Investigating the role of the extracellular matrix (ECM) on pluripotent stem cell differentiation towards retinal lineages

PhD ThesisHuman pluripotent stem cells (hPSCs) can be differentiated into retinal organoids to study inherited and age related retinal dystrophies, to screen new drugs and to use them as replacement tissues. Published evidence suggests that retinal pigmented epithelium (RPE) and decellularised extracellular matrix (ECM) from RPE and neural retina contain several ECM molecules that are important for retinal development and synaptic formation between various cell types. To date, there has been limited detailed analysis of ECM components distribution during human retinal ontogenesis and the functional importance of several components is poorly understood. In this study, the expression of key ECM components in adult mouse and monkey retina, developing and adult human retina and hPSC-derived retinal organoids was studied. The results demonstrate that different ECM components have distinct distribution patterns throughout the adult retina of different species and a well conserved expression pattern between adult and developing human retinae. Furthermore, the expression of ECM components examined in retinal organoids was found to recapitulate at large human retinal development in vivo. The functional role of ECM on the differentiation of hPSC-derived retinal organoids was investigated either via blocking the action of two ECMs: cluster of differentiation 44 (CD44) and interphotoreceptor matrix proteoglycan 1 (IMPG1) in the organoids or via supplementation of culture media with RPE conditioned medium, decellularised ECM of neural retina or RPE. The findings indicate that IMPG1 and CD44 play an important role on photoreceptor development, their inner and outer segments, connecting cilia and IPM formation; with IMPG1 acting earlier and having more significant effect than CD44. All three supplements enhanced the light response in retinal organoids suggesting a beneficial effect of ECM on the development and function of hPSC-derived retinal organoids. Together, the study highlights a conserved expression of ECMs between human adult and developing retinae and retinal organoids as well as an important role for ECM in retinal development in vitro.King Abdulaziz University, Saudi Arabi

A performance simulation tool for the analysis of data gathering in both terrestrial and underwater sensor networks

Wireless sensor networks (WSNs) have greatly contributed to human-associated technologies. The deployment of WSNs has transcended several paradigms. Two of the most significant features of WSNs are the intensity of deployment and the criticalness of the applications that they govern. The tradeoff between volume and cost requires justified investments for evaluating the multitudes of hardware and complementary software options. In underwater sensor networks (USNs), testing any technique is not only costly but also difficult in terms of full deployment. Therefore, evaluation prior to the actual procurement and setup of a WSN and USN is an extremely important step. The spectrum of performance analysis tools encompassing the test-bed, analysis, and simulation has been able to provide the prerequisites that these evaluations require. Simulations have proven to be an extensively used tool for analysis in the computer network field. A number of simulation tools have been developed for wired/wireless radio networks. However, each simulation tool has several restrictions when extended to the analysis of WSNs. These restrictions are largely attributed to the unique nature of each WSN within a designated area of research. In addition, these tools cannot be used for underwater environments with an acoustic communication medium, because there is a wide range of differences between radio and acoustic communications. The primary purpose of this paper is to present, propose, and develop a discrete event simulation designed specifically for mobile data gathering in WSNs. In addition, this simulator has the ability to simulate 2-D USNs. This simulator has been tailored to cater to both mobile and static data gathering techniques for both topologies, which are either dense or light. The results obtained using this simulator have shown an evolving efficient simulator for both WSNs and USNs. The developed simulator has been extensively tested in terms of its validity and scope of governance

Antibiotic-resistant salmonellae in pet reptiles in Saudi Arabia

We investigated the occurrence rate of antibiotic-resistant salmonellae in exotic pet reptiles in Saudi Arabia. Salmonellae samples were collected from eight different genera of pet reptiles (snakes and lizards). Selective enrichment and selective plating procedures were carried out in order to detect salmonellae. Isolated bacteria were identified using biochemical tests, API 20E strips, and the VITEK compact system. Antimicrobial susceptibility testing was performed using the disc diffusion method. Salmonella spp. belonging to subspecies I (Salmonella enterica ssp. enterica) were detected in 29.2% of the samples. All of the detected salmonellae showed multidrug resistance (p<0.001, χ2 ). The results demonstrated that pet reptiles in private households could present health hazards to humans. Therefore, these animals should be carefully handled to avoid infection. To the best of our knowledge, this is the first report regarding the occurrence rate of antibiotic-resistant salmonellae in pet reptiles in Saudi Arabia. The detected Salmonella serovars should be subjected to further in-depth molecular analyses in order to understand the overall epidemiology of salmonellosis in Saudi Arabia.We investigated the occurrence rate of antibiotic-resistant salmonellae in exotic pet reptiles in Saudi Arabia. Salmonellae samples were collected from eight different genera of pet reptiles (snakes and lizards). Selective enrichment and selective plating procedures were carried out in order to detect salmonellae. Isolated bacteria were identified using biochemical tests, API 20E strips, and the VITEK compact system. Antimicrobial susceptibility testing was performed using the disc diffusion method. Salmonella spp. belonging to subspecies I (Salmonella enterica ssp. enterica) were detected in 29.2% of the samples. All of the detected salmonellae showed multidrug resistance (p<0.001, χ2 ). The results demonstrated that pet reptiles in private households could present health hazards to humans. Therefore, these animals should be carefully handled to avoid infection. To the best of our knowledge, this is the first report regarding the occurrence rate of antibiotic-resistant salmonellae in pet reptiles in Saudi Arabia. The detected Salmonella serovars should be subjected to further in-depth molecular analyses in order to understand the overall epidemiology of salmonellosis in Saudi Arabia

