1,720,988 research outputs found
ASSESSING THE CURRENT STANDING OF HAMAD MEDICAL CORPORATION BLOOD DONOR CENTER IN QATAR AND DEVELOPING A FORECAST MODEL FOR THE BLOOD STOCK NEEDS DURING THE 2022 WORLD CUP EVENT
Get PDFBackground: In four years from now, Qatar will host the 2022 World Cup competition which requires high level of preparedness and readiness in different sectors including health care. Among different sub-sections of health, the blood bank and the Blood Donor Center will have a major role in this event especially in case of unforeseen incidences. Accordingly, a proper assessment of the current blood resource availability and a prediction of future blood needs helps in overcoming any obstacle that could be faced during the event. Objectives: (1) Highlight the process of the blood supply chain, with a detailed delineation of the needed amount of blood components for both routine and emergency situations services, and outline the proper measures taken to deliver the safest and most appropriate blood units and reduce wastage of blood component. (2) Assess the current standing of the Blood Donor Center and corresponding units in Qatar. (3) Develop a forecast model that predicts the number of blood donors in the next four years as a method to evaluate the readiness of the Blood Donor facility to host the world cup event. (4) Explore the potential challenges that could be faced when meeting the benchmark of donation and established an action plan to overcome these anticipated challenges. Materials and Methods: Both qualitative (interviews) and a quantitative (data collection and analysis) approaches have been implemented in our study. We also established a time series forecast model using Autoregressive Integrated Moving Average (ARIMA). Results: The number of donors in the next four years, which is predicted to increase by 26%, will not be able to get accommodated in the current Blood Donor Center facility. Therefore, the established blood stock benchmark will not be met despite that the Center and its corresponding units are fully equipped with high standard equipment and follow international guidelines in the process of blood withdrawal. Conclusion: Infrastructure improvements and logistics support for Hamad Medical Corporation Blood Donor Center are required to support the continuously increasing numbers of blood donors for daily demand and during mega events
VASCULAR REMODELING IN HYPERTENSION: IN-VITRO/ EX-VIVO MECHANICAL STRETCH-INDUCED ALTERATIONS AND OMICS ANALYSIS
No full textHypertension, being a primary vasculature disorder, contributes significantly to premature death globally. Over the years, numerical figures have evidenced a dramatic increase in hypertension’s global prevalence, affecting approximately 1.3 billion individuals, according to the World Health Organization (WHO). Hypertension mainly develops as a result of excessive mechanical stretch exerted by the pulsatile blood flow on the vessel wall and endothelial cells (ECs), lining the inner face of the blood vessel, chiefly respond to these hemodynamic mechanical forces. Although physiological levels of mechanical stretch are crucial for maintaining vascular homeostasis, excessive levels, such as those reported in hypertension conditions, can induce pathological consequences, leading to structural and functional alterations in the blood vessel, a phenotype referred to as 'vascular remodeling'.
In this study, we aim to (1) characterize structural and functional alterations occurring in ECs in response to mechanical stretch using an in-vitro model, (2) unravel the role of ECs in mechanical stretch-induced vascular remodeling using an ex-vivo model, and (3) uncover potential biomarkers that serve as plausible indicators for hypertension development through omics analysis.
To address this, immortalized human umbilical vein endothelial cells (EA.hy 926) and Rat portal Vein (RPV) were subjected to mechanical stretch for 24 hours. Actin cytoskeleton remodeling, monocytes adhesion, and reactive oxygen species (ROS) generation were evaluated using immunofluorescence staining. Real-time PCR was employed to assess mRNA levels of inflammatory cytokines, adhesion molecules, and adipokines. Moreover, proteomics and metabolomics data of hypertensive patients, obtained from Qatar Biobank, were analyzed.
The outcome of this study firstly, revealed significant morphological changes in ECs exposed to mechanical stretch, characterized by actin filament alignment perpendicular to the stretching axis and an increase in the F to G actin ratio. Interestingly, inhibition of Rho-associated protein kinase (ROCK), using Y-27632, prevented this orientation and the increase in F-actin. Furthermore, mechanical stretch significantly upregulated the transcript levels of several inflammatory cytokines including IL8, IL6, and IL1B, as well as adhesion molecules, including ICAM1, VCAM1, and E selectin, along with NFκB activation. Increased mRNA expression of leptin and adiponectin was also observed. Moreover, mechanical stretch of ECs stimulated the adhesion of THP-1 monocytes and increased CCL2 expression. ROS production was also significantly elevated under mechanical stretch conditions. Furthermore, denudation of the endothelium from the RPV was able to inhibit mechanical stretch-induced vascular hypertrophy, oxidative stress, and leptin synthesis.
