An in silico approach to analyze HCV genotype-specific binding-site variation and its effect on drug-protein interaction

Genotype variation in viruses can affect the response of antiviral treatment. Several studies have established approaches to determine genotype-specific variations; however, analyses to determine the effect of these variations on drug-protein interactions remain unraveled. We present an in-silico approach to explore genotype-specific variations and their effect on drug-protein interaction. We have used HCV NS3 helicase and fluoroquinolones as a model for drug-protein interaction and have investigated the effect of amino acid variations in HCV NS3 of genotype 1a, 1b, 2b and 3a on NS3-fluoroquinolone interaction. We retrieved 687, 667, 101 and 248 nucleotide sequences of HCV NS3 genotypes 1a, 1b, 2b, and 3a, respectively, and translated these into amino acid sequences and used for genotype variation analysis, and also to construct 3D protein models for 2b and 3a genotypes. For 1a and 1b, crystal structures were used. Drug-protein interactions were determined using molecular docking analyses. Our results revealed that individual genotype-specific HCV NS3 showed substantial sequence heterogeneity that resulted in variations in docking interactions. We believe that our approach can be extrapolated to include other viruses to study the clinical significance of genotype-specific variations in drug-protein interactions

A Discrete Event Simulation Analysis of the Bullwhip Effect in a Multi-Product and Multi-Echelon Supply Chain of Fast Moving Consumer Goods

Timely delivery is the major issue in Fast Moving Consumer Good (FMCG) since it depends on the lead time which is stochastic and long due to several reasons; e.g., delay in processing orders and transportation. Stochastic lead time can cause inventory inaccuracy where echelons have to keep high product stocks. Such performance inefficiency reflects the existence of the bullwhip effect (BWE), which is a common challenge in supply chain networks. Thus, this paper studies the impact of stochastic lead time on the BWE in a multi-product and multi-echelon supply chain of FMCG industries under two information-sharing strategies; i.e., decentralized and centralized. The impact was measured using a discrete event simulation approach, where a simulation model of a four-tier supply chain whose echelons adopt the same lead time distribution and continuous review inventory policy was developed and simulated. Different lead time cases under the information-sharing strategies were experimented and the BWE was measured using the standard deviation of demand ratios between echelons. The results show that the BWE cannot be eliminated but can be reduced under centralized information sharing. All the research analyses help the practitioners in FMCG industries get insight into the impact of sharing demand information on the performance of a supply chain when lead time is stochastic

Awareness of dental practitioners regarding oral radiology

Background: The damaging radiations exposure can causes harm to body cells and DNA. It also leads to shortening of life expectancy. Many Dental techniques and equipment made to lower the radiation dose for staff and patients. Objective: In this study the knowledge, attitude and practice based questions were asked to analyze the awareness level of house officers regarding oral radiology. Study design: It is a questionnaire-based study conducted for the duration of the six months from Feb 2022 to July 2022. Material and Methods: The study comprised of 105 house officers that were practicing dentistry after completion of their degrees. They were fully aware of the objective of the study. They were practicing in institutes like Liaqat College of medicine and dentistry, Fatima Jinnah dental College and Bahria university medical and dental College. Results: All the subjects had taken the radiographs and 38 subjects reported about using both conventional and digital method during practice. The average age of the subjects was 25 years. There were 32 subjects that prefer using conventional method and among them 27 reported that they had only one equipment that’s why they have to use it

Utilization of Banana Fiber-Reinforced Hybrid Composites in the Sports Industry

The sports industry is an ever-growing sector worldwide. With technological advancements in information technologies, the sports industry has merged with the entertainment industry, reaching and influencing billions of people globally. However, to ensure and advance the safety, security, and sustainability of the sports industry, technological innovations are always needed in several manufacturing and materials processes to achieve cost-effectiveness, efficiency, durability, reusability, and recyclability of products used in this industry. For example, 90% of the field hockey equipment produced in the world comes from Sialkot, Pakistan. Most export quality field hockey equipment is currently produced via reinforcement of glass/carbon fibers in epoxy resin. The current study aimed to introduce new materials for field hockey equipment to reduce manufacturing costs and the environmental impact of synthetic materials, without comprising the quality of the final product. Our literature review on natural fibers revealed that they offer excellent and compatible mechanical properties. Based on extensive experimental studies, we concluded that banana fiber reinforced hybrid composites could be an alternative to pure glass fiber reinforced composites, with comparable and even higher load withstanding capabilities. Using banana fiber reinforced hybrid composites for the fabrication of hockey products would cut costs and lower the environmental impact stemming from the uses of biodegradable organic materials. It will also lead to the development of a domestic economy based on domestic resources

