Calcineurin inhibitors and immunosuppression – a tale of two isoforms

2012 ◽  
Vol 14 ◽  
Author(s):  
Clintoria R. Williams ◽  
Jennifer L. Gooch
Keyword(s):  
Immune System ◽  
Cell Function ◽  
Survival Rates ◽  
Calcineurin Inhibitors ◽  
The Past ◽  
Current State ◽  
Organ Systems ◽  
The Usa ◽  
End Stage ◽  
Calcineurin Inhibition

Organ transplantation is the state of the art for treating end-stage organ failure. Over 25 000 organ transplants are performed in the USA each year. Survival rates following transplantation are now approaching 90% for 1 year and 75% for 5 years. Central to this success was the introduction of drugs that suppress the immune system and prevent rejection. The most commonly used class of immunosuppressing drugs are calcineurin inhibitors (CNIs). Calcineurin is a ubiquitous enzyme that is important for T-cell function. With more people taking CNIs for longer and longer periods of time the consequences of calcineurin inhibition on other organ systems – particularly the kidney – have become a growing concern. Virtually all people who take a CNI will develop some degree of kidney toxicity and up to 10% will progress to kidney failure. In the past 15 years, research into calcineurin action has identified distinct actions of the two main isoforms of the catalytic subunit of the enzyme. The α-isoform is required for kidney function whereas the β-isoform has a predominant role in the immune system. This review will discuss the current state of knowledge about calcineurin isoforms and how these new insights may reshape post-transplant immunosuppression.

Anesthesia for Lung Transplantation

2019 ◽  
pp. 322-329
Author(s):  
J. Devin Roberts
Keyword(s):  
Lung Transplantation ◽  
Transesophageal Echocardiography ◽  
Gold Standard ◽  
Anesthetic Management ◽  
Survival Rates ◽  
Anesthesia Care ◽  
Lung Isolation ◽  
The Past ◽  
Lung Transplants ◽  
End Stage

Since the first human procedure in 1963, lung transplantation has become the gold standard treatment of a variety of end-stage lung diseases. With over 4000 lung transplants performed in 2015 and steadily improving survival rates over the past three decades, anesthetic management of patients undergoing lung transplant can significantly contribute to patient outcomes. Anesthesia care for lung transplantation can be both complex and clinically challenging. Anesthesiologists taking part in these procedures need to have specific skills regarding thoracic and cardiac anesthesia. There are both technical and physiological challenges, such as achieving adequate lung isolation and oxygenation, interpretation and use of transesophageal echocardiography, and the management of respiratory and myocardial impairments. This chapter provides an overview of these perioperative anesthetic management considerations utilizing a problem-based format.

EZH2 function in immune cell development

2020 ◽  
Vol 401 (8) ◽  
pp. 933-943 ◽  
Author(s):  
Stephen L. Nutt ◽  
Christine Keenan ◽  
Michaël Chopin ◽  
Rhys S. Allan
Keyword(s):  
Immune System ◽  
Cell Function ◽  
Immune Cell ◽  
Proliferating Cells ◽  
Hematopoietic Stem ◽  
Polycomb Repressive Complex 2 ◽  
Current State ◽  
Core Components ◽  
And Function ◽  
Cell Cycle Inhibitors

AbstractThe polycomb repressive complex 2 (PRC2) consists of three core components EZH2, SUZ12 and EED. EZH2 catalyzes the methylation of lysine 27 of histone H3, a modification associated with gene silencing. Through gene duplication higher vertebrate genomes also encode a second partially redundant methyltransferase, EZH1. Within the mammalian immune system most research has concentrated on EZH2 which is expressed predominantly in proliferating cells. EZH2 and other PRC2 components are required for hematopoietic stem cell function and lymphocyte development, at least in part by repressing cell cycle inhibitors. At later stages of immune cell differentiation, EZH2 plays essential roles in humoral and cell-mediated adaptive immunity, as well as the maintenance of immune homeostasis. EZH2 is often overactive in cancers, through both gain-of-function mutations and over-expression, an observation that has led to the development and clinical testing of specific EZH2 inhibitors. Such inhibitors may also be of use in inflammatory and autoimmune settings, as EZH2 inhibition dampens the immune response. Here, we will review the current state of understanding of the roles for EZH2, and PRC2 more generally, in the development and function of the immune system.