Secondly, proteomics analysis revealed a group of proteins, including the proto-oncogene tyrosine-protein kinase Src (SRC) family, calcium/calmodulin-dependent protein kinase 2 beta and delta subunits (CAMK2B and CAMK2D), Tec Protein Tyrosine Kinase (TEC), Glycogen synthase kinase-3 (GSK3), Vav Guanine Nucleotide Exchange Factor 1 (VAV1), and Ras-related C3 botulinum toxin substrate 1 (RAC1), markedly upregulated in patients with hypertension compared to those with prehypertension. Pathway analysis showed that the majority of these proteins play a role in actin cytoskeleton remodeling.
Thirdly, metabolomics analysis identified six metabolites including stearidonate, hexadecadienoate, N6-carbamoylthreonyladenosine, 9 and 13-S-hydroxyoctadecadienoic acid (HODE), 2,3-dihydroxy-5-methylthio-4-pentenoate (DMTPA), and linolenate associated with an increased risk of developing hypertension.
Taken together, our findings illustrate significant structural and functional changes in ECs subjected to mechanical stretch, mimicking the hypertension condition, and demonstrate a chief role of ECs in mechanical stretch-induced vascular remodeling. Additionally, our findings also identify novel proteins and metabolites involved in hypertension progression, shedding further insight into the underlying pathological mechanisms involved in hypertension and paving the way for novel diagnostic and therapeutic approaches for the treatment of hypertension and its associated complications
INVESTIGATING THE MOLECULAR MECHANISMS OF SHEAR STRESS INDUCED ENDOTHELIAL DYSFUNCTION AND PROGRESSION OF ATHEROSCLEROSIS
No full textBackground: Atherosclerotic vascular disease, such as coronary artery disease (CAD) and ischemic stroke is the leading cause of mortality and disability worldwide. Therefore, understanding the mechanisms underlying atherosclerosis is crucial for prevention and treatment. Atherosclerosis, characterized by plaque buildup in arteries, is influenced by factors such as disturbed blood flow, endothelial dysfunction, inflammation, and dyslipidemia. Endothelial cells (ECs) play a pivotal role in vascular health, responding to shear stress and maintaining homeostasis. In the vascular system, shear stress on ECs was generated by mainly two types of blood flow: "laminar" and "disturbed". ECs that are exposed to laminar flow exhibit healthy cellular functions including cell alignment, enhanced barrier function, nitric oxide (NO) production, and autophagy. However, disturbed flow induces endothelial dysfunction, inflammation, oxidative stress, and atherosclerosis in presence of cardiovascular risk factors which could be hypercholesterolemia (HC), hyperglycemia, or hypertension. Additionally, elevated blood leptin is also considered to be related to risk for cardiovascular diseases (CVDs). Distinct behavior of ECs in response to shear stress is a key stage for the development of vascular diseases and therefore an important research area. In vitro models, such as orbital shakers, provide valuable tools for studying shear stress-induced endothelial responses and investigating potential therapeutic targets. On the other side, exploring biomarkers for atherosclerosis is significant for early diagnosis and prediction of prognosis of the disease. Omics studies, with its holistic examination of biological samples, offer a significant advantage over conventional single-biomarker studies to gain insights into the molecular mechanisms of atherosclerosis and facilitate biomarker discovery. Objectives: The study involves two independent, yet interrelated aims directed towards (1) unraveling the mechanisms underlying disturbed flow-induced endothelial dysfunction and (2) identifying potential biomarkers for atherosclerosis progression. To address those aims, we established an in vitro flow system set up to study endothelial dysfunction. We examined intracellular protein alterations of EC line and rat aorta tissue, in response to shear stress. We also conducted proteomics and metabolomics profiling in patients with atherosclerosis and dyslipidemia. Methods: The in vitro and ex vivo arms of our study were conducted on human ECs and rat aortic tissues, respectively, and our proteomics and metabolomics studies were done on human blood plasma. The in vitro experiments involved EC culture, exposure to laminar and disturbed flow using an orbital shaker and the ex vivo experiments involved utilizing isolated rat aorta for examining the effect of shear stress on vascular cell behavior. Proteomics data were analyzed using multiple statistical methods. The data generated using Slow Off-rate Modified Aptamer (SOMAmer)-based protein array, was provided by Qatar Biobank. Our