Advances in pharmacogenomics: optimizing antiepileptic drug therapy for drug-resistant epilepsy

Epilepsy, a complex neurological disorder, is influenced by intricate interactions within cortical, hippocampal, or thalamocortical neuronal networks, presenting a genetically complex condition with non-Mendelian inheritance patterns. This complexity is underscored by the involvement of numerous “susceptibilities” or “modifier” genes, complicating the assessment of risk and therapy outcomes. A critical inquiry in epilepsy treatment involves understanding how genetic diversity impacts treatment strategies and efficacy. Pharmacogenomic advancements have elaborated the connection between genetic variants and antiseizure medication (ASM) safety and response, marking a shift towards precision medicine in epilepsy care. Notably, genetic screening for variants such as HLA-B*1502 and HLA-A*3101 has demonstrated significant efficacy in preventing severe hypersensitivity reactions, including toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS), particularly among specific ethnic populations. However, putting pharmacogenomic discoveries into clinical practice faces numerous challenges, including educational, legal, and economic barriers, emphasizing the need for broader acceptance and integration of pharmacogenomic data. This review synthesizes recent studies on pharmacogenomics in epilepsy, highlighting the current advances and prospects for personalizing epilepsy treatment through genetic insights, aiming to enhance ASM safety, reduce adverse effects, and improve treatment outcomes. Through a comprehensive examination of the genetic basis of epilepsy and its influence on pharmacotherapy, this review endeavors to contribute to the evolving landscape of precision medicine in epilepsy care, advocating for a more individualized and effective treatment approach

Effect of Different Preparations of Fluoride Gel on Salivary pH of Albino Rats

Objective: To evaluate the effect of different preparations of fluoride gels on the salivary pH of albino rats. Material and Methods: This experimental study consisted of 40 Albino rats randomly divided into four equal groups. Group A was the control group and received no intervention. Experimental group B received a topical application of 0.2% sodium fluoride gel. Experimental group C received topical application of stannous fluoride gel 0.4%. Experimental group D received topical application of APF gel (1.23% acidulated phosphate fluoride gel). The different preparations of the gels were applied once daily for 4 minutes on the occlusal surface of the right maxillary molars for 14 days. Salivary pH values were recorded immediately after the application of gels with the help of pH paper on day 1 and day 14. Results: There was a significant difference in the pH level of groups B, C and D after 14 days of fluoride application (p < 0.05). The non-parametric Kruskal Wallis test was applied for the comparison between the groups. Conclusion: This study concluded that all the fluoride gels after administration caused the acidic pH of saliva with the most acidic effect produced by APF gel

Desarda Vs Lichtenstein “Hernioplasty” A One Year Comparative Study at a Teaching Hospital Lahore

Acomparative, prospective study was carried out in surgical department of LGH to evaluate the efficacy of Dessardahernioplsty technique by comparing with Lichtenstein repair in terms of post operative pain, hospital stay, rate of early and late complications and recurrence. Total (n=60) cases were divided in two groups A and B. with mean age 41.5 and 43.5 years for dessarda and Lichtenstein groups respectively. Insignificant statistical difference was noted in both groups as for as severity of acute pain, post operative hospital stay and wound infections are concerned. Regarding chronic pain and recurrence rate, patients in group A (Dessarda) show statistically significant advantage over group B (Lichtenstein). It, therefore was concluded that Dessarda-hernioplasty technique is useful in our patients as no foreign material has to be inserted that makes it cost effective with advantage of less chronic pain and zero recurrence rate at the end of one year

Relationship between the use of drugs and changes in body weight among patients: A systematic review and meta-analysis

