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Background: Setting of conventional glass ionomers cement and dental resin composites as filling materials is predominantly through polymerization reaction, which is usually induced by light. The objective of this study was to assess the temperature changes, light intensities, sorption and solubility capability and comparative micro hardness in Dental Resin Composites (DRC) by using two different light curing units that is Quartz Tungsten Halogen (QTH) and Light Emitting Diodes (LED). Methods: This analytical, experimental, in-vitro study was spanned over one month, conducted in the laboratory of Dental Materials, Dr. Ishrat-ul-Ibad Khan Institute of Oral Health Sciences. Through non-probability, convenient sampling, 60 samples of DRCs was prepared as 10mm in diameter and 2mm in thickness in the steel moulds by a single trained operator. Effect of heat generation, light intensities, sorption and solubility and micro hardness during polymerization of DRCs were all measured. Statistical analysis was done using SPSS with descriptive statistics and two sample independent t-tests. The p-value of

Abstract The benefits of large-scale genetic studies for healthcare of the populations studied are well documented, but these genetic studies have traditionally ignored people from some parts of the world, such as South Asia. Here we describe whole genome sequence (WGS) data from 4806 individuals recruited from the healthcare delivery systems of Pakistan, India and Bangladesh, combined with WGS from 927 individuals from isolated South Asian populations. We characterize population structure in South Asia and describe a genotyping array (SARGAM) and imputation reference panel that are optimized for South Asian genomes. We find evidence for high rates of reproductive isolation, endogamy and consanguinity that vary across the subcontinent and that lead to levels of rare homozygotes that reach 100 times that seen in outbred populations. Founder effects increase the power to associate functional variants with disease processes and make South Asia a uniquely powerful place for population-scale genetic studies.

In the current study, matrices of losartan potassium were formulated with two different polymers (Ethocel 10 premium and Ethocel 10FP premium), along with a filler and a lubricant, at different drug-to-polymer w/w ratios (10:3, 10:4, and 10:5). The matrices were tested by the direct compression method, and their hardness, diameter, thickness, friability, weight variation, content uniformity, and in vitro dissolution tests were assessed to determine 24-h drug release rates. The matrices with Ethocel 10 FP at a 10:4 ratio exhibited pseudo-zero-order kinetics (n-value of 0.986), while the dissolution data of the test matrices and reference tablets did not match. The new test-optimized matrices were also tested in rabbits, and their pharmacokinetic parameters were investigated: half-life (11.78 ± 0.018 h), Tmax (2.105 ± 1.131 h), Cmax (205.98 ± 0.321 μg/mL), AUCo (5931.10 ± 1.232 μg·h/mL), AUCo-inf (7348.46 ± 0.234 μg·h/mL), MRTo-48h (17.34 ± 0.184 h), and Cl (0.002 ± 0.134 mL/min). A correlation value of 0.985 between the in vitro and in vivo results observed for the test-optimized matrices was observed, indicating a level-A correlation between the percentage of the drug released in vitro and the percentage of the drug absorbed in vivo. The matrices might improve patient compliance with once-a-day dosing and therapeutic outcomes.

Abstract Background Genetic, lifestyle, and environmental factors can lead to perturbations in circulating lipid levels and increase the risk of cardiovascular and metabolic diseases. However, how changes in individual lipid species contribute to disease risk is often unclear. Moreover, little is known about the role of lipids on cardiovascular disease in Pakistan, a population historically underrepresented in cardiovascular studies. Methods We characterised the genetic architecture of the human blood lipidome in 5662 hospital controls from the Pakistan Risk of Myocardial Infarction Study (PROMIS) and 13,814 healthy British blood donors from the INTERVAL study. We applied a candidate causal gene prioritisation tool to link the genetic variants associated with each lipid to the most likely causal genes, and Gaussian Graphical Modelling network analysis to identify and illustrate relationships between lipids and genetic loci. Results We identified 253 genetic associations with 181 lipids measured using direct infusion high-resolution mass spectrometry in PROMIS, and 502 genetic associations with 244 lipids in INTERVAL. Our analyses revealed new biological insights at genetic loci associated with cardiometabolic diseases, including novel lipid associations at the LPL, MBOAT7, LIPC, APOE-C1-C2-C4, SGPP1, and SPTLC3 loci. Conclusions Our findings, generated using a distinctive lipidomics platform in an understudied South Asian population, strengthen and expand the knowledge base of the genetic determinants of lipids and their association with cardiometabolic disease-related loci.

