Machine learning base models to predict the punching shear capacity of posttensioned UHPC flat slabs.

The aim of this research is to present correction factors for the punching shear formulas of ACI-318 and EC2 design codes to adopt the punching capacity of post tensioned ultra-high-performance concrete (PT-UHPC) flat slabs. To achieve that goal, the results of previously tested PT-UHPC flat slabs were used to validate the developed finite element method (FEM) model in terms of punching shear capacity. Then, a parametric study was conducted using the validated FEM to generate two databases, each database included concrete compressive strength, strands layout, shear reinforcement capacity and the aspect ratio of the column besides the correction factor (the ratio between the FEM punching capacity and the design code punching capacity). The first considered design code in the first database was ACI-318 and in the second database was EC2. Finally, there different "Machine Learning" (ML) techniques manly "Genetic programming" (GP), "Artificial Neural Network" (ANN) and "Evolutionary Polynomial Regression" (EPR) were applied on the two generated databases to predict the correction factors as functions of the considered parameters. The results of the study indicated that all the developed (ML) models showed almost the same level of accuracy in terms of the punching ultimate load (about 96%) and the ACI-318 correction factor depends mainly on the concrete compressive strength and aspect ratio of the column, while the EC2 correction factor depends mainly on the concrete compressive strength and the shear reinforcement capacity.

Study the association of microRNA polymorphisms (miR-146a, miR-4513) with the risk of coronary heart diseases in Egyptian population.

Coronary heart disease (CHD) is the most prevalent cause of cardiovascular mortality in the world. It is well established that microRNAs (miRNAs) and their variants have an essential role in regulating the development of cardiovascular physiology, thus impacting the pathophysiology of heart diseases. This study was designed to determine the possible association of miRNA polymorphisms (miRNA-146a rs2910164C/G and miR-4513 rs2168518G/A) with susceptibility to CHD in Egyptian patients and their correlation with different biochemical parameters. The study comprised 300 participants, including 200 unrelated patients with CHD and 100 healthy controls. Anthropometric and blood biochemical parameters were measured as well genetic analysis for rs2910164C/G and rs2168518G/A polymorphisms were performed for all subjects using TaqMan real-time PCR assay. Our results revealed that the biomedical parameters have a significant correlation between CHD patients and healthy controls with a p < 0.05. Analyses of genotype distribution for (rs2910164 and rs2168518) revealed a significant association with CHD [odd ratio = 4.54, confidence interval (CI 95%) = (2.41-8.53)] and [odd ratio = 0.88, (CI 95%) = (0.83-0.92)], respectively. Furthermore, a statistically significant difference was detected between lipid profile levels and both rs2910164 and rs2168518 polymorphisms. The present study's findings indicated that the selected polymorphisms, miR-146a rs2910164 and miR-4513 rs2168518 could represent a useful biomarker for susceptibility to CHD in the Egyptian population. These genetic characteristics and personal habits and environmental factors may contribute to the development of CHD.

Effects of Iron Deficiency and Its Indicators on Lymphocyte Subsets: A Study at King Fahd Hospital of the University, Saudi Arabia.

BACKGROUND: Iron deficiency plays an important role in our body's immunity. Several studies have shown that it is frequently associated with infections. OBJECTIVE: This study aimed to discover the effect of iron deficiency on immunity by demonstrating changes occurring in lymphocyte subsets among patients with an established diagnosis of iron deficiency. METHODS: A total of 64 iron-deficient patients and 19 healthy controls were included. Complete blood counts, serum iron, ferritin, and total iron-binding capacity were assessed. Lymphocyte subsets were evaluated by flow cytometry. RESULTS: Among iron-deficient patients, the anemic ones (Hb ≤11 g/dL) showed significantly lower absolute lymphocyte counts (p=0.013), lower relative and absolute NK-cell counts (p=0.025 and p=0.003, respectively), higher relative T-cell and CD4+-cell counts (p=0.026 and p=0.002, respectively). B cells and CD8+ T cells were not affected by any iron-deficiency indicators. Iron-deficient anemia patients showed a three- to fourfold increase in risk of having recurrent infections. CONCLUSION: Iron deficiency has an obvious effect on lymphocyte subsets. Changes in lymphocyte subsets started mainly in response to decreased hemoglobin, rather than decreased ferritin and/or iron. Synchronously decreased hemoglobin and increased total iron-binding capacity led to absolute decreases in total lymphocytes, mainly NK cells, and relative increases in T cells, mainly the helper ones. Monitoring changes in lymphocyte subsets may be helpful in identifying patients at risk of recurrent infections.