scholarly journals A Bibliometric Analysis of Atopic Dermatitis Research over the Past Three Decades and Future Perspectives

Healthcare ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1749
Author(s):  
Dongwon Kim ◽  
Younbyoung Chae ◽  
Hi-Joon Park ◽  
In-Seon Lee
Keyword(s):  
Atopic Dermatitis ◽  
Immune System ◽  
Skin Barrier ◽  
Food Allergies ◽  
Annual Number ◽  
Network Analyses ◽  
The Past ◽  
Keywords Atopic Dermatitis ◽  
The Usa ◽  
The Uk

Atopic dermatitis (AD) has been increasing in prevalence over the past few decades; however, AD has never been analyzed using a bibliometric approach. We searched for AD studies in the dermatology and allergy category of the Web of Science and SCOPUS databases using the keywords “atopic dermatitis”, “eczema”, and “atopy”. In total, 53,460 documents were retrieved. We analyzed annual publication trends and performed keyword and co-authorship network analyses. The annual number of AD publications has increased over the years. Asthma, food allergies, the skin barrier, IgE, and epidemiology have received extensive attention. The keywords ‘allergic rhinitis’, ‘child(ren)’, ‘quality of life’, and ‘probiotics’ have become more commonly used in recent years. AD research has been led by only a few countries, such as the USA, Germany, and the UK, and longstanding research topics such as asthma, allergy, and the immune system continue to be important. We suggest that global collaborations, research in developing countries, and research that is more holistic (thus exploring how genes, the immune system, the environment, and the microbiome together impact AD) are necessary.

The Fate of Older Diabetic Patients on Peritoneal Dialysis: Myths and Mysteries and Suggestions for Further Research

2007 ◽  
Vol 27 (6) ◽  
pp. 611-618 ◽  
Author(s):  
Steven Van Laecke ◽  
Nic Veys ◽  
Francis Verbeke ◽  
Raymond Vanholder ◽  
Wim Van Biesen
Keyword(s):  
Peritoneal Dialysis ◽  
Negative Impact ◽  
Diabetic Patients ◽  
Fluid Restriction ◽  
Treatment Practices ◽  
The Past ◽  
Hormone Balance ◽  
The Usa ◽  
Stage Renal Disease ◽  
End Stage

The outcome of older and especially of female diabetic patients appears to be worse on peritoneal dialysis (PD) than on hemodialysis (HD). This opinion is based mostly on data coming from the USA, whereas data from other regions seem to give a more balanced picture. The questions arise whether indeed outcome is worse in this patient group, and what might be the underlying reasons for this; further research to unravel this phenomenon is warranted. This review proposes several suggestions for further exploration. The observed differences in outcome might be attributable to differences in treatment practices and experience with PD versus HD. As cardiovascular mortality is a major killer in end-stage renal disease patients, differences in fluid homeostasis and how it is achieved are potential explanations. Fluid balance is potentially more difficult to obtain in PD patients, especially as in the past it was spuriously suggested that fluid restriction was less important in PD patients. PD and HD might also have different impacts on factors related to inflammation, insulin resistance, and hormone balance. The adipocytokine network is of special interest in this respect. It is also possible that bias introduced by the way we measure body composition might have a more negative impact on PD than on HD patients. Finally, it still is not fully established that if diabetic patients are treated appropriately, their outcome on PD is worse than that on HD; further observational trials in this respect are needed. All these topics require further clarification and investigation.

scholarly journals Human Microbiota in Esophageal Adenocarcinoma: Pathogenesis, Diagnosis, Prognosis and Therapeutic Implications

2022 ◽  
Vol 12 ◽  
Author(s):  
Wanyue Dan ◽  
Lihua Peng ◽  
Bin Yan ◽  
Zhengpeng Li ◽  
Fei Pan
Keyword(s):  
Esophageal Adenocarcinoma ◽  
Genetic Factors ◽  
Survival Rates ◽  
Relative Survival ◽  
Therapeutic Implications ◽  
The Past ◽  
Human Microbiota ◽  
Current State ◽  
Esophageal Carcinogenesis ◽  
The Relationship

