Oral and topical analgesia in pediatric electrodiagnostic studies.

INTRODUCTION/AIMS: Electrodiagnostic examinations, such as nerve conduction studies (NCS) and needle electromyography (EMG), are perceived as painful by children and their parents/guardians. Methods to reduce peri-procedural pain improve compliance and have neurocognitive and neuropsychiatric benefits. This study aimed to assess the efficacy of combined oral and topical analgesics (COTA), oral analgesics (OA), and placebo in reducing pain during NCS/EMG in children. METHODS: We performed a double-blind, randomized, placebo-controlled trial on children presenting to our neurophysiology lab. Patients were stratified into two age groups (6M-6Y and 7Y-18Y) and randomized into three arms: COTA, OA, and placebo. Pain scores post-NCS/EMG were assessed using the Modified Behavioral Pain Scale (MBPS) and Faces Pain Scale-Revised (FPS-R). RESULTS: One hundred thirteen participants were enrolled. A comparison of participants from both age groups combined revealed no significant differences in guardian FPS-R scores across all arms for NCS and EMG. A significant difference in the distribution of post-NCS FPS-R score severities in children aged 7Y-18Y was noted between OA and placebo (p = .007). EMG was more painful than NCS across all arms (p < .05). In children aged 6M-6Y undergoing at least 10 muscle samplings during EMG, those receiving COTA had significantly lower pain scores (p = .014). DISCUSSION: This study reveals the complexity of pediatric pain perception during NCS/EMG and highlights that other methods to reduce experienced pain are required. Our findings suggest that procedural characteristics, such as number of muscles sampled, may influence the effectiveness of analgesia and serve as a foundation for future research aimed at optimizing pain management strategies.

Progressive muscle relaxation in pandemic times: bolstering medical student resilience through IPRMP and Gagne's model.

Background: Medical education, already demanding, has been further strained by the COVID-19 pandemic's challenges and the shift to distance learning. This context underscores the need for effective stress reduction techniques in competency-based medical curricula (CBMC). Objective: We assessed the feasibility and benefits of integrating a Progressive Muscle Relaxation (PMR) module-a known effective stress-reducing technique-into a time-restricted CBMC, particularly given such modules often find placement as elective rather than mandatory. Methods: Adapting Gagne's nine events of instruction, a 2-h PMR program was designed and implemented during the pandemic. Twenty participants were engaged on a first-come, first-served basis, ensuring adherence to social distancing measures. Feedback was continuously gathered, leading to two post-program focus group sessions. Qualitative data underwent thematic analysis following Braun and Clarke's approach, with study quality maintained by the Standards for Reporting Qualitative Research (SRQR). To gauge adaptability, we aligned the program with various learning outcomes frameworks and explored its fit within CBMC using Bourdieu's Theory of Practice. Results: The pilot PMR program was well-received and effectively incorporated into our CBMC. Our analysis revealed five central themes tied to PMR's impact: Self-control, Self-realization, Liberation, Awareness, and Interpersonal relationships. Feedback indicated the program's capacity to mitigate stress during the pandemic. The SRQR confirmed the study's alignment with qualitative research standards. Further, the PMR program's contents resonated with principal domains of learning outcomes, and its integration into CBMC was supported by Bourdieu's Theory. These observations led us to propose the Integrative Psychological Resilience Model in Medical Practice (IPRMP), a model that captures the intricate interplay between the identified psychological constructs. Conclusion: This research showcases an innovative, theory-guided approach to embed a wellbeing program within CBMC, accentuating PMR's role in fostering resilience among medical students. Our PMR model offers a feasible, cost-effective strategy suitable for global adoption in medical institutions. By instilling resilience and advanced stress-management techniques, PMR ensures that upcoming healthcare professionals are better equipped to manage crises like pandemics efficiently.

Exploring Cassia mimosoïdes as a promising natural source of steroids with potent anti-cancer, urease inhibition, and antimicrobial properties.