Novel drug targets for sustained reduction in body mass index (BMI) are needed to curb the epidemic of obesity, which affects 650 million individuals worldwide and is a causal driver of cardiovascular and metabolic disease and mortality. Previous studies reported that the Arg95Ter nonsense variant of GPR151, an orphan G protein-coupled receptor, is associated with reduced BMI and reduced risk of Type 2 Diabetes (T2D). Here, we further investigate GPR151 with the Pakistan Genome Resource (PGR), which is one of the largest exome biobanks of human homozygous loss-of-function carriers (knockouts) in the world. Among PGR participants, we identify eleven GPR151 putative loss-of-function (plof) variants, three of which are present at homozygosity (Arg95Ter, Tyr99Ter, and Phe175LeufsTer7), with a cumulative allele frequency of 2.2%. We confirm these alleles in vitro as loss-of-function. We test if GPR151 plof is associated with BMI, T2D, or other metabolic traits and find that GPR151 deficiency in complete human knockouts is not associated with clinically significant differences in these traits. Relative to Gpr151+/+ mice, Gpr151-/- animals exhibit no difference in body weight on normal chow and higher body weight on a high-fat diet. Together, our findings indicate that GPR151 antagonism is not a compelling therapeutic approach to treatment of obesity.

The coloring behavior of santalin, a natural reddish-brown dye derived from sandalwood, has been investigated in this work for the dyeing of silk fabrics while being heated in MW radiation. Microwave (MW) radiation up to 5 min has been employed to isolate colorant (Santalin) from red sandalwood (Ptrecarpus santalinus) in selected medium, and bio-mordants in competing with salts as chemical-mordants have been included. Statistical analysis was made and dyeing variables were selected for getting dark shades though mordants. MW treatment for 3 min. to both extract and fabric was selected and mild dyeing conditions were optimized statistically to get dark shades. On applying chemical mordants, selected amount of salts of Al+3, Fe+2 and T.A. before and after dyeing, has given good results. Comparatively, selected extracts of plant based sources have shown colorfast shades of high strength. The MW radiation has excellent potential to extract dye form plants using optimum medium through less time and energy, and the application of plant extracts along with sustainable salts have developed colorfast shades.

Objective: To determine the effect of pre-cooling agent on the intensity of pricking pain at the intraoral injection site in adult patients. Method: An in-vivo interventional study, using split-mouth technique was conducted in the Department of Operative Dentistry, Dr. Ishrat-ul-Ebad Khan Institute of Oral Health Sciences, DUHS, Karachi, between September 2018 to August 2019. Total 152 adult patients meeting the inclusion criteria were selected, and consent form was signed to investigate the pricking pain perception during needle administration. Topical anesthesia (benzocaine gel) was applied on left side (control) for 1 min whereas on the experimental (right) side the refrigerated cartridge was placed for 2 minutes. Infiltration anesthesia was then administered on both sides respectively. Patient’s pain perception ratings were measured through Visual analog scale (VAS). After profound anesthesia was achieved, restorative treatment was performed under rubber dam isolation. Statistical analysis was done using SPSS Version 24. Results: The effect of pre-cooling agent i.e. refrigerated cartridge, was statistically significant (P-value

This study focuses on the experimental and molecular-level investigation of epoxy acrylate formation. Epoxy acrylate vinyl ester resin was prepared by a reaction of diglycidyl ether of bisphenol-A-based epoxy resin and acrylic acid, using benzimidazole as a catalyst. It was confirmed that benzimidazole can effectively catalyze this reaction. FTIR analysis of the product revealed a simple addition esterification reaction between the epoxide group and carboxylic group of acrylic acid excluding the side reactions (e.g., etherification). DFT computational studies were performed to theoretically explore the insights of reaction mechanisms. The calculations revealed that the benzimidazole-catalyzed reaction dominates the uncatalyzed reaction. A comparison of calculated activation energies showed that concerted mechanisms are less significant in such reactions owing to their high activation barriers.

