A comprehensive computational mutation structurefunction approach for determining potential drug target sites in poliovirus 2A protease

Purpose: To investigate a computational approach for analysing the structure-function relationship of poliovirus 2A protease using various bioinformatics tools. Methods: The three-dimensional structure of 2Apro was modelled and analyzed using the crystal structure of coxsakievirus B4 as a template to understand the function of this protein. Structural validation programs, VADAR and QMEAN, were used to verify the 2Apro model. Analysis of protein stability changes in poliovirus 2A protease-mutated sequences using various servers was also performed. Furthermore, mutation pattern, intrinsic disorder regions (IDRs), hydrophobic regions, drug binding sites (DBS) and subcellular localization were identified. Results: Hydrophobicity results confirmed the suitability and reliability of 2A protease as a potential drug target. Less IDRs were observed in the protein. Moreover, the results showed the presence of various important drug binding targets among conserved regions of the protease. The predicted drug binding sites indicate their suitability for the inhibition and development of anti-viral drugs against poliovirus 2A protease. Conclusion: The current study resulted in the detection of important ligand interactions with respect to the binding site of the targeted protein. Thus, these compounds may be potent drug candidates and their potency may be increased against poliovirus 2A protease with relatively simple structural changes. Keywords: 2A Protease, Computational analysis, Drug binding sites, Intrinsic disorder regions, Hydrophobicit

Mediastinitis as a complication of Epstein-Barr virus infection: a rare entity

Epstein-Barr virus (EBV) is a member of the herpes virus family that can infect humans. Common manifestations of Epstein-Barr virus infection include fever, lymphadenopathy and pharyngitis with some rare complications including mediastinitis, myocarditis, pancreatitis, acute kidney failure and neurological disorders. Clinical findings along with serological evidences are needed to diagnose the infection. Early investigation for EBV in febrile patients can expedite both diagnosis and treatment

The Influence of Urbanization on Natural Overland Flow Paths

This paper studies the influence of urbanization on the natural overland flow paths on topography. The main objectives of this study are to: measure the effectiveness of drainage networks, study the influences of urban structure, compare the pre-and post-urban overland flow paths, and provide recommendations for flood prevention. The study was conducted on a catchment (81 km2) in Qatar that lies between Doha and Al-Rayan. Land cover, soil data, rain data, and digital elevation model (DEM) were the main inputs of the study to obtain run-off depths, time of concentration, and peak flows. The Soil Conservation Service (SCS) method was applied, where Curve Numbers (CNs) were identified for each land cover based on soil groups concerning the infiltration rate. A geographic information system (GIS) integration has provided better results. ArcMap tools have been used to study flow changes such as flow direction, flow accumulation, and stream definition. The result of the study shows that urbanization has a significant effect on the characteristics of the flow path as it causes the time of concentration to decrease, resulting in increased run-off depth and peak flow

Steering Mirror System with Closed-Loop Feedback for Free-Space Optical Communication Terminals

Precision beam pointing plays a critical role in free-space optical communications terminals in uplink, downlink and inter-satellite link scenarios. Among the various methods of beam steering, the use of fast steering mirrors (FSM) is widely adopted, with many commercial solutions employing diverse technologies, particularly focusing on small, high-bandwidth mirrors. This paper introduces a method using lightweight, commercial off-the-shelf components to construct a custom closed-loop steering mirror platform, suitable for mirror apertures exceeding 100 mm. The approach involves integrating optical encoders into two off-the-shelf open-loop actuators. These encoders read the signal reflected on purposefully diamond-machined knurled screw knobs, providing maximum contrast between light and dark lines. The resulting steering mirror has the potential to complement or replace FSM in applications requiring a larger stroke, at the expense of motion speed. In the presented setup, the mirror tilt resolution achieved based on the encoder closed-loop signal feedback is 45 μrad, with a mean slew rate of 1.5 mrad/s. Importantly, the steering assembly is self-locking, requiring no power to maintain a steady pointing angle. Using the mirror to actively correct for a constantly moving incoming beam, a 5-fold increase in concentration of the beam spot on the center of the detector was obtained compared to a fixed position mirror, demonstrating the mirrors ability to correct for satellite platform jitter and drift

Self-Medication Practice Among the General Community Of An Urban Squatter Settlement Near PNS Shifa Karachi

