFN-γ defect seen in the Tpl2-deficient mice, confirming a T cell–intrinsic defect. CD4+ T cells isolated from Tpl2−/− mice showed poor induction of T-bet and failure to up-regulate Stat4 protein, which is associated with impaired TCR-dependent extracellular signal-regulated kinase activation. These data underscore the role of Tpl2 as a regulator of T helper cell lineage decisions and demonstrate that Tpl2 has an important functional role in the regulation of Th1 responses

Type 2 Innate Lymphoid Cells Protect against Colorectal Cancer Progression and Predict Improved Patient Survival.

Chronic inflammation of the gastrointestinal (GI) tract contributes to colorectal cancer (CRC) progression. While the role of adaptive T cells in CRC is now well established, the role of innate immune cells, specifically innate lymphoid cells (ILCs), is not well understood. To define the role of ILCs in CRC we employed complementary heterotopic and chemically-induced CRC mouse models. We discovered that ILCs were abundant in CRC tumours and contributed to anti-tumour immunity. We focused on ILC2 and showed that ILC2-deficient mice developed a higher tumour burden compared with littermate wild-type controls. We generated an ILC2 gene signature and using machine learning models revealed that CRC patients with a high intratumor ILC2 gene signature had a favourable clinical prognosis. Collectively, our results highlight a critical role for ILC2 in CRC, suggesting a potential new avenue to improve clinical outcomes through ILC2-agonist based therapeutic approaches

Evaluating evidence-based content, features of exercise instruction, and expert involvement in physical activity apps for pregnant women: systematic search and content analysis

Background: Guidelines for physical activity and exercise during pregnancy recommend that all women without contraindications engage in regular physical activity to improve both their own health and the health of their baby. Many women are uncertain how to safely engage in physical activity and exercise during this life stage and are increasingly using mobile apps to access health-related information. However, the extent to which apps that provide physical activity and exercise advice align with current evidence-based pregnancy recommendations is unclear. Objective: This study aims to conduct a systematic search and content analysis of apps that promote physical activity and exercise in pregnancy to examine the alignment of the content with current evidence-based recommendations; delivery, format, and features of physical activity and exercise instruction; and credentials of the app developers. Methods: Systematic searches were conducted in the Australian App Store and Google Play Store in October 2020. Apps were identified using combinations of search terms relevant to pregnancy and exercise or physical activity and screened for inclusion (with a primary focus on physical activity and exercise during pregnancy, free to download or did not require immediate paid subscription, and an average user rating of ≥4 out of 5). Apps were then independently reviewed using an author-designed extraction tool. Results: Overall, 27 apps were included in this review (Google Play Store: 16/27, 59%, and App Store: 11/27, 41%). Two-thirds of the apps provided some information relating to the frequency, intensity, time, and type principles of exercise; only 11% (3/27) provided this information in line with current evidence-based guidelines. Approximately one-third of the apps provided information about contraindications to exercise during pregnancy and referenced the supporting evidence. None of the apps actively engaged in screening for potential contraindications. Only 15% (4/27) of the apps collected information about the user’s current exercise behaviors, 11% (3/27) allowed users to personalize features relating to their exercise preferences, and a little more than one-third provided information about developer credentials. Conclusions: Few exercise apps designed for pregnancy aligned with current evidence-based physical activity guidelines. None of the apps screened users for contraindications to physical activity and exercise during pregnancy, and most lacked appropriate personalization features to account for an individual’s characteristics. Few involved qualified experts during the development of the app. There is a need to improve the quality of apps that promote exercise in pregnancy to ensure that women are appropriately supported to engage in exercise and the potential risk of injury, complications, and adverse pregnancy outcomes for both mother and child is minimized. This could be done by providing expert guidance that aligns with current recommendations, introducing screening measures and features that enable personalization and tailoring to individual users, or by developing a recognized system for regulating apps

The German National Registry of Primary Immunodeficiencies (2012-2017)

Introduction: The German PID-NET registry was founded in 2009, serving as the first national registry of patients with primary immunodeficiencies (PID) in Germany. It is part of the European Society for Immunodeficiencies (ESID) registry. The primary purpose of the registry is to gather data on the epidemiology, diagnostic delay, diagnosis, and treatment of PIDs. Methods: Clinical and laboratory data was collected from 2,453 patients from 36 German PID centres in an online registry. Data was analysed with the software Stata® and Excel. Results: The minimum prevalence of PID in Germany is 2.72 per 100,000 inhabitants. Among patients aged 1–25, there was a clear predominance of males. The median age of living patients ranged between 7 and 40 years, depending on the respective PID. Predominantly antibody disorders were the most prevalent group with 57% of all 2,453 PID patients (including 728 CVID patients). A gene defect was identified in 36% of patients. Familial cases were observed in 21% of patients. The age of onset for presenting symptoms ranged from birth to late adulthood (range 0–88 years). Presenting symptoms comprised infections (74%) and immune dysregulation (22%). Ninety-three patients were diagnosed without prior clinical symptoms. Regarding the general and clinical diagnostic delay, no PID had undergone a slight decrease within the last decade. However, both, SCID and hyper IgE- syndrome showed a substantial improvement in shortening the time between onset of symptoms and genetic diagnosis. Regarding treatment, 49% of all patients received immunoglobulin G (IgG) substitution (70%—subcutaneous; 29%—intravenous; 1%—unknown). Three-hundred patients underwent at least one hematopoietic stem cell transplantation (HSCT). Five patients had gene therapy. Conclusion: The German PID-NET registry is a precious tool for physicians, researchers, the pharmaceutical industry, politicians, and ultimately the patients, for whom the outcomes will eventually lead to a more timely diagnosis and better treatment