Comparative Analysis of Extracellular Vesicles from Cytotoxic CD8 αβ T Cells and γδ T Cells.

Background: Although belonging to different branches of the immune system, cytotoxic CD8 αβ T cells and γδ T cells utilize common cytolytic effectors including FasL, granzymes, perforin and granulysin. The effector proteins are stored in different subsets of lysosome-related effector vesicles (LREVs) and released to the immunological synapse upon target cell encounter. Notably, in activated cells, LREVs and potentially other vesicles are continuously produced and released as extracellular vesicles (EVs).

Analysis of Cytotoxic Granules and Constitutively Produced Extracellular Vesicles from Large Granular Lymphocytic Leukemia Cell Lines.

Background: Large granular lymphocyte leukemias (LGLLs) are rare lymphoproliferative malignancies caused by clonal expansion of granular lymphocytes. T-cell LGLL and natural killer (NK) cell LGLL are defined based on their cellular origin. Their clinical manifestation and pathophysiology vary depending on the subtype and include, e.

Kontsevich-Segal Criterion in the No-Boundary State Constrains Inflation.

We show that the Kontsevich-Segal (KS) criterion, applied to the complex saddles that specify the semiclassical no-boundary wave function, acts as a selection mechanism on inflationary scalar field potentials. Completing the observable phase of slow-roll inflation with a no-boundary origin, the KS criterion effectively bounds the tensor-to-scalar ratio of cosmic microwave background fluctuations to be less than 0.08, in line with current observations.

Chemotherapy-induced release of ADAM17 bearing EV as a potential resistance mechanism in ovarian cancer.

Ovarian cancer (OvCa) is the gynaecological disorder with the poorest prognosis due to the fast development of chemoresistance. We sought to connect chemoresistance and cancer cell-derived extracellular vesicles (EV). The mechanisms of how chemoresistance is sustained by EV remained elusive.

Sequential Treatment with Temozolomide Plus Naturally Derived AT101 as an Alternative Therapeutic Strategy: Insights into Chemoresistance Mechanisms of Surviving Glioblastoma Cells.

Glioblastoma (GBM) is a poorly treatable disease due to the fast development of tumor recurrences and high resistance to chemo- and radiotherapy. To overcome the highly adaptive behavior of GBMs, especially multimodal therapeutic approaches also including natural adjuvants have been investigated. However, despite increased efficiency, some GBM cells are still able to survive these advanced treatment regimens.

Effect of stress hyperglycaemia on acute kidney injury in non-diabetic critically ill patients?

Background: Stress hyperglycaemia (SH) and acute kidney injury (AKI) occur frequently in critically ill patients, and particularly non-diabetics are associated with adverse outcome. Data is scarce on the effect of SH on AKI. We assessed whether SH (i) preceded AKI, (ii) was a risk factor of subsequent AKI, and (iii) how SH and tubular injury interacted in AKI development in critically ill, non-diabetics.

Stromal cells support the survival of human primary chronic lymphocytic leukemia (CLL) cells through Lyn-driven extracellular vesicles.

Introduction: In chronic lymphocytic leukemia (CLL), the tumor cells receive survival support from stromal cells through direct cell contact, soluble factors and extracellular vesicles (EVs). The protein tyrosine kinase Lyn is aberrantly expressed in the malignant and stromal cells in CLL tissue. We studied the role of Lyn in the EV-based communication and tumor support.

Analysis of the Seasonal Fluctuation of γδ T Cells and Its Potential Relation with Vitamin D.

In addition to its role in bone metabolism, vitamin D exerts immunomodulatory effects and has been proposed to contribute to seasonal variation of immune cells. This might be linked to higher vitamin D levels in summer than in winter due to differential sun exposure. γδ T cells comprise a numerically small subset of T cells in the blood, which contribute to anti-infective and antitumor immunity.

Intra- and Extracellular Effector Vesicles From Human T And NK Cells: Same-Same, but Different?

Cytotoxic T lymphocytes (CTL) and Natural Killer (NK) cells utilize an overlapping effector arsenal for the elimination of target cells. It was initially proposed that all cytotoxic effector proteins are stored in lysosome-related effector vesicles (LREV) termed "secretory lysosomes" as a common storage compartment and are only released into the immunological synapse formed between the effector and target cell. The analysis of enriched LREV, however, revealed an uneven distribution of individual effectors in morphologically distinct vesicular entities.

The Serine Protease CD26/DPP4 in Non-Transformed and Malignant T Cells.

CD26/Dipeptidylpeptidase 4 is a transmembrane serine protease that cleaves off N-terminal dipeptides. CD26/DPP4 is expressed on several immune cell types including T and NK cells, dendritic cells, and activated B cells. A catalytically active soluble form of CD26/DPP4 can be released from the plasma membrane.

CD30-Positive Extracellular Vesicles Enable the Targeting of CD30-Negative DLBCL Cells by the CD30 Antibody-Drug Conjugate Brentuximab Vedotin.