The genus Cassia is a rich source of physiologically active secondary metabolites, including a novel compound named 21-methylene-24-ethylidene lophenol, alongside 15 known compounds. These compounds were characterized using different spectroscopic techniques. They exhibited promising antimicrobial activity, particularly against bacteria causing gastrointestinal infections. Compound 1 showed strong anti-bacterial activity against H. pylori and S. aur with MIC values of 0.28 and 0.12 µg mL-1 respectively. The study investigated their impact on H. pylori, a contributor to ulcer development, by inhibiting the urease enzyme. Inhibiting urease can reduce H. pylori's pathogenic potential, evident from the fact that the compounds evaluated toward urease enzyme showed higher inhibitory activity (1.024 ± 0.43 6.678±0.11 µM) compared to standard thiourea (IC50 = 18.61 ± 0.11 µM). Molecular docking studies confirmed their inhibitory action, with compound 7 notably outperforming thiourea in inhibiting urease (-6.95 kcal mol-1vs. -3.13 kcal mol-1). Additionally, these compounds showed positive effects on liver functioning, which H. pylori can impair. Compound 9 shows the best response against human HepG2 liver cancer cell lines i.e., % viability is 14.47% ± 0.69 and IC50 is 7.8 µM ± 0.21. These compounds hold potential as lead compounds for addressing gastrointestinal and liver disorders caused by H. pylori.

The Interplay of Mitochondrial Bioenergetics and Dopamine Agonists as an Effective Disease-Modifying Therapy for Parkinson's Disease.

Parkinson's disease (PD) is a progressive neurological ailment with a slower rate of advancement that is more common in older adults. The biggest risk factor for PD is getting older, and those over 60 have an exponentially higher incidence of this condition. The failure of the mitochondrial electron chain, changes in the dynamics of the mitochondria, and abnormalities in calcium and ion homeostasis are all symptoms of Parkinson's disease (PD). Increased mitochondrial reactive oxygen species (mROS) and an energy deficit are linked to these alterations. Levodopa (L-DOPA) is a medication that is typically used to treat most PD patients, but because of its negative effects, additional medications have been created utilizing L-DOPA as the parent molecule. Ergot and non-ergot derivatives make up most PD medications. PD is successfully managed with the use of dopamine agonists (DA). To get around the motor issues produced by L-DOPA, these dopamine derivatives can directly excite DA receptors in the postsynaptic membrane. In the past 10 years, two non-ergoline DA with strong binding properties for the dopamine D2 receptor (D2R) and a preference for the dopamine D3 receptor (D3R) subtype, ropinirole, and pramipexole (PPx) have been developed for the treatment of PD. This review covers the most recent research on the efficacy and safety of non-ergot drugs like ropinirole and PPx as supplementary therapy to DOPA for the treatment of PD.

Exploring the Effect of Cetylpyridinium Chloride Addition on the Antibacterial Activity and Surface Hardness of Resin-Based Dental Composites.

The aim of this study was to evaluate the effect of cetylpyridinium chloride (CPC) addition on the antibacterial and surface hardness characteristics of two commercial resin-based dental composites (RBDCs). A total of two hundred and seventy (n = 270) specimens from Filtek Z250 Universal and Filtek Z350 XT flowable RBDCs were fabricated with the addition of CPC at 2 %wt and 4 %wt concentrations to assess their antibacterial activity using the agar diffusion test and direct contact inhibition test, and their surface hardness using the Vickers microhardness test after 1 day, 30 days, and 90 days of aging. A surface morphology analysis of the specimens was performed using a scanning electron microscope (SEM). The RBDCs that contained 2 %wt and 4 %wt CPC demonstrated significant antibacterial activity against Streptococcus mutans up to 90 days, with the highest activity observed for the 4 %wt concentration. Nevertheless, there was a reduction in antibacterial effectiveness over time. Moreover, compared to the control (0 %wt) and 2 %wt CPC groups, the universal RBDCs containing 4 %wt CPC exhibited a notable decrease in surface hardness, while all groups showed a decline in hardness over time. In conclusion, the satisfactory combination of the antibacterial effect and surface hardness property of RBDCs was revealed with the addition of a 2 %wt CPC concentration.

Exploring the clinical potentials of zuranolone in managing postpartum depression: A new therapeutic horizon.