The pathophysiology of post-traumatic arthritis (PTOA) is not fully understood. This study used non-invasive repetitive mechanical loading (ML) mouse models to study biochemical, biomechanical, and pain-related behavioral changes induced in mice. Mouse models reflected the effects of the early stages of PTOA in humans. For the PTOA model, cyclic comprehensive loading (9N) was applied to each mouse’s left knee joint. ML-induced biochemical and molecular changes were analyzed after loading completion. Cartilage samples were examined using gene expression analysis. Tissue sections were used in subsequent OA severity scoring. Biomechanical features and pain-related behavior were studied after 24 h and three weeks post-ML sessions to examine the development of PTOA. The loaded left knee joint showed a greater ROS/RNS signal than the right knee, which was not loaded. There was a significant increase in cartilage damage and MMP activity in the mechanically loaded joints relative to non-loaded control knee joints. Similarly, we found a difference in the viscoelastic tangent, which highlights significant changes in mechanical properties. Biochemical analyses revealed significant increases in total NO, caspase-3 activity, H2O2, and PGE2 levels. Gene expression analysis highlighted increased catabolism (MMP-13, IL-1β, TNF-α) with a concomitant decrease in anabolism (ACAN, COL2A1). Histopathology scores clearly indicated increases in OA progression and synovitis. The gait pattern was significantly altered, suggesting signs of joint damage. This study showed that biomechanical, biochemical, and behavioral characteristics of the murine PTOA groups are significantly different from the control group. These results confirm that the current mouse model can be considered for translational PTOA studies.

Erosive beverages cause dissolution of natural teeth and intra-oral restorations, resulting in surface characteristic changes, particularly roughness and degradation. The purpose of this study was to evaluate the surface roughness and topography of a dental ceramic following immersion in locally available erosive solutions. A total of 160 disc specimens of a nano-fluorapatite type ceramic (12 mm diameter and 2 mm thickness) were fabricated and equally distributed into two groups (n = 80) and then evenly distributed among the following five testing groups (n = 16): lemon juice, citrate buffer solution, 4% acetic acid, soft cola drink, and distilled water which served as a control. The surface roughness (Ra) and topography were evaluated using a profilometer and scanning electron microscope at baseline, 24 h, 96 h, and 168 h respectively. Data were analyzed using ANOVA and Tukey’s multiple comparisons (p ≤ 0.05). Surface changes were observed upon exposure to all acidic beverages except distilled water. Amongst all immersion media, 4% acetic acid produced the most severe surface roughness across all time periods (i.e., baseline, 24 h, 96 h, and 168 h). A statistically significant difference in the surface roughness values between all immersion media and across all four time intervals was observed. Erosive agents had a negative effect on the surface roughness and topography of the tested ceramic. The surface roughness increased with increased storage time intervals.

Abstract Severe pollution-induced flashovers on insulators present a pressing challenge to power system safety. The frequent failure of high-voltage insulators, particularly in the polluted environments of Pakistan, poses a critical concern. This paper investigates the impact of insulator profile on reducing pollution flashovers, testing two designs as per IEC standard 60383 and simulated using the Finite Element Method in COMSOL Multiphysics®. The test results revealed that deep under-ribs insulators exhibited a 5.008% reduction in flashover voltage, while alternating shed insulators experienced a 3.233% decrease in polluted conditions compared to clean conditions. Notably, under both clean and polluted conditions, alternating shed insulators consistently outperformed deep under-ribs insulators, with a 25.377% higher flashover voltage in clean conditions and a 27.400% superiority in polluted conditions. Computational analysis through the Finite Element Method in COMSOL Multiphysics shows a consistent pattern in potential distribution with increasing insulator count, but the presence of a pollution layer introduces spikes in the electric field distribution, validating experimental results. These findings highlight the superior performance of alternating shed insulators, especially in polluted environments.

The benefits of large-scale genetic studies for healthcare of the populations studied are well documented, but these genetic studies have traditionally ignored people from some parts of the world, such as South Asia. Here we describe whole genome sequence (WGS) data from 4806 individuals recruited from the healthcare delivery systems of Pakistan, India and Bangladesh, combined with WGS from 927 individuals from isolated South Asian populations. We characterize population structure in South Asia and describe a genotyping array (SARGAM) and imputation reference panel that are optimized for South Asian genomes. We find evidence for high rates of reproductive isolation, endogamy and consanguinity that vary across the subcontinent and that lead to levels of rare homozygotes that reach 100 times that seen in outbred populations. Founder effects increase the power to associate functional variants with disease processes and make South Asia a uniquely powerful place for population-scale genetic studies.

