Distinct immunopathological mechanisms of EBV-positive and EBV-negative posttransplant lymphoproliferative disorders

EBV-positive and EBV-negative posttransplant lymphoproliferative disorders (PTLDs) arise in different immunovirological contexts and might have distinct pathophysiologies. To examine this hypothesis, we conducted a multicentric prospective study with 56 EBV-positive and 39 EBV-negative PTLD patients of the K-VIROGREF cohort, recruited at PTLD diagnosis and before treatment (2013–2019), and compared them to PTLD-free Transplant Controls (TC, n = 21). We measured absolute lymphocyte counts (n = 108), analyzed NK- and T cell phenotypes (n = 49 and 94), and performed EBV-specific functional assays (n = 16 and 42) by multiparameter flow cytometry and ELISpot-IFNγ assays (n = 50). EBV-negative PTLD patients, NK cells overexpressed Tim-3; the 2-year progression-free survival (PFS) was poorer in patients with a CD4 lymphopenia (CD4⁺<300 cells/mm³, p <  .001). EBV-positive PTLD patients presented a profound NK-cell lymphopenia (median = 60 cells/mm³) and a high proportion of NK cells expressing PD-1 (vs. TC, p = .029) and apoptosis markers (vs. TC, p < .001). EBV-specific T cells of EBV-positive PTLD patients circulated in low proportions, showed immune exhaustion (p = .013 vs. TC) and poorly recognized the N-terminal portion of EBNA-3A viral protein. Altogether, this broad comparison of EBV-positive and EBV-negative PTLDs highlight distinct patterns of immunopathological mechanisms between these two diseases and provide new clues for immunotherapeutic strategies and PTLD prognosis.     

T cell antigenicity and immunogenicity of allogeneic exosomes

Extracellular vesicles, including exosomes, are regularly released by allogeneic cells after transplantation. Recipient antigen-presenting cells (APCs) capture these vesicles and subsequently display donor MHC molecules on their surface. Recent evidence suggests that activation of alloreactive T cells by the so-called cross-dressed APCs plays an important role in initiating the alloresponse associated with allograft rejection. On the other hand, whether allogeneic exosomes can bind to T cells on their own and activate them remains unclear. In this study, we showed that allogeneic exosomes can bind to T cells but do not stimulate them in vitro unless they are cultured with APCs. On the other hand, allogeneic exosomes activate T cells in vivo and sensitize mice to alloantigens but only when delivered in an inflammatory environment.     

Targeting NF-κB c-Rel in regulatory T cells to treat corneal transplantation rejection

The relevance of Tregs in the induction of tolerance against corneal allografts has been well established. Although it is well known that the conversion of Tregs into effector-like cells contributes to the loss of corneal immune privilege, the underlying mechanism is still not fully understood. Using heterologous penetrating keratoplasty model, we found that Tregs from corneal allograft rejected mice (inflam-Tregs) exhibit impaired function and characteristics of effector T cells. Further study showed that the expression of NF-κB c-Rel, a key mediator of effector T cell function, was significantly increased in inflam-Tregs. Mechanistic study revealed that elevated NF-κB c-Rel level in inflam-Tregs impaired Treg function through the promotion of inflammatory cytokine production and glycolysis. More importantly, we demonstrated that targeting NF-κB c-Rel was able to improve the immune suppressive function of inflam-Tregs in vitro and enhance the potential of them to suppress corneal transplantation rejection. Therefore, our current study identified NF-κB c-Rel as a key mediator of the conversion of Tregs into effector-like cells when under inflammatory environment.     

Hospital‐based health systems 20 years later: A taxonomy for policy research and analysis

ObjectiveBuilding on the original taxonomy of hospital‐based health systems from 20 years ago, we develop a new taxonomy to inform emerging public policy and practice developments.Data SourcesThe 2016 American Hospital Association''s (AHA) Annual Survey; the 2016 IQVIA Healthcare Organizations and Systems (HCOS) database; and the 2017‐2018 National Survey of Healthcare Organizations and Systems (NSHOS).Study DesignCluster analysis of the 2016 AHA Annual Survey data to derive measures of differentiation, centralization, and integration to create categories or types of hospital‐based health systems.Data CollectionPrincipal components factor analysis with varimax rotation generating the factors used in the cluster algorithms.Principal FindingsAmong the four cluster types, 54% (N = 202) of systems are decentralized (−0.35) and relatively less differentiated (−0.37); 23% of systems (N = 85) are highly differentiated (1.28) but relatively decentralized (−0.29); 15% (N = 57) are highly centralized (2.04) and highly differentiated (0.65); and approximately 9 percent (N = 33) are least differentiated (−1.35) and most decentralized (−0.64). Despite differences in calculation, the Highly Centralized, Highly Differentiated System Cluster and the Undifferentiated, Decentralized System Cluster were similar to those identified 20 years ago. The other two system clusters contained similarities as well as differences from those 20 years ago. Overall, 82 percent of the systems remain relatively decentralized suggesting they operate largely as holding companies allowing autonomy to individual hospitals operating within the system.ConclusionsThe new taxonomy of hospital‐based health systems bears similarities as well as differences from 20 years ago. Important applications of the taxonomy for addressing current challenges facing the healthcare system, such as the transition to value‐based payment models, continued consolidation, and the growing importance of the social determinants of health, are highlighted.     