Postpartum depression (PPD) poses a major threat to maternal mental health and wellbeing while also adversely affecting the mother's relationship with her baby, leading to significant repercussions that may hinder the growth and cognitive development of the child. For decades, antidepressants have been the mainstay of treating PPD; however, recent evidence suggests that antidepressants are not as effective as they are believed to be and there is a dire need to explore new treatment options. In 2023, a breakthrough in treating PPD emerged with the recent FDA approval of zuranolone, a gamma-aminobutyric acid (GABAA) receptor selective positive allosteric modulator. The implementation of zuranolone in treating PPD can prove to be revolutionary, considering it is the first oral medication available for PPD. Our review aims to discuss the various clinical trials that have been conducted to validate the efficacy of zuranolone in mitigating the symptoms of PPD, hence, leading to better outcomes for mothers.

Impact of Tracheostomy on COVID-19 ICU Patients in Saudi Arabia: A Retrospective Analysis.

Introduction The COVID-19 pandemic has prompted the development of novel medical interventions, including tracheostomy, a surgical procedure for a direct airway. This study investigates the intricacies of managing critically ill patients in the ICU, focusing on its debated utility in the global crisis. Methods The study assessed the impact of tracheostomy on COVID-19 patients at Al-Ahsa Hospital, Saudi Arabia, using a retrospective cohort design and data from electronic health records and databases. It aimed to provide insights into treatment outcomes and practices. Results The findings of this study shed light on the significant impact of tracheostomy on the course of ICU treatment for COVID-19 patients. Total number of participants were 1389. The study cohort consisted of predominantly non-pregnant individuals with an average body mass index reflective of the regional population. Among the COVID-19 patients, only a small percentage, 63 (4.5%), required tracheostomy, while the majority, 1326 (95.5%), did not undergo this procedure. Analysis of ICU outcomes revealed that a substantial proportion of patients, 223 (16.1%), achieved total cure, while the remaining patients did not. After a 28-day ICU stay, the majority of individuals, 1287 (92.7%), were discharged, while a smaller percentage remained in the ICU, with 77 (5.5%) still requiring mechanical ventilation. Notably, patients who underwent tracheostomy had a significantly longer ICU stay compared to those who did not, with an average of 59 days versus 19 days, respectively. Furthermore, the study found that tracheostomy did not significantly impact ICU discharge outcomes, including death, discharge home, and transfer to another facility. However, it did influence hospital discharge outcomes, with lower mortality rates and a higher rate of transfer to another facility among patients who underwent tracheostomy. These results provide valuable insights into the management and outcomes of critically ill COVID-19 patients in the ICU, particularly in relation to the use of tracheostomy as a treatment intervention. Conclusion The study highlights the dual benefits of tracheostomy in COVID-19 care, extending hospital stays but not increasing ICU discharge rates, emphasizing the need for tailored clinical strategies.

Public policy interventions to mitigate household food insecurity in Canada: a systematic review.

OBJECTIVE: The objective of this systematic review is to synthesise the evidence on public policy interventions and their ability to reduce household food insecurity (HFI) in Canada. DESIGN: Four databases were searched up to October 2023. Only studies that reported on public policy interventions that might reduce HFI were included, regardless of whether that was the primary purpose of the study. Title and abstract screening, full-text screening, data extraction, risk of bias and certainty of the evidence assessments were conducted by two reviewers. RESULTS: Seventeen relevant studies covering three intervention categories were included: income supplementation, housing assistance programmes and food retailer subsidies. Income supplementation had a positive effect on reducing HFI with a moderate to high level of certainty. Housing assistance programmes and food retailer studies may have little to no effect on HFI; however, there is low certainty in the evidence that could change as evidence emerges. CONCLUSION: The evidence suggests that income supplementation likely reduces HFI for low-income Canadians. Many questions remain in terms of how to optimise this intervention and additional high-quality studies are still needed.

Computational exploration of allosteric inhibitors targeting CDK4/CDK6 proteins: a promising approach for multi-target drug development.

