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EULAR recommendations for cardiovascular disease risk management in patients with rheumatoid arthritis and other forms of inflammatory joint disorders: 2015/2016 update
Patients with rheumatoid arthritis (RA) and other inflammatory joint disorders (IJD) have increased cardiovascular disease (CVD) risk compared with the general population. In 2009, the European League Against Rheumatism (EULAR) taskforce recommended screening, identification of CVD risk factors and CVD risk management largely based on expert opinion. In view of substantial new evidence, an update was conducted with the aim of producing CVD risk management recommendations for patients with IJD that now incorporates an increasing evidence base. A multidisciplinary steering committee (representing 13 European countries) comprised 26 members including patient representatives, rheumatologists, cardiologists, internists, epidemiologists, a health professional and fellows. Systematic literature searches were performed and evidence was categorised according to standard guidelines. The evidence was discussed and summarised by the experts in the course of a consensus finding and voting process. Three overarching principles were defined. First, there is a higher risk for CVD in patients with RA, and this may also apply to ankylosing spondylitis and psoriatic arthritis. Second, the rheumatologist is responsible for CVD risk management in patients with IJD. Third, the use of non-steroidal anti-inflammatory drugs and corticosteroids should be in accordance with treatment-specific recommendations from EULAR and Assessment of Spondyloarthritis International Society. Ten recommendations were defined, of which one is new and six were changed compared with the 2009 recommendations. Each designated an appropriate evidence support level. The present update extends on the evidence that CVD risk in the whole spectrum of IJD is increased. This underscores the need for CVD risk management in these patients. These recommendations are defined to provide assistance in CVD risk management in IJD, based on expert opinion and scientific evidence.
Journal Article
Fibroblast activation protein-targeted radionuclide therapy: background, opportunities, and challenges of first (pre)clinical studies
IntroductionFibroblast activation protein (FAP) is highly overexpressed in stromal tissue of various cancers. While FAP has been recognized as a potential diagnostic or therapeutic cancer target for decades, the surge of radiolabeled FAP-targeting molecules has the potential to revolutionize its perspective. It is presently hypothesized that FAP targeted radioligand therapy (TRT) may become a novel treatment for various types of cancer. To date, several preclinical and case series have been reported on FAP TRT using varying compounds and showing effective and tolerant results in advanced cancer patients. Here, we review the current (pre)clinical data on FAP TRT and discuss its perspective towards broader clinical implementation. MethodsA PubMed search was performed to identify all FAP tracers used for TRT. Both preclinical and clinical studies were included if they reported on dosimetry, treatment response or adverse events. The last search was performed on July 22 2022. In addition, a database search was performed on clinical trial registries (date 15th of July 2022) to search for prospective trials on FAP TRT.ResultsIn total, 35 papers were identified that were related to FAP TRT. This resulted in the inclusion of the following tracers for review: FAPI-04, FAPI-46, FAP-2286, SA.FAP, ND-bisFAPI, PNT6555, TEFAPI-06/07, FAPI-C12/C16, and FSDD.ConclusionTo date, data was reported on more than 100 patients that were treated with different FAP targeted radionuclide therapies such as [177Lu]Lu-FAPI-04, [90Y]Y-FAPI-46, [177Lu]Lu-FAP-2286, [177Lu]Lu-DOTA.SA.FAPI and [177Lu]Lu-DOTAGA.(SA.FAPi)2. In these studies, FAP targeted radionuclide therapy has resulted in objective responses in difficult to treat end stage cancer patients with manageable adverse events. Although no prospective data is yet available, these early data encourages further research.
Journal Article
تعليم العلوم في المرحلة الأساسية : الأساليب-المفاهيم-الاستقصاءات
يزود هذا الكتاب المعلمين بالخبرة العملية والفهم الشامل لمواضيع الغذاء والصحة والأمن وحاجات الأطفال منذ الميلاد وحتى دخولهم المدرسة بالإضافة إلى إعداد المعلمين ليكونوا قادرين على خدمة المجتمع وتقديم الخدمة للمجتمعات المتباينة للأطفال من حيث الرعاية وإعداد مراكز التعليم للطفولة المبكرة والحضانة والروضة والمرحلة الأساسية وهدفنا من ذلك تزويد الأطفال بفهم ووعي قوي بالمفاهيم وتشجيعهم على توظيف هذه الخبرات الصحية للمساهمة في الحفاظ على صحتهم.