Microneedles and their application in transdermal delivery of antihypertensive drugs—a review

One of the most cutting-edge, effective, and least invasive pharmaceutical innovations is the utilization of microneedles (MNs) for drug delivery, patient monitoring, diagnostics, medicine or vaccine delivery, and other medical procedures (e.g., intradermal vaccination, allergy testing, dermatology, and blood sampling). The MN-based system offers many advantages, such as minimal cost, high medical effectiveness, comparatively good safety, and painless drug application. Drug delivery through MNs can possibly be viewed as a viable instrument for various macromolecules (e.g., proteins, peptides, and nucleic acids) that are not efficiently administered through traditional approaches. This review article provides an overview of MN-based research in the transdermal delivery of hypertensive drugs. The critical attributes of microneedles are discussed, including the mechanism of drug release, pharmacokinetics, fabrication techniques, therapeutic applications, and upcoming challenges. Furthermore, the therapeutic perspective and improved bioavailability of hypertensive drugs that are poorly aqueous-soluble are also discussed. This focused review provides an overview of reported studies and the recent progress of MN-based delivery of hypertensive drugs, paving the way for future pharmaceutical uses. As MN-based drug administration bypasses first-pass metabolism and the high variability in drug plasma levels, it has grown significantly more important for systemic therapy. In conclusion, MN-based drug delivery of hypertensive drugs for increasing bioavailability and patient compliance could support a new trend of hypertensive drug delivery and provide an alternative option, overcoming the restrictions of the current dosage forms

Determination of Knowledge of Caregivers about Dietary Practices of Autistic Children

Background and Objective: Autism belongs to a complex neurodevelopmental disorder. The lack of knowledge about dietary practices of autistic caregivers is perceived as the triggering factor of &lsquo;Autistic Spectrum Disorder (ASD). In this particular &lsquo;Knowledge, Attitude and Practice (KAP) Survey&rsquo; the knowledge (K) of nutrition, attitude (A) of children towards such nutrition and dietary practices (P) among the caregivers of autistic children. The pre-testing and post-testing for knowledge has been observed. Theknowledge questionnaire was designed to facilitate the caregivers to determine their knowledge regarding the dietary patterns of autistic children.Methods: This quasi-experimental study comprised of 50 caregivers (particularly mothers, and fathers in a few instances) of autistic children enrolled at Amin Maktab Center for Special Education Lahore. The nutrition education program was developed and participants were enrolled. Analysis of the change in knowledge, attitude and practice of autistic caregivers through pre-testing and post-testing at a gap of four months was carried out using statistical tests.Results: The pre-testing and post-testing phase of the study revealed significant improvement in (a) basic knowledge about nutritional needs of autistic children (22% vs. 100%), (b) practicing patient-tailored special diet (34% vs. 92%) and (c) resolution of food allergies (62% vs. 16%) in autistic children. The most important benchmark in this regard was Body Mass Index (BMI) of children where deranged BMI improved significantly (p = 0.000) to normal BMI in pre- and post-testing phases.Conclusions: Lack of knowledge is higher among aforementioned caregivers of concerned autistic children. Adoption of nutrition education programs by anutistic caregivers helps in creating optimal knowledge, attitude and practices regarding nutritional needs of autistic children for effective targeted behavior and management.</p

Application of an integrated cheminformatics-molecular docking approach for discovery for physicochemically similar analogs of fluoroquinolones as putative HCV inhibitors

Background: Hepatitis C Virus (HCV) infection is a major public health concern across the globe. At present, direct-acting antivirals are the treatment of choice. However, the long-term effect of this therapy has yet to be ascertained. Previously, fluoroquinolones have been reported to inhibit HCV replication by targeting NS3 protein. Therefore, it is logical to hypothesize that the natural analogs of fluoroquinolones will exhibit NS3 inhibitory activity with substantially lesser side effects.Method: In this study, we tested the application of a recently devised integrated in-silico Cheminformatics-Molecular Docking approach to identify physicochemically similar natural analogs of fluoroquinolones from the available databases (Ambinter, Analyticon, Indofines, Specs, and TimTec). Molecular docking and ROC curve analyses were performed, using PatchDock and Graphpad software, respectively, to compare and analyze drug-protein interactions between active natural analogs, Fluoroquinolones, and HCV NS3 protein.Result: In our analysis, we were able to shortlist 18 active natural analogs, out of 10,399, that shared physicochemical properties with the template drugs (fluoroquinolones). These analogs showed comparable binding efficacy with fluoroquinolones in targeting 32 amino acids in the HCV NS3 active site that are crucial for NS3 activity. Our approach had around 80 % sensitivity and 70 % specificity in identifying physicochemically similar analogs of fluoroquinolones.Conclusion: Our current data suggest that our approach can be efficiently applied to identify putative HCV drug inhibitors that can be taken for in vitro testing. This approach can be applied to discover physicochemically similar analogs of virtually any drug, thus providing a speedy and inexpensive approach to complement drug discovery and design, which can tremendously economize on time and money spent on the screening of putative drugs