Esophageal adenocarcinoma (EAC) is one of the main subtypes of esophageal cancer. The incidence rate of EAC increased progressively while the 5-year relative survival rates were poor in the past two decades. The mechanism of EAC has been studied extensively in relation to genetic factors, but less so with respect to human microbiota. Currently, researches about the relationship between EAC and the human microbiota is a newly emerging field of study. Herein, we present the current state of knowledge linking human microbiota to esophageal adenocarcinoma and its precursor lesion—gastroesophageal reflux disease and Barrett’s esophagus. There are specific human bacterial alternations in the process of esophageal carcinogenesis. And bacterial dysbiosis plays an important role in the process of esophageal carcinogenesis via inflammation, microbial metabolism and genotoxicity. Based on the human microbiota alternation in the EAC cascade, it provides potential microbiome-based clinical application. This review is focused on novel targets in prevention, diagnosis, prognosis, and therapy for esophageal adenocarcinoma.

scholarly journals Telemedicine, the current COVID-19 pandemic and the future: a narrative review and perspectives moving forward in the USA

2020 ◽  
Vol 8 (3) ◽  
pp. e000530 ◽  
Author(s):  
Asim Kichloo ◽  
Michael Albosta ◽  
Kirk Dettloff ◽  
Farah Wani ◽  
Zain El-Amir ◽  
...  
Keyword(s):  
Narrative Review ◽  
Cochrane Library ◽  
Physician Shortage ◽  
Careful Selection ◽  
The Past ◽  
Ovid Medline ◽  
Current State ◽  
The Future ◽  
The Usa ◽  
Full Immersion

A narrative review was conducted to examine the current state of the utilisation of telemedicine amid the current COVID-19 pandemic and to evaluate the benefits of continuing telemedicine usage in the future. A literature review was performed for articles related to telemedicine. Databases including PubMed, Google Scholar, Cochrane Library and Ovid MEDLINE were searched. Three reviewers independently performed article selection based on relevance to our topic. We included all articles between 1990 and 2020 related to telemedicine using the following keywords: ‘telemedicine’, ‘telehealth’, ‘policy’, ‘COVID-19’, ‘regulation’, ‘rural’, ‘physical examination’, ‘future’. A total of 60 articles were identified, and through careful selection we narrowed the final number of articles to 42 based on relevance to our topic. Telemedicine has been rapidly evolving over the past several decades. Issues with regulation and reimbursement have prevented its full immersion into the healthcare system. During the current pandemic, Centers for Medicare and Medicaid services have expanded access to telemedicine services. The advantages of telemedicine moving forward include its cost-effectiveness, ability to extend access to specialty services and its potential to help mitigate the looming physician shortage. Disadvantages include lack of available technological resources in certain parts of the country, issues with security of patient data, and challenges in performing the traditional patient examination. It is critically important that changes are made to fully immerse telemedicine services into the healthcare landscape in order to be prepared for future pandemics as well as to reap the benefits of this service in the future.

A Year in K-12 AI Education

AI Magazine ◽  
2019 ◽  
Vol 40 (4) ◽  
pp. 88-90 ◽  
Author(s):  
David Touretzky ◽  
Christina Gardner-McCune ◽  
Cynthia Breazeal ◽  
Fred Martin ◽  
Deborah Seehorn
Keyword(s):  
Decision Makers ◽  
Local School District ◽  
Column Editor ◽  
National Guidelines ◽  
Future Developments ◽  
The Past ◽  
Current State ◽  
The Usa ◽  
K 12 ◽  
New Curricula

