Proceedings of the Pakistan Academy of Sciences: B. Life and Environmental Sciences

Genomic Variation in Dengue Virus Non-Structural Protein 1 (NS1)

Saira Mushtaq — 2024-04-24

To understand in an improved way how the dengue virus (DENV) spreads, presents, and becomes hazardous, researching its genetic makeup is necessary. The positive sense RNA of DENV encodes three structural proteins and seven non-structural proteins. One of the non-structural proteins that aids in the replication of viral RNA is the non-structural protein 1 (NS1). The objective was to identify the most frequently repeated mutations in the NS1 protein in DENV RNA isolated from dengue patients in the province Punjab, Pakistan. Selection of 120 DENV isolates was done from laboratories of tertiary care hospitals of Punjab for analysis of sequencing of the whole genome. Only 23 samples were sequenced after viral isolation, quantification and cDNA synthesis. A total of 133 different types of mutations were detected along the entire length of NS.1. The most common mutations with the highest frequency were, K324R and K347R (n=7), D278N (n=6), K174R, and F178S (n=4), found at c-terminal of NS.1 protein. Mutations K347R, K174R, and F178S are novel. Future DENV vaccination development research will be especially profited by the mutations found in the current study. During each DENV outbreak in different places, studying genomic variations is
crucial for strengthening societal health and developing new policies for future outbreaks.

Implementing GRADE-ADOLOPMENT for Clinical Practice Guidelines in Resource-Limited Settings: The AKU Experience

Ainan Arshad — 2024-04-24

In regions grappling with limited resources to support the formulation of evidence-based Clinical Practice Guidelines (CPGs), GRADE-ADOLOPMENT offers a unique pathway to craft guidelines tailored to the specific needs of areas with sparse CPGs. The Aga Khan University in Karachi, Pakistan, used GRADE-ADOLOPMENT to create guidelines for prevalent diseases in Pakistan. An adaptation of the GRADE-ADOLOPMENT methodology was employed in collaboration with the US GRADE working group. ADOLOPMENT is a combination of de-novo creation, adoption (use as is or with minor changes), or adaptation (modification based on local context) of recommendations. After the selection of a source guideline (SG), the recommendations were either adopted, adapted, or excluded. Adaptations were done using the Evidence-To-Decision table. Contextualized CPGs were developed for Pakistan, covering over 25 medical specialties. The article discusses the wide variety of topics and specialties covered using GRADE-ADOLOPMENT in Pakistan for the first time. The lessons learned from this resource-constrained GRADEADOLOPMENT experience provide valuable guidance for teams undertaking projects in similar resource-limited settings. The GRADE-ADOLOPMENT experience at AKU in Pakistan serves as a valuable example, showcasing both the challenges and creative solutions in the context of medical guideline development in resource-limited regions.

Synthesis and In vitro Evaluation of Doxorubicin loaded Polymeric Nanoparticles on Cancer Cells

Nimra Batool — 2024-04-24

Cancer is the second biggest mortality rate globally. Most of anti-cancer drugs are hydrophobic and when they are administered in the body, they get clear from the blood. That’s why polymeric nanoparticles (NPs) have been used for delivering anti-cancer drugs to targeted sites. Biodegradable and self-assembled nature, PEG-PLGA has been used as a nanocarrier for biomedical applications. We developed PEG-PLGA NP for the doxorubicin (DOX) delivery to cancerous cells. The successful PEG-PLGA synthesis was confirmed by its 1 H NMR spectrum. All NPs displayed individual spherical morphology and 100 nm size range with -18.5mV zeta potential. Drug release profile showed DOX had sustained release pattern from DOX@NPs. In vitro, MTT assay and apoptosis analysis revealed that low-dose DOX@NPs exhibited more toxic effects on cancerous cells as compared to DOX alone. Overall results demonstrate that polymeric-based nanosystems increase the efficacy of DOX on cancer cells.

Contemporary Strategies for Managing and Controlling Viral Outbreaks: An Overview

Mohammad Ejaz — 2024-04-24

Viruses are notorious for causing a significant array of infectious diseases, rendering them a prominent contributor to global morbidity and mortality rates. Throughout history, various regions have experienced outbreaks, epidemics, and pandemics, resulting in significant mortality rates. The Influenza virus gave rise to highly fatal outbreaks that disseminated on a global scale, subsequently resulting in a pandemic during the initial decades of the 20th century. This catastrophic event led to >75 million fatalities, accompanied by a substantial incidence of illnesses. In addition to the development of efficacious treatments for viral diseases, it is imperative to establish and implement various preventive measures to mitigate the transmission of diseases within both local and global populations. Furthermore, it is critical to implement proven conventional and contemporary strategies for managing viral infections, alongside bolstered surveillance systems. Viruses employ diverse modes of transmission, encompassing respiratory, oral-fecal, blood-borne, and vector-borne pathways. Consequently, effective measures to mitigate viral dissemination must be tailored to address each distinct route of transmission. This review discusses the existing strategies employed to mitigate the transmission and containment of viral outbreaks, as well as the dissemination of the disease within a sizable population, intending to reduce their detrimental and fatal impacts on a community.