Differentiation of Human Embryonic Stem Cells to Sympathetic Neurons: A Potential Model for Understanding Neuroblastoma Pathogenesis

Background and Aims: Previous studies modelling human neural crest differentiation from stem cells have resulted in a low yield of sympathetic neurons. Our aim was to optimise a method for the differentiation of human embryonic stem cells (hESCs) to sympathetic neuron-like cells (SN) to model normal human SNS development. Results: Using stromal-derived inducing activity (SDIA) of PA6 cells plus BMP4 and B27 supplements, the H9 hESC line was differentiated to neural crest stem-like cells and SN-like cells. After 7 days of PA6 cell coculture, mRNA expression of SNAIL and SOX-9 neural crest specifier genes and the neural marker peripherin (PRPH) increased. Expression of the pluripotency marker OCT 4 decreased, whereas TP53 and LIN28B expression remained high at levels similar to SHSY5Y and IMR32 neuroblastoma cell lines. A 5-fold increase in the expression of the catecholaminergic marker tyrosine hydroxylase (TH) and the noradrenergic marker dopamine betahydroxylase (DBH) was observed by day 7 of differentiation. Fluorescence-activated cell sorting for the neural crest marker p75, enriched for cells expressing p75, DBH, TH, and PRPH, was more specific than p75 neural crest stem cell (NCSC) microbeads. On day 28 post p75 sorting, dual immunofluorescence identified sympathetic neurons by PRPH and TH copositivity cells in 20% of the cell population. Noradrenergic sympathetic neurons, identified by copositivity for both PHOX2B and DBH, were present in 9.4% ± 5.5% of cells. Conclusions: We have optimised a method for noradrenergic SNS development using the H9 hESC line to improve our understanding of normal human SNS development and, in a future work, the pathogenesis of neuroblastoma

Influence of cell type of origin to the differentiation potential of induced pluripotent stem cells derived from human urinary tract cells

PhD ThesisBackground: Direct reprogramming of human somatic cells to pluripotent embryonic stem (ES) cell -like cells, termed induced pluripotent stem (iPS) cells, can be achieved by expression of defined transcription factors. The potential use of iPS cells derived from the urinary tract provides a substantial opportunity in developing new disease models, drug screening and tissue engineering. We aimed to generate, for the first time, human induced pluripotent stem cells derived from the urinary tract (UT-iPS) cells and to assess capacity for directed differentiation into bladder lineages. Methods: Human primary culture cells derived from benign bladder and ureters were transduced with OCT4, SOX2, KLF4 and C-MYC genes to generate human UT-iPS cells. Generated cells were characterised using RT-PCR and immunofluorescence. Differentiation capacity was evaluated by embryoid body formation in vitro and teratoma assay in vivo. Established co-culture based directed differentiation into bladder cells was assessed in comparison with classical skin-derived iPS cells. Results: We demonstrated successful re-programming of adult urinary tract cells from both bladder and ureter into human UT-iPS cells. Most of the clones showed efficient transgene silencing and maintained a normal diploid karyotype. Specifically, we showed expression of ES cell markers and functional pluripotency by the generation of endodermal, ectodermal and mesodermal lineages. Differentiation into bladder lineages was demonstrated by expression of urothelial-specific markers, uroplakins (UPIb, UPII, UPIIIa, and UPIIIb), claudins (CLD1 and CLD5) and cytokeratin (CK7); and stromal smooth muscle markers a-SMA, calponin, and desmin. Human UT-iPS cells were shown to be more efficient than skin-derived iPS cells in undergoing bladder differentiation, underlining the importance of the origin of the parent cell for re-programming. Conclusions: We demonstrated that the induction of human urinary tract cells into iPS cells is possible, offering a new exciting opportunity for tissue engineering and for the study of bladder disease.Syrian ministry of higher educatio

Mathematical & Physical Modelling of a Quadrotor UAV

Unmanned aerial vehicles (UAVs) are now becoming a major topic of interest due to their flying capabilities attracting researchers who are working within various application. Quadrotors in particular are one of main types of UAVs that are now currently studied, where some of the main focuses are positional and attitude tracking. Currently, verifying these systems in simulation is generally processed through MATLAB/Simulink where the dynamics are thoroughly analyzed. In this paper, the results attained from the mathematical dynamics implemented in Simulink will be justified using ADAMS environment. This software was purposely developed to accurately model the dynamics of mechanical systems in 3D without considering any equations of motion. SolidWorks is used to design the quadrotor frame that satisfies the properties of the proposed system in Simulink. Setting the control inputs as angular velocity of each motor will generate a relative thrust in order for the vehicle to achieve motion. Finally, the dynamic behavior on ADAMS and Simulink are compared as the control inputs are identically applied, which has revealed a marginal difference between the resultant motions

