Clinical and Preclinical Lung Transplantation in the aspects of improving outcome

Lung transplantation (LTx) is an established therapeutic option for end-stage pulmonary disease. However, it remains restricted by donor lung scarcity. Donor's lungs are rejected frequently due to severe lung damage caused by aspiration or neurogenic pulmonary oedema that can all lead to acute lung injury (ALI), and more severe acute respiratory distress syndrome (ARDS). Lung transplant patients face poor survival rates in comparison with other solid organ transplantations. This is primarily due to a high incidence of postoperative complications, such as primary graft dysfunction (PGD) and chronic lung allograft dysfunction (CLAD), especially bronchiolitis obliterans syndrome (BOS). The aim of this thesis was to expand the availability of a donor's lungs for transplantation. We sought to increase the chances of a lifesaving opportunity for recipients who may otherwise have remained on the transplant waiting list for years. We did this preclinically by utilising a variety of techniques to regain lung function in discarded lungs, thus increasing the donor pool. We investigated the role of cytokine adsorption during ex vivo lung perfusion (EVLP), and extracorporeal haemofiltration post-transplant as a means of treating and restoring the ARDS-damaged lungs and reducing the incidence of PGD post-transplantation. The lungs were evaluated regarding the development of primary graft dysfunction (PGD) in which cytokines seem to be an essential target given the outcome of significantly less PGD in the group receiving cytokine adsorption. We suggest this treatment method will increase the availability of the donor's lungs and increase the tolerability of the donor's lungs in the recipient. The results of this study formed the basis for our idea to investigate the effect of mesenchymal stromal cell (MSC) therapy to restore gastric content aspirations damaged lungs and reduce the incidence of PGD at 72 hours’ post-transplantation. Furthermore, we explored pulmonary function, survival, and the incidence of CLAD between patients receiving marginal lungs after ex vivo lung perfusion (EVLP) reconditioning and patients receiving clinically standard lungs (conventional lungs) at our centre. These patients were followed for over 10 years. We did not find any difference in pulmonary function, survival, or incidence of CLAD, indicating that EVLP is safe to use and does not increase mortality. We also explored the impact of allograft ischaemic time (IT) in lung transplantation survival rate which showed superior outcomes for IT between 120 and 240 minutes. Every 2-hour increase in IT was equivalent to an increased mortality of up to 24% within 5 years. This indicates that IT has a key role in improving LTx outcomes. We explored the role of plasma biomarkers in the largest subgroup of CLAD, patients with BOS. Plasma from lung- transplanted patients with different BOS grades was analysed for protein biomarkers using Olink proteomics. A selective number of biomarkers were then validated using an enzyme-linked immunosorbent assay (ELISA) at baseline and after 1 year. Corticotropin-releasing hormone (CRH) levels were found to be related to different stages of BOS which identified CRH as a potential marker in a novel diagnostic tool to detect BOS. In conclusion, using EVLP is a safe effective platform for cytokine adsorption therapy and MSC therapy which can restore pulmonary function in damaged donor lungs, thus increasing the donor pool. CRH is a novel potential biomarker in the progression of post-transplantation BOS grades

Prediction of delamination in glass fibre reinforced composite materials using elasto-plastic modelling

Glass Fibre reinforced composite (GFRC) has been used for numerous structural applications in Aerospace, Chemical, Automotive and Civil infrastructure fields over a hundred of years. Due to this reason, understanding the intricate fracture behaviour of GFRC materials is crucial and essential for designing critical structural components. Voids and micro-cracks are considered as imperfections in Glass Fibre Reinforced composites. Much research has been undertaken on approaches to calculate and evaluate the effects of the imperfections on mechanical properties. However, it is an established fact that the micro-mechanical approach alone is not sufficient to understand a complete damage accumulation process during delamination. The damage mechanism which largely affects the performance of GFRC structures is commonly known as 'delamination'. Since the delamination is invisible, and hard to detect with ordinary non-destructive evaluation methods, therefore it is considered as a hidden killer which can cause catastrophic failure without any prior warnings. Due to this reason, research work on delamination modelling, damage detection and self-healing materials have been the highly placed research topics for more than five decades. Unfortunately there are a number of unresolved problems in delamination damage modelling and prediction, and few grey areas regarding application of Structural Health Monitoring systems to monitor delamination damages. This thesis has proposed to study the insight into the cause of delamination damage and its propagation mechanisms, by analytical modelling and experimental verifications. Within this research project, extension of the work by Tsukrov and Kachanov (2000) – “An innovative Elasto-plastic model” has been undertaken to evaluate, investigate and model the onset and propagation of delamination damages. Mode I, Mode II as well as Mixed Mode I/II delamination damage analysis has been utilised to study the proposed model predictions for GFRC structures for both in-plane and out-of-plane load applications. The proposed model has been validated using the Double Cantilever Beam (DCB), End Notch Flexure configurations (ENF) and Cracked Lap Shear (CLS) experiments on 0/90-glass woven cloth specimens. For the validation process, the procedures stipulated by ASTM standards were employed. It was observed that there were significant discrepancies between calculated fracture energies using standard procedures and the proposed model. Interestingly these observations have revealed some inconsistencies associated with the standard method for strain measurements that majorly controls the fracture energy calculations. This research project has demonstrated and evidently proven the accuracy of the proposed model predictions using the strain measured with embedded Fibre Bragg Grating (FBG) sensors, located inside the sample in proximity of the crack tip. The extended use of FBG strain measurement has created a breakthrough in Structural Health Monitoring (SHM) of composite structures. Non-availability of a suitable damage prediction model is an issue for accurate damage monitoring process. The proposed model has also demonstrated the potential for its integration with Structural Health Monitoring (SHM) systems. Additionally, Thermoplastic Stress Analysis (TSA) has been employed to monitor delamination. The potential for integration of FBG sensors and TSA techniques has been experimentally demonstrated during this project and, it is another breakthrough in SHM field as a result of this research. In addition to analytical model, a detailed Finite Element model was also created on ABAQUS commercial software. The cohesive elements with state variables (SDV) and UMAT codes were used for FEA simulations. Interestingly, the FEA results have shown an excellent correlation with the experimental results. Finally, this thesis has evidently proved the validity of the proposed model and integration of model with SHM system based on FBG sensors and TSA techniques. The outcomes of the thesis have provided a novel and innovative damage prediction model and a breakthrough technology for SHM systems

