Developmental Expression and Cellular Origin of the Laminin α2, α4, and α5 Chains in the Intestine

AbstractLaminins are extracellular matrix glycoproteins that are involved in various cellular functions, including adhesion, proliferation, and differentiation. In this study, we examine the expression patterns and the cellular origins of the laminin α2, α4, and α5 chains in the developing mouse intestine and inin vitromouse/chick or chick/mouse interspecies hybrid intestines.In situhybridization and Northern blot analysis revealed that mRNA levels for all three laminin α chains are highest in the fetal intestine undergoing intense morphogenetic movements. Laminin α4 mRNA and polypeptide are associated with mesenchyme-derived cell populations such as endothelium and smooth muscle. In contrast, laminin α2 and α5 chains participate in the structural organization of the subepithelial basement membrane and, in the mature intestine, show a complementary pattern of expression. All three laminin α chains occur in the smooth muscle basement membrane, with a differential expression of laminin α5 chain in the circular and longitudinal smooth muscle layers. The cellular origin of laminin α2 and α5 chains found in the subepithelial cell basement membrane was studied by immunocytochemical analysis of mouse/chick or chick/mouse interspecies hybrid intestines at various stages of development using mouse-specific antibodies. Laminin α2 was found to be deposited into the basement membrane exclusively by mesenchymal cells, while the laminin α5 chain was deposited by both epithelial and mesenchymal cells in an apparently developmentally regulated pattern. We conclude that (1) multiple laminin α chains are expressed in the intestine, implying specific roles for individual laminin isoforms during intestinal development, and (2) reciprocal epithelial/mesenchymal interactions are essential for the formation of a structured subepithelial basement membrane

Kreislaufanlagen - Positionen des Ökosektors

Geeignete Standorte für herkömmliche Formen der Aquakultur werden weltweit knapp, und eine Erhöhung der Produktion gerät zunehmend mit Zielen des Umwelt- und Naturschutzes in Konflikt. Der in Deutschland extrem geringe Selbstversorgungsgrad mit Fisch kann daher in erster Linie über eine Produktionssteigerung in Kreislaufanlagen (KLA), d.h. in geschlossenen, standortunabhängigen und entsprechend technisierten Systemen, erhöht werden. Im Nationalen Strategieplan Aquakultur für Deutschland wird insofern ein besonderer Fokus auf das Produktionspotential in KLA gelegt, bzw. ein deutliches Wachstum nur in diesem Bereich (Steigerung auf 20.000 t bis 2020) als möglich erachtet. Bei dem hier beantragten Vorhaben wird geklärt, wie relevante Interessensgruppen die Vereinbarkeit von Aquakultur in KLA mit der Ökologischen Lebensmittelwirtschaft bewerten. Die Frage stellt sich einerseits aus Sicht der Erzeuger, denn die Produktion in KLA ist durch hohe Umweltauflagen sowie komplexe Haltungssysteme aufwändig und benötigt daher Wege, ihre Alleinstellungsmerkmale (z.B. Transparenz, Regionalität, Verzicht auf Chemie und Tierarznei) auf glaubhaftem Weg an den Verbraucher zu kommunizieren. Andererseits aus Sicht der richtliniengebenden Ökoverbände und Institutionen, denn sie sind von Seiten des Marktes und der Gesellschaft aufgefordert, zu dieser immer wichtiger werdenden Zukunftstechnologie fundiert Stellung zu beziehen

