Immunology of the genital tract - a review

The objective of this work was to systematically review and discuss recent studies and articles dealing with the subject of the immunology of female genital tract mucosal tissue. The emphasis hereby lies on the evaluation of studies concerning the basics of female reproductive immunology, research on immunology of the most important genital infections and vaccination strategies, immunologic principles at the fetomaternal interface during normal pregnancy and its complications as well as on immunologic data on infertility and immunocontraception. It is now established that the mucosal immune system is a distinct and separate component of the host`s immune apparatus and differs from the lymphoid tissues in peripheral sites. Furthermore, despite some common features, the female genital tract mucosal system displays some distinct characteristics which outlines its special role. Analysis of the female genital tract indicates that the key cells of the innate and adaptive immune systems are present and functionally responsive to antigens; however, there is a certain degree of compartmentalization within the tract. The identification of TLRs in the fallopian tubes, uterus, cervix, and vagina and the presence of ECs, macrophages, DCs, NK cells, and neutrophils throughout the reproductive tract along with their responsiveness to selected PAMPs indicate that the female reproductive tract has evolved to meet the challenges of STDs, while at the same time supporting an immunologically distinct fetal placental unit. To meet these diverse challenges, innate and adaptive immune system in the female genital tract are precisely regulated not only by a network of cytokines and chemokines, but also by the sex hormones estrogen and progesterone. Understanding the specialty of the genital tract immune system is of critical importance, because STDs are and will be a major worldwide health problem. Despite extensive efforts, only limited success has been achieved in dealing with a growing list of STDs. The role of immune factors in the control of genital viral and bacterial infections appears complex and needs further studying, also with respect to creating vaccines. Despite the recognition that innate immunity as the first line of defense and adaptive immunity, especially Th1 immune responses, play a critical role in preventing infection and in limiting viral replication, factors such as antimicrobials and TLRs that contribute to the mucosal response in the female genital tract have only recently begun to receive attention. Further studies are also needed to elucidate the relationship between mucosal immunity, the hormonal environment, and response to pathogen challenge. More data must be collected on the mechanisms of immune evasion by several pathogens such as HSV, N. gonorrheae or Chlamydia. While considerable information can be obtained from animal experiments, important differences in the physiology of reproduction and the immune sytem result in the need for studies in humans. Further knowledge on female tract immunology will also impact on immunological approaches to contraception, immunological infertility and the immunological aspects of pregnancy. This does not only involve new options for diagnostics but also for treatment of pregnancy complications such as preeclampsia, preterm birth and early pregnancy loss as well as for infertility. Pregnancy involves maternal tolerance of the semiallogenic histoincompatible fetus and is characterized by the enhancement of the innate immune system and suppression of the adaptive immune response, probably with progesterone as the important regulator. In opposite to normal pregnancy, improper immune responses and an unbalanced cytokine network may characterize implantation failures, pregnancy loss and obstetric complications. These are the presence of elevated Th1/Th2 cell ratios, high concentrations of Th1 cytokines, elevated NK cell cytotoxicity and levels, and emergence of various autoantibodies. These immunological approaches needs to be investigated and evaluated further with respect to widening of treatment options by modification of immune responses