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Disruption of histone methylation in developing sperm impairs offspring health transgenerationally
Parent and even grandparent environmental exposure can transmit adverse health effects to offspring. The mechanism of transmission is unclear, but some studies have implicated variations in DNA methylation. In a mouse model, Siklenka et al. found that alterations in histone methylation during sperm formation in one generation leads to reduced survival and developmental abnormalities in three subsequent generations (see the Perspective by McCarrey). Although changes in DNA methylation were not observed, altered sperm RNA content and abnormal gene expression in offspring were measured. Thus, chromatin may act as a mediator of molecular memory in transgenerational inheritance. Science , this issue p. 10.1126/science.aab2006 ; see also p. 634 Overexpression of a histone demethylase in the mouse germ line reveals a mode of transgenerational epigenetic inheritance. [Also see Perspective by McCarrey ] A father’s lifetime experiences can be transmitted to his offspring to affect health and development. However, the mechanisms underlying paternal epigenetic transmission are unclear. Unlike in somatic cells, there are few nucleosomes in sperm, and their function in epigenetic inheritance is unknown. We generated transgenic mice in which overexpression of the histone H3 lysine 4 (H3K4) demethylase KDM1A (also known as LSD1) during spermatogenesis reduced H3K4 dimethylation in sperm. KDM1A overexpression in one generation severely impaired development and survivability of offspring. These defects persisted transgenerationally in the absence of KDM1A germline expression and were associated with altered RNA profiles in sperm and offspring. We show that epigenetic inheritance of aberrant development can be initiated by histone demethylase activity in developing sperm, without changes to DNA methylation at CpG-rich regions.
Journal Article
Towards the Human Colorectal Cancer Microbiome
Multiple factors drive the progression from healthy mucosa towards sporadic colorectal carcinomas and accumulating evidence associates intestinal bacteria with disease initiation and progression. Therefore, the aim of this study was to provide a first high-resolution map of colonic dysbiosis that is associated with human colorectal cancer (CRC). To this purpose, the microbiomes colonizing colon tumor tissue and adjacent non-malignant mucosa were compared by deep rRNA sequencing. The results revealed striking differences in microbial colonization patterns between these two sites. Although inter-individual colonization in CRC patients was variable, tumors consistently formed a niche for Coriobacteria and other proposed probiotic bacterial species, while potentially pathogenic Enterobacteria were underrepresented in tumor tissue. As the intestinal microbiota is generally stable during adult life, these findings suggest that CRC-associated physiological and metabolic changes recruit tumor-foraging commensal-like bacteria. These microbes thus have an apparent competitive advantage in the tumor microenvironment and thereby seem to replace pathogenic bacteria that may be implicated in CRC etiology. This first glimpse of the CRC microbiome provides an important step towards full understanding of the dynamic interplay between intestinal microbial ecology and sporadic CRC, which may provide important leads towards novel microbiome-related diagnostic tools and therapeutic interventions.
Journal Article
Scoping reviews and their role in identifying research priorities
Scoping reviews have been identified as appropriate methodologies to contribute to our knowledge. The objective of this review is to summarize how scoping reviews can be used to identify research priorities.
Based on our experience as evidence synthesis methodologists and researchers, the Joanna Briggs Institute (JBI) scoping review methodology group, have identified the potential roles of scoping reviews in identification of research priorities.
Scoping reviews typically ask broad questions that allow researchers to obtain an overview or map of the existing evidence. Scoping reviews also incorporate multiple levels of evidence that enriches the strength of the knowledge that is gained. This value is revealed by the use of scoping reviews to contribute to and perform the following functions: 1) map a research area and identify gaps that need to be addressed; 2) prioritize research topics by identifying key issues to investigate; 3) identify the type of study designs that have been used to investigate a particular topic, and/or the range of outcomes measured following a specific intervention; 4) identify the essential contextual factors that are relevant to the study of a particular research topic; 5) identify equity issues in the research field; 6) assist in engaging stakeholders and/or experts in the field by facilitating the inclusion of these stakeholders within the research process; and 7) provide the relevant new knowledge to enhance and support applications for funding.
To ensure this contribution to identifying research priorities is reliable, scoping reviews must be performed following the existing rigorous methodological processes and adhere to the currently available reporting guidelines. By doing so, scoping reviews have great potential to identify research priorities, to guide the expansion of research and the generation of new knowledge.
•Scoping reviews offer a broad evidence map including research priorities.•Seven methods show how scoping reviews pinpoint research priorities.•They include mapping gaps, topic prioritization, study designs, and context.•They cover equity, stakeholder engagement, and funding advocacy.•Scoping reviews act as synthesis tools to set research priorities.
Journal Article