Cyclin-dependent kinases (CDKs) play a pivotal role in orchestrating the intricate regulation of the cell cycle, a fundamental process governing cell growth and division. In particular, CDK4 and CDK6 are critical for the transition from the G1 phase to the S phase, where Deoxyribonucleic acid (DNA) replication occurs, and their dysregulation is linked to various diseases, notably cancer. While ATP-binding site inhibitors for CDKs are well-documented, this study focuses on uncovering allosteric inhibitors, providing a fresh perspective on CDK inhibition. Computational techniques were employed in this investigation, utilizing Molecular Operating Environment (MOE) for virtual screening of a drug-like compound library. Moreover, the stability of the most promising binding inhibitors was assessed through Molecular Dynamics (MD) simulations and MMPBSA/MMGBSA analyses. The outcome reveals that three inhibitors (C1, C2, and C3) exhibited the strongest binding affinity for CDK4/CDK6, as corroborated by docking and simulation analyses. The computed binding energies ranged from -6.1 to -7.6 kcal/mol, underscoring the potency of these allosteric inhibitors. Notably, this study identifies key residues (PHE31, HIS95, HIS100, VAL101, ASP102, ASP104, and THR107) that play pivotal roles in mediating inhibitor binding within the allosteric sites. Among the findings, the C1-CDK4 complex and C2-CDK6 complex emerge as particularly promising inhibitors, exhibiting high binding energies, favorable interaction patterns, and sustained presence within the active site. This study contributes significantly to the pursuit of multi-target drugs against CDK4/CDK6 proteins, with potential implications for the development of innovative therapies across various disorders, including cancer and other cell cycle-related conditions.Communicated by Ramaswamy H. Sarma.

Morbidity and mortality of twins and triplets compared to singleton infants delivered between 26-34 weeks gestation in the United States.

OBJECTIVE: To describe in-hospital morbidities and mortality among twins and triplets delivered at ≥26 to ≤34 weeks gestational age (GA) while controlling for prematurity and growth restriction. STUDY DESIGN: Retrospective analysis of inborn infants discharged from a neonatal intensive care unit (NICU) managed by the Pediatrix Medical Group between 2010 and 2018. RESULT: Among 247 437 infants included, 27.4% were multiples. Adjusted for GA and other factors typically known prior to delivery, in-hospital morbidities varied by plurality and generally were more common in singletons. The odds of death prior to discharge were less for twins at 0.74 (95% CI: 0.67-0.83) and triplets at 0.69 (95% CI: 0.51-0.92) compared to singletons. CONCLUSION: Singletons experience greater morbidity and mortality compared to twins and triplets born ≥26 weeks to ≤34 weeks GA, except PDA requiring procedural intervention, ROP requiring treatment, and longer length of stay.

Exploring the relationship between SARS-CoV-2 variants, illness severity at presentation, in-hospital mortality and COVID-19 vaccination in a low middle-income country: A retrospective cross-sectional study.

Background and Aims: COVID-19 morbidity and mortality varied globally through the pandemic. We studied the relationship of SARS-CoV-2 variants of concern (VOC) with COVID-19 severity and mortality among hospitalized patients in Pakistan. Methods: A retrospective review of clinical, laboratory, and vaccination data of 197 COVID-19 adult patients at the Aga Khan University Hospital, Karachi between April 2021, and February 2022 was performed. SARS-CoV-2 VOC identified in respiratory samples were analyzed. Univariate and multivariate analysis was conducted to identify factors associated with COVID-19 outcomes. Results: The median age of cases was 55 years and 51.8% were males. Twenty-four percent of females were pregnant. Of COVID-19 cases, 48.2% had nonsevere disease, while 52.8% had severe/critical disease. Hypertension (48%) and diabetes mellitus (41%) were common comorbids. SARS-CoV-2 VOC identified comprised; Omicron (55.3%), Beta (14.7%), Alpha (13.7%), Delta (12.7%), and Gamma (3.6%) variants. Most (59.7%) study subjects were unvaccinated. Of vaccines, 88% had received inactivated virus COVID-19 vaccines. Increased risk of severe disease was associated with age ≥50 years (odds ratio [OR]: 5.73; 95% confidence interval [CI]: [2.45-13.7]), as well as with diabetes mellitus (OR: 4.24; 95% CI: [1.82-9.85]). Full vaccination (OR: 0.25; 95% CI: [0.11-0.58]) or infection with Omicron (OR: 0.42; 95% CI: [0.23-0.74]) was associated with reduced disease severity. The risk of mortality increased with age ≥50 years (OR: 5.07; 95% CI: [1.92-13.42]) and a history of myocardial infarction (OR: 5.11; 95% CI: [1.45-17.93]) whilst, infection with Omicron was found to reduce the risk (OR: 0.22; 95% CI: [0.10-0.53]). Conclusion: Our study describes the relationship between the severity of COVID-19, in-hospital mortality in relation to SARS-CoV-2 variants, and the impact of COVID-19 vaccination in Pakistan. Outcomes were more favorable in younger individuals, after vaccinations and with Omicron variant infections. Most cases received inactivated virus vaccines therefore these data highlight the protection provided against severe COVID-19.