Immunology of the genital tract - a review

The objective of this work was to systematically review and discuss recent studies and articles dealing with the subject of the immunology of female genital tract mucosal tissue. The emphasis hereby lies on the evaluation of studies concerning the basics of female reproductive immunology, research on immunology of the most important genital infections and vaccination strategies, immunologic principles at the fetomaternal interface during normal pregnancy and its complications as well as on immunologic data on infertility and immunocontraception. It is now established that the mucosal immune system is a distinct and separate component of the host`s immune apparatus and differs from the lymphoid tissues in peripheral sites. Furthermore, despite some common features, the female genital tract mucosal system displays some distinct characteristics which outlines its special role. Analysis of the female genital tract indicates that the key cells of the innate and adaptive immune systems are present and functionally responsive to antigens; however, there is a certain degree of compartmentalization within the tract. The identification of TLRs in the fallopian tubes, uterus, cervix, and vagina and the presence of ECs, macrophages, DCs, NK cells, and neutrophils throughout the reproductive tract along with their responsiveness to selected PAMPs indicate that the female reproductive tract has evolved to meet the challenges of STDs, while at the same time supporting an immunologically distinct fetal placental unit. To meet these diverse challenges, innate and adaptive immune system in the female genital tract are precisely regulated not only by a network of cytokines and chemokines, but also by the sex hormones estrogen and progesterone. Understanding the specialty of the genital tract immune system is of critical importance, because STDs are and will be a major worldwide health problem. Despite extensive efforts, only limited success has been achieved in dealing with a growing list of STDs. The role of immune factors in the control of genital viral and bacterial infections appears complex and needs further studying, also with respect to creating vaccines. Despite the recognition that innate immunity as the first line of defense and adaptive immunity, especially Th1 immune responses, play a critical role in preventing infection and in limiting viral replication, factors such as antimicrobials and TLRs that contribute to the mucosal response in the female genital tract have only recently begun to receive attention. Further studies are also needed to elucidate the relationship between mucosal immunity, the hormonal environment, and response to pathogen challenge. More data must be collected on the mechanisms of immune evasion by several pathogens such as HSV, N. gonorrheae or Chlamydia. While considerable information can be obtained from animal experiments, important differences in the physiology of reproduction and the immune sytem result in the need for studies in humans. Further knowledge on female tract immunology will also impact on immunological approaches to contraception, immunological infertility and the immunological aspects of pregnancy. This does not only involve new options for diagnostics but also for treatment of pregnancy complications such as preeclampsia, preterm birth and early pregnancy loss as well as for infertility. Pregnancy involves maternal tolerance of the semiallogenic histoincompatible fetus and is characterized by the enhancement of the innate immune system and suppression of the adaptive immune response, probably with progesterone as the important regulator. In opposite to normal pregnancy, improper immune responses and an unbalanced cytokine network may characterize implantation failures, pregnancy loss and obstetric complications. These are the presence of elevated Th1/Th2 cell ratios, high concentrations of Th1 cytokines, elevated NK cell cytotoxicity and levels, and emergence of various autoantibodies. These immunological approaches needs to be investigated and evaluated further with respect to widening of treatment options by modification of immune responses

Sicherheit von autonomem Fahren

Die vorliegende Arbeit zeigt Gefahren und Risiken des autonomen Busses "Trapizio" der Firma AMoTech GmbH auf, welcher in Neuhausen am Rheinfall in der Schweiz zum Einsatz kommt. Der Fokus der Arbeit liegt auf streckenspezifischen Aspekten, deren Analyse nach der Norm ISO-26262 zur funktionalen Sicherheit, welche in der Automobilindustrie etabliert ist. Die aus der Analyse hervorgegangenen Risiken wurden der Strecke zugeordnet und zur besseren Visualisierung wurden Karten angefertigt. Auf diesen Karten sollen die kritischen Punkte ersichtlich sein. Risiken, welche gemäss der Norm weitere Massnahmen erfordern, wurden genauer evaluiert und es wurden – soweit nötig – detailliertere Lösungsansätze erarbeitet. Auf der Basis dieser Methoden lassen sich wenige Risiken auf der Strecke identifizieren. Das Fahrzeug wurde ebenfalls etwas genauer betrachtet und eine grobe Visualisierung des Systems wurde angefertigt. Bei der Risikoanalyse wurde die Sensorik nicht betrachtet, weshalb die Resultate noch nicht vollständig repräsentativ sind. Zwischenzeitlich erhielt der autonome Shuttle bereits eine Bewilligung für den Betrieb auf einem Teil der Strecke. Diese Arbeit ist für die Zulassung auf der gesamten Strecke nützlich, da sie die systematische Analyse und Zuordnung der jeweiligen Risiken ermöglicht und damit die Grundlage zur Festlegung von Massnahmen zur Risikominderung darstellt. Das vorgestellte Vorgehen ist auch dafür geeignet, um ähnliche Projekte einer solchen Risikoanalyse zu unterziehen

Social innovations in tourism: Analysing processes, actors, and tipping points.