Peripartum Cardiomyopathy: Facts and Figures

Peripartum cardiomyopathy (PPCM) is a rare clinical entity during pregnancy. PPCM is a diagnosis of exclusion. These patients do not have prior history of heart disease, and there are no other known possible causes of heart failure. It is more common in African countries, may be related to the consumption of kanwa, in the postpartum period. The multiparity, African descent and pregnancy-induced hypertension are a few risk factors for PPCM. The exact etiology of PPCM is not known; possible theories range from myocarditis to the maladaptation to the changes of pregnancy. The clinical manifestation varies from shortness of breath to thromboembolic phenomenon. Echocardiography is essential for diagnosis as well as differential diagnosis of PPCM. These patients preferably are managed in tertiary healthcare facilities. Anticoagulation and antiarrhythmic medications are pillars for the management of PPCM patients. If required, mechanical devices should be used temporarily. PPCM patients may need heart transplant. The beneficial role of bromocriptine and immunosuppression is not clear in PPCM patients. Subsequent pregnancies should be avoided to prevent the PPCM occurrence

Increasing frailty is associated with higher prevalence and reduced recognition of delirium in older hospitalised inpatients: results of a multi-centre study

Purpose: Delirium is a neuropsychiatric disorder delineated by an acute change in cognition, attention, and consciousness. It is common, particularly in older adults, but poorly recognised. Frailty is the accumulation of deficits conferring an increased risk of adverse outcomes. We set out to determine how severity of frailty, as measured using the CFS, affected delirium rates, and recognition in hospitalised older people in the United Kingdom. Methods: Adults over 65 years were included in an observational multi-centre audit across UK hospitals, two prospective rounds, and one retrospective note review. Clinical Frailty Scale (CFS), delirium status, and 30-day outcomes were recorded. Results: The overall prevalence of delirium was 16.3% (483). Patients with delirium were more frail than patients without delirium (median CFS 6 vs 4). The risk of delirium was greater with increasing frailty [OR 2.9 (1.8–4.6) in CFS 4 vs 1–3; OR 12.4 (6.2–24.5) in CFS 8 vs 1–3]. Higher CFS was associated with reduced recognition of delirium (OR of 0.7 (0.3–1.9) in CFS 4 compared to 0.2 (0.1–0.7) in CFS 8). These risks were both independent of age and dementia. Conclusion: We have demonstrated an incremental increase in risk of delirium with increasing frailty. This has important clinical implications, suggesting that frailty may provide a more nuanced measure of vulnerability to delirium and poor outcomes. However, the most frail patients are least likely to have their delirium diagnosed and there is a significant lack of research into the underlying pathophysiology of both of these common geriatric syndromes

Modelling, simulation and control of a novel structure varying quadrotor

In this work, a novel structure of a Quadrotor Unmanned Aerial Vehicle (UAV) is proposed to change the dynamics during flight. The proposed mechanism is presented which consists of extendable plates that move along the horizontal axes from the body frame respectively. Essentially, the main goal behind this novel architecture is to enhance performance and improve flight duration in reaching the desired position. The Euler dynamic model is derived to represent the multirotor equation of motion. Basic PID controllers were implemented to demonstrate the concept and to analyse the vehicle behaviour as the structure is altered during flight. A physical modelling software is also used to study the multi-body interactions of rigid bodies as well as the dynamic response. By comparing the performance between the proposed system and the traditional version, the paper reveals improved flight performance for attitude and position tracking. The mathematical representation of the dynamic system was also verified using Msc ADAMS as identical control inputs where simultaneously applied.</p

A Review of Quadrotor Unmanned Aerial Vehicles: Applications, Architectural Design and Control Algorithms

AbstractOver the past decade, unmanned aerial vehicles (UAVs) have received a significant attention due to their diverse capabilities for non-combatant and military applications. The primary aim of this study is to unveil a clear categorization overview for more than a decade worth of substantial progress in UAVs. The paper will begin with a general overview of the advancements, followed by an up-to-date explanation of the different mechanical structures and technical elements that have been included. The paper will then explore and examine various vertical take-off and landing (VTOL) configurations, followed by expressing the dynamics, applicable simulation tools and control strategies for a Quadrotor. In conclusion to this review, the dynamic system presented will always face limitations such as internal and/or external disturbances. Hence, this can be minimised by the choice of introducing appropriate control techniques or mechanical enhancements.</jats:p