Histological Changes in the Lung and Liver of Mice Treated with Brake Pad Particles

في الدراسة الحالية ، تم تقييم تأثيرات جزيئات وسائد مكابح السيارات في المقاطع النسيجية لكل من الرئة والكبد في (60)من ذكور الفئران البالغين.قسمت حيوانات التجربة إلى ثلاث مجموعات (C.B.A) وفقا لفترات التعرض التي كانت (12,8,4) أسبوع على التوالي وكانت تتعرض لجزيئات وسائد مكابح السيارات فضلا عن مجموعه السيطره التي كانت تتعرض للهواء النقي فقط. تم استخدام حجرة تعرض استنشاقي خاصة تم تصميمها محليًا لتعرض حيوانات التجربة فيها. كان التعرض لجسيمات وسائد مكابح السيارات بتركيز (2.228) ميكروغرام / م3 لمدة (30) دقيقة / يوم, 5 أيام / أسبوع لمدة (12,8,4) أسبوع على التوالي. أظهرت نتائج الفحص للمقاطع النسجية تثخنات في جدران الأسناخ الرئوية واحتقان الشعيرات الدموية السنخية.كما اظهرت الرئة نفاخ سنخي منتشر بشكل باحات وارتشاح في خلايا البلعم الكبير وقد اجتاحتها (دقائق وسائد مكابح السيارات) داخل السيتوبلازم وتليف محيط بالقصيبة الهوائية في المجموعة (A). وقد لوحظ تواجد دقائق وسائد المكابح  مع التهاب في الشعب الهوائية وفرط تنسج في  الخلايا الظهارية لها وارتشاح كريات الدم البيضاء أحادية النواة وتنخر فصي بؤري في المجموعة (B). بينما اظهرت المجموعة (C) التهاب قصبي رئوي حاد وتنخربؤري حول القصيبات مع وذمه رئويه  وتفحم الاسناخ الرئويه.أما تغيرات انسجة الكبد كانت تتضمن التهاب كبدي حاد واحتقان وريدي مركزي في المجموعة (A). واظهرت بعض الخلايا الكبدية إنقسام النواة من (2 الى 3انوية ) في المجموعة (B).وظهور احتقان شديد في الوريد المركزي وتجمع النشا فيه وتنخر في معظم خلايا الكبد في المجموعة (C). ولوحظت زيادة هذه التغييرات مع زيادة فترات التعرض وتصبح أكثر وضوحًا في المجموعات المعرضة لمدة 12 أسبوع. ان استمرار التعرض لدقائق وسائد مكابح السيارات يقود لحدوث اضرار في انسجة الجسم المهمه وبالتالي صحة الانسان, كما يمكن اعتبار هذة الدقائق نوع من الملوثات التي تضاف لملوثات الهواء في مدن العراق المختلفة.In the present study, the effects of brake pad particles of lung and liver histological sections were evaluated for (60) adult male mice. The animals were divided into three groups ( A,B,C) according to the periods of exposure (4, 8, and 12) weeks respectively exposed to brake pad particles in addition to the control groups (F) exposed to fresh air only. A special inhalation chamber designed locally has been used to expose the animals. The exposure to brake pad particles was (2.228) µg/m³ for 30 min/day, 5 days/week for (4,8and12) weeks respectively. The examination in group (A) of the histological sections of the lung showed the thickness of interalveolar septa.  Also, a congestion of alveolar capillary was marked indicating pulmonary emphysema. The infiltration of alveolar macrophages showed the engulfed foreign particles (pad particles) within their cytoplasm, and peribronchial fibrosis. Group (B) showed the presence of pad particles (anthracosis), whereas the bronchial tree showed bronchitis with the bronchus-hyperplasia of mucin-producing cells (epithelial hyperplasia). Still another section showed an infiltration of mononuclear leukocytes and focal lobar necrosis. The third group (C), in turn, revealed acute interstitial bronchopneumonia with peribronchial focal necrosis and mild pulmonary edema with alveolar anthracosis. As regards the liver, group (A) showed mild central venous congestion. Group (B), on the other hand, gave acute hepatitis, congestion of the central vein hyaline degeneration and mitotic figure having 2-3 nuclei. Severe congestion of the central vein with vascular amyloid deposition and most of the hepatocytes revealed coagulate necrosis in group (C). These changing tissues increased with increasing the exposure periods and were clearer in group (C) which was exposed for 12 weeks. The continuous exposure to brake pad particles lead to damaging important body organs tissues and effect on human health, these particles can be considered as a type of pollutants added to air pollutants in different cities of Iraq. &nbsp