The time is ripe to consider what 21st-century digital citizens should know about artificial intelligence (AI). Efforts are under way in the USA, China, and many other countries to promote AI education in kindergarten through high school (K–12). The past year has seen the release of new curricula and online resources for the K–12 audience, and new professional development opportunities for K–12 teachers to learn the basics of AI. This column surveys the current state of K–12 AI education and introduces the work of the AI4K12 Initiative, which is developing national guidelines for AI education in the USA.   A Note to the Reader This is the inaugural column on AI education. It aims to inform the AAAI community of current and future developments in AI education. We hope that the reader finds the columns to be informative and that they stimulate debate. It is our fond hope that this and subsequent columns inspire the reader to get involved in the broad field of AI education, by volunteering their expertise in their local school district, by providing level-headed input when discussing AI with family and friends or by lending their considerable expertise to various decision makers. We welcome your feedback, whether in the form of a response to an article or a suggestion for a future article. – Michael Wollowski, AI in Education Column Editor  

Critical Care of Heart-Lung and Lung Transplant Recipients

2019 ◽  
pp. 446-452
Author(s):  
Ramachandra R. Sista
Keyword(s):  
Critical Care ◽  
Lung Transplant ◽  
Survival Rates ◽  
Transplant Recipients ◽  
Successful Therapy ◽  
Heart Lung Transplant ◽  
The Past ◽  
Complex Procedure ◽  
Lung Transplant Recipients ◽  
End Stage

Lung transplant is a complex procedure that has been a successful therapy for various end-stage lung diseases since the 1980s. Combined heart-lung transplant, however, is performed much less frequently than in the past. Survival rates after lung transplant have been stable over the past several years (90% survival at 3 months, 80% at 1 year, 60% at 3 years, and 45% at 5 years). The types of transplant procedures available and the general indications for lung transplant are listed in this chapter.

scholarly journals Cancer Moonshot Immuno-Oncology Translational Network (IOTN): accelerating the clinical translation of basic discoveries for improving immunotherapy and immunoprevention of cancer

2020 ◽  
Vol 8 (1) ◽  
pp. e000796
Author(s):  
Ananth Annapragada ◽  
Andrew Sikora ◽  
Catherine Bollard ◽  
Jose Conejo-Garcia ◽  
Conrad Russell Cruz ◽  
...  
Keyword(s):  
Immune System ◽  
Cancer Prevention ◽  
Resource Sharing ◽  
Therapeutic Potential ◽  
Open Data ◽  
Team Science ◽  
Preclinical Research ◽  
Patients With Cancer ◽  
The Past ◽  
The Usa

Despite regulatory approval of several immune-based treatments for cancer in the past decade, a number of barriers remain to be addressed in order to fully harness the therapeutic potential of the immune system and provide benefits for patients with cancer. As part of the Cancer Moonshot initiative, the Immuno-Oncology Translational Network (IOTN) was established to accelerate the translation of basic discoveries to improve immunotherapy outcomes across the spectrum of adult cancers and to develop immune-based approaches that prevent cancers before they occur. The IOTN currently consists of 32 academic institutions in the USA. By leveraging cutting-edge preclinical research in immunotherapy and immunoprevention, open data and resource sharing, and fostering highly collaborative team science across the immuno-oncology ecosystem, the IOTN is designed to accelerate the generation of novel mechanism-driven immune-based cancer prevention and therapies, and the development of safe and effective personalized immuno-oncology approaches.

On Future Directions in Pathology

1982 ◽  
Vol 40 ◽  
pp. 274-277
Author(s):  
Benjamin F. Trump ◽  
Irene K. Berezesky ◽  
Raymond T. Jones
Keyword(s):  
Electron Microscopy ◽  
Transmission Electron Microscopy ◽  
Clinical Pathology ◽  
Future Directions ◽  
Diagnostic Pathology ◽  
The Past ◽  
Transmission Electron ◽  
Organ Systems ◽  
The Many

The role of electron microscopy and associated techniques is assured in diagnostic pathology. At the present time, most of the progress has been made on tissues examined by transmission electron microscopy (TEM) and correlated with light microscopy (LM) and by cytochemistry using both plastic and paraffin-embedded materials. As mentioned elsewhere in this symposium, this has revolutionized many fields of pathology including diagnostic, anatomic and clinical pathology. It began with the kidney; however, it has now been extended to most other organ systems and to tumor diagnosis in general. The results of the past few years tend to indicate the future directions and needs of this expanding field. Now, in addition to routine EM, pathologists have access to the many newly developed methods and instruments mentioned below which should aid considerably not only in diagnostic pathology but in investigative pathology as well.

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