CD4+ T-cell, CD8+ T-cell, CD4+/CD8+ ratio, and apoptosis as a response to induction phase chemotherapy in pediatric acute lymphoblastic leukemia

Background Acute lymphoblastic leukemia (ALL) is a neoplastic disease resulting from somatic mutation in the lymphoid progenitor cells, often occuring in children aged 2-5 years, predominantly in males. Results from the induction phase of chemtherapy are used to measure success, but the failure remission rate is still high. Increased apoptosis of cancer cells, as induced by CD4+ and CD8+T-cells, is an indicator of prognosis and response to chemotherapy. Objective To assess for correlations between CD4+, CD8+, or CD4+/CD8+ ratio to the chemotherapy induction phase response (i.e., apoptosis) in pediatric ALL patients. Methods This observational analytical cohort study was done in 25 pediatric ALL patients. Whole blood (3 mL) with EDTA anticoagulant were used to measure absolute counts of CD4+, CD8+, and CD4+/CD8+ ratio. Peripheral blood mononuclear cells (PBMC) were examined for apoptosis. The principle of CD4+, CD8+ examination was bond between antigens on the surface of the leukocyte in the blood with fluorochrome labeled antibodies in the reagents, while the principle of apoptosis examination was FITC Annexin V will bonds with phosphatidylserine that moves out of the cell when the cell undergoes apoptosis, then intercalation with propidium iodide (PI). All examination were detected by flow cytometry BD FACSCalibur. Results Subjects were 25 newly-diagnosed, pediatric ALL patients (64% males and 36% females). Most subjects were 3 years of age (20%). Numbers of CD4+ and CD8+ cells, as well as CD4+/CD8+ were significantly decreased after chemotherapy. However, apoptosis was not significantly different before and after chemotherapy (P=0.689), There were significant negative correlations between apoptosis and CD4+ (P=0.002; rs=-0.584), and CD8+ (rs=-0.556; P=0.004), before chemotherapy. In addition, CD4+-delta and apoptosis-delta also had a significant positive correlation (rs=0.478; P=0.016). However, no correlation was found between the CD4+/CD8+ ratio and apoptosis, before or after chemotherapy. Conclusion There are significantly lower mean CD4+, CD8+, and CD4+/CD8+ ratio after chemotherapy than before. Also, there are significant correlations between CD4+-delta and apoptosis-delta, as well as between apoptosis and CD4+, CD8+, and CD4+/CD8+, before chemotherapy. CD4+, CD8+, and CD4+/CD8+ can be used to predict apoptosis before chemotherapy. In addition, CD4+-delta can be used to predict apoptosis-delta as a response to induction phase chemotherapy in pediatric ALL

TINJAUAN PUSTAKA: PATOGENESIS DAN DIAGNOSIS SISTEMIK LUPUS ERITEMATOSUS

Sistemik Lupus Eritematosus (SLE) adalah penyakit inflamasi autoimun kronis dengan manifestasi klinis yang luas. Perjalanan penyakit dan prognosis dari SLE pun juga beragam. Faktor lingkungan, imunologi, hormonal, dan genetik diketahui memegang peranan dalam perkembangan SLE. Penyakit SLE lebih banyak menyerang wanita terutama usia produktif. Patogenesis SLE mengikutsertakan berbagai sel dan molekul yang berperan pada proses apoptosis, respons imun innate dan adaptif. Diagnosis SLE ditegakkan berdasarkan manifestasi klinis, yang harus memenuhi 4 dari 11 kriteria American Rheumatology Association (ARA) (1997), dan pemeriksaan laboratorium. Terapi SLE bersifat individual berdasarkan manifestasi klinis yang dialami pasien, aktivitas penyakit dan derajat keparahan penyakit serta komorbiditas. Prognosis SLE bervariasi mulai dari ringan hingga berkembang cepat menjadi berat disertai kegagalan multiorgan bahkan kematian. Studi pustaka ini diharapkan dapat memberikan informasi lebih mendalam mengenai patogenesis dan cara menegakkan diagnosis SLE sehingga dapat menjadi dasar dalam pengembangan penelitian mengenai SLE di masa yang akan datang