Differences in patient perceptions of integrated care among black,hispanic, and white Medicare beneficiaries

ObjectiveThis study sought to identify potential disparities among racial/ethnic groups in patient perceptions of integrated care (PPIC) and to explore how methodological differences may influence measured disparities.Data SourceData from Medicare beneficiaries who completed the 2015 Medicare Current Beneficiary Survey (MCBS) and were enrolled in Part A benefits for an entire year.Study DesignWe used 4‐point measures of eight dimensions of PPIC and assessed differences in dimensions among racial/ethnic groups. To estimate differences, we applied a “rank and replace” method using multiple regression models in three steps, balancing differences in health status among racial groups and adjusting for differences in socioeconomic status. We reran all analyses with additional SES controls and using standard multiple variable regression.Data Collection/Extraction MethodsNot applicable.Principal FindingsWe found several significant differences in perceived integrated care between Black versus White (three of eight measures) and Hispanic versus White (one of eight) Medicare beneficiaries. On average, Black beneficiaries perceived more integrated support for self‐care than did White beneficiaries (mean difference = 0.14, SE = 0.06, P =.02). Black beneficiaries perceived more integrated specialists’ knowledge of past medical history than did White beneficiaries (mean difference = 0.12, SE = 0.06, P =.01). Black and Hispanic beneficiaries also each reported, on average, 0.18 more integrated medication and home health management than did White beneficiaries (P <.01 and P <.01). These findings were robust to sensitivity analyses and model specifications.ConclusionsThere exist some aspects of care for which Black and Hispanic beneficiaries may perceive greater integrated care than non‐Hispanic White beneficiaries. Further studies should test theories explaining why racial/ethnic groups perceive differences in integrated care.     

Patients' and family members' perspectives on the benefits and working mechanisms of family nursing conversations in Dutch home healthcare

The aim of this study is to propose a model of the benefits and working mechanisms of family nursing conversations in home healthcare from the perspective of participating patients and their family members. Family nursing conversations in this study are intended to optimise family functioning, improve collaboration between family and professional caregivers and ultimately prevent or reduce overburden of family caregivers. In a qualitative grounded theory design, data were collected in 2017 using intensive interviewing with participants of family nursing conversations in home healthcare. A total of 26 participants (9 patients and 17 family members) from 11 families participated in a family nursing conversation and the study. Seven nurses who received extensive education in family nursing conversations conducted them as part of their daily practice. Interviews occurred 4–6 weeks after the family nursing conversation. The model that was constructed in close collaboration with the families consists of three parts. The first part outlines working mechanisms of the conversation itself according to participants, i.e. structured and open communication about the care situation and the presence of all of the people who are involved. The second part consists of the benefits that participants experienced during and immediately after the conversation – an increased sense of overview and improved contact among the people involved – and the related working mechanisms. The last part consists of benefits that emerged in the weeks after the conversation – reduced caregiver burden and improved quality of care – and the related working mechanisms. Insight into the benefits and working mechanisms of family nursing conversations may assist healthcare professionals in their application of the intervention and provides directions for outcomes and processes to include in future studies.     

磁处理水对抗癌药物的解毒作用

我们的实验发现，磁处理水对环磷酰胺等五种抗癌药物的毒性具有不同程度的缓解作用，能增加小鼠的存活率，能降低药物引起的白细胞减少。对目前癌化疗中使用率最高的环磷酰胺，其作用最明显。     

Design and application research of nucleotide sequence analysis system software

INTRODUCTION　　From integrallevel and celllevel,the research of organism and diseasediagnosishave already entered molecular level.Molecular biology is the science to researchstructure and function of organism macromolecule.Based on differentgene code se-…     

A Theoretical Model for the Margination of Particles within Blood Vessels

The margination of a particle circulating in the blood stream has been analyzed. The contribution of buoyancy, hemodynamic forces, van der Waals, electrostatic and steric interactions between the circulating particle and the endothelium lining the vasculature has been considered. For practical applications, the contribution of buoyancy, hemodynamic forces and van der Waals interactions should be only taken into account, whilst the effect of electrostatic and steric repulsion becomes important only at very short distances from the endothelium (1–10 nm). The margination speed and the time for margination t_s have been estimated as a function of the density of the particle relative to blood , the Hamaker constant A and radius R of the particle. A critical radius R_c exists for which the margination time t_s has a maximum, which is influenced by both and A: the critical radius decreases as the relative density increases and the Hamaker constant decreases. Therefore, particles used for drug delivery should have a radius smaller than the critical value (in the range of 100 nm) to facilitate margination and interaction with the endothelium. While particles used as nanoharvesting agents in proteomics or genomics analysis should have a radius close to the critical value to minimize margination and increase their circulation time.