Objective: To determine the outcome of early and late-onset Fontan operation in patients with univentricular heart repair. Study Design: Quasi-experimental study. Place and Duration of the Study: Department of Paediatric Cardiology, National Institute of Cardiovascular Diseases, Karachi Pakistan, from Jan 2019 to Dec 2021. Methodology: During the study period, 121 patients of both genders, up to any age, with functionally univentricular hearts and who planned to undergo Fontan procedures were included. All cases were divided into two groups, Group-A had patients who underwent extra-cardiac Fontan at age ≤6 years, while Group B had patients who underwent extra-cardiac Fontan at age >6 years. Pre-procedure diagnosis, demographic, anatomic and hemodynamic characteristics, post-Fontan procedure morbidity and mortality were noted. Results: As per inclusion/exclusion criteria, 121 cases underwent Fontan surgery during the study period. There were 61(50.4%) male patients. Overall, the mean age was 7.02±4.6 years. Seventy-six 76(61.2%) cases were in Group-A and 45(38.8%) in Group-B. Mortality (within 30 days post-surgery) was reported in 11(9.1%) patients. Except for the mean duration of chest tube drainage ((0.010), there was no difference in terms of post-Fontan surgery outcomes between both study groups (p>0.05). Conclusion: The age of the patients at the time of the Fontan procedure did not affect the outcomes.

Objective: To compare the surgical outcome of Tetralogy of Fallot patients with and without right ventricular diastolic dysfunction after repair. Study Design: Quasi-experimental study. Place and Duration of Study: Department of Cardiology, National Institute of Cardiovascular Disease, Karachi Pakistan, from May to Oct 2021. Methodology: Patients above 5 months of age, of either gender, undergoing surgery for Tetralogy of Fallot were enrolled. Patients were divided into two groups according to the Gatzoulis’ criterion for right ventricular restriction i.e. Group-A had right ventricle with restriction, and Group-B had right ventricle without restriction. Velocities of E and A waves was recorded, and their ratio (E/A) was calculated. The outcome such as aortic cross clamp, cardiopulmonary bypass time, ventilation time, intensive care unit stay, drain time, and transannular patch was noted. Results: Of 54 patients, restrictive physiology patients had significantly higher mean for aortic cross-clamp (p-value 0.004, 95%CI 3.54 - 17.35), ventilation time (p-value

EDSS1, a syndrome characterized by ectodermal dysplasia-syndactyly, is inherited in an autosomal recessive manner due to mutations in the NECTIN4/PVRL4 gene. Clinical manifestations of the syndrome include defective nail plate, sparse to absent scalp and body hair, spaced teeth with enamel hypoplasia, and bilateral cutaneous syndactyly in the fingers and toes. Here, we report a consanguineous family of Kashmiri origin presenting features of EDSS1. Using whole exome sequencing, we found a recurrent nonsense mutation (NM_030916: c.181C > T, p.(Gln61 ∗)) in the NECTIN4 gene. The variant segregated perfectly with the disorder within the family. The candidate variant was absent in 50 in-house exomes pertaining to other disorders from the same population. In addition to the previously reported clinical phenotype, an upper lip cleft was found in one of the affected members as a novel phenotype that is not reported by previous studies in EDSS1 patients. Therefore, the study presented here, which was conducted on the Kashmiri population, is the first to document a NECTIN4 mutation associated with the upper lip cleft as a novel phenotype. This finding broadens the molecular and phenotypic spectrum of EDSS1.

The notion of f-graphs and f-ideals are relatively new and have been studied in many papers. In this paper, we have generalized the idea of f-graphs and f-ideals to quasi f-graphs and quasi f-ideals, respectively. We have characterized all quasi f-graphs and quasi f-ideals of degree 2 and determined all the minimal primes ideals of these ideals. Furthermore, construction of quasi f-ideals of degree 2 has been described; the formula for computing Hilbert function and Hilbert series of the polynomial ring modulo the edge ideal of the quasi f-graph has been provided.