Report on existing vocational European Fission Training Schemes and their accreditation

This report was produced as a deliverable in the frame of the ENEN Plus project. It provides an overview of all twenty-five projects carried out under the Euratom Fission Training Schemes (EFTS) and their main achievements. Almost all projects are completed to date except for three. The EFTS's ultimate goal is to develop a European passport for Continuous Professional Development, which relies on the principles of modularity of courses and common qualification criteria, a common mutual recognition system, and the facilitation of teacher, student and worker mobility across the EU. The conclusions of this review will be published in a separate report.JRC.G.10-Knowledge for Nuclear Security and Safet

Inhibition of a new AXL isoform (AXL3) induces apoptosis of mantle cell lymphoma cells

Mantle cell lymphoma (MCL) is an aggressive B-cell non-Hodgkin lymphoma having a poor overall survival that is in need for the development of new therapeutics. In this study, we report the identification and expression of a new isoform splice variant of the tyrosine kinase receptor AXL in MCL cells. This new AXL isoform, called AXL3, lacks the ligand-binding domain of the commonly described AXL splice variants and is constitutively activated in MCL cells. Interestingly, functional characterization of AXL3, using CRISPRi, revealed that only the knockdown of this isoform leads to apoptosis of MCL cells. Importantly, pharmacological inhibition of AXL activity resulted in a significant decrease in the activation of well-known pro-proliferative and survival pathways activated in MCL cells (i.e.b-catenin, AKT, and NF-kB). Therapeutically, pre-clinical studies using a xenograft mouse model of MCL indicated that bemcentinib is more effective than ibrutinib in reducing the tumour burden and to increase the overall survival. Our study highlights the importance of a previously unidentified AXL splice variant in cancer and the potential of bemcentinib as a targeted therapy for MCL

Early-to-mid idiopathic Parkinson’s disease shows a more cytotoxic but declined CD8-regulatory peripheral immune profile

Parkinson’s disease (PD) is the second most common neurodegenerative disease. Brain neuroinflammation plays a role in PD pathogenesis. However, the involvement of the peripheral immune system has not been systematically investigated. Here we analyzed >700 combinatorial immunological features in fresh blood of 28 early-to-mid-stage PD patients and 24 matched controls. We found an enhanced cytotoxic immune profile in idiopathic PD patients (iPD), with a higher frequency of terminally-differentiated effector CD8 T (TEMRA), late-differentiated CD8+ natural killer T cells and neutrophils. This immune profile was intensified by elevated serum granzyme A, reduced percentages of CD8+FOXP3+ regulatory T cells and group 2 innate lymphoid cells with immunosuppressive or tolerance-inducing functions. The frequency of CD8 TEMRA was negatively correlated with disease duration, suggesting a contribution to PD pathogenesis. Our work provides a comprehensive map on disturbed peripheral adaptive and innate immune cells in early-to-mid iPD, proposing easily-accessible candidates for early diagnosis and treatments

Pain and Opioid Consumption After Laparoscopic Versus Open Gastrectomy for Gastric Cancer:A Secondary Analysis of a Multicenter Randomized Clinical Trial (LOGICA-Trial)

Background:Laparoscopic gastrectomy could reduce pain and opioid consumption, compared to open gastrectomy. However, it is difficult to judge the clinical relevance of this reduction, since these outcomes are reported in few randomized trials and in limited detail. Methods: This secondary analysis of a multicenter randomized trial compared laparoscopic versus open gastrectomy for resectable gastric adenocarcinoma (cT1-4aN0-3bM0). Postoperative pain was analyzed by opioid consumption in oral morphine equivalents (OME, mg/day) at postoperative day (POD) 1–5, WHO analgesic steps, and Numeric Rating Scales (NRS, 0–10) at POD 1–10 and discharge. Regression and mixed model analyses were performed, with and without correction for epidural analgesia. Results: Between 2015 and 2018, 115 patients in the laparoscopic group and 110 in the open group underwent surgery. Some 16 patients (14%) in the laparoscopic group and 73 patients (66%) in the open group received epidural analgesia. At POD 1–3, mean opioid consumption was 131, 118, and 53 mg OME lower in the laparoscopic group, compared to the open group, respectively (all p &lt; 0.001). After correcting for epidural analgesia, these differences remained significant at POD 1–2 (47 mg OME, p = 0.002 and 69 mg OME, p &lt; 0.001, respectively). At discharge, 27% of patients in the laparoscopic group and 43% patients in the open group used oral opioids (p = 0.006). Mean highest daily pain scores were between 2 and 4 at all PODs, &lt; 2 at discharge, and did not relevantly differ between treatment arms. Conclusion: In this multicenter randomized trial, postoperative pain was comparable between laparoscopic and open gastrectomy. After laparoscopic gastrectomy, this was generally achieved without epidural analgesia and with fewer opioids. Trial Registration: NCT02248519.</p