cross-sectional study involved healthy controls (n=45), and patients diagnosed with HC (n=51), or with CAD (n=32). Our metabolomics study employed a total of 221 participants including healthy controls, CAD patients, and HC patients with complications (i.e. hypertension and diabetes). A linear regression model was used to demonstrate how variations in the ordered categorical groups (stages of atherosclerosis progression) influenced changes in metabolite levels. Results: Shear stress experiments conducted in vitro showed distinct alignment and differential gene expression patterns in ECs exposed to either laminar flow or disturbed flow conditions. Along this, our findings from the in vitro studies also revealed leptin involvement in EC response to disturbed flow. Similar changes were observed using the ex vivo model too, particularly in the inner curve of the rat aorta, where the blood flow was disturbed. Our proteomics analysis, which was conducted pairwise comparisons among the study groups, revealed a total of 65 proteins differentially expressions, as well as strong diagnostic value for CAD and HC with area under the curve (AUC) values exceeding 0.75. Notably, among these proteins, 14 showed significant correlations with blood cholesterol levels. Additionally, 22 of the identified proteins were associated with CAD or HC pathways, with nine proteins including Apo E, Apo E3, MMP-3, PCSK9, SDF-1, Apo B, PAFAH, HSP 60, and TAK1-TAB1being common to both conditions. Our metabolomics analysis revealed differential metabolite levels associated with CAD progression, with notable changes in carbohydrate and lipid metabolism linked to CAD risk. Specifically, mannitol/sorbitol, mannose, glucose, and ribitol exhibited positive associations, while pregnenediol sulfate, oleoylcarnitine, and quinolinate were negatively associated with an increased risk of CAD. Correlation analysis further elucidated the relationship between clinical traits and metabolites, providing insights into the underlying mechanisms of CAD progression. Conclusion: In conclusion, this study provides comprehensive insights into the complex interplay between flow conditions, EC responses, inflammatory processes, and metabolic alterations in the context of CVD. By elucidating these molecular mechanisms, the study paves the way for the development of novel diagnostic tools and therapeutic strategies aimed at combating atherosclerosis in specific and reducing the burden of CVD in general
The Use of Data-driven Quality Strategy to Improve the Processes of Patient Identification and Pre-transfusion Specimen Collection Documentation at Sidra Medicine
Get PDFBackground: Regardless of healthcare technology advancements and widespread use of barcode identification technology, patient identification errors still occur. Several studies and benchmark programs have shown that patient misidentification is the leading cause of transfusion-associated reactions and fatalities. Therefore, it is recommended to use barcode technology to reduce and possibly eliminate avoidable blood transfusion errors. However, none of the available studies so far has investigated the compliance with using barcode technology to identify patients and specimens during the process of specimen collection for transfusion. Aims: This project aims are (1) Identify the prevalence of noncompliance in barcode scanning assisted patient identification at the pre-analytical phase during specimen collection at Sidra Medicine; and (2) Evaluate the causes of barcode scanning noncompliance; and finally (3) Develop quality improvement action plans that could reduce noncompliance events. Materials and Methods: The frequency of blood typing specimen collection noncompliance events between January 1, 2019 and December 31, 2019 were retrieved from the Laboratory Information System (LIS) module of Transfusion Medicine Laboratory report. Quantitative and qualitative analyses of data included stratification of collections by role and collection event, and finding possible sources of errors were performed. Accordingly, process improvement plans specific to each department involved in specimen collection were established. Results: Collection compliance rates of a total of 6387 blood typing specimens were evaluated. Full barcode scanning identification of both patient and specimen was utilized in only 33.6% of total collections during the baseline study period. The remaining two thirds of collections were override events, in which no barcode scanning at all represented 31.3%, and the sample accession label was scanned but not the patient armband in 32.3% of total collections. In addition, there were significant differences between phlebotomists and nurses with more phlebotomists performing the full scanning and specimen label scanning only, while more nurses obtained specimens without scanning either identification of patient or specimen (p<.001). Conclusion: Our study highlights poor utilization of barcode scanning to verify patient and specimen identification during specimen collection. We launched a quality improvement project that identified the causes contributing to non-compliance practices, and formulated improvement strategies