Social innovations consist of new forms of cooperation of individ- uals or organisations and they provide new solutions to societal problems. they typically evolve along three phases and have the potential to solve region-specific challenges. in the operating phase, social innovations can overcome the so-called tipping point. the tipping point is an elusive moment at which the social inno- vation can begin to spread or at which it could also fail. to exam- ine the social innovation characteristics that contribute to overcome tipping points and to identify the role and motivations of actors to participate in the process of developing social innovations in tourism, we applied innovation biographies to seven social inno- vations in a swiss mountain region. Data were drawn from 29 interviews with the involved actors. Our results show that social innovations in tourism that overcame the tipping point fulfil three conditions: First, new actors join the social innovations in the operating phase. second, all the actors involved benefit from the social innovation for their own business strategy. third, the social innovation is accepted in the region and among the actors involved and therefore does not face strong headwinds. Furthermore, developers, supporters, and promoters are important throughout the entire social innovation process. the findings sug- gest the need for a more comprehensive understanding of inno- vations in tourism that incorporates the complexity of different actors involved

Change agency in social innovation: an analysis of activities in social innovation processes

We examine the role of change agency in social innovations. Agency in social innovations can create new resources and capacities for transformative change in a region. To date, there is a lack of empirical studies investigating how agency manifests itself in social innovations. In particular, research has not yet investigated the detailed activities of social innovation actors throughout the phases of social innovation processes. In this paper we apply the concept of trinity of change agency to investigate the activities of social innovation actors. Using innovation biographies and data from 61 interviews for 11 case studies of social innovation in a peripheral mountain region in Switzerland, we analyse the social innovation process from an actor-oriented perspective. Our findings show that the various types of change agency are highly present in social innovations. The significance of change agency alters throughout the innovation process. Our analysis shows that all kinds of actors performed change agency during the social innovation process. Interestingly, same actors performed different types of change agency during the social innovation process. The findings suggest that change agency is as a significant element in social innovations and that we need to consider it as a transformative element of social innovation processes. When policymakers take change agency into account in creating an environment in which social innovations can flourish, there is a great chance that social innovations can contribute to changing regional development paths and perhaps even to regional transformation

Attenuated palmitoylation of serotonin receptor 5-HT1A affects receptor function and contributes to depression-like behaviors

The serotonergic system and in particular serotonin 1A receptor (5-HT1AR) are implicated in major depressive disorder (MDD). Here we demonstrated that 5-HT1AR is palmitoylated in human and rodent brains, and identified ZDHHC21 as a major palmitoyl acyltransferase, whose depletion reduced palmitoylation and consequently signaling functions of 5-HT1AR. Two rodent models for depression-like behavior show reduced brain ZDHHC21 expression and attenuated 5-HT1AR palmitoylation. Moreover, selective knock-down of ZDHHC21 in the murine forebrain induced depression-like behavior. We also identified the microRNA miR-30e as a negative regulator of Zdhhc21 expression. Through analysis of the post-mortem brain samples in individuals with MDD that died by suicide we find that miR-30e expression is increased, while ZDHHC21 expression, as well as palmitoylation of 5-HT1AR, are reduced within the prefrontal cortex. Our study suggests that downregulation of 5-HT1AR palmitoylation is a mechanism involved in depression, making the restoration of 5-HT1AR palmitoylation a promising clinical strategy for the treatment of MDD

Nano- and micro-structures in lunar zircon from Apollo 15 and 16 impactites: implications for age interpretations