Integrated chemoinformatics-molecular docking approach to drug discovery against viruses

Background: In the current study, we have used an integrated in silico approach that combines chemoinformatics and molecular docking to screen and test potential therapeutic compounds against viruses in a computer-simulated environment. Fluoroquinolones have been shown to inhibit HCV replication by targeting the helicase activity of HCV NS3. Based on this observation, we hypothesized that natural analogs of fluoroquinolones will have similar or superior inhibitory potential, while having potentially fewer adverse effects.Methods: To screen for natural analogs of fluoroquinolones, we devised an integrated in silico Chemoinformatics-Molecular Docking approach. Using the structural features of 17 fluoroquinolones as bait reference, we screened large databases of natural analogs. 10399 natural compounds and their derivatives were retrieved from the databases. From these compounds, molecules bearing physicochemical similarities with fluoroquinolones were screened using a chemoinformatics approach.Results: Twenty compounds were picked up in this screening. These compounds were then docked on the structure of HCV NS3 helicase to analyze mutual interactions of the two molecules. Results from the molecular docking analysis showed 32 amino acids in the HCV NS3 active site that were most frequently targeted by fluoroquinolones as well as by their natural analogues, indicating a functional similarity between the two groups of compounds.Conclusion: This study describes a speedy and inexpensive approach to complement drug discovery and design. The in silico analyses we used here can be employed to short-list promising compounds prior to their testing in wet-lab. This will tremendously economize on time and money spent on the screening of putative drugs

AN IN SILICO APPROACH TO ANALYZE HCV GENOTYPE‑SPECIFC BINDING‑SITE VARIATION AND ITS EFECT ON DRUG–PROTEIN INTERACTION

Genotype variation in viruses can afect the response of antiviral treatment. Several studies have established approaches to determine genotype-specifc variations; however, analyses to determine the efect of these variations on drug–protein interactions remain unraveled. We present an in-silico approach to explore genotype-specifc variations and their efect on drug–protein interaction. We have used HCV NS3 helicase and fuoroquinolones as a model for drug–protein interaction and have investigated the efect of amino acid variations in HCV NS3 of genotype 1a, 1b, 2b and 3a on NS3fuoroquinolone interaction. We retrieved 687, 667, 101 and 248 nucleotide sequences of HCV NS3 genotypes 1a, 1b, 2b, and 3a, respectively, and translated these into amino acid sequences and used for genotype variation analysis, and also to construct 3D protein models for 2b and 3a genotypes. For 1a and 1b, crystal structures were used. Drug–protein interactions were determined using molecular docking analyses. Our results revealed that individual genotype-specifc HCV NS3 showed substantial sequence heterogeneity that resulted in variations in docking interactions. We believe that our approach can be extrapolated to include other viruses to study the clinical signifcance of genotypespecifc variations in drug–protein interactions

Developments in Chemical Treatments, Manufacturing Techniques and Potential Applications of Natural-FibersBased Biodegradable Composites

The utilization of synthetic materials stimulates environmental concerns, and researchers worldwide are effectively reacting to environmental concerns by transitioning towards biodegradable and sustainable materials. Natural fibers like jute and sisal have been being utilized for ages in several applications, such as ropes, building materials, particle boards, etc. The absence of essential information in preparing the natural-fiber-reinforced materials is still a challenge for future applications. Chemical treatments and surface modifications can improve the quality of the natural fibers. Natural-fiber-based composites are a potential candidate for many lightweight engineering applications with significant mechanical properties. In the view of the progressive literature reported in the field, this work aims to present the significance of natural fibers, their composites, and the main factors influencing these materials for various applications (automotive industry, for instance). Secondly, we aim to address different surface modifications and chemical treatments on natural fibers and finally provide an overview of natural fiber reinforced polymer composites’ potential applications