CD30, a member of the TNF receptor superfamily, is selectively expressed on a subset of activated lymphocytes and on malignant cells of certain lymphomas, such as classical Hodgkin Lymphoma (cHL), where it activates critical bystander cells in the tumor microenvironment. Therefore, it is not surprising that the CD30 antibody-drug conjugate Brentuximab Vedotin (BV) represents a powerful, FDA-approved treatment option for CD30 hematological malignancies. However, BV also exerts a strong anti-cancer efficacy in many cases of diffuse large B cell lymphoma (DLBCL) with poor CD30 expression, even when lacking detectable CD30 tumor cells.

Respiratory and glycemic control outcomes of late preterm infants after antenatal corticosteroid exposure.

Objective: To quantify changes in respiratory and glycemic control outcomes following antenatal corticosteroids (ANCS) exposure in late preterm neonates.

Design/methods: The study included 500 neonates born between 34 0/7 and 36 6/7 weeks of gestation. Study population was divided into two groups: an immature group (34 0/7-35 6/7 weeks) and a mature group (36 0/7-36 6/7 weeks).

Postnatal IVIG treatment for persistent anaemia in neonate due to congenital parvovirus infection.

Congenital parvovirus B19 infection is a rare but serious condition that can result in hydrops fetalis and fetal death. Due to the virus' cytotoxic effect on fetal red blood cell precursors, postnatal infection can cause a neonatal viremia and secondary pure red cell aplasia. Here, we describe a case of congenital parvovirus infection in a preterm infant complicated by hydrops fetalis and chronic anaemia that responded to postnatal treatment with intravenous immunoglobulin administered on day of life 44.

The Dark Side of Relational Leadership: Positive and Negative Reciprocity as Fundamental Drivers of Follower's Intended Pro-leader and Pro-self Unethical Behavior.

In this study, we use a social exchange perspective to examine when [i.e., high- vs.

Health Self-Management Applications in the Work Environment: The Effects on Employee Autonomy.

Organizations increasingly use Health Self-Management Applications (HSMAs) that provide feedback information on health-related behaviors to their employees so that they can self-regulate a healthy lifestyle. Building upon Self-Determination Theory, this paper empirically investigates the basic assumption of HSMAs that their self-management feature provides employees with autonomy to self-regulate their health-related behavior. The two-phase experimental study contained a 4-weeks HSMA intervention in a healthcare work environment with a feedback factor (performance vs.

Real-world evidence in Alzheimer's disease: The ROADMAP Data Cube.

Introduction: The ROADMAP project aimed to provide an integrated overview of European real-world data on Alzheimer's disease (AD) across the disease spectrum.

Methods: Metadata were identified from data sources in catalogs of European AD projects. Priority outcomes for different stakeholders were identified through systematic literature review, patient and public consultations, and stakeholder surveys.

Duration of Care Trajectories in Persons With Dementia Differs According to Demographic and Clinical Characteristics.

Objectives: To estimate (1) the duration of no formal care, home care, and institutional care after dementia diagnosis, and (2) the effect of age, sex, living situation, dementia medication, migration background, and income on this dementia care duration.

Design: Longitudinal retrospective study using routinely recorded general practice electronic health records linked with population-based healthcare and mortality data.

Setting And Participants: In total, 11,012 community-dwelling persons who received an incident dementia diagnosis and were listed in a Dutch general practitioner database from 448 general practices in the Netherlands.

Time from diagnosis to institutionalization and death in people with dementia.

Introduction: Reliable estimates of time from diagnosis until institutionalization and death in people with dementia from routine nationally representative databases are lacking.

Methods: We selected 9230 people with dementia and 24,624 matched controls from family physicians' electronic records linked with national administrative databases to analyze time until institutionalization and death and associated factors.

Results: Median time from recorded diagnosis until institutionalization and until death for people with dementia was 3.

Deficient knowledge in adult Turner syndrome care as an incentive to found Turner centers in Germany.

Objective: Turner syndrome (TS) is characterized by the complete or partial loss of the second sex chromosome and associated with a wide range of clinical manifestations. We aimed to assess the medical care of adult patients with TS in Germany.

Design: Retrospective multicenter observational study.

Long-term Outcome of Subacute Thyroiditis.

Background: Subacute thyroiditis (SAT) is a rare inflammatory disease that presents diagnostic challenges. The underlying pathophysiology and prediction of outcomes are elusive. We investigated the long-term follow-up of SAT for up to 30 years and determined predictors for later hypothyroidism.

Degranulation of human cytotoxic lymphocytes is a major source of proteolytically active soluble CD26/DPP4.

Dipeptidyl peptidase 4 (DPP4, CD26) is a serine protease detected on several immune cells and on epithelial cells of various organs. Besides the membrane-bound enzyme, a catalytically active soluble form (sCD26/DPP4) is detected in several body fluids. Both variants cleave off dipeptides from the N-termini of various chemokines, neuropeptides, and hormones.