Objective: To assess the frequencyof self-medication amongst the residents of urban squatter settlement near PNS Shifa Karachiand to assess the factors leading to this practice. Materials and Methods: This cross-sectional descriptive study was conducted in the city of Karachi. The subjects were the community in general. A total of 60 subjects were enrolled and were either interviewed face-to-face or were asked to fill out the questionnaire relating to their self-medication practice. Results: Out of 60 subjects, 38 (63.3%) preferred the practice of self-medication. Minor ailment was the main reason for self-medication, 27 (45%) subjects responded headache as the most common reason and paracetamol was the most frequently used drug for self medication. It was used by 44(73.3%) of the subjects Conclusion: The practice of self medication is high in the community and there is a need to develop awareness of self-medication practice in the public along with restrictions for the pharmacies providing drugs without prescription

GIS-Based Solutions for Monitoring and Controlling COVID-19 in ASHGHAL Construction Projects: Improving Construction Sector Resilience

Early in 2020, doctors around the globe identified the virus responsible for Coronavirus disease 2019 (COVID-19). Rapidly spreading, the virus reached every continent. As part of its efforts to prepare for the FIFA World Cup in 2022 and Qatar National Vision 2030, the Public Works Authority (Ashghal), the State of Qatar, is on a fast-track mission to implement major infrastructure projects to revamp roads and sewer networks. Managing the human workforce on construction project sites becomes a significant challenge considering the pandemic. Large infrastructure projects are always characterized by many workers interacting in proximity at the work site. Immediately at the pandemic's beginning, management was instructed to leverage technology to empower decision-makers with COVID-19 monitoring tools across all the infrastructure construction projects. Thus, the Engineering Services Department created an ArcGIS Dashboard for engineers, contractors, and higher management to track the construction projects' COVID-19 status. Maps and data are combined in ArcGIS Dashboards to highlight significant patterns and measures. This paper explores the workflow established with direct communication and a submission system from the contractors and project managers to help collect and monitor critical health parameters of workers to prevent the propagation of COVID-19 infection. The study concluded that implementing a GIS safety dashboard for workers can help reduce the risk of project shutdowns due to novel Coronaviruses and provide an effective tool for organizations to improve occupational health and safety standards at worksites

Diagnostic accuracy of strain ultrasound elastography in differentiating benign and malignant thyroid nodules, taking histopathology as gold standard

Background: Elastography is a method recently being used in the evaluation of thyroid nodules by comparing tissue elasticity. Strain and shear wave elastography are two types of elastography still being used in clinical practice. Two kinds of elasticity can be assessed by strain elastography. First, colors around and within the nodules are evaluated and visually scored according to the 4-5 scale scoring systems. The aim of this study was to determine the diagnostic accuracy of strain ultrasound elastography in differentiation between benign and malignant thyroid nodules, taking histopathology as gold standardMethods: Total of 101 patients with palpable thyroid nodule of any size of age 30-70 years of either gender were included. Patients with previous thyroid surgery and already proven histopathology were excluded. Strain ultrasound elastography was performed in every patient by using a highresolution unit with a linear array probe centred at 7.5 MHz. Strain ultrasound elastography was performed in every patient by a consultant radiologist in the presence of researcher and benign or malignant thyroid nodules was noted. Strain USG elastography findings were compared with histopathology report.Results: All the patients were subjected to strain ultrasound elastography. USG supported the diagnosis of malignant thyroid nodules in all 52 patients. Histopathology confirmed malignant thyroid nodules in 47 (true positive) cases where as 5 (false positive) had no malignant lesion on histopathology. In USG negative patients, 46 were true negative while 3 were false negative. Overall sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy of strain ultrasound elastography in differentiation between benign and malignant thyroid nodules, taking histopathology as gold standard is 94.0%, 90.20%, 90.38%, 93.88% and 92.08% respectively.Conclusions: According to this study, strain ultrasound elastography is the non-invasive modality of choice with high diagnostic accuracy in diagnosing malignant thyroid nodules

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

A narrative review on the role of folate-mediated one-carbon metabolism and its associated gene polymorphisms in posing risk to preeclampsia

Preeclampsia (PE) presents a major obstetrical problem for mother and fetus which is characterized by the onset of hypertension and proteinuria in formerly normotensive women. Altered folate-mediated one-carbon metabolism is one of the factors for PE development either due to nutritional insufficiencies such as folate deficiency or polymorphisms in genes that code for the key enzymes of the cycle. Commonly, there are four genes in the cycle whose polymorphisms have been described in relation to PE. These factors could cause elevation of homocysteine; the toxic metabolite, which subsequently leads to the development of PE. Sufficient levels of folate have been considered important during pregnancy and may reduce the risk of development of PE. This review aims at discussing genetic polymorphisms and nutritional deficiencies as probable predisposing factors and suggests considering fetal genotypes, varied ethnicities, and interaction of various other factors involved to render better conclusiveness to the present studies