Purpose: To investigate the impact of drugs on the body weight of patients.Methods: All the randomized controlled trials that evaluated the impact of medications on the body weight of patients were searched in various databases. Studies quantifying the impact of drugs on body weight when compared to placebo or any other treatment were considered for this review. Moreover, the quantitative synthesis of evidence was also performed by generating the forest plot.Results: A total of 20 studies involving 18,547 participants were included in the current review. Weight gains ranging from 0.5 to 2.6 kg were associated with the use of pioglitazone, espindolol, brexpiprazole, glimepiride and ezogabine while weight loss ranging from 1.1 to 12 kg was linked with the use of betahistine, naltrexone, bupropion, liraglutide, phentermine, topiramate, orlistat, zonisamide, duloxetine, semaglutide, metformin and linagliptin. The quantitative synthesis suggested that drugs can significantly reduce body weight by -0.53 kg (CI 95 % -1.01, -0.04, p < 0.04) when compared to standard treatment.Conclusion: The findings of this review suggest substantial association of drugs and weight change during pharmacotherapy. Pioglitzone, brexpiprazole, espindolol, ezogabine and glimepiride cause weight gain while naltrexone, bupropion, betahistine, topiramate, phentermine, zonisamide, semaglutide, linagliptin, liraglutide, orlistat, duloxetine and metformin were associated with weight loss. Drug-induced changes in body weight might cause serious consequences and should be addressed before initiating treatment

PERCEPTRON: an open-source GPU-accelerated proteoform identification pipeline for top-down proteomics

PERCEPTRON is a next-generation freely available web-based proteoform identification and characterization platform for top-down proteomics (TDP). PERCEPTRON search pipeline brings together algorithms for (i) intact protein mass tuning, (ii) de novo sequence tags-based filtering, (iii) characterization of terminal as well as post-translational modifications, (iv) identification of truncated proteoforms, (v) in silico spectral comparison, and (vi) weight-based candidate protein scoring. High-throughput performance is achieved through the execution of optimized code via multiple threads in parallel, on graphics processing units (GPUs) using NVidia Compute Unified Device Architecture (CUDA) framework. An intuitive graphical web interface allows for setting up of search parameters as well as for visualization of results. The accuracy and performance of the tool have been validated on several TDP datasets and against available TDP software. Specifically, results obtained from searching two published TDP datasets demonstrate that PERCEPTRON outperforms all other tools by up to 135% in terms of reported proteins and 10-fold in terms of runtime. In conclusion, the proposed tool significantly enhances the state-of-the-art in TDP search software and is publicly available at https://perceptron.lums.edu.pk. Users can also create in-house deployments of the tool by building code available on the GitHub repository (http://github.com/BIRL/Perceptron)

Optimizing Windows Redstone 3 Boot Process

Almost every Microsoft Windows user at some point in life must have experience that his/her laptop or desktop has gone down slow and is just not performing swiftly as it used to do when Windows was initially installed on that system. This results in decreased performance of the system in over a few weeks of fresh installation of Microsoft Redstone 3 OS, the system starts to show degraded performance and increased bootup and shutdown times. This is not only the case, the loading of documents and power point files along with other programs gets slow. The system gets slower and slower. To tackle this challenge, we propose a solution in this paper that will optimize the starting and shutdown times of Redstone 3 OS with marked improvement

Monkeypox Virus: A Comprehensive Overview of Viral Pathology, Immune Response, and Antiviral Strategies

Background: The years 2022–2023 witnessed a monkeypox virus (mpox) outbreak in some countries worldwide, where it exists in an endemic form. However, the number of infectious cases is continuously on the rise, and there has been an unexpected, drastic increase in cases that result from sustained transmission in non-endemic regions of the world. Under this scenario, it is pertinent for the world to be aware of healthcare threats to mpox infection. This review aimed to compile advanced data regarding the different aspects of mpox disease. Methods: A comprehensive strategy for the compilation of recent data was adopted to add data regarding mpox, biology, viral pathology, immune response, and brief details on the antiviral strategies under trial; the search was limited to 2016–2023. The aim is to make the scientific community aware of diverse aspects of mpox. Results: Consequently, detailed insights have been drawn with regard to the nature, epidemiology, etiology, and biological nature of mpox. Additionally, its host interaction and viral infectious cycle and immune interventions have been briefly elaborated. This comprehensively drawn literature review delivers brief insights into the biological nature, immune responses, and clinical developments in the form of therapeutics against mpox. This study will help scientists understand the biological nature and responses in hosts, which will further help clinicians with therapeutic handling, diagnosis, and treatment options. Conclusions: This study will provide updated information on mpox’s pathology, immune responses, and antiviral strategies. Moreover, it will also help the public to become educated on the healthcare-associated threat and take timely mitigation measures against expected mpox outbreaks in the future

Characterization of genetic lesions in apoptosis-regulating and proliferation control genes in diffuse large B-cell non-hodgkin\u27s lymphoma.