Cardiac Progenitor Cells.

Cardiovascular diseases top the list of fatal illnesses worldwide. Cardiac tissues is known to be one of te least proliferative in the human body, with very limited regenraive capacity. Stem cell therapy has shown great potential for treatment of cardiovascular diseases in the experimental setting, but success in human trials has been limited. Applications of stem cell therapy for cardiovascular regeneration necessitate understamding of the complex and unique structure of the heart unit, and the embryologic development of the heart muscles and vessels. This chapter aims to provide an insight into cardiac progenitor cells and their potential applications in regenerative medicine. It also provides an overview of the embryological development of cardiac tissue, and the major findings on the development of cardiac stem cells, their characterization, and differentiation, and their regenerative potential. It concludes with clinical applications in treating cardiac disease using different approaches, and concludes with areas for future research.

Wnt Signaling: The double-edged sword diminishing the potential of stem cell therapy in congenital heart disease.

Stem cell therapy using bone marrow derived or mesenchymal stem cells has become a popular option for cardiovascular disease treatment, however the administration of embryonic stem cells has been mostly experimental. Remarkably, most of these ongoing clinical trials involve adult patients, but little is known regarding the safety and efficacy of stem cell therapy in newborns and children battling congenital heart diseases. Furthermore, cell delivery methods involve the administration of stem cells without pre-differentiation, and without consideration for the consequent process of cardiac development. Interestingly, in-vitro studies have demonstrated that the differentiation of embryonic stem cells into cardiomyocytes imitates the stages of cardiogenesis. Wnt signaling plays a profound role during the earliest stages of cardiogenesis and cardiac differentiation. In fact inappropriate Wnt signaling is associated with numerous cardiac disorders especially congenital heart disease. Furthermore, cell-extracellular matrix interactions were shown to be critical for stem cell differentiation and adequate cardiogenesis. Since extracellular matrix molecules are fundamental for maintenance and repair during heart disease and congenital heart disease, they may offer a novel approach for therapy. Herein we aim to review the critical role of Wnt signaling, as well as the profound importance of cell extracellular matrix interaction, during cardiogenesis. Both of these processes are crucial for precise stem cell differentiation into cardiomyocytes and developing efficacious regenerative therapy for congenital heart disease.

Effect of low-level laser-treated mesenchymal stem cells on myocardial infarction.

Cardiovascular disease is the leading cause of death worldwide. Although cardiac transplantation is considered the most effective therapy for end-stage cardiac diseases, it is limited by the availability of matching donors and the complications of the immune suppressive regimen used to prevent graft rejection. Application of stem cell therapy in experimental animal models was shown to reverse cardiac remodeling, attenuate cardiac fibrosis, improve heart functions, and stimulate angiogenesis. The efficacy of stem cell therapy can be amplified by low-level laser radiation. It is well established that the bio-stimulatory effect of low-level laser is influenced by the following parameters: wavelength, power density, duration, energy density, delivery time, and the type of irradiated target. In this review, we evaluate the available experimental data on treatment of myocardial infarction using low-level laser. Eligible papers were characterized as in vivo experimental studies that evaluated the use of low-level laser therapy on stem cells in order to attenuate myocardial infarction. The following descriptors were used separately and in combination: laser therapy, low-level laser, low-power laser, stem cell, and myocardial infarction. The assessed low-level laser parameters were wavelength (635-804 nm), power density (6-50 mW/cm2), duration (20-150 s), energy density (0.96-1 J/cm2), delivery time (20 min-3 weeks after myocardial infarction), and the type of irradiated target (bone marrow or in vitro-cultured bone marrow mesenchymal stem cells). The analysis focused on the cardioprotective effect of this form of therapy, the attenuation of scar tissue, and the enhancement of angiogenesis as primary targets. Other effects such as cell survival, cell differentiation, and homing are also included. Among the evaluated protocols using different parameters, the best outcome for treating myocardial infarction was achieved by treating the bone marrow by one dose of low-level laser with 804 nm wavelength and 1 J/cm2 energy density within 4 h of the infarction. This approach increased stem cell survival, proliferation, and homing. It has also decreased the infarct size and cell apoptosis, leading to enhanced heart functions. These effects were stable for 6 weeks. However, more studies are still required to assess the effects of low-level laser on the genetic makeup of the cell, the nuclei, and the mitochondria of mesenchymal stromal cells (MSCs).

