Multicomponent synthesis of pyrido[2,3-b]pyrazine derivatives: electrochemical DNA sensing, nonlinear optical properties and biological activity.

We synthesized novel pyrido[2,3-b]pyrazin based heterocyclic compounds (4-7) and their chemical structures were ascertained by spectral techniques (NMR, FT-IR). Besides experimental investigation, density functional theory (DFT) computations with B3LYP/6-31G(d,p) level of theory were executed to obtain spectroscopic and electronic properties. Nonlinear optical (NLO) properties, frontier molecular orbitals (FMOs), UV-visible, vibrational analysis, natural bond orbitals (NBOs), transition density matrix (TDM) and density of states (DOS) analyses of molecules (4-7) were accomplished at B3LYP/6-31G (d,p) level. Global reactivity parameters (GRPs) were correlated with the band gap (Egap) values; compound 7 with lower Egap (3.444 eV), exhibited smaller value of hardness (1.722 eV) with greater softness value (0.290 eV-1). The dipole moment (µ), average polarizability 〈α〉, first (ßtot) and second 〈γ〉 hyper-polarizabilities were calculated for compounds (4-7). Compound 7 showed less Egap, highest absorption wavelength and remarkable NLO response. The highest 〈α〉, ßtot and 〈γ〉 values for compound 7 were observed as 3.90 × 10-23, 15.6 × 10-30 and 6.63 × 10-35 esu, respectively. High NLO response revealed that pyrido[2,3-b]pyrazin based heterocyclic compounds had very remarkable contributions towards NLO technological applications. Further compounds (4-7) are utilized for the first time in electrochemical sensing of DNA, in vitro antioxidant and antiurease activity.

Identification and Functional Characterization of Mutation in FYCO1 in Families with Congenital Cataract.

Congenital cataract (CC) causes a third of the cases of treatable childhood blindness worldwide. CC is a disorder of the crystalline lens which is established as clinically divergent and has complex heterogeneity. This study aimed to determine the genetic basis of CC. Whole blood was obtained from four consanguineous families with CC. Genomic DNA was extracted from the blood, and the combination of targeted and Sanger sequencing was used to identify the causative gene. The mutations detected were analyzed in silico for structural and protein-protein interactions to predict their impact on protein activities. The sequencing found a known FYCO1 mutation (c.2206C>T; p.Gln736Term) in autosomal recessive mode in families with CC. Co-segregation analysis showed affected individuals as homozygous and carriers as heterozygous for the mutation and the unaffected as wild-type. Bioinformatics tools uncovered the loss of the Znf domain and structural compactness of the mutant protein. In conclusion, a previously reported nonsense mutation was identified in four consanguineous families with CC. Structural analysis predicted the protein as disordered and coordinated with other structural proteins. The autophagy process was found to be significant for the development of the lens and maintenance of its transparency. The identification of these markers expands the scientific knowledge of CC; the future goal should be to understand the mechanism of disease severity. Ascertaining the genetic etiology of CC in a family member facilitates establishing a molecular diagnosis, unlocks the prospect of prenatal diagnosis in pregnancies, and guides the successive generations by genetic counseling.

Impact of green human resource management on green creativity in pharmaceutical companies: mediation role of green mindset.

This research study analyzed the impact of green human resource management on the green creativity of the employees of the pharmaceutical companies of Lahore, Pakistan, with the mediating role of a green mindset and the moderating role of green concern. The convenience sampling technique was used to sample employees of pharmaceutical companies. The study was quantitative and cross-sectional in nature, and it used correlation and regression analysis to investigate the hypothesis. A sample of 226 employees (including managers, supervisors, and other staff members) was drawn from different pharmaceutical companies in Lahore, Pakistan. The results of the study indicate that green human resource management has a positive significant effect on the green creativity of employees. Findings further explain that the green mindset acts as a mediator and partially mediates the relationship between green human resource management and green creativity. Furthermore, this study examined the role of green concern as a moderator and the results explain the insignificant relation which shows that green concern does not moderate the relationship between the green mindset and green creativity of the employees of pharmaceutical companies in Lahore, Pakistan. The practical implications of this research study are also discussed.

Local Tranexamic Acid for Preventing Hemorrhage in Anticoagulated Patients Undergoing Dental and Minor Oral Procedures: A Systematic Review and Meta-Analysis.

Dental procedures have posed challenges in managing anticoagulated patients due to early reports of oral hemorrhage. This study aims to evaluate the risks of postoperative bleeding with the local application of tranexamic acid. A systematic search was conducted until 31 March 2022, with keywords including tranexamic acid, oral hemorrhage, dental, and/or coagulation. The following databases were searched: PubMed, Scopus, Web of Science, CINAHL Plus, and Cochrane Library. Statistical analysis was conducted using Review Manager 5.4. In total, 430 patients were pooled in with the local application of tranexamic acid using mouthwash, irrigation, and compression with a gauze/gauze pad. The mean age was 61.8 years in the intervention group and 58.7 in the control group. Only 4 patients in the intervened group out of the 210 discontinued the trial due to non-drug-related adverse events. The risk difference was computed as -0.07 (p = 0.05), meaning that patients administered with local antifibrinolytic therapy for postoperative bleeding reduction for dental procedures were at a 7% less risk of oral bleeding. Current evidence on managing anticoagulated patients undergoing dental or oral procedures remains unclear. The present study presents favorable outcomes of postoperative bleeding with local tranexamic acid used in the postoperative period.

Impact of Refractive Errors on the Academic Performance of High School Children of Lahore.

