Health-related quality of life among people with diabetes: A cross-sectional study in Hail region, Saudi Arabia ​.

BACKGROUND: Diabetes Mellitus is a serious and expanding health problem, together with the issues of health- related quality of life (HRQoL). This further puts pressure on the government to allocate more funds for public healthcare. OBJECTIVES: This study was devised to evaluate the health-related quality of life of people living with diabetes in Hail region of Saudi Arabia. METHODS: This cross-sectional research was carried out at eight locations in the Hail region of Saudi Arabia between 21st March-20th May 2022 using the adapted version of the Euro QoL-5 dimension (EQ-5D-3L) questionnaire. A multistage random sample approach was used to choose the diabetes clinics, and data collectors approached the participants in the waiting areas to collect the information. The data were analyzed using logistic regression analysis, Mann-Whitney test, and Kruskal-Wallis tests in IBM SPSS statistics 21.0. RESULTS: The mean HRQoL score was 0.71±0.21 with a visual analog score of 68.4±16.2. Despite having much higher levels of quality of life in terms of self-care (85.8%), regular activity (73.8%) and anxiety (71.8%), nearly one half of the people reported moderate pain or discomfort, and more than one third reported having moderate mobility issues. In general, the quality of life for women was poorer than for men. Individuals with diabetes who were unmarried, young, educated, financially secure, and taking only oral medication had much improved HRQoL. The Euro QoL of people with diabetes patients were significantly influenced by gender, marital status, age, education, employment and treatment modality (p-values < 0.05), whereas only treatment modality had a significant impact on the patients' visual analogue measures (p-values < 0.05). CONCLUSIONS: The HRQoL of people with diabetes in Hail region was moderate in general, with pain and mobility issues being particularly prevalent. Gender, marital status, age, education, employment and type of medication therapy are significant predictors of HRQoL of patients with diabetes. Hence, planning and programs to enhance the HRQoL of people with diabetes, especially women is recommended.

Exposure to secondary traumatic stress and its related factors among emergency nurses in Saudi Arabia: a mixed method study.

BACKGROUND: Emergency department (ED) nurses are exposed to the risk of secondary traumatic stress (STS), which poses a threat not only to nurses' health and psychological well-being but also adversely affects the execution of their professional duties. The quality and outcome of their nursing services are negatively affected by STS. PURPOSE: The purpose of this study is to comprehensively investigate the prevalence and intensity of Secondary Traumatic Stress (STS) among Emergency Department (ED) nurses. It aims to identify and analyze the socio-demographic, occupational, and psychological factors that influence the severity and variation of STS experienced by these nurses. METHODS: The study utilized a sequential explanatory mixed methods approach, including two phases. Phase 1 employed a cross-sectional study design, utilizing a convenience sample of 181 nurses to explore the levels of STS and the factors associated with it. Following this, Phase 2 was structured as a qualitative descriptive study, which involved conducting semi-structured interviews with a purposefully selected group of ten ED nurses. Data collection took place at three major hospitals in Saudi Arabia during the period from January to June 2022. RESULTS: A total of 181 participants were included in the study. The mean STSS score reported by the nurses was 51 (SD = 13.23) out of the maximum possible score of 85, indicating severe STS among ED nurses. Factors associated with an increase in the levels of STS among ED nurses included being female, older in age, married, possessing higher education and experience, having a positive relationship with colleagues, receiving organisational support, and dealing with a higher number of trauma cases. Several themes emerged from the qualitative interviews including: ED Characteristics: Dual Impact on STS, Emotional Resonance and Vulnerability, Personal Life Stressors, The Ability to Cope, and Social Support. CONCLUSION AND IMPLICATIONS FOR PRACTICE: Future strategies and interventions targeting STS should be prioritized to effectively manage its impact on ED nurses. It is crucial to develop targeted interventions that address the specific factors contributing to STS, as identified in this study. Additionally, these findings aim to enhance awareness among nursing administrators, managers, and supervisors about the critical factors associated with STS. This awareness is essential for accurately assessing and developing interventions that mitigate STS among nursing staff.

