Prognostic effect of CTLA4/LAG3 Expression by T-Cells Subsets on Acute Myeloid Leukemia Patients.

BACKGROUND: Deregulation of immune checkpoint is an important point in cancer evolution as well as patients outcome. T-cells is an important arm in immunity against cancer. This study aimed to assess CTLA4/LAG3 expression on different T-cell subsets and its effect on disease outcome. METHODS: This study included 81 newly diagnosed Egyptian adult AML patients. For each one of the patients CTLA4/ LAG3 expression on T-cell subsets was identified by flowcytometry before start of induction chemotherapy. RESULTS: Total CD3 count in AML patients was lower than control. LAG3 expression were significantly higher in total CD3, T-cell subsets (CD4, CD8) as compared to healthy control. Moreover, co-expression of LAG3/CTLA4 on T-cell subsets were significantly higher in AML as compared to healthy control . NPM-/ FLT3+ was significantly associated with high LAG3 expression in T-cells subsets as compared to other molecular subtypes. Shorter OS, DFS were significantly associated with higher expression of LAG3 on T-cells subsets as compared to patients harbor low expression. COX regression analysis revealed that high expression of CD3/LAG3, CD4/LAG3, CD8/LAG4, CD3/CTLA4/LAG3 were considered a poor prognostic risk factor. CONCLUSION: High LAG3/CTLA4 expression could predict AML Patients' outcome Conclusion: Our findings indicated that high expression of LAG3/CTL4 on T cells subsets identify a subgroup of AML patients with poor prognosis.

Degradation and energy performance evaluation of mono-crystalline photovoltaic modules in Egypt.

Degradation reduces the capability of solar photovoltaic (PV) production over time. Studies on PV module degradation are typically based on time-consuming and labor-intensive accelerated or field experiments. Understanding the modes and methodologies of degradation is critical to certifying PV module lifetimes of 25 years. Both technological and environmental conditions affect the PV module degradation rate. This paper investigates the degradation of 24 mono-crystalline silicon PV modules mounted on the rooftop of Egypt's electronics research institute (ERI) after 25 years of outdoor operation. Degradation rates were determined using the module's performance ratio, temperature losses, and energy yield. Visual inspection, I-V characteristic measurement, and degradation rate have all been calculated as part of the PV evaluation process. The results demonstrate that the modules' maximum power ([Formula: see text]) has decreased in an average manner by 23.3% over time. The degradation rates of short-circuit current ([Formula: see text]) and maximum current ([Formula: see text]) are 12.16% and 7.2%, respectively. The open-circuit voltage ([Formula: see text]), maximum voltage ([Formula: see text]), and fill factor ([Formula: see text]) degradation rates are 2.28%, 12.16%, and 15.3%, respectively. The overall performance ratio obtained for the PV system is 85.9%. After a long time of operation in outdoor conditions, the single diode model's five parameters are used for parameter identification of each module to study the effect of aging on PV module performance.

Prevalence of Musculoskeletal Disorders among General and Technical Secondary School Students in Egypt.

(1) Background: Children spend a lot of time within schools. The school setting generally has many ergonomic hazards and reinforced behavior patterns which put children at greater risk of environmental hazards than adults during their critical developmental stages. (2) Objective: The aim of the current study was to investigate the prevalence of musculoskeletal disorders (MSDs) and detect spinal deformities amongst general and technical secondary school students. (3) Methods: A total of 418 students from the second grade of secondary school in Shaquira governorate, Egypt participated in this cross-sectional study. Each student in the study was screened via Nordic Musculoskeletal Questionnaire (NMQ) and had their upper limb posture measured via RULA (Rapid Upper Limb assessment), and the deviation in their thoracic curve was measured using a scoliometer. (4) Results: There was a prevalence of MSDs amongst students as there were 69.7% of general school students and 83.8% of the technical school students suffering from MSDs with a statistically significant difference between both technical and general school students in RULA score and musculoskeletal complaints, whereas there were non-statistical differences in the scoliometer scale in both general and technical education students. (5) Conclusions: Musculoskeletal problems are prevalent among Egyptian secondary school students, with higher prevalence between technical school students. Therefore, preventive measures and strategies are recommended to overcome the future complications of these musculoskeletal disorders.

