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IntroductionHumanization is typically adopted to reduce the immunogenicity of murine antibodies generated by hybridoma technology when used in humans.MethodsTwo different strategies of antibody humanization are popularly employed, including “complementarity determining region (CDR) grafting” and “framework (FR) shuffling” to humanize a murine antibody against human programmed death-1 (PD-1), XM PD1. In CDR-grafting humanization, the CDRs of XM PD-1, were grafted into the human FR regions with high homology to the murine FR counterparts, and back mutations of key residues were performed to retain the antigen-binding affinities. While in FR-shuffling humanization, a combinatorial library of the six murine CDRs in-frame of XM PD-1 was constructed to a pool of human germline FRs for high-throughput screening for the most favorable variants. We evaluated many aspects which were important during antibody development of the molecules obtained by the two methods, including antibody purity, thermal stability, binding efficacy, predicted humanness, and immunogenicity, along with T cell epitope prediction for the humanized antibodies.ResultsWhile the ideal molecule was not achieved through CDR grafting in this particular instance, FR-shuffling proved successful in identifying a suitable candidate. The study highlights FR-shuffling as an effective complementary approach that potentially increases the success rate of antibody humanization. It is particularly noted for its accessibility to those with a biological rather than a computational background. DiscussionThe insights from this comparison are intended to assist other researchers in selecting appropriate humanization strategies for drug development, contributing to broader application and understanding in the field.

This retrospective cohort study analysed the trends and complications of vaginal hysterectomy conducted at Services Hospital, Lahore, from January 1, 2015 to December 31, 2020. Demographics, indications, surgery duration, complications (haemorrhage, urological or rectal problems, infection), and hospital stay were recorded. Out of 819 hysterectomies performed for benign gynaecological conditions, 112 (13.68%) were vaginal hysterectomies. Non-descent vaginal hysterectomy (NDVH) accounted for 33(29.46%) and uterine prolapse for 79(70.53%) of the cases. Mean age was 52.35 ±8.74 years, parity was 5.01±1.32, intraoperative haemorrhage was 796.87±450.1 ml, surgery duration was 48.61±12.28 minutes, and hospital stay was 2.58±0.41 days. Complications occurred in 19(16.97%) of the cases, while 93(83.03%) cases had no complications. Outcomes were comparable between NDVH and vaginal hysterectomy for prolapse (p=0.552). This indicates that vaginal hysterectomy is a safe procedure with minimal complications and quick recovery for uterine prolapse and non-descent uterus. However, a declining trend was observed over the study period.

OBJECTIVES: To determine the frequency of lumber puncture-proven acute bacterial meningitis among children with fever and seizures of first onset. METHODOLOGY From March 2020 to March 2021, a hospital-based descriptive cross-sectional study was conducted at the paediatrics department of Hayatabad Medical Complex Peshawar. The sample size for a total of 342 people was estimated using WHO software. The study included all children who had first-onset febrile seizures through OPD and the emergency department. All children underwent lumber punctures using a stringent aseptic procedure, and the hospital laboratory received the samples to look for bacterial meningitis. On a pre-made Proforma, details including name, age, and gender were entered. The gathered data were input into the computer for additional SPSS analysis (version 23). RESULTS Most individuals were male and were lies in the 21-40 months of age group. Mean weight and length/height were evaluated, respectively. The majority had a history of 6-10 days of disease duration. Bacterial meningitis was found significantly (p0.05) associated with the duration of diseases. CONCLUSION All children between the ages of 6 months and 60 months who presented with episodes of fever and seizures were found to have a statistically significant (p

Nanoparticles have numerous applications as drug carriers in drug delivery. The aim of the study was to produce tamoxifen nanoparticles with a defined size and higher encapsulation for efficient tissue uptake with controlled drug release. The quality by design approach was utilized to produce tamoxifen-loaded Eudragit nanoparticles by identifying the significant process variables using the nanoprecipitation method. The process variables (amount of drug, polymer, and surfactant) were altered to analyze the influence on particle size (PS), % encapsulation efficiency (EE). The results showed that the drug and polymer individually as well as collectively have an impact on PS, while the surfactant has no impact on the PS. The %EE was influenced by the surfactant individually and in interaction with the drug. The linear regression model was endorsed to fit the data showing high R2 values (PS, 0.9146, %EE, 0.9070) and low p values (PS, 0.0004, EE, 0.0005). The PS and EE were confirmed to be 178 nm and 90%, respectively. The nanoparticles were of spherical shape, as confirmed by SEM and TEM. The FTIR confirmed the absence of any incompatibility among the ingredients. The TGA confirmed that the NPs were thermally stable. The in vitro release predicted that the drug release followed Higuchi model.

