Investigating the prevalence of halitosis and its associated factors amongst the general population of Karachi, Pakistan.

Objective: To assess the prevalence of halitosis among the general population of Karachi, and to identify factors contributing to its occurrence. METHODS: The cross-sectional study was conducted from March to July 2022 in Karachi after approval from the ethics review board of Dow University of Health Sciences, Karachi, and comprised the adult population of Karachi. Data was collected online using a questionnaire that was piloted before its link was distributed through social media platforms. The questionnaire evaluated the association of demographic features with self-perceived halitosis on the basis of which factors predictive of halitosis were determined. Data was analysed using SPSS 26. RESULTS: Of a total of 342 subjects, 182(53%) were females and 160(47%) were males. There were 141(41$) subjects aged 18-25 years, and 166(48%) were graduates. Overall, 240(70%) subjects reported to have self-perceived halitosis. Age, monthly household income, niswar and tea consumption, irregular use of dental floss and tongue cleaning were associated with higher incidence of halitosis (p<0.05). Carrying water bottle while outside was associated with decreased halitosis (p=0.007). Symptoms of gastroesophageal reflux disease, sinusitis, asthma, diabetes, hypertension and mental stress were associated with halitosis (p<0.05). Higher monthly household income and daily use of dental floss predicted lower odds of halitosis (p<0.05). Conclusion: Maintaining good oral hygiene and hydration reduced, while comorbid conditions increased the probability of halitosis.

Transcript-Level In Silico Analysis of Alzheimer's Disease-Related Gene Biomarkers and Their Evaluation with Bioactive Flavonoids to Explore Therapeutic Interactions.

Alzheimer's disease (AD) is a progressive brain disorder that can significantly affect the quality of life. We used a variety of in silico tools to investigate the transcript-level mutational impact of exonic missense rare variations (single nucleotide polymorphisms, SNPs) on protein function and to identify potential druggable protein cavities that correspond to potential therapeutic targets for the management of AD. According to the NIA-AA (National Institute on Aging-Alzheimer's Association) framework, we selected three AD biomarker genes (APP, NEFL, and MAPT). We systematically screened transcript-level exonic rare SNPs from these genes with a minor allele frequency of 1% in 1KGD (1000 Genomes Project Database) and gnomAD (Genome Aggregation Database). With downstream functional effect predictions, a single variation (rs182024939: K > N) of the MAPT gene with nine transcript SNPs was identified as the most pathogenic variation from the large dataset of mutations. The machine learning consensus classifier predictor categorized these transcript-level SNPs as the most deleterious variations, resulting in a large decrease in protein structural stability (ΔΔG kcal/mol). The bioactive flavonoid library was screened for drug-likeness and toxicity risk. Virtual screening of eligible flavonoids was performed using the MAPT protein. Identification of druggable protein-binding cavities showed VAL305, GLU655, and LYS657 as consensus-interacting residues present in the MAPT-docked top-ranked flavonoid compounds. The MM/PB(GB)SA analysis indicated hesperetin (-5.64 kcal/mol), eriodictyol (-5.63 kcal/mol), and sakuranetin (-5.60 kcal/mol) as the best docked flavonoids with the near-native binding pose. The findings of this study provide important insights into the potential of hesperetin as a promising flavonoid that can be utilized for further rational drug design and lead optimization to open new gateways in the field of AD therapeutics.

Comparison Of Potential Plasma Biomarkers In Alzheimer's Disease And Neurodegenerative Dementias In Pakistani Population.

This study aimed to compare the mean plasma levels of Amyloid ß42, Phosphorylated Tau and Neurofilament Light chain in patients diagnosed with Alzheimer's Clinical Syndrome (ACS), and other neurodegenerative dementias to find affordable and less-invasive means of diagnosing Alzheimer's disease (AD) early in its course. Blood samples of 36 subjects presenting with cognitive decline to the neurology OPDs of Dow and Civil hospitals, Karachi, were centrifuged, and plasma was stored at -80℃. Before analysis, it was thawed at 4℃ and protein levels were measured through ELISA. Two-thirds of the patients were females but age distribution across both the groups was not significantly different (p=0.21). No difference was observed in the mean plasma concentrations of Aß42, P-Tau, and NFL between the two groups (p-values 0.78 and 0.27 and 0.09 respectively). Our study suggests that despite being promising in CSF, Aß42, P-Tau, and NFL cannot differentiate between different neurodegenerative dementias when measured in plasma.

Confronting Challenges: An Inductive Thematic Analysis Of Barriers And Solutions To Undergraduate Medical Research In Pakistan.

OBJECTIVE: To qualitatively analyse the barriers in pursuing undergraduate research, and to propose solutions for the problems identified. METHODS: The qualitative study was conducted from May to October 2021 after approval from the institutional ethics review board of the Dow University of Health Sciences, Karachi, and comprised undergraduate students of either gender at various public and private medical universities across Pakistan having some level of research experience and good communication skills. Data triangulation was employed to collect qualitative data through open-ended survey, face-to-face interviews and focus group discussions. Using the information of one method to inform the rest, linked trajectories were established that allowed validation of information at each level. Data was coded manually by two researchers independently. Data was subjected to inductive thematic analysis. RESULTS: Of the 33 subjects, 17(51.5%) were males, 17(51.5%) were from private medical colleges, 18(54.5%) were from Karachi, and 11(33.3%) were in the final year of medical school. Overall, 13(39.4%) students completed the open-ended survey, 6(18.2%) completed face-to-face interviews, and 14(42.4%) participated in focus group discussions. Thematic analysis showed that students were interested in research to improve their career prospects, but not all were passionate about it. Students were not satisfied with the quality of research being conducted in the country. Dearth of motivated faculty, unavailability of well-maintained and digitalised data registries, ineffective research methodology teaching and lack of access to medical journals and research software were the major barriers in undergraduate research. Time constraint was a projecting problem which challenged the students. Frequent research workshops and conferences, strong networking, reorienting curriculum to provide early exposure to research and student-led initiatives were suggested to improve undergraduate research in Pakistan. CONCLUSIONS: Students' lack of initiative coupled with administrative and faculty-related issues pose a serious threat to the future of evidence-based medicine. Proposed solutions offer a ray of hope to the future of undergraduate research in Pakistan.

Advances in viral oncolytics for treatment of multiple myeloma - a focused review.

INTRODUCTION: Oncolytic viruses are genetically engineered viruses that target myeloma-affected cells by detecting specific cell surface receptors (CD46, CD138), causing cell death by activating the signaling pathway to induce apoptosis or by immune-mediated cellular destruction. AREAS COVERED: This article summarizes oncolytic virotherapy advancements such as the therapeutic use of viruses by targeting cell surface proteins of myeloma cells as well as the carriers to deliver viruses to the target tissues safely. The major classes of viruses that have been studied for this include measles, myxoma, adenovirus, reovirus, vaccinia, vesicular-stomatitis virus, coxsackie, and others. The measles virus acts as oncolytic viral therapy by binding to the CD46 receptors on the myeloma cells to utilize its surface H protein. These H-protein and CD46 interactions lead to cellular syncytia formation resulting in cellular apoptosis. Vesicular-stomatitis virus acts by downregulation of anti-apoptotic factors (Mcl-2, BCL-2). Based upon the published literature searches till December 2020, we have summarized the data supporting the advances in viral oncolytic for the treatment of MM. EXPERT OPINION: Oncolytic virotherapy is an experimental approach in multiple myeloma (MM); many issues need to be addressed for safe viral delivery to the target tissue.