Clinical Implication of Toll-Like Receptors (TLR2 and TLR4) Polymorphisms in Adult Patients with Acute B-cell Lymphoblastic Leukemia.

BACKGROUNDS: Neutropenia after intensive chemotherapy of acute lymphoblastic leukemia (ALL) could lead to infectious complications that affect outcome of acute leukemia patients. Many single-nucleotide polymorphisms (SNPs) of Toll-like receptors (TLRs) can affect the genetic susceptibility to infections. We investigated the impact of different SNPs on the incidence of developing sepsis and pneumonia in patients with newly diagnosed B-ALL following induction chemotherapy. SUBJECTS AND METHODS: We analyzed three SNPs in the TLR2 (Arg753Gln) and TLR4 (Asp299Gly& Thr399Ile) genes using polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP) in a case control study of 40 precursor B-ALL patients and 50 control subjects. The risk of developing sepsis and pneumonia were assessed by multiple logistic regression analyses. RESULTS: The presence of the TLR-2 AG polymorphism was significantly associated with pneumonia in B-ALL patients. Furthermore, TLR4 Thr399Ile AG was a risk factor for sepsis in B-ALL patients. Moreover; Significant association between TLR-2 AA, TLR-4 CC and TL-4 AA genotypes and longer OS were detected in studied B-ALL patients. CONCLUSION: We concluded that TLR-4 (AG and CT) genotypes are associated with high susceptibility to sepsis and pneumonia respectively; while, TLR-2, TLR-4 AA and TLR-4 CC genotypes  could predict good B-ALL patients outcome.

Circulating CXCL13 could be serving as a biomarker for chronic lymphocytic leukemia severity.

BACKGROUND: Recent reports indicated the importance of chemotractant CXCL-13 in solid tumors and lymphoid malignancies. However, the prognostic value of the mentioned cytokines as biomarkers in chronic lymphocytic leukemia patient's remains to be identified. Therefore; this study was designed in order to address the relation between CXCL-13 concentrations levels and markers of severity in CLL patients. METHODS: Our study included 150 CLL patients and 20 controls. Serum CXCL-13 was determined by ELISA for CLL patients at diagnosis as well as controls. RESULTS: The serum CXCL-13 levels were significantly higher in CLL patients as compared to controls. The high CXCL-13 concentration levels was significantly associated with high number of smudge cells; high LDH; high grade of Rai stage, short time to first treatment (TTT). Cox regression analysis was conducted for prediction of TTT, using age, gender, WBCs, smudge cells, CXCL-13, LDH, ZAP70, CD38, ß2-microglobulin, Rai staging as covariates. High LDH, CXCL-13 and CD38% were significantly independent predictor for shorter TTT. CONCLUSION: High CXCL-13 serum levels at CLL diagnosis is correlated with other markers of disease activity; and could be served as biomarkers that predict CLL patient's outcome.

Predictive Value of miR-146a rs2431697 Polymorphism to Myelofibrosis Progression in Patients with Myeloproliferative Neoplasm.