Enabling comparison of UrQMD with Geant4 hadronic models

Geant4 has an abundant set of physics models that handle the diverse interaction of particles with matter across a wide energy range. However, there are also many well established reaction codes currently used in the same fields where Geant4 is applied. One such code is the Ultra-relativistic Quantum Molecular Dynamics (UrQMD) model. In order to take advantage of the UrQMD code, we create a tool to enable comparisons among UrQMD and Geant4 hadronic models. This tool allows a user to process the output file of UrQMD through Geant4 toolkit, while at the same time, can choose among different Geant4 hadronic model generators. As an example, the UrQMD model is compared with the HARP-CDP experimental data and with the Binary and FRITIOF generators, in the framework of Geant4. It is shown that the UrQMD model can better reproduce charged pion production for p+Cu and Pb interactions at 3, 8 and 15 GeV/c, and is a good candidate for Geant4 hadronic models.Comment: 17 pages, 5 Figure

Stigmatisation of Obesity and its Relation to the Perception of Controllability in Riyadh, Saudi Arabia: A cross-sectional study

Objectives: This study assessed the stigmatisation of obesity among a sample of the general population in Riyadh and its association with the perception of controllability. Methods: A cross-sectional analytical study was carried out in Riyadh, Saudi Arabia, during January–February 2021 and included 384 participants who were recruited through a convenience sampling method. The data were collected using a self-administrated online questionnaire. Statistical analysis was performed using John’s Macintosh Project Version 16.0.0. Results: Most of the participants had a low level of stigma towards obesity (72.8%), and gender and BMI were significantly associated with the level of stigma at (p = .0023) and (p = .0360) respectively. The association between the perception of controllable factors and the level of stigma was also significant (p = 0.0001). Conclusions: The data supported the hypothesis that there would be a significant association between stigmatisation on obesity and perception of controllability among the general population in Riyadh City. Regarding recommendations, the authors suggest that they should be based on joint international consensus statements for ending the stigma of obesity in different settings and categories, and should include the education of healthcare service providers and obese patients on the relationships shown in the findings. Keywords: Obesity, stigmatisation, perceptio

Practice of wound closure techniques among emergency physicians and surgeons in Makkah City Hospitals in Saudi Arabia

Background: Wound suturing is a procedure performed by medical and surgical specialists. While there are many different suturing techniques and materials used to treat patients, the choice of which to employ depends on different variables that affect the outcome of the procedure.Design and Methods: This is a cross-sectional study conducted to provide descriptive data regarding the practice of wound closure techniques, and to develop an awareness of scar formation factors. A total of 172 general surgery (GS) surgeons and emergency (EM) physicians in Makkah city hospitals in Saudi Arabia participated in the study.Results: More than 50% of the practitioners favored the simple interrupted technique for the treatment of all types of studied wounds. The other most common techniques among participants were the subcuticular and vertical mattress methods, respectively, while the use of a stapler was limited to certain wound types. Regarding suturing material, polyglycolic acid was the most frequent material used by 50.1% of participants, whereas only 22% of the participants selected nylon material for wound suturing. However, this study showed a good level of awareness among participants, with significant p-values (p<0.05) of strongly agree and agree regarding the essential factors affecting wound healing and scar formation.Conclusions: The result provides insight into the most common suture techniques and materials used in wound closure. There are wide variations in selecting these techniques and materials among the participants. Also, we found that there is good awareness among participants about factors that lead to scar formation

Synthesis and gas permeation properties of tetraoxidethianthrene-based polymers of intrinsic microporosity

A series of nine polymers of intrinsic microporosity (PIMs) derived from different bis-catechol monomers and 2,3,7,8-tetrafluoro-5,5′,10,10′-tetraoxidethianthrene (TOT) were synthesised and tested for their potential use as gas separation membranes. As powders, they demonstrate significant nitrogen adsorption at 77 K allowing apparent BET surface areas ranging from 432-785 m2g−1to be calculated. Six of the polymers were found to be soluble in quinoline facilitating the casting of self-standing films to allow the assessment of their gas separation properties. Spirobifluorene-based polymers exhibited the highest gas permeability, approaching the performance of the archetypalPIM-1, and the data for some are placed close to the 2008 Robeson upper bounds for O2/N2and CO2/CH4. Ageing studies showed a gradual decrease in permeability, accompanied by an increase in selectivity that moved the data more-or-less parallel to the Robeson upper bounds. The two polymers with the lowest and highest gas permeability were both tested over the temperature range 25-55 °C and an enhancement in permeability for all gases, with the exception of CO2, was observed along with decreased selectivity for almost all gas pairs. The latter seems to be due to the simultaneous drop in both diffusivity selectivity and solubility selectivity for all gas pairs, but especially those involving CO2, due to a strong decrease in solubility with increasing temperature. The analysis of the energetic and entropic selectivity provides further insight into the remarkable transport properties of PIMs. Overall, the tetraoxidethianthrene unit proves to be a suitable building block for use in PIM synthesis for applications in gas separation membranes and these PIMs have a one to two orders of magnitude higher permeability than more common polysulfones.</p