Dilated cardiomyopathy-induced disruption of basement membrane alters the lever systems acting on the heart.

Dilated cardiomyopathy (DCM) is considered the most common form of non-ischemic heart diseases. DCM, occurs in response to both non-genetic and genetic factors, and has been associated with cytoskeletal protein mutations, impairing the contractile apparatus of cardiac myocytes. However, the pathology underlying the marked left ventricular dilatation remains unclear. Moreover, patients with end-stage DCM show alterations in the composition of the extracellular matrix (ECM), and myocardial fibrosis even when the cardiac myocytes are intact. Therefore we hypothesize that DCM is a disease of basement membrane, which functions to support sarcomeric interactions with the ECM, and not only impaired cardiac contractility. We propose that under physiological conditions, the heart could be considered a second-class lever system. Disruption of the basement membrane in DCM would cause disarray in the alignment of cardiac myocytes and alteration in the second-class lever system of the heart. Thus, current inotropic agents show minimal or no effect on therapy as they target cardiac contractility rather than cardiac architecture and the lever systems of the heart.

Vitamin D Deficiency in Egyptian Systemic Lupus Erythematosus Patients: How Prevalent and Does It Impact Disease Activity?

BACKGROUND: The emerging role of vitamin D in immunology and autoimmune disorders has been a worldwide interest in the last decade. Systemic lupus erythematosus (SLE) patients are particularly at a delicate position predisposing them to suffer from vitamin D deficiency due to the multiple risk factors accompanying the disease. Whether vitamin D deficiency is also involved as a risk factor for developing SLE and affecting its course is a considerable concern. OBJECTIVES: The objective of this study was to estimate the prevalence of vitamin D deficiency in SLE patients and its relation to disease. MATERIALS AND METHODS: In our observational cross-sectional study, serum levels of vitamin D [25(OH)D] in 60 SLE patients and 30 age- and sex-matched healthy controls were assessed and estimated for deficiency and insufficiency at 10 and 30 ng/mL, respectively. Disease activity was evaluated by SLE disease activity index (SLEDAI), irreversible organ damage by Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC/ACR DI), and severity by Severity of Disease Index. Fatigue was measured by visual analog scale. RESULTS: Significantly lower levels of 25(OH)D were found in SLE patients (17.6 ± 6.9 ng/mL) in comparison to controls (79.0 ± 28.7 ng/mL), with a statistically high significant difference (t = -11.2, P < 0.001). High prevalence of vitamin D insufficiency and deficiency was detected as 73.3% and 23.3%, respectively. Vitamin D had a highly significant negative correlation with SLEDAI (r = -0.495, P < 0.001), SLICC (r = -0.431, P < 0.05), and fatigue (r = -0.436, P < 0.05). CONCLUSION: Vitamin D deficiency and insufficiency were found to be prevalent in SLE patients in our study and related to disease activity and fatigue. If needed, routine screening and consequent repletion of vitamin D are recommended in SLE patients. Restoring adequate vitamin D levels in SLE patients should be more explored as a potential yet simple measure to their usual management to improve their condition.

Study of prognostic significance of marrow angiogenesis assessment in patients with de novo acute leukemia.

BACKGROUND: Angiogenesis is the highly ordered formation of new blood vessels from pre-existing vessels. It is seen throughout growth, in wound healing, menses, and is important in cancer, where pro- and antiangiogenic signals can be released by cancer cells, endothelial cells, stromal cells, blood, and the extracellular matrix. Aim of the study is to use standardized method for counting blood vessels to verify the significance and prognostic value of assessing marrow angiogenesis at diagnosis of de novo acute leukemia. SUBJECTS AND METHODS: The study included 70 newly diagnosed acute leukemia cases and a control group composed of 35 bone marrow biopsy sections obtained from breast cancer patients. Examination of CD34 immunohistochemically stained sections for the assessment of marrow angiogenesis by quantification of its microvessel density (MVD). RESULTS: MVD was significantly increased in acute leukemia patients in comparison to control group (P-value <0.001). Increased MVD was associated with unfavorable outcome. CONCLUSION: The study demonstrated an evidence of increased angiogenesis in acute leukemia detected by high bone marrow MVD which may play a significant role in leukemic process. Understanding its role may help in designing new therapeutic strategies for acute leukemia.