THE ROLE OF ENTEROENDOCRINE SECRETED GUT PEPTIDE HORMONES IN MODULATING IMMUNITY AND METABOLISM IN DROSOPHILA MELANOGASTER
Get PDFThe intestine of all living organisms fosters an ecosystem of commensal microbiota that plays key roles in the maintenance of host health and pathology. Captivatingly, the influence of dysbiosis on the host has demonstrated the significance of the existing crosstalk between the gut microbiota, nutrient balance, and immune processes. Intestinal enteroendocrine cells (EE)-secreted gut peptide hormones represent an emerging area of exploration, with a gut flora-dependent role in modulating metabolism and innate immune signaling yet to be determined. In this study, we utilize the Drosophila melanogaster model organism to understand the systemic and/or tissue-specific roles of Tachykinin (Tk), Diuretic Hormone 31 (DH31), and Allatostatin A (AstA) EE secreted peptide hormones in maintaining metabolic homeostasis and modulating innate immune signaling. Our findings reveal significant disruptions in gut flora distribution and in several metabolic parameters including: body weight, systemic glucose and triglyceride levels, lipid transport from gut, and fat body lipid storage in three systemic mutant lines (TkEY20174, Dh31KG09001 and AstAMB10261) and in the Tk>AstARNAi transgenic line. We also report altered immune status and host susceptibility profiles TkEY20174, Dh31KG09001, AstAMB10261, and Tk>AstARNAi flies infected with bacteria. Consistent with these results, RNA-sequencing on the whole intestine of these systemic mutants and transgenic flies identified several differentially expressed genes associated with the processes of metabolism and immunity. Together, the findings of this project provide further insight into the contribution of EE-secreted peptide hormones in the maintenance of immune-metabolic homeostasis in a host, a foundation that could have profound implications on the therapy of metabolic and immune illnesses as well as for metabolic ramifications of intestinal dysbiosis
GENERATION AND CHARACTERIZATION OF "OFF-THE-SHELF" CHIMERIC ANTIGEN RECEPTOR ENGINEERED T CELLS (CAR-T) TO TARGET CANCER PATIENTS WITH HEMATOLOGICAL MALIGNANCIES
Get PDFBackground: The usage of T cells engineered with a tumor-specific chimeric antigen receptor (CAR) for the therapeutic treatment of some types of hematological malignancies demonstrated great clinical success. However, the manufacturing of these medicinal products is commonly performed in an autologous setting, with a relatively lengthy and complex process. Therefore, not all the patients with the defined blood cancer can have access to this type of therapy. Allogenic CAR-T cells, due to their "off-the-shelf" availability can overcome some of the limitations associated with the use of the autologous approach. The principal aim of this study was to optimize the generation of "off-the-shelf" CAR-T cells utilizing the umbilical cord blood (UCB) as a source of T lymphocytes. Methods: UCBs were collected at Sidra Medicine from newborn babies at the time of birth. T lymphocytes where isolated by magnetic selection and then activated in vitro using anti-CD3/CD28 agonistic monoclonal antibodies. The activated T cells were then transduced with lentiviral vectors encoding for two types of CARs, CD19-CD28? and CD19-4-1BB? CARs. The characterization of the efficiency of transduction, the in vitro expansion, phenotype analyses and anti-tumor activity of these CD19-CAR-T cells was performed. PBMCs were utilized as source of CAR-T cells as reference of our experiments. Results: UCB-derived CD19-CAR-T cells showed an enrichment of CAR-T cells at early stage of differentiation (T stem cell memory/central memory T cells) associated with different activation markers. These cells demonstrated high in vitro expansion and exerted an efficient anti-tumor activity against target cell lines. Conclusions: Our results allowed to identify the method for the efficient isolation ex vivo of UCB-derived CD19-CAR-T cells. UCB can be considered an efficient source of T lymphocytes to generate "off the shelf" CAR-T cells endowed with anti-tumor activity and favorable phenotypic properties