Glimepiride (GM) is a hydrophobic drug that dissolves slowly and yields inconsistent clinical responses after oral administration. Transdermal drug delivery (TDD) is an appropriate alternative to oral administration. Microneedles (MNs) offer a promising delivery system that penetrates the skin, while polymeric micelles can enhance the solubility; hence, the combination of both results in high drug bioavailability. This study aims to improve glimepiride’s solubility, dissolution rate, and bioavailability by incorporating nanomicelles into MNs for TDD. The nanomicelles formulated with 10% Soluplus® (SP) and 40% GM had a mean particle size of 82.6 ± 0.54, PDI of 0.1 ± 0.01, −16.2 ± 0.18 zeta potential, and achieved a 250-fold increase in solubility. The fabricated pyramid shaped GM-dissolving MNs were thermally stable and had no formulation incompatibility, as confirmed by thermal and FTIR analysis. The in vitro dissolution profile revealed that the GM release from nanomicelles and nanomicelle-loaded DMN was concentration-independent following non-Fickian transport mechanism. Improved pharmacokinetic parameters were obtained with dose of 240 µg as compared to 1 mg of GM oral tablet, in healthy human volunteers. The observed Cmax, Tmax and MRT were 1.56 μg/mL ± 0.06, 4 h, and 40.04 h ± 3.37, respectively. The safety profile assessment indicated that microneedles are safe with no adverse effects on skin or health. This study provides an alternative delivery system for the administration of glimepiride, resulting in improved bioavailability, enhanced patient compliance, and reduced dosing frequency.

Microneedles have recently emerged as a promising platform for delivering therapeutic agents by disrupting the skin, resulting in improved and high drug delivery via this route. Ibuprofen is widely used topically and orally for chronic pain conditions; to avoid untoward gastric effects, topical application is preferred over the oral route. This study aimed to enhance the solubility of the poorly water-soluble ibuprofen using Soluplus (SP) as a solubilizer and to fabricate dissolving microneedle patches of the drug. The fabricated patches were compared with marketed oral and topical formulations of ibuprofen. A 432-fold increase was observed in the solubility of the drug at 8% SP. The FTIR studies revealed that the drug and polymers were compatible. MNs were of uniform morphology and released the drug in a predictable manner. The in vivo analysis on healthy human volunteers revealed a Cmax of 28.7 µg/mL ± 0.5 with a Tmax of 24 h and a MRT of 19.5 h, which was significantly higher than that observed for commercially available topical formulations. The prepared ibuprofen microneedles have higher bioavailability and MRT at a lower dose (165 µg) as compared to tablet and cream doses (200 mg).

The present research work was carried out to determine the bioaccumulation of manganese and chromium in the gills, intestine, muscles, skin and bones, as well as its acute toxicity and effects on hematological and biochemical parameters in Common carp (Cyprinus carpio). Adult carps were exposed for 96 h to manganese sulphate and chromium chloride solution, a sub lethal concentration was used in the experiment. Bioaccumulation was highest in the gills followed by intestine > muscles > skin > bones. The concentration of hematocrit (HCT) (37.3 ± 0.36), hemoglobin (HGB) (9.0 ± 0.04), Red Blood Cells (RBCs) (3.7 ± 0.025), mean corpuscular volume (MCV) (121.2 ± 0.36), mean corpuscular hemoglobin (MCH) (41.3 ± 0.3) and mean corpuscular hemoglobin concentration (MCHC) (41.06 ± 0.072) was significantly higher at 96 h (P