Phenyl Saligenin Phosphate Induced Caspase-3 and c-Jun N-Terminal Kinase Activation in Cardiomyocyte-Like Cells

At present, little is known about the effect(s) of organophosphorous compounds (OPs) on cardiomyocytes. In this study we have investigated the effects of phenyl saligenin phosphate (PSP), two organophosphorothioate insecticides (diazinon and chlorpyrifos) and their acutely toxic metabolites (diazoxon and chlorpyrifos oxon) on mitotic and differentiated H9c2 cardiomyoblasts. OP-induced cytotoxicity was assessed by monitoring MTT reduction, LDH release and caspase-3 activity. Cytotoxicity was not observed with diazinon, diazoxon or chlorpyrifos oxon (48 h exposure; 200 μM). Chlorpyrifos-induced cytotoxicity was only evident at concentrations >100 μM. In marked contrast, PSP displayed pronounced cytotoxicity towards mitotic and differentiated H9c2 cells. PSP triggered the activation of JNK1/2, but not ERK1/2, p38 MAPK or PKB, suggesting a role for this pro-apoptotic protein kinase in PSP-induced cell death. The JNK1/2 inhibitor SP 600125 attenuated PSP-induced caspase-3 and JNK1/2 activation, confirming the role of JNK1/2 in PSP-induced cytotoxicity. Fluorescently labelled PSP (dansylated PSP) was used to identify novel PSP binding proteins. Dansylated PSP displayed cytotoxicity towards differentiated H9c2 cells. 2D-gel electrophoresis profiles of cells treated with dansylated PSP (25 μM) were used to identify proteins fluorescently labelled with dansylated PSP. Proteomic analysis identified tropomyosin, heat shock protein β-1 and nucleolar protein 58 as novel protein targets for PSP. In summary, PSP triggers cytotoxicity in differentiated H9c2 cardiomyoblasts via JNK1/2-mediated activation of caspase-3. Further studies are required to investigate whether the identified novel protein targets of PSP play a role in the cytotoxicity of this OP, which is usually associated with the development of OP-induced delayed neuropathy

Tuberculosis Trends in Saudis and Non-Saudis in the Kingdom of Saudi Arabia – A 10 Year Retrospective Study (2000–2009)

Tuberculosis (TB) remains a public health problem in the Kingdom of Saudi Arabia (KSA), which has a very large labour force from high TB endemic countries. Understanding the epidemiological and clinical features of the TB problem, and the TB burden in the immigrant workforce, is necessary for improved planning and implementation of TB services and prevention measures

Maternal Serum Macrophage Inhibitory Cytokine-1 as a Biomarker for Ectopic Pregnancy in Women with a Pregnancy of Unknown Location

Ectopic pregnancy (EP) occurs in 1-2% of pregnancies, but is over-represented as a leading cause of maternal death in early pregnancy. It remains a challenge to diagnose early and accurately. Women often present in early pregnancy with a 'pregnancy of unknown location' (PUL) and the diagnosis and exclusion of EP is difficult due to a lack of reliable biomarkers. A serum biomarker able to clearly distinguish between EP and other pregnancy outcomes would greatly assist clinicians in diagnosing and safely managing PULs. This study evaluates the ability of maternal serum macrophage inhibitory cytokine-1 (MIC-1) levels to differentiate between EP and other pregnancy outcomes in women with a PUL.Sera were collected from 120 women with a PUL at first clinical presentation and assayed for MIC-1 by ELISA. Results were classified according to ultimate pregnancy outcome and the discriminatory ability of MIC-1 to diagnose EP was assessed.Serum MIC-1 levels were lower in women with histologically confirmed (definite) EP (dEP) (median 552 ng/mL; interquartile range (IQR) 414-693 ng/mL) compared to women with definite viable intra-uterine pregnancies (dVIUPs) (722 ng/mL; IQR 412-1122 ng/mL), and higher when compared to women with definite non-viable intra-uterine pregnancies (dNVIUPs) (465 ng/mL; IQR 341-675 ng/mL). MIC-1 levels were significantly higher in women with dEP compared to women whose PULs resolved without medical intervention (srPUL) (401 ng/mL; IQR 315-475 ng/mL) (p<0.003). There were no women with an ectopic pregnancy where serum MIC-1>1000 ng/mL.Serum MIC-1 levels in PUL were not able to categorically diagnose EP, however, MIC-1 could distinguish women with an EP that required medical intervention and those women whose PULs spontaneously resolved. A single serum MIC-1 measurement also excluded EP at levels above 1000 ng/mL. MIC-1 may play a role in the development of a combined assay of biomarkers for the diagnosis of EP