Introduction: The process of learning begins in childhood and accurate vision can greatly affects a child's learning capacity. It is documented that visual impairment in children can have a significant impact on their performance at school as well as their social interaction and development. Objective: This research aimed to study the impact of refractive corrections on the academic performance of high school children in Lahore. Methodology: A total of 2,000 students with equal distribution of gender, public, private school, and locality were included in the study. All students were screened for defective vision. The academic performance before and after corrections was recorded on the prescribed proforma. Results: The prevalence of refractive error was high among the public high schools 244 (59.2%) as compared to the private schools 168 (40.8%). The area-based prevalence was higher among the students in urban settings 255 (62%) while in rural it was 157 (38%). It was found that in the public sector, the average score of academic results before the intervention was 56.39 ± 13.24 which was increased to 60.27 ± 14.94 after the intervention while in the private sector, before the intervention, the average score was 63.53 ± 17.50 which was improved to 67.12 ± 18.48. It was found to be statistically significant at p-value < 0.05. Conclusion: A significant impact was observed in the average academic scores of the results after refractive corrections.

Delineating Novel and Known Pathogenic Variants in TYR, OCA2 and HPS-1 Genes in Eight Oculocutaneous Albinism (OCA) Pakistani Families.

Oculocutaneous albinism (OCA) is associated with a wide range of clinical presentations and has been categorized with syndromic and non-syndromic features. The most common causative genes in non-syndromic OCA are TYR and OCA2 and HSP1 is in the syndromic albinism. The objective of this study was to identify pathogenic variants in congenital OCA families from Pakistan. Eight consanguineous families were recruited, and clinical and ophthalmological examination was carried out to diagnose the disease. Whole blood was collected from the participating individuals, and genomic DNA was extracted for sequencing analysis. TruSight one-panel sequencing was carried out on one affected individual of each family, and termination Sanger sequencing was carried out to establish the co-segregation of the causative gene or genes. In silico analysis was conducted to predict the causative pathogenic variants. Two families were found to have novel genetic pathogenic variants, and six families harbored previously reported variants. One novel compound heterozygous pathogenic variant in the TYR gene, c.1002delA; p.Ala335LeufsTer20, a novel frameshift deletion pathogenic variant and c.832C>T; and p.Arg278Ter (a known pathogenic variant) were found in one family, whereas HPS1; c.437G>A; and p.Trp146Ter were detected in another family. The identification of new and previous pathogenic variants in TYR, OCA2, and HPS1 genes are causative of congenital OCA, and these findings are expanding the heterogeneity of OCA.

Tyrosinase (TYR) gene sequencing and literature review reveals recurrent mutations and multiple population founder gene mutations as causative of oculocutaneous albinism (OCA) in Pakistani families.

PURPOSE: To investigate eight previously unreported Pakistani families with genetically undefined OCA for mutations in TYR. METHODS: Sanger sequencing of TYR has been performed in eight families with OCA phenotype. Mutation analysis was performed to establish the pathogenic role of novel mutation. Bioinformatics analysis was performed to predict the structural and functional impacts on protein due to the mutation. RESULTS: In this study, we identified six likely pathogenic variants of TYR (c.272 G>A, c.308 G>A, c.346C>T, c.715 C>T, c.832 C>T and c.1255 G>A), including one novel variant (c.308 G>A; p.Cys103Tyr), segregating as appropriate in each family. Cys103 lies in the highly conserved region of the tyrosinase enzyme, and p.Cys103Tyr is predicted to disturb enzymatic function via alteration of the configurational orientation of TYR leading to a more rigid polypeptide structure. We have also reviewed the mutation spectrum of TYR in Pakistani ethnicity. Published data on OCA families proposed that ~40% have been associated with genetic variations in the TYR gene. The mutations reported in this study have now been described with varying frequencies in Pakistani families, including very rare/unique mutations. CONCLUSION: A literature review of TYR gene mutations in Pakistani populations, combined with our genetic data, identified a number of gene mutations likely to represent regional ancestral founder mutations of relevance to Pakistani populations, in addition to sporadic and recurrent 'hotspot' mutations present repeatedly in other regions worldwide.

Verification of absorbed dose using diodes in cobalt-60 radiation therapy.

The objective of this work was to enhance the quality and safety of dose delivery in the practice of radiation oncology. To achieve this goal, the absorbed dose verification program was initiated by using the diode in vivo dosimetry (IVD) system (for entrance and exit). This practice was implemented at BINO, Bahawalpur, Pakistan. Diodes were calibrated for making absorbed dose measurements. Various correction factors (SSD, dose non-linearity, field size, angle of incidence, and wedge) were determined for diode IVD system. The measurements were performed in phantom in order to validate the IVD procedure. One hundred and nineteen patients were monitored and 995 measurements were performed. For phantom, the percentage difference between measured and calculated dose for entrance setting remained within ±2% and for exit setting ±3%. For patient measurements, the percentage difference between measured and calculated dose remained within ±5% for entrance/open fields and ±7% for exit/wedge/oblique fields. One hundred and nineteen patients and 995 fields have been monitored during the period of 6 months. The analysis of all available measurements gave a mean percent deviation of ±1.19% and standard deviation of ±2.87%. Larger variations have been noticed in oblique, wedge and exit measurements. This investigation revealed that clinical dosimetry using diodes is simple, provides immediate results and is a useful quality assurance tool for dose delivery. It has enhanced the quality of radiation dose delivery and increased/improved the reliability of the radiation therapy practice in BINO.