Novel Coumarin Derivatives as Potential Urease Inhibitors for Kidney Stone Prevention and Antiulcer Therapy: From Synthesis to In Vivo Evaluation.

The presence of ammonium ions in urine, along with basic pH in the presence of urease-producing bacteria, promotes the production of struvite stones. This causes renal malfunction, which is manifested by symptoms such as fever, nausea, vomiting, and blood in the urine. The involvement of urease in stone formation makes it a good target for finding urease enzyme inhibitors, which have the potential to be developed as lead drugs against kidney stones in the future. The documented ethnopharmacology of coumarin 2-one against bacterial, fungal and viral strains encouraged us to synthesize new derivatives of coumarins by reacting aromatic aldehydes with 4-aminocoumarin. The synthesized compounds (2a to 11a) were evaluated for their antimicrobial, in vitro, and in silico properties against the urease enzyme. The study also covers in vivo determination of the synthesized compounds with respect to different types of induced ulcers. The molecular docking study along with extended MD simulations (100 ns each) and MMPBSA study confirmed the potential inhibitory candidates as evident from computed ∆Gbind (3a = -11.62 and 5a = -12.08 Kcal/mol) against the urease enzyme. The in silico analyses were augmented by an enzymatic assay, which revealed that compounds 3a and 5a had strong inhibitory action, with IC50 of 0.412 µM (64.0% inhibition) and 0.322 µM (77.7% inhibition), respectively, compared to standard (Thiourea) with 82% inhibition at 0.14 µM. Moreover, the most active compound, 5a, was further tested in vivo for antiulcer activity by different types of induced ulcers, including pyloric ligation-, ethanol-, aspirin-, and histamine-induced ulcers. Compound 5a effectively reduced gastric acidity, lipid peroxidation, and ulceration in a rat model while also inhibiting gastric ATPase activity, which makes it a promising candidate for ulcer treatment. As a result of the current research, 3a and 5a may be used as new molecules for developing potent urease inhibitors. Additionally, the compound 3a showed antibacterial activity against Staphylococcus aureus and Salmonella typhimurium, with zones of inhibition of 41 ± 0.9 mm and 35 ± 0.9 mm, respectively. Compound 7a showed antibacterial activity against Staphylococcus aureus and Salmonella typhimurium, with zones of inhibition of 30 ± 0.8 mm and 42 ± 0.8 mm, respectively. These results prove that the synthesized compounds also possess good antibacterial potential against Gram-positive and Gram-negative bacterial strains.

Assessment of industrial effluents for heavy metals concentration and evaluation of grass (Phalaris minor) as a pollution indicator.

This study was conducted to investigate the impact of industrial activities on heavy metals status in wastewater, sludge and flora on the bank of selected main drains of the Hayatabad Industrial estate, Peshawar. Plants, sludge and wastewater samples of selected sites were collected and analyzed for heavy metals distribution; cadmium (Cd), chromium (Cr), lead (Pb) and zinc (Zn) levels. Bioconcentration factor (BCF) values were calculated for plants (Phalaris minor) grass species found naturally at all sites. The results showed that the levels of metals in wastewater were lower than permissible limits except Cd and the concentration of metals in plants and sludge were within permissible limits when compared to their respective standards. Metal distribution was in the following order; sludge > plants > wastewater and the concentration of metals varied according to the distance from the source with no specific pattern. Sludge samples for all sites showed a high concentration of metals as compared to plants and wastewater samples. In grass samples, Zn was highest and Cd was low for all sites. Metals accumulation in plants was in order of; roots > shoot. Pearson's coefficient correlation showed that Cr in plant roots and Zn in shoots showed significantly high correlation with Cd in sludge while Pb in roots showed significant negative correlation with Zn in sludge. BCF values for Cr, Pb and Zn were >1, showing the phytoremediation potential of plants.