OBJECTIVE: To determine the frequency and causes of maternal near miss and mortality among pregnant women. METHODS: This cross-sectional study was conducted Jan 2016 - Dec 2018. All near miss cases, admitted in Gynecology department of Services Hospital Lahore during the study period, were prospectively recruited. WHO criteria was used to identify maternal near miss cases. Primary outcome measures were frequency and causes of near miss and maternal mortality to near miss ratio. Secondary outcome measures were delays, need for massive blood transfusion, ICU admission, obstetric hysterectomy and hospital stay> 7 days. RESULTS: During the study period, there were 10,739 live births, 305 near miss cases and 29 maternal deaths. Frequency of near miss was 28.4/ 1000 live births and maternal mortality to near miss ratio was 1:10.5. There were 215(70.4%) unbooked patients and 23(79.3%) of them died (p

OBJECTIVES: The aim of this study was to determine the prevalent aerobic vaginal bacteria and their antibiogram to commonly prescribed antibiotics for the treatment of aerobic vaginitis (AV). METHODOLOGY: A total of 200 high vaginal swabs (HVS) samples were collected from different AV suspected patients visiting Khyber Teaching Hospital (KTH) and processed for identification of bacterial isolates followed by antibiotic susceptibility patterns as per CLSI protocols. RESULTS: Out of 200 clinical samples, 70 (35%) HVS isolates yielded bacterial growth. Of the isolates, E.coli was the common pathogen 36 (51.4%) followed by S.aureus 20 (28.5%), Enterobacter spp 08 (11.4%), Pseudomonas spp 04 (5.7%) and Citrobacter spp 02 (2.8%). The highest prevalence was observed in the age group of 21-35 years (31.4%) followed by age groups 16-20 years (25.7%) and 26-30 years. S.aureus isolates (n=20) were resistant to ciprofloxacin (90%), cephradine (70%), erythromycin (70%), gentamicin (50%) and cefotaxime (40%) while 1 (5%) of each isolate was resistant to methicillin and vancomycin. Majority of the gram-negative isolates (n=50) were resistant to cotrimoxazole, cephalosporins, quinolones, aminoglycosides and susceptible to carbapenems, tigecycline, sulbactam and tazobactam. CONCLUSION: Aerobic vaginitis should be treated very selectively in order not to kill the beneficial bacteria. Before treating AV, the causative agents should be accurately identified and tested for drug susceptibility patterns and empirical antibiotic therapy should be avoided.

The book titled ‘UN Peacekeeping in Africa: A Critical Examination and Recommendations for Improvement’, authored by Kwame Akonor,2 lays out a significant overview of the UN peace operations in the African region. The argument of this book revolves around those circumstances where the peacekeepers themselves become the perpetrators of crime; thereby, this book represents the ‘dark side’ of the U.N. peacekeeping, which remains a fundamental problem in jeopardizing the future of peacekeeping. By reviewing the reports and publications on UN Preventing Sexual Exploitation and Abuse (PSEA),3 Akonor discusses four factors regarding why abuses occur and why the abusers barely face criminal prosecution. The paramount factor in the book is the prevailing hyper-masculinity in the military culture and the tendency to protect each other against civilian complaints. The other two factors include the economic deprivation and variation in the legal and cultural system among the Troop Contributing Countries (TCC). Finally, the physical and psychological repercussions of conflict on civilians expose them to Sexual Exploitation and Abuse (SEA).

Purpose – The study aims to examine the impact of website design, e-fulfillment, e-service and e-security on overall e-service quality and its impact on brand attachment. Design/methodology/approach – Data of 425 respondents was collected from the internet banking industry users through an online survey. Further, PLS-SEM was employed to analyze the data. Findings – Results indicate that the impact of e-security, e- customer service, and e-fulfillment on overall e-customer service quality was supported. In contrast, the impact of website design was not supported. Further, overall, e-service quality also has a significant impact on brand attachment. Originality/value – This study suggested and tested a brand attachment framework for the banking industry to support strategy formulation for managers.

The current study was conducted to quantify zinc in nail samples of iron welders from different areas of Lahore, Pakistan. This study intended to assess nutritional deficiencies of zinc in welders. As nails serve a beneficial biomarker of concentrations of trace elements, hence in the present study the nails of welders were used for monitoring. The total number of nail samples collected from workers of iron welding shops, were 40. In a standardized washing procedure the nail samples were scrapped and cleaned of dust particles with nonionic detergent (Triton X-100) and then nail samples were digested afterwards in acid mixture. The concentration of zinc was evaluated by atomic absorption spectrophotometer. The results revealed that concentration of zinc in nail samples ranged 0.297 – 1.718 mg/kg and averaged at 0.88±0.39 mg/kg which is below the ideal zinc levels in nail samples. Correlation of zinc (mg/kg) was significant with age (0.214< 0.5), weight (0.320< 0.5) and Body Mass Index (0.268< 0.5) of the welders, while a weak correlation of zinc (mg/kg) was found with height (0.042< 0.5) of the welders.