Voitures de société et mobilité durable. Diagnostic et enjeux

La voiture de société est, sans aucun doute, un des avantages de toute nature (ATN) les plus fréquemment proposés par les entreprises à leurs employés. Combien compte-t-on de voitures de société en Belgique ? Quels sont les profils des usagers ? Et quels sont les impacts sociétaux, environnementaux et économiques de cet « avantage »

Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer.

To identify common alleles associated with different histotypes of epithelial ovarian cancer (EOC), we pooled data from multiple genome-wide genotyping projects totaling 25,509 EOC cases and 40,941 controls. We identified nine new susceptibility loci for different EOC histotypes: six for serous EOC histotypes (3q28, 4q32.3, 8q21.11, 10q24.33, 18q11.2 and 22q12.1), two for mucinous EOC (3q22.3 and 9q31.1) and one for endometrioid EOC (5q12.3). We then performed meta-analysis on the results for high-grade serous ovarian cancer with the results from analysis of 31,448 BRCA1 and BRCA2 mutation carriers, including 3,887 mutation carriers with EOC. This identified three additional susceptibility loci at 2q13, 8q24.1 and 12q24.31. Integrated analyses of genes and regulatory biofeatures at each locus predicted candidate susceptibility genes, including OBFC1, a new candidate susceptibility gene for low-grade and borderline serous EOC

On the issue of transparency and reproducibility in nanomedicine.

Following our call to join in the discussion over the suitability of implementing a reporting checklist for bio-nano papers, the community responds

Polygenic Risk Modelling for Prediction of Epithelial Ovarian Cancer Risk

Funder: Funding details are provided in the Supplementary MaterialAbstractPolygenic risk scores (PRS) for epithelial ovarian cancer (EOC) have the potential to improve risk stratification. Joint estimation of Single Nucleotide Polymorphism (SNP) effects in models could improve predictive performance over standard approaches of PRS construction. Here, we implemented computationally-efficient, penalized, logistic regression models (lasso, elastic net, stepwise) to individual level genotype data and a Bayesian framework with continuous shrinkage, “select and shrink for summary statistics” (S4), to summary level data for epithelial non-mucinous ovarian cancer risk prediction. We developed the models in a dataset consisting of 23,564 non-mucinous EOC cases and 40,138 controls participating in the Ovarian Cancer Association Consortium (OCAC) and validated the best models in three populations of different ancestries: prospective data from 198,101 women of European ancestry; 7,669 women of East Asian ancestry; 1,072 women of African ancestry, and in 18,915 BRCA1 and 12,337 BRCA2 pathogenic variant carriers of European ancestry. In the external validation data, the model with the strongest association for non-mucinous EOC risk derived from the OCAC model development data was the S4 model (27,240 SNPs) with odds ratios (OR) of 1.38(95%CI:1.28–1.48,AUC:0.588) per unit standard deviation, in women of European ancestry; 1.14(95%CI:1.08–1.19,AUC:0.538) in women of East Asian ancestry; 1.38(95%CI:1.21-1.58,AUC:0.593) in women of African ancestry; hazard ratios of 1.37(95%CI:1.30–1.44,AUC:0.592) in BRCA1 pathogenic variant carriers and 1.51(95%CI:1.36-1.67,AUC:0.624) in BRCA2 pathogenic variant carriers. Incorporation of the S4 PRS in risk prediction models for ovarian cancer may have clinical utility in ovarian cancer prevention programs.</jats:p