Prognostic value of IDH1 mutations identified with PCR-RFLP assay in acute myeloid leukemia patients.

BACKGROUND: Somatic mutations in isocitrate dehydrogenase 1 (IDH1) gene occur frequently in primary brain tumors. Recently theses mutations were demonstrated in acute myeloid leukemia (AML). So far, assessment of these mutations relied on the DNA sequencing technique. AIM OF THE WORK: The aim of this study was to detect somatic mutations in IDH1 gene using mismatched primers suitable for endonuclease based detection, without the need for DNA sequencing, and to estimate its prognostic value, on patients with de novo AML. METHODS: Residual DNA extracted from pretreatment bone marrow (BM) samples of 100 patients with de novo AML was used. The polymerase chain reaction-restriction fragment length polymorphism method (PCR-RFLP) was adapted to IDH1gene, codon 132 mutations screening. RESULTS: The frequency of IDH1 mutations was 13%. In the non-acute promyelocytic leukemia group (non-APL), IDH1 mutations were significantly associated with FLT3-ITD negative patients (p=0.03). Patients with IDH1 mutations did not achieve complete remission (CR). There was a trend for shorter overall survival (OS) in patients with IDH1 mutation compared to those with wild type (p=0.08). CONCLUSION: IDH1 mutations are recurring genetic alterations in AML and they may have unfavorable impact on clinical outcome in adult AML. The PCR-RFLP method allows for a fast, inexpensive, and sensitive method for the detection of IDH1 mutations in AML.

Evaluation of morphological/immunohistochemical versus nuclear medicine imaging modalities in detecting metastatic bone and/or marrow deposits in neuroblastoma patients.

BACKGROUND & PURPOSE: In planning diagnostic or follow-up investigational strategies, neuroblastoma (NB) metastatic deposits in bone and/or bone marrow (BM) should be detected as early as possible. Therefore, all investigational detection tools should be conducted simultaneously for precise staging. However, because of the financial conditions in our developing countries and in view of the cost/benefit relationship, the question is, can one detection tool only become satisfactory and replacing others? The purpose of our study is to compare simultaneous results of bone and metaiodobenzylguanidine (MIBG) scans versus BM biopsies with immunohistochemical (IHC) staining; in detecting bone and/or BM metastatic deposits in NB patients. MATERIAL AND METHODS: This study included 138 NB patients; 46 were de novo and 92 were under follow-up. They were subjected to bilateral BM biopsies, IHC staining (using NSE McAb) and Tc-99m methylene diphosphonate (Tc-99m MDP) bone scan (BS). Only 57/138 patients were, in addition, subjected to I-131 MIBG scan. RESULTS: Matched results between IHC-stained BM sections and bone scans (BSs) 107/138 (77.5%) were higher than the un-matched ones 31/138 (22.5%). There was a moderate agreement between the two methods in all studied cases (Kappa=0.538) and it was higher among de novo (Kappa=0.603) than follow-up group (Kappa=0.511). Among the 31 un-matched results, the most frequent (17/31) were due to the presence of minute amount of infiltrating NB cells that could be detected by IHC-stained BM sections and not by BSs. The less frequent (12/31) were due to the presence of metastatic deposits outside pelvic bones that could be detected by BSs and not by IHC-stained BM sections mainly in the follow-up cases (11/12) rather than de novo cases (1/12). The matched results between IHC-stained BM sections and MIBG scans 54/57 (94.7%) were higher than the un-matched ones 3/57 (5.3%). The agreement between the two methods was higher among de novo (Kappa=1.000) than follow-up group (Kappa=0.847). The agreement between IHC-stained BM sections and MIBG scans was substantial (Kappa=0.890) while that between IHC-stained BM sections and BSs was moderate (Kappa=0.538). CONCLUSIONS: We suggest a step-wise strategy to be applied, at least in developing countries, in approaching de novo and follow-up NB cases for detecting bone and/or BM metastatic deposits. This strategy might be beneficial if it is considered during application of NB guide-lines for diagnosis and follow-up.