Clostridioides difficile Infection in Inflammatory Bowel Disease Patients: A Systematic Review of Risk Factors and Approach in Management.

Clostridioides difficile infection (CDI) is one of the most common diseases associated with medical care, having a more significant impact on patients with inflammatory bowel disease (IBD). The latest studies have proposed a change in management for CDI in IBD patients. This study aims to perform a systematic review that explores the risk factors associated with the infection and the most optimal approach in management. Multiple databases were used for this research, including PubMed, Google Scholar, Science Direct, and Cochrane Library. Studies published in the last five years in the English language were selected based on pre-established criteria. The quality assessment used was the Assessment of Multiple Systematic Review, the Newcastle-Ottawa Scale, and the Scale for the Assessment of Narrative Review Articles. Twelve studies met the inclusion criteria in this systematic review, including literature reviews, a case and control study, and systematic reviews and meta-analyses. Based on the findings in this research, we conclude that the treatment for an initial episode of CDI in IBD patients is the use of antibiotics, vancomycin, or fidaxomicin. For episodes of recurrent CDI (rCDI), fetal microbiota transplantation should be considered. The most common risk factors associated are gut microbiota disturbances, the use of antibiotics, and hospitalization. Due to a wide range of risk factors mentioned in some studies but disregarded in others, further research is needed to determine the most prevalent risk factors.

Bioactivity-Guided Synthesis: In Silico and In Vitro Studies of ß-Glucosidase Inhibitors to Cope with Hepatic Cytotoxicity.

The major cause of hyperglycemia can generally be attributed to ß-glucosidase as per its involvement in non-alcoholic fatty liver disease. This clinical condition leads to liver carcinoma (HepG2 cancer). The phthalimides and phthalamic acid classes possess inhibitory potential against glucosidase, forming the basis for designing new phthalimide and phthalamic acid analogs to test their ability as potent inhibitors of ß-glucosidase. The study also covers in silico (molecular docking and MD simulations) and in vitro (ß-glucosidase and HepG2 cancer cell line assays) analyses. The phthalimide and phthalamic acid derivatives were synthesized, followed by spectroscopic characterization. The mechanistic complexities associated with ß-glucosidase inhibition were identified via the docking of the synthesized compounds inside the active site of the protein, and the results were analyzed in terms of the best binding energy and appropriate docking pose. The top-ranked compounds were subjected to extensive MD simulation studies to understand the mode of interaction of the synthesized compounds and binding energies, as well as the contribution of individual residues towards binding affinities. Lower RMSD/RMSF values were observed for 2c and 3c, respectively, in the active site, confirming more stabilized, ligand-bound complexes when compared to the free state. An anisotropic network model was used to unravel the role of loop fluctuation in the context of ligand binding and the dynamics that are distinct to the bound and free states, supported by a 3D surface plot. An in vitro study revealed that 1c (IC50 = 1.26 µM) is far better than standard acarbose (2.15 µM), confirming the potential of this compound against the target protein. Given the appreciable potential of the candidate compounds against ß-glucosidase, the synthesized compounds were further tested for their cytotoxic activity against hepatic carcinoma on HepG2 cancer cell lines. The cytotoxicity profile of the synthesized compounds was performed against HepG2 cancer cell lines. The resultant IC50 value (0.048 µM) for 3c is better than the standard (thalidomide: IC50 0.053 µM). The results promise the hypothesis that the synthesized compounds might become potential drug candidates, given the fact that the ß-glucosidase inhibition of 1c is 40% better than the standard, whereas compound 3c holds more anti-tumor activity (greater than 9%) against the HepG2 cell line than the known drug.

Neurological disorders and disability in Pakistan: A cross-sectional multicenter study.