Men’s Use of Cosmetic Surgery and the Role of Traditional Masculinity Ideologies

Background: In western countries, men are increasingly using cosmetic surgery. However, despite this trend, there remains a dearth of information on the prevalence, acceptance, and motivations behind men's use of cosmetic surgery. Furthermore, the potential association between men's use of cosmetic surgery and in particular male-specific cosmetic surgery procedures such as head hair transplant or penis enlargement and traditional masculinity ideologies (TMI) has not been investigated so far. Methods: A cross-sectional anonymous online survey was conducted among 241 self-identifying men aged 18 years or older from the German-speaking part of Europe. Participants responded to questions about cosmetic surgery use and experiences, and completed the Conformity to Masculine Ideologies - Short Form (CMNI-SF) and Male Role Norms Inventory - Short Form (MRNI-SF) questionnaires to assess conformity with and endorsement of TMI. Results: Of the 241 men, 47 (19.5%) have undergone cosmetic surgery. The most common types of cosmetic surgeries reported were wrinkle treatment, eyelid correction, and head-hair transplant. Penis enlargement procedures were reported by three (6.4%) of the 47 men that have performed cosmetic surgery procedures. The main reasons for undergoing surgery were to feel better (72.3%) and look better (55.3%), while to increase sexual success (17.0%) and to increase manliness (14.9%) were also reported. Logistic regression models showed that higher conformity to TMI (CMNI-SF) was associated with higher odds of having undergone cosmetic surgery. Specifically, an increase of one standard-deviation in the CMNI-SF increased the odds of having undergone cosmetic surgery by a factor of 2.29, and the odds of having undergone head-hair transplant surgery by a factor of 3.84. Conclusion: The results highlight overall increased use and specific characteristics of men’s cosmetic surgery use. The significant positive association between conformity to TMI and men's use of cosmetic surgery points towards men’s use of cosmetic surgery as increasingly used mean to assert power, success, dominance and sexual success

A subset of dendritic cells as a major and constitutive source of IL-22BP

Poster presentationInternational audienc

Autoantibodies from Patients with Scleroderma Renal Crisis Promote PAR-1 Receptor Activation and IL-6 Production in Endothelial Cells

Background. Scleroderma renal crisis (SRC) is a life-threatening complication of systemic sclerosis (SSc). Autoantibodies (Abs) against endothelial cell antigens have been implicated in SSc and SRC. However, their detailed roles remain poorly defined. Pro-inflammatory cytokine interleukin-6 (IL-6) has been found to be increased in SSc, but its role in SRC is unclear. Here, we aimed to determine how the autoantibodies from patients with SSc and SRC affect IL-6 secretion by micro-vascular endothelial cells (HMECs). Methods. Serum IgG fractions were isolated from either SSc patients with SRC (n = 4) or healthy individuals (n = 4) and then each experiment with HMECs was performed with SSc-IgG from a separate patient or separate healthy control. IL-6 expression and release by HMECs was assessed by quantitative reverse transcription and quantitative PCR (RT-qPCR) and immunoassays, respectively. The mechanisms underlying the production of IL-6 were analyzed by transient HMEC transfections with IL-6 promoter constructs, electrophoretic mobility shift assays, Western blots and flow cytometry. Results. Exposure of HMECs to IgG from SSc patients, but not from healthy controls, resulted in a time- and dose-dependent increase in IL-6 secretion, which was associated with increased AKT, p70S6K, and ERK1/2 signalling, as well as increased c-FOS/AP-1 transcriptional activity. All these effects could be reduced by the blockade of the endothelial PAR-1 receptor and/or c-FOS/AP-1silencing. Conclusions. Autoantibodies against PAR-1 found in patients with SSc and SRC induce IL-6 production by endothelial cells through signalling pathways controlled by the AP-1 transcription factor. These observations offer a greater understanding of adverse endothelial cell responses to autoantibodies present in patients with SRC

Fat Content and Fatty Acids Profile in Follow-on Formulas Commercialized in Côte d'Ivoire

This study evaluates the follow-on formula for infants. These products are available under several brands in the Ivorian market. In order to verify their conformity to the WHO standards a post-market control by gravimetric method and gas chromatography with mass spectrometry is executed to evaluate the quantity and quality of fat products contained in the milks of brands available in Côte d’Ivoire. Out of the nine brands of milks analyzed, only four of them were close to the values revealed by their manufacturers, whereas the other products had their values below their respective indications

Identification of Cryptic MHC I–restricted Epitopes Encoded by HIV-1 Alternative Reading Frames