Evrim Gul,1 Ebru Celik Kavak2 1Department of Emergency Medicine, Elazig Education and Research Hospital, Elazig, Turkey; 2Department of Obstetrics and Gynecology, School of Medicine, Firat University, Elazig, Turkey Purpose: Primary dysmenorrhea (PD) is a common cause of pelvic pain that can cause limitations in daily activities. Treatment options sometimes result in failure, suggesting that different mechanisms may be effective in etiopathogenesis. Eosinophils are cells that are present in endometrium only in the perimenstrual period. The aim of this study was to evaluate the levels of eotaxin, a potent eosinophilic chemoattractant, in patients with PD.Patients and methods: Thirty patients with PD and thirty healthy women were included in the study. Venous blood sample of 10 mL was collected from each participant. Blood samples were taken in the first 2 days of the menstrual cycle at any period of the day. Serum eotaxin levels were determined by enzyme-linked immunofluorescence assay.Results: There were no statistically significant differences between the demographic properties of groups in terms of age and body mass index. Eotaxin levels were significantly different in patients with PD than the control subjects (p=0.012).Conclusion: Detection of different levels of eotaxin in patients with PD may be a new and important step in determining the factors contributing to the pathogenesis of dysmenorrhea. Keywords: primary dysmenorrhea, eotaxin, eosinophil, ELISA, etiopathogenesis

Aim: A functional food, herbal jam, developed using Phyllanthus emblica (Amla fruit), Moringa oliefera (Moringa) leaves powder and Stevia rebaudiana (natural sweetener) used as sugar replacer to make low caloric jam that can boost up immunity against COVID-19. Stevia present in the jam made it suitable for diabetic patients. Experimental: A control was developed by replacing stevia with sugar with same composition. The ratios of amla and moringa were altered and the best one was selected on the bases of sensory evaluation using 9-point headonic scale. The jams were characterized at different storage days to check the stability and nutritional composition by carrying proximate analysis and mean values were compared. Results: The energy value calculations showed significant difference between the control jam (sugar based) & optimized jam (stevia based). Sensory evaluation concludes high score value of sugar based jam. Microbial analysis was done using Total Plate Count (TPC) and Yeast Mold Count (YMC). Moreover, studies are required to improve the textural attributes of stevia based jam. [ABSTRACT FROM AUTHOR]

Atherosclerosis is characterised by the accumulation of fatty deposits and plaque as a result of a continuously high level of low-density lipoprotein cholesterol (LDL-C) in the blood. The primary objective of this research is to assess the current status of knowledge, research endeavours and developmental trajectories about proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors in correlation with atherosclerosis treatment. Additionally, this study aims to compile bibliometric and scientometric investigations within this domain through rigorous scientometric analysis. Analysing the bibliometric landscape and global research trends associated with PCSK9 inhibitors can contribute valuable insights into comprehending atherosclerosis. This is exemplified by examining publications within the Web of Science Core Collection (WOSCC) database from 2008 to 2022. Citespace was used for frequency, co-occurrence, co-citation, grouping and burst analysis, and Microsoft Excel was used to manage descriptive datasets. Eight hundred eighty-five publications available from WOSCC database between the years 2008 and 2022 were extracted and examined. Over the period, 3,138 collaborating institutions from 87 countries, a staggering 7,750 writers involved and 325 distinct journals published about PCSK9 inhibitors studies. Among authors, Sabatine et al. and the journal The New England Journal of Medicine has had the most significant impact. Lipid-lowering therapy and bempedoic acid are the most prominent topical clusters associated with PCSK9 inhibitors, and the most often used keywords are efficacy, safety and PCSK9 inhibitors. We believe this is the first comprehensive analysis of PCSK9 inhibitors research and publications conducted using Scientometric. These results demonstrate the nascence of PCSK9 inhibitors research. They may encourage a wide range of stakeholders, particularly early career researchers from various disciplines, to work together in the future. [ABSTRACT FROM AUTHOR]