BackgroundType 2 Diabetes-related medication errors are frequently reported from the hospitals and consequently are of major concern. However, such reports are insufficient when developing healthcare settings are pursued in literature. Keeping this inadequacy in mind, we therefore aimed to explore physicians' perceptions, experiences and expectations of medication errors when managing patients with Type 2 Diabetes Mellitus.MethodsA qualitative design was adopted. By using a semi-structured interview guide through the phenomenology-based approach, in-depth, face-to-face interviews were conducted. Physicians practicing at the medicine ward of Sandeman Provincial Hospital, Quetta, were purposively approached for the study. All interviews were audio-taped, transcribed verbatim, and were then analyzed for thematic contents by the standard content analysis framework.ResultsAlthough the saturation was reached at the 13th interview, we conducted additional two interviews to ensure the saturation. Fifteen physicians were interviewed, and thematic content analysis revealed six themes and nine subthemes. Mixed conceptualization and characterization of medication errors were identified. Medication errors were encountered by all physicians however poor understanding of the system, deficiency of logistics and materials were rated as barriers in reporting medication errors. Among contributors of medication errors, physicians themselves as well as dispensing and patient-related factors were identified. Physicians suggested targeted training sessions on medication error-related guidelines and reporting system. Parallel, establishment of an independent unit, involving the pharmacists, and strict supervision of paramedics to minimize medication errors was also acknowledged during data analysis.ConclusionWith a longer life expectancy and a trend of growing population, the incidences of medication errors are also expected to increase. Our study highlighted prescribing, dispensing and administration phases as contributing factors of medication errors. Although, physicians had poor understanding of medication errors and reporting system, they believed getting insights on guidelines and reporting system is essential. A review of admission and discharge reconciliation must be prioritized and a culture of teamwork, communication and learning from mistakes is needed.

A study was conducted to determine the prevalence and drug resistance of Escherichia coli present in urinary tract infected patients and hospital drinking water. A total of eighty urine samples from clinically suspected patients and thirty tap water samples from hospital vicinity were collected and analyzed for the presence of E. coli. The isolates were preliminary identified based on morphological characteristics, biochemical test and further confirmed by polymerase chain reaction (PCR) using uidA primer. Isolates were subjected to antibiogram studies and analyzed for the presence of drug resistance (ESBL blaCTX-M-15, tetA, and TMP-SMX dfrA1) and pathogenicity associated pyelonephritis-associated pili (PAP) and Heat-labile (LT) toxin genes. Urine samples 19/80 (23.75%) and water samples 8/30 (26.7%) were found contaminated with E. coli. It was found that 12/19 (63%) bacterial isolates were extended spectrum beta-lactamase (ESBL) producers in clinical and 6/8 (75%) in water isolates whereas tetracycline resistance in clinical and water isolates was 11/19 (58%) and 6/8 (75%), respectively. The trimethoprim resistance gene was confirmed in 12/19 (63%) in clinical and 2/8 (25%) in water isolates. All the clinical and water isolates were found carrying pili PAP gene. It was concluded that the presence of drug resistant and pathogenic E. coli in clinical and water samples is extremely alarming for public health due to cross contamination and bacterial transfer from clinical samples to water and vice versa.

In the current study, matrices of losartan potassium were formulated with two different polymers (Ethocel 10 premium and Ethocel 10FP premium), along with a filler and a lubricant, at different drug-to-polymer w/w ratios (10:3, 10:4, and 10:5). The matrices were tested by the direct compression method, and their hardness, diameter, thickness, friability, weight variation, content uniformity, and in vitro dissolution tests were assessed to determine 24-h drug release rates. The matrices with Ethocel 10 FP at a 10:4 ratio exhibited pseudo-zero-order kinetics (n-value of 0.986), while the dissolution data of the test matrices and reference tablets did not match. The new test-optimized matrices were also tested in rabbits, and their pharmacokinetic parameters were investigated: half-life (11.78 ± 0.018 h), Tmax (2.105 ± 1.131 h), Cmax (205.98 ± 0.321 μg/mL), AUCo (5931.10 ± 1.232 μg·h/mL), AUCo-inf (7348.46 ± 0.234 μg·h/mL), MRTo-48h (17.34 ± 0.184 h), and Cl (0.002 ± 0.134 mL/min). A correlation value of 0.985 between the in vitro and in vivo results observed for the test-optimized matrices was observed, indicating a level-A correlation between the percentage of the drug released in vitro and the percentage of the drug absorbed in vivo. The matrices might improve patient compliance with once-a-day dosing and therapeutic outcomes. [ABSTRACT FROM AUTHOR]