Human immunodeficiency virus (HIV) 1 major histocompatibility complex (MHC) I–restricted epitopes are widely believed to be derived from viral proteins encoded by primary open reading frames. However, the HIV-1 genome contains alternative reading frames (ARFs) potentially encoding small polypeptides. We have identified a panel of epitopes encoded by ARFs within the gag, pol, and env genes. The corresponding epitopic peptides were immunogenic in mice humanized for MHC-I molecules. In addition, cytotoxic T lymphocytes recognizing these epitopes were found in HIV-infected patients. These results reveal the existence of atypical mechanisms of HIV-1 epitope generation. They indicate that the repertoire of epitopes recognized by the cellular anti–HIV-1 immune response is broader than initially thought. This should be taken into account when designing vaccine strategies aimed at activating these responses

Specialised Paediatric PAlliativE CaRe: Assessing family, healthcare professionals and health system outcomes in a multi-site context of various care settings: SPhAERA study protocol

The number of children and adolescents living with life-limiting conditions and potentially in need for specialised paediatric palliative care (SPPC) is rising. Ideally, a specialised multiprofessional team responds to the complex healthcare needs of children and their families. The questions of, how SPPC is beneficial, for whom, and under what circumstances, remain largely unanswered in the current literature. This study's overall target is to evaluate the effectiveness of a SPPC programme in Switzerland with respect to its potential to improve patient-, family-, health professional-, and healthcare-related outcomes.; This comparative effectiveness study applies a quasi-experimental design exploring the effectiveness of SPPC as a complex intervention at one treatment site in comparison with routine care provided in a generalised PPC environment at three comparison sites. As the key goal of palliative care, quality of life - assessed at the level of the patient-, the family- and the healthcare professional - will be the main outcome of this comparative effectiveness research. Other clinical, service, and economic outcomes will include patient symptom severity and distress, parental grief processes, healthcare resource utilisation and costs, direct and indirect health-related expenditure, place of death, and introduction of SPPC. Data will be mainly collected through questionnaire surveys and chart analysis.; The need for SPPC has been demonstrated through numerous epidemiological and observational studies. However, in a healthcare environment focused on curative treatment and struggling with limited resources, the lack of evidence contributes to a lack of acceptance and financing of SPPC which is a major barrier against its sustainability. This study will contribute to current knowledge by reporting individual and child level outcomes at the family level and by collecting detailed contextual information on healthcare provision. We hope that the results of this study can help guiding the expansion and sustainability of SPPC and improve the quality of care for children with life-limiting conditions and their families internationally.; Registered prospectively on ClinicalTrials.gov on January 22, 2020. NCT04236180 PROTOCOL VERSION: Amendment 2, March 01, 2021

The role of immune checkpoint inhibitors in clinical practice: an analysis of the treatment patterns, survival and toxicity rates by sex.

PURPOSE Our aim is to describe the role of immune checkpoint inhibitors (ICI) in clinical practice by providing the patient and tumor characteristics as well as survival and toxicity rates by sex. METHODS We used electronic health records to identify patients treated at the Cancer Center of the University Hospital Bern, Switzerland between January 1, 2017 and June 16, 2021. RESULTS We identified 5109 patients, 689 of whom (13.5%) received at least one dose of ICI. The fraction of patients who were prescribed ICI increased from 8.6% in 2017 to 22.9% in 2021. ICI represented 13.2% of the anticancer treatments in 2017 and increased to 28.2% in 2021. The majority of patients were male (68.7%), who were older than the female patients (median age 67 vs. 61 years). Over time, adjuvant and first line treatments increased for both sexes. Lung cancer and melanoma were the most common cancer types in males and females. The incidence of irAEs was higher among females (38.4% vs. 28.1%) and lead more often to treatment discontination in females than in males (21.1% vs. 16.8%). Independent of sex, the occurrence of irAEs was associated with greater median overall survival (OS, not reached vs. 1.1 years). Female patients had a longer median OS than males (1.9 vs. 1.5 years). CONCLUSIONS ICI play an increasingly important role in oncology. irAEs are more frequent in female patients and are associated with a longer OS. More research is needed to understand the association between patient sex and toxicity and survival