BACKGROUND: Bone marrow myelofibrosis (BMF) that develop on top of Polycythaemia vera (PV) and essential thrombocythemia leads to shortening of the patient's overall survival. This study aimed to address the impact of miR-146a rs2431697 polymorphism on inflammatory biomarkers and genes expression and the hazards of myelofibrosis progression. PATIENTS AND METHODS: The study included 88 myeloproliferative neoplasm (40 PV; 27 ET; 21 MF) and 90 healthy controls. For all investigated subjects miR-146a rs2431697 genotypes were identified by sequencing and the expression of miR-146a; IL-1ß; NF-κB; a NOD-like receptor family, pyrin domain containing 3 (NLRP3) (NLRP3) genes were estimated by real time PCR. RESULTS: miR146a genotypes revealed that there was significant association between TT and TC genotypes with MF. The degree of miR146a expression was significantly reduced in MF as compared to both PV and ET. In contrast; the levels of IL-1ß; NF-κB; NLRP3 genes expression were significantly elevated in MF patients group as compared to PV and ET patients' group. Multivariate analysis identified TT genotype as poor predictor of MF progression. CONCLUSION: miR-146a rs2431697 TT genotype is associated with high risk of MF progression in MPN patients. Targeting of IL-1ß; NF-κB; NLRP3 genes might help  in hindering of  MF progression in  MPN patients,
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Prognostic Relevance of Concordant Expression CD69 and CD56 in Response to Bortezomib Combination Therapy in Multiple Myeloma Patients.

OBJECTIVE: Multiple myeloma is an incurable hematological malignancy. Currently, the use of proteasome inhibitors could be superior to chemotherapy-based regimen in the treatment of this disease. However, resistance to bortezomib combination therapy still occurs in some patients. So, this research work aims to assess CD69 and CD56 expression in these cases and their relation to the response to therapy. MATERIALS AND METHODS: Immunophenotyping by 4-color multi-parameter flow cytometry was carried out on 98 multiple myeloma cases. Clonal plasma cells were gated by co-expression of CD38 with CD138 with low SSC, negative or dim CD45. RESULTS: Double negative CD69 and CD56 (47.9%) multiple myeloma cases were associated with high serum ß2 microglobulin, creatinine, calcium and low serum albumin. There was also a significant correlation between the absence of these markers with osteolytic lesions and unfavorable cytogenetic t (4;14) (p < 0.001). Moreover, there was a highly significant correlation between CD69- and CD56- with non-response to bortezomib combination therapy in multiple myeloma patients (p < 0.0001). Regression analysis for the prediction of non- response to treatment in these cases using different prognostic indicators revealed that high serum ß2 microglobulin, unfavorable cytogenetic, advanced stage, and low expression of CD69 and CD56 were poor predictors of non-response. CONCLUSION: CD69 in association with CD56 could be an independent prognostic factor in multiple myeloma cases. It could be used in the routine laboratory assessment for refining stratification and timely therapeutic decision for highly cost therapy in developing countries.

Prognostic Value of TLE1 Gene Expression in Patients with T-cell Acute Lymphoblastic Leukemia.

BACKGROUND: Transducin-like enhancer of split 1 (TLE1( is a member of the TLE family of transcriptional co-repressors that control the transcription of a wide range of genes. The aim of this study was to evaluate the prognostic role of TLE1 gene expression in patients with T-cell acute lymphoblastic leukemia (T-ALL). METHOD: This study was conducted on 97 newly diagnosed T-ALL patients admitted to the Mansoura University oncology center (59 males and 38 females) with median age (33 years) in addition to 102 apparently healthy individuals served as a control group. TLE1 gene expression was measured in both patients and control groups by real time - PCR. The calculation of relative gene expression was done using the ΔΔCt method. RESULTS: TEL1 gene expression was significantly down regulated in T-ALL cases (median 2.83) as compared to controls (median 84.65) (p < 0.001). The low TEL1 gene expression was significantly associated with CNS infiltration, non-remission and higher relapse rate (p < 0.001, 0.001 and 0.023 respectively). Likewise, Low TEL1 gene expression was significantly associated with shorter OS and DFS (P= 0.012 and 0.011 respectively). Furthermore, Low TEL1 gene expression was considered as risk predictor of relapse with OR 3.636(CI.1.422-9.295) (P =0.007); and OR 0.803(CI. 0.609-0.96) (P=0.021) and independent predictor of T-ALL patient's outcome with OR 0.619 (CI. 0.44-0.872) (P=0.006). CONCLUSION: TLE1 gene expression was significantly down regulated in T-ALL cases as compared with controls. Low TLE1 expression is independent predictor of the T-ALL patient's outcome.
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