Meteorite impact processes are ubiquitous on the surfaces of rocky and icy bodies in the Solar System, including the Moon. One of the most common accessory minerals, zircon, when shocked, produces specific micro-structures that may become indicative of the age and shock conditions of these impact processes. To better understand the shock mechanisms in zircon from Apollo 15 and 16 impact breccias, we applied transmission electron microscopy (TEM) and studied nano-structures in eight lunar zircons displaying four different morphologies from breccias 15455, 67915, and 67955. Our observations revealed a range of shock-related features in zircon: (1) planar and non-planar fractures, (2) “columnar” zircon rims around baddeleyite cores, (3) granular textured zircon, in most cases with sub-µm-size inclusions of monoclinic ZrO2 (baddeleyite) and cubic ZrO2 (zirconia), (4) silica-rich glass and metal inclusions of FeS and FeNi present at triple junctions in granular zircon and in baddeleyite, (5) inclusions of rutile in shocked baddeleyite, (6) amorphous domains, (7) recrystallized domains. In many grain aggregates, shock-related micro-structures overprint each other, indicating either different stages of a single impact process or multiple impact events. During shock, some zircons were transformed to diaplectic glass (6), and others (7) were completely decomposed into SiO2 and Zr-oxide, evident from the observed round shapes of cubic zirconia and silica-rich glass filling triple junctions of zircon granules. Despite the highly variable effect on textures and Zr phases, shock-related features show no correlation with relatively homogeneous U–Pb or 207Pb/206Pb ages of zircons. Either the shock events occurred very soon after the solidification or recrystallization of the different Zr phases, or the shock events were too brief to result in noticeable Pb loss during shock metamorphism

How to write a successful grant application: guidance provided by the European Society of Clinical Pharmacy.

Considering a rejection rate of 80–90%, the preparation of a research grant is often considered a daunting task since it is resource intensive and there is no guarantee of success, even for seasoned researchers. This commentary provides a summary of the key points a researcher needs to consider when writing a research grant proposal, outlining: (1) how to conceptualise the research idea; (2) how to find the right funding call; (3) the importance of planning; (4) how to write; (5) what to write, and (6) key questions for reflection during preparation. It attempts to explain the difficulties associated with finding calls in clinical pharmacy and advanced pharmacy practice, and how to overcome them. The commentary aims to assist all pharmacy practice and health services research colleagues new to the grant application process, as well as experienced researchers striving to improve their grant review scores. The guidance in this paper is part of ESCP’s commitment to stimulate "innovative and high-quality research in all areas of clinical pharmacy"

Scope, content and quality of clinical pharmacy practice guidelines:a systematic review

Background Guidelines for pharmacy practitioners regarding various clinical pharmacy activities have been published ina number of countries. There is a need to review the guidelines and identify the scope of activities covered as a prelude todeveloping internationally acceptable common guidelines.Aim To review the scope of clinical pharmacy guidelines and assess the extent to which these guidelines conform to qualitystandards as per the AGREE II instrument.Method Medline, Embase, Guideline Central, International Pharmaceutical Abstracts, Google Scholar and Google (for greyliterature) were searched for the period 2010 to January 2023. Guidelines which focused on any health care setting and anyclinical pharmacy activity were included. Data were extracted and quality assessed independently by two reviewers usingthe English version of the AGREE II instrument.Results Thirty-eight guidelines were included, mostly originating from Australia (n = 10), Ireland (n = 8), UK (n = 7) andUSA (n = 5). Areas covered included medication reconciliation, medicines optimisation, medication management and transi-tion of care. As per the AGREE II assessment, the highest score was obtained for the scope and purpose domain and the low-est score for rigour of development, mainly due to non-consideration of literature/evidence to inform guideline development.Conclusion Clinical pharmacy guidelines development processes need to focus on all quality domains and should take asystematic approach to guideline development. Guidelines need to further emphasise person-centred care and clinical com-munication. There is a scope to harmonise the guidelines internationally considering the diverse practices, standards and legislations across different geographie