Materials and Methods: All the variants' information was retrieved from the Ensembl genome database, and then different variation prediction analyses were performed. UTRScan was used to predict UTR variants while MaxEntScan was used to predict splice site variants. Meta-analysis by PredictSNP2 was used to predict sSNPs. Parallel prediction analyses by five different software packages including SIFT, PolyPhen-2, Mutation Assessor, I-Mutant2.0 and SNPs&GO were used to predict the effects of nsSNPs. The level of evolutionary conservation of deleterious nsSNPs was further analyzed using ConSurf server. Mutant protein structures of deleterious nsSNPs were modelled and refined using SPARKS-X and ModRefiner for structural comparison.
Results: A total of 56 deleterious variants were identified in this study, including 12 UTR variants, 18 splice site variants, eight sSNPs and 18 nsSNPs. Among these 56 deleterious variants, seven variants were also identified in the Alzheimer's Disease Sequencing Project (ADSP), Alzheimer's Disease Neuroimaging Initiative (ADNI) and Mount Sinai Brain Bank (MSBB) studies.
Discussion: The 56 deleterious variants were predicted to affect the regulation of gene expression, or have functional impacts on these three endocytosis genes and their gene products. The deleterious variants in these genes are expected to affect their cellular function in endocytosis and may be implicated in the pathogenesis of AD as well. The biological consequences of these deleterious variants and their potential impacts on the disease risks could be further validated experimentally and may be useful for gene-disease association study.
METHODS: This review article discusses the experimental and computational methods in the study of HUA. The discussion includes computational fluid dynamics approach and steps involved in the modeling used to investigate the flow characteristics of HUA. From inception to May 2020, databases of PubMed, Embase, Scopus, the Cochrane Library, BioMed Central, and Web of Science have been utilized to conduct a thorough investigation of the literature. There had been no language restrictions in publication and study design of the database searches. A total of 117 articles relevant to the topic under investigation were thoroughly and critically reviewed to give a clear information about the subject. The article summarizes the review in the form of method of studying the HUA, CFD approach in HUA, and the application of CFD for predicting HUA obstacle, including the type of CFD commercial software are used in this research area.
RESULTS: This review found that the human upper airway was well studied through the application of computational fluid dynamics, which had considerably enhanced the understanding of flow in HUA. In addition, it assisted in making strategic and reasonable decision regarding the adoption of treatment methods in clinical settings. The literature suggests that most studies were related to HUA simulation that considerably focused on the aspects of fluid dynamics. However, there is a literature gap in obtaining information on the effects of fluid-structure interaction (FSI). The application of FSI in HUA is still limited in the literature; as such, this could be a potential area for future researchers. Furthermore, majority of researchers present the findings of their work through the mechanism of airflow, such as that of velocity, pressure, and shear stress. This includes the use of Navier-Stokes equation via CFD to help visualize the actual mechanism of the airflow. The above-mentioned technique expresses the turbulent kinetic energy (TKE) in its result to demonstrate the real mechanism of the airflow. Apart from that, key result such as wall shear stress (WSS) can be revealed via turbulent kinetic energy (TKE) and turbulent energy dissipation (TED), where it can be suggestive of wall injury and collapsibility tissue to the HUA.
METHODS: A cross-sectional study was conducted to evaluate the corneal cell morphology of 47 keratoconus patients and 32 healthy eyes without any ocular disease. New keratoconus patients with different disease severities and without any other ocular co-morbidity were recruited from the ophthalmology department of a public hospital in Malaysia from June 2013 to May 2014. Corneal cell morphology was evaluated using an in vivo slit-scanning confocal microscope. Qualitative and quantitative data were analysed using a grading scale and the Nidek Advanced Visual Information System software, respectively.
RESULTS: The corneal cell morphology of patients with keratoconus was significantly different from that of healthy eyes except in endothelial cell density (P = 0.072). In the keratoconus group, increased level of stromal haze, alterations such as the elongation of keratocyte nuclei and clustering of cells at the anterior stroma, and dark bands in the posterior stroma were observed with increased severity of the disease. The mean anterior and posterior stromal keratocyte densities and cell areas among the different stages of keratoconus were significantly different (P < 0.001 and P = 0.044, respectively). However, the changes observed in the endothelium were not significantly different (P > 0.05) among the three stages of keratoconus.
CONCLUSION: Confocal microscopy observation showed significant changes in corneal cell morphology in keratoconic cornea from normal healthy cornea. Analysis also showed significant changes in different severities of keratoconus. Understanding the corneal cell morphology changes in keratoconus may help in the long-term monitoring and management of keratoconus.
METHODS: A sample of 111 plaster study models of Down syndrome (DS) patients were digitized using a blue light three-dimensional (3D) scanner. Digital and manual measurements of defined parameters were performed using Geomagic analysis software (Geomagic Studio 2014 software, 3D Systems, Rock Hill, SC, USA) on digital models and with a digital calliper (Tuten, Germany) on plaster study models. Both measurements were repeated twice to validate the intraexaminer reliability based on intraclass correlation coefficients (ICCs) using the independent t test and Pearson's correlation, respectively. The Bland-Altman method of analysis was used to evaluate the agreement of the measurement between the digital and plaster models.
RESULTS: No statistically significant differences (p > 0.05) were found between the manual and digital methods when measuring the arch width, arch length, and space analysis. In addition, all parameters showed a significant correlation coefficient (r ≥ 0.972; p
Objectives: This pilot study compared the motor evoked potential (MEP) changes using different settings of rTMS in the post-ischemic stroke patient. The goal of the study is to identify effect sizes for a further trial and evaluate safety aspects.
Methods: Eight post-stroke patients with upper limb hemiparesis for at least six months duration were studied in a tertiary hospital in Northeast Malaysia. Quasi experimental design was applied and the participants were randomised into two groups using software generated random numbers. One of the two settings: i) inhibitory setting, or ii) facilitatory setting have been applied randomly during the first meeting. The motor evoked potential (MEP) were recorded before and after application of the rTMS setting. A week later, a similar procedure will be repeated but using different setting than the first intervention. Each patient will serve as their own control. Repeated measures ANOVA test was applied to determine the effect sizes for both intervention through the options of partial eta-squared (η2p).
Result: The study observed large effect sizes (η2p > 0.14) for both rTMS settings in the lesion and non-lesion sides. For safety aspects, no minor or major side effects associated with the rTMS was reported by the participants.
Conclusions: The partial eta square of MEP value for both rTMS settings (fascilitatory and inhibitory) in both lesion and non-lesion sides represents large effect sizes. We recommend further trial to increase number of sample in order to study the effectiveness of both settings in ischemic stroke patient. Our preliminary data showed both settings may improve the MEP of the upper extremity in the ischemic stroke patient. No significant improvement noted when comparing both settings.