Background: This study was conducted to analyze the frequency, expression patterns, and the impact of individual proteins BCL2, BCL6, and p53 on overall survival (OS) in adult, diffuse large B-cell lymphoma (DLBCL) Patients. BCL2 gene was further investigated for potential alterations at the DNA level and correlated with OS. Materials andMethods: A total of 117 adult well-characterized DLBCL cases were included. The panel of antibodies comprised CD45, CD20, CD79a, CD3, BCL2, BCL6, and p53. PCR was also employed to correlate the events at the DNA level in BCL2.Results: The mean and median ages were 47.74 and 49 with a M:F ratio of 2.07:1. The incidence of BCL2, BCL6, and p53 expression was observed in 64.10%, 37.60%, and 52.13% of cases, respectively. Amplifiable quality DNA was available from 90 cases. BCL2/IGH translocation was found in 35/90 Patients (38.88%) with 24 cases showing BCL2 (MBR)/IGH and 11 cases BCL2 (mcr)/IGH translocation. No association between BCL2 overexpression and BCL2 /IGH translocation was seen. Clinical data were available for 52 Patients treated by CHOP therapy. It was found that Patients with p53 overexpression had decreased overall survival (P = 0.0004) whereas BCL2, BCL6 expression, and BCL2/IGH translocation had no impact on overall survival.Conclusion: Our data suggest that simple p53 protein expression by IHC at the time of diagnosis may help to identify high-risk Patients, who may benefit with more aggressive and newer treatments in addition to standard CHOP

Fetomaternal Outcome in Women with COVID-19 in a COVID Designated Hospital in Lahore, Pakistan

Background and Objective: The pandemic caused by Coronavirus disease-2019 (COVID-19) is notably becoming similar to severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome viruses (MERS) for causing poor feto-maternal outcome. There is not much data available about COVID-19 during pregnancy in Pakistan therefore the objective of this study is to determine maternal and fetal outcome in pregnant women affected with COVID-19 and to find out frequency of vertical transmission. Methods: This descriptive case series was conducted from 1st April 2020 to 10th May 2020 at Department of Obstetrics and Gynecology, COVID ward, Sir Ganga Ram Hospital, Lahore. A total of 20 women were included in the study that were found positive for viral RNA by Real-Time Reverse TranscriptionPolymerase Chain Reaction (rRT-PCR) of nasopharyngeal specimens. Demographics, duration of gestation, fetomaternal outcome and vertical transmission were noted in the respected proformas. The data was analyzed using Statistical Package for Social Sciences version 20. Results: The mean age of these gravid females was 29.3 &plusmn; 4.17 years. The mean gravidity was 2.60 &plusmn; 1.14 and mean gestational age was 29 &plusmn; 9.53 weeks. Among 20 patients, 4(20%) were primigravida, 5(25%) females were gravida 2 and remaining 11(55%) cases were gravida 3 and 4. The most common presenting complaints were fever followed by dry cough, myalgia and shortness of breath. Nine patients were delivered by lower segment cesarean section in which fetal distress was observed in 5(55.6%) newborns and 1(10%) newborn was preterm. Among all newborns, 02 developed respiratory distress syndrome and were admitted in pediatric intensive care unit. All pharyngeal swabs of newborns were negative at 12 and 24 hours of life. Conclusion: COVID-19 in pregnant females is not different than in general population. The fetomaternal outcome is usually good and there is no evidence of vertical transmission in any newborn.</p