Gut intraepithelial lymphocyte development

CD8alphabeta(+) and CD4(+) intraepithelial lymphocytes, the progeny of double-positive thymocytes, are oligoclonal T-cell populations that have accumulated in the gut wall as the result of repeated antigenic stimulations, which lead to rounds of traffic through the lymph/blood circuit ending in an alpha4beta7-integrin-driven homing all along the gut mucosa. In contrast, CD8alphaalpha(+) intraepithelial lymphocytes, which may be TCRgammadelta(+) or alphabeta(+), result in part from local differentiation in the gut, but studies comparing euthymic and athymic mice suggest a thymic double-negative origin for many of them.     

EoE disease monitoring: Where we are and where we are going

ObjectiveTo review literature on various methods of monitoring and characterizing eosinophilic esophagitis (EoE) with respect to their validity as well as risk to the patient.Data SourcesA literature search was performed using PubMed with keyword combinations of EoE and monitoring as well as various techniques used for monitoring, including but not limited to, symptoms, endoscopy, histology, fluoroscopy, FLIP, noninvasive monitoring, and biomarkers.Study SelectionsCase-control studies, observational studies, peer-reviewed reviews and guidelines, and systematic reviews were selected, reviewed, and summarized here.ResultsA wealth of research regarding monitoring of EoE is currently being undertaken and published. Our review highlights those that have been validated and are currently being used, as well as some that show promise for future monitoring and disease characterization.ConclusionEosinophilic esophagitis is a chronic condition that at this time requires upper endoscopy as the gold standard of diagnosis and monitoring. There is a great need in the field for less invasive monitoring tools and better ways to characterize disease to allow for personalization of therapies.     

Genetic feedback for psychiatric conditions: Where are we now and where are we going

Genome‐wide association studies are rapidly advancing our understanding of the genetic architecture of complex disorders, including many psychiatric conditions such as major depression, schizophrenia, and substance use disorders. One common goal of genome‐wide association studies is to use findings for enhanced clinical prediction in the future, which can aid in identifying at‐risk individuals to enable more effective prevention screening and treatment strategies. In order to achieve this goal, we first need to gain a better understanding of the issues surrounding the return of complex genetic results. In this article, we summarize the current literature on: (a) genetic literacy in the general population, (b) the public's interest in receiving genetic test results for psychiatric conditions, (c) how individuals react to and interpret their genotypic information for specific psychiatric conditions, and (d) gaps in our knowledge that will be critical to address as we move toward returning genotypic information for psychiatric conditions in both research and clinical settings. By reviewing extant studies, we aim to increase awareness of the potential benefits and consequences of returning genotypic information for psychiatric conditions.     

Yellow fever control in Cameroon: Where are we now and where are we going?

Background  

Cameroon is one of 12 African countries that bear most of the global burden of yellow fever. In 2002 the country developed a five-year strategic plan for yellow fever control, which included strategies for prevention as well as rapid detection and response to outbreaks when they occur. We have used data collected by the national Expanded Programme on Immunisation to assess the progress made and challenges faced during the first four years of implementing the plan.     

Conference summary: What we have learned and where we are headed

This overview highlights the actionable near‐term objectives for the TRN drawn from discussions in the breakout sessions. A major purpose of the symposium was to focus attention on establishing priorities, setting goals, and identifying the steps toward accomplishing those goals. Two major objectives were identified. One is to establish Turner syndrome as a priority area of research for the National Institutes of Health. Turner syndrome should not only be viewed as a rare disorder, but also as a model for common diseases that have a male sex bias in the general population attributable to the lack of a second X chromosome. Barriers to recognition of Turner syndrome as an important area of research were identified, and new approaches to enhancing visibility are discussed. The second major objective is to further development of the Turner Syndrome Research Registry (TSRR). This patient‐powered research registry is a paradigm‐shifting model for how human‐based research can be improved through equal partnerships between researchers and study subjects. The TSRR is founded on an agreement that study participants are the ultimate owners of their personal data. The major challenges to establishing a maximally functional registry of this design were discussed, and a clear path forward was established.     

淋巴细胞穿越血管内皮机制的研究进展

淋巴细胞和多形核细胞向血管外迁移是一个复杂的过程 ,其中涉及了大量的粘附分子 ,包括选择素、整合素、免疫球蛋白基因超家族、钙依赖性粘附素家族等 ,是目前研究的热点 ,白细胞的大量浸润在某些疾病的发生发展过程中起重要作用 ,明确其机理对于疾病的防治有重要意义。现将近几年有关粘附分子在淋巴细胞穿越内皮过程中的作用及机理的研究进展作一综述     

Forensic Neuropsychology: are we there yet?

Forensic Neuropsychology is a new and rapidly evolving subspecialty of clinical neuropsychology that applies neuropsychological principles and practices to matters that pertain to legal decision-making. Forensic neuropsychologists provide the trier of fact with specialized information regarding brain-behavior relationships. The primary responsibility of the forensic neuropsychologist is to provide information based on scientifically-validated neuropsychological principles and clinical methodology that is pertinent to the Forensic Question at hand-which is not just whether the patient has dysfunction, but whether the dysfunction results from the event under consideration. To best answer the Forensic Question, the neuropsychologist must use a methodology that has been scientifically-validated on brain-impaired individuals, and can distinguish various brain conditions from each other as well as from normal variation. The methodology must be able to determine whether any dysfunction found is, in fact, the result of a neurological condition as opposed to non-neurological, psychological, or even factitious disorders. This paper discusses neuropsychological methodology in the context of forensic application and the requirements of the legal process and illustrates these issues with case examples.     

Clinical trials: where are we now?

Summary:  Clinical trials in transplantation have focused on improving outcomes and minimizing side effects associated with renal transplantation. Although immunologic tolerance, which means complete freedom from immunosuppressive drugs and maintenance of excellent long-term graft function, has seldom been achieved, in rare cases, this has been accomplished. Most current clinical trials focus on minimization of steroid use and calcineurin inhibitor use as a step toward tolerance, sometimes termed prope tolerance. Alternatively, new immunosuppressive agents are studied to assess their efficacy in preventing graft rejection with the anticipation of lesser toxicity. This review is organized in a case presentation style with actual cases from the University of Wisconsin kidney transplant experience presented as illustrations of actual scenarios in clinical trials. Lessons learned from these particular patients are then summarized with reference to the literature associated with the case. Using this format, some of the important lessons learned from clinical trials are outlined and directions for future study are noted. Clinical trials have permitted a dramatic improvement in graft survival and lowering of infectious and malignant side effects over the past 30–40 years. Nevertheless, we remain far from achieving true tolerance in patients for a variety of reasons.     

Rodent models of lymphocyte migration.

The ability of leukocytes to migrate out of blood into tissues enables them to perform their surveillance functions. Understanding the molecular mechanisms by which this migration is accomplished has the potential of unveiling new methods of regulating immune responses. The existing knowledge of rodent physiology and the recent development of knockout mice makes rodents attractive models for studying the mechanisms of leukocyte migration in vivo. This review considers the existing rodent models in light of the knowledge gained from them in lymphocyte migration, and in addition, shows the advantages and limitations of using rodent models in studying lymphocyte migration.     

Mechanisms and regulation of lymphocyte migration

Lymphocyte traffic seems to be an essential requirement for an adequate immune response both in lymphoid tissues and local inflammatory sites. In this review, Adrian Duijvestijn and Alf Hamann discuss how selective migration of lymphocytes is directed by lymphocyte-endothelial interactions and what mechanisms may control this.