Editorial: Unconventional Animal Models in Infectious Disease Research
Get PDFBeyond an in vitro setting, the use of a biological system is considered imperious to unravel the enigma of host-pathogen interactions, particularly those eventuating in an infectious disease scenery. In the past two-decades, the use of animal models, especially the unconventional ones, in studying infectious disease occurrence and progression has stemmed out. This rise in the use of animal models in research was greatly reinforced by the furtherance advancements in the field of genetics that has opened up for feasible genetic manipulation of both the host and the pathogen as needed throughout the course of conducted studies. Within this frame of reference, our launched topic envisioned to bring in research work that have used a broad spectrum of unconventional animal models to introduce pioneering findings in host-pathogen interaction studies. These findings will not only shed more light on our understanding of host-pathogen interfaces, but also set the foundation for innovative therapeutic regimens to control infectious diseases
THE EFFECT OF NATURAL AND SYNTHETIC COMPOUNDS ON COLORECTAL CANCER: IN VITRO AND IN VIVO STUDIES
No full textColorectal cancer (CRC) is one of the deadliest malignancies in the world. Despite improved treatment, CRC incidence and mortality rates have been increasing lately. Current conventional therapies are associated with severe side effects that affect patients' quality of life. Drug resistance, severe pain, hair loss, and blood abnormalities are the most common side effects. Therefore, novel, and safe alternatives are required to control metastasis and prevent CRC with minimum or no side effects. Recently, natural products became an attractive target as a safe resource for anticancer agents. Flavonoids are a group of biologically active compounds naturally found in a wide range of human dietary. Additionally, flavonoids from natural and synthetic sources, showed significant therapeutic effects against CRC. Elaeagnus Angustifolia (EA) is a natural resource for flavonoids traditionally used to treat different illnesses. Another resource for flavonoids is synthetic chalcone analogs. Previous work from our team explored the effect of EA and chalcone compounds against various types of cancer. In this study, we sought to particularly illustrate the impact of the EA flower’s aqueous extract and the nitrogen-based-synthetically designed chalcone analogs (DK13 and DK14) and their underlying mechanisms of action on CRC using in vitro (the human CRC cell lines [-116 and LoVo]) and in vivo (the Drosophila melanogaster Ras mutant fly lines) model systems. Our results showed that EA extract inhibits cell proliferation and alters cell cycle progression of both CRC cell lines as compared to the control group. Moreover, EA extract significantly reduces colony formation and cell invasive ability of HCT-116 and LoVo cell lines; a phenotype accompanied by a significant upregulation of E-cadherin and a downregulation of vimentin and β-catenin, which are important epithelialmesenchymal transition (EMT) biomarkers. Also, and as detected in our in vivo model, EA-treated Ras85D mutant fly lines exhibited a significantly increased survival rate as compared to their control. Furthermore, molecular pathway analysis in vitro revealed a significant suppression in total and phosphorylated EGFR and AKT expression in EAtreated cells as compared to controls, suggesting the EGFR-RAS and PI3K-AKT pathways as key molecular pathway targeted by EA to control ongoing oncogenic events. Along this, our data related to DK13 and DK14 also revealed that these compounds inhibit cell proliferation and deregulate cell-cycle progression in both cell lines. Additionally, DK13 and DK14 significantly reduce cell invasion and colony formation of both cell lines compared to the action of conventional anticancer 5'fluorouracil (5-FU) and DMSO-treated control. This was translated into a significant increase in the survival rates of D. melanogaster Ras85D mutant fly lines as compared to their controls. Moreover, the molecular pathway analysis of chalcone- treated cells revealed an inhibitory effect of DK13 and DK14 on the expression patterns of both AKT and mTOR, highlighting RAS/MAPK and PI3K/AKT/mTOR pathways as key molecular pathway targeted by DK13 and DK14 to control ongoing oncogenic events. Collectively, our study findings demonstrate an apparent anticancer effect of EA extract and chalcone compounds on CRC, presenting EA, Dk13, and Dk14 as promising chemotherapeutic agents
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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