Co-morbidity in Geriatric Patients Attend Elderly Clinic in Al-Yarmouk Teaching Hospital

Introduction: Ageing is an inevitable stage of life, it carries two inconvenient events: physiologic decline and disease state. It is a challenge for the health system. By descriptive study the authors reviewed the medical record files organized to patients attend the clinic during last year starting from November 2016 through October 2017.   This study covered 72 elderly patients. Mean age of patients was 66.31+ 6.44. Quarter of patients presented with chest pain, followed by dyspnea at a rate of 23.6%. Patients with a combination of chronic diseases, hypertension, diabetes mellitus, and ischemic heart disease formed 30.6%. Hypertension alone was found in 18.1% of the total sample, diabetes mellitus in 4.2%, and ischemic heart disease in 11.1% of cases.   Ageing process cause deterioration in some functions of the body, also it increases the prevalence of chronic diseases. Key words: Baghdad, chronic diseases, presenting symptom, age

Measurement the Economic Efficiency and Risk Management Strategy for Projects of Table Eggs Production in Diyala Governorate

Purpose: The aim of the research is to estimate the cost efficiency and technical and Allocavtive components of egg production projects and to identify risk management strategies.   Theoretical framework: These include Data Envelopment Analysis Program (DEAP), a method of linear programming in estimating the economic efficiency in addition to strategic use in risk management.   Design/methodology/approach: The data was collected from 44 egg chicken projects, collected randomly from Diyala county districts for 2018, for achieving economic efficiency of agriculture and  risk management strategic for projects of  table egg production .   Findings: by using of Data Envelopment Analysis with a input orientation. technical efficiency about averaged 0.995, which is highly efficient,. Allocavtive efficiency was 0.99. By linking the relationship between economic efficiency and some administrative variables, some of which are direct and inverse.   Practical & Social implications: The study benefits table egg producers, including their knowledge of the optimal use of resources for the actual use of resources through the study of economic efficiency. The study showed how to deal with risks in their projects. Outside the farm, the coping strategy to face risks is in lending, and thus this study is used at present and in the future in these investment projects..   Originality/value:  That the poultry sector is an investment and commercial sector, it is necessary to study the resources efficiency used and because it contains risks, so a strategy must be developed to protect the product from these risks

A role for genetic susceptibility in sporadic focal segmental glomerulosclerosis

Focal segmental glomerulosclerosis (FSGS) is a syndrome that involves kidney podocyte dysfunction and causes chronic kidney disease. Multiple factors including chemical toxicity, inflammation, and infection underlie FSGS; however, highly penetrant disease genes have been identified in a small fraction of patients with a family history of FSGS. Variants of apolipoprotein L1 (APOL1) have been linked to FSGS in African Americans with HIV or hypertension, supporting the proposal that genetic factors enhance FSGS susceptibility. Here, we used sequencing to investigate whether genetics plays a role in the majority of FSGS cases that are identified as primary or sporadic FSGS and have no known cause. Given the limited number of biopsy-proven cases with ethnically matched controls, we devised an analytic strategy to identify and rank potential candidate genes and used an animal model for validation. Nine candidate FSGS susceptibility genes were identified in our patient cohort, and three were validated using a high-throughput mouse method that we developed. Specifically, we introduced a podocyte-specific, doxycycline-inducible transactivator into a murine embryonic stem cell line with an FSGS-susceptible genetic background that allows shRNA-mediated targeting of candidate genes in the adult kidney. Our analysis supports a broader role for genetic susceptibility of both sporadic and familial cases of FSGS and provides a tool to rapidly evaluate candidate FSGS-associated genes