BACKGROUND/OBJECTIVE: The aim of this study is to identify frequencies of various neurological disorders (NDs) and associated disability in patients attending neurologic clinics in rural and urban centers in Pakistan. METHODS: This is an observational study conducted in 39 neurological centers in both rural and urban areas, public and private health sectors all over Pakistan. This study was conducted between august 2017 to December 2019. RESULTS: A total of 28,845 adults were enrolled. Mean age of the study participants was 46.2 ± 17.2 years, 15,252 (52.9%) were men and 13,593 (47.1%) were women. Most common comorbid medical condition was hypertension 7622(26.4%) followed by Diabetes 3409(11.8%). Among neurological diagnoses, vascular diseases (20%) were the most common followed by Headache disorders (18.6%), Epilepsy (12.5%), nerve and root diseases (12.4%), Psychiatric diseases (10%), Dementias (8%) and movement disorders (7.9%). Half of the patients 15,503(53.7%) had no neurological disability, while minor disability was present in 10,442(36.2%) of cases. Moderate to severe disability was present in 2876(10%) cases. Headache disorders, psychiatric diseases, muscle pain/muscle related disorders and demyelinating diseases were more common in women. Vascular diseases, movement disorders and Dementias were more common in 46 years and above age group whereas headache disorders, Epilepsy and Psychiatric disorders were more prevalent in <46 years age groups. CONCLUSION: Vascular diseases are the most common presentation of patients in neurology clinics followed by headache disorders and epilepsies. Minor disability was present in 36% while moderate to severe disability was present in 10% cases.

SAR and lead optimization of (Z)-5-(4-hydroxy-3-methoxybenzylidene)-3-(2-morpholinoacetyl)thiazolidine-2,4-dione as a potential multi-target antidiabetic agent.

In case of metabolic disorder like Diabetes mellitus (DM), a number of key enzymes are abnormally expressed and hence they might be excellent targets for antidiabetic drug design. Multi-target design strategy has recently attracted great attention to treat challenging diseases. We have previously reported a vanillin-thiazolidine-2,4-dione hybrid 3 as multitarget inhibitor of α-glucosidase, α-amylase, PTP-1B and DPP-4. The reported compound predominantly exhibited good in-vitro DPP-4 inhibition only. Current research describes the goal to optimize an early lead compound. The efforts were focused on enhancing the capability of manipulating multiple pathways at the same time for the treatment of diabetes. The central 5-benzylidinethiazolidine-2,4-dione for Lead compound (Z)-5-(4-hydroxy-3-methoxybenzylidene)-3-(2-morpholinoacetyl)thiazolidine-2,4-dione (Z-HMMTD) was left unchanged. While East and West moieties were altered by the introduction of different building blocks conceived by using a number of rounds of predictive docking studies performed on X-ray crystal structures of four target enzymes. This systematic SAR led to the syntheses of new potent multi-target antidiabetic compounds 47-49 and 55-57 with many fold increase in the in-vitro potency compared to Z-HMMTD. The potent compounds showed good in-vitro and in-vivo safety profile. Compound 56 emerged excellent as glucose-uptake promotor via hemi diaphragm of the rat. Moreover, the compounds demonstrated antidiabetic activity in STZ-induced diabetic animal model.

Targeted vaccine development against Bilophila wadsworthia to curb colon diseases: A multiepitope approach based on reverse vaccinology and computational analysis.

The presence of excessive hydrogen sulfide (H2S)-producing bacteria, particularly Bilophila wadsworthia in appendices, is linked to a weaker colonic mucus barrier, inflammatory bowel disease, and colorectal cancer. Thus, targeting this bacterium could reduce sulfide levels and address associated health concerns. Here, we utilized reverse vaccinology and immunoinformatics to design a chimeric vaccine against B. wadsworthia, focusing on membrane-bound and extracellular proteins. Subtractive proteome analysis identified 18 potential vaccine candidates (PVCs), from which six B-cell, eight CD8+ T cell, and six CD4+ T cell epitopes were predicted. Chosen epitopes were assessed for immunological properties and cross-reactivity with human and mouse proteomes. Subsequently, these epitopes were fused with appropriate linkers, PADRE epitope, TAT peptide, and Cholera Toxin B subunit adjuvant to form a robust multi-epitope vaccine (MEV). The MEV's tertiary structure was modelled and validated for reliable analysis. Molecular docking and dynamics simulations demonstrated stable binding of MEV with Toll-like receptor 4. The MEV showed favorable physicochemical characteristics, high expression potential in Escherichia coli, broad population coverage (∼98 %), and cross-protection against different B. wadsworthia strains. Immune simulation suggested induction of strong B and T cell responses, including primary, secondary, and tertiary immune responses. Further experimental studies are necessary to validate these findings.