Tuberculous meningitis with stroke: A case report of diagnostic dilemma and therapeutic triumph.

Tuberculous Meningitis (TBM) is a rare manifestation of Mycobacterium tuberculosis infection affecting the meninges. We present a case of a 40-year-old male initially presenting with neurological deficits mimicking ischemic stroke. Despite classic signs, including fever, headache, and neck stiffness, TBM was initially overlooked, leading to delayed treatment. Comprehensive assessment, imaging findings, and characteristic cerebrospinal fluid findings, confirming TBM with tubercular stroke. The patient responded positively to antitubercular therapy and steroids. This case underscores the diagnostic challenges of TBM, emphasizing the need for a broad differential diagnosis, particularly in regions with a high tuberculosis prevalence. Recognition of atypical presentations is crucial for timely intervention and improved outcomes.

Integrated computational approaches for designing potent pyrimidine-based CDK9 inhibitors: 3D-QSAR, docking, and molecular dynamics simulations.

CDK9 is an emerging target for the development of anticancer drugs. The development of CDK9 inhibitors with significant potency had consistently posed a formidable challenge. In the current research, a number of computational methodologies, such as, 3D-QSAR, molecular docking, fingerprint analysis, molecular dynamic (MD) simulations followed by MMGB/PBSA and ADMET studies were used systemically to uncover the binding mechanism of pyrimidine derivatives against CDK9. The CoMFA and CoMSIA models having high q2 (0.53, 0.54) and r2 values (0.96, 0.93) respectively indicating that model could accurately predict the bioactivities of CDK9 inhibitors. Using the R-group exploration technique implemented by the Spark™ by Cresset group, the structural requirements revealed by the contour maps of model were utilized strategically to create an in-house library of 100 new CDK9 inhibitors. Additionally, the compounds from the in-house library were mapped into 3D-QSAR model which predicted pIC50 values comparable to the experimental values. A comparison between 3D-QSAR generated contours and molecular docking conformation of ligands was performed to elucidate the essentials of CDK9 inhibitor design. MD simulations (100 ns) were performed on the selected docked complexes A21, A14 and D98 which contributed in validating the binding interactions. According to the findings of binding free energy analysis (MMGB/PBSA), It was observed that residues CYS106 and GLU107 had a considerable tendency to facilitate ligand-protein interactions via H-bond interactions. The aforementioned findings have the potential to enhance researchers comprehension of the mechanism underlying CDK9 inhibition and may be utilized in the development of innovative and efficacious CDK9 inhibitors.

Measurement of portal vein indices and splenic index by ultrasound and their association with gastroesophageal varices in cirrhosis of liver.

Background and Objectives: Esophageal and gastric fundic varices are common in liver cirrhosis patients. Ultrasound with the Doppler study assesses liver cirrhosis severity, measuring portal vein and splenic indices' association with gastroesophageal varices. Methodology: This study was conducted on 64 subjects with sonographic features of chronic liver disease who were referred for routine follow-up scans. Portal vein diameter, average velocity, splenic index, congestion index (CI), and portal vein area and velocity were measured. Result: Subjects with gastroesophageal varices had significantly larger portal vein diameters (14.7±1.64 mm) compared to those without varices (12.05±1.26 mm) (P<0.05). Conversely, subjects without varices exhibited a higher portal vein velocity of (17.9±0.6 cm/s) than with varices (13.91±2.01 cm/s) (P=0.0005). The splenic index was higher in subjects with varices (1120±494 cm3) than those without varices (419 cm3) (P<0.05). The CI was also higher in subjects with varices. Portal vein velocity showed the highest sensitivity (94%) with a cutoff of 19 cm/s, while the CI had the highest diagnostic accuracy (93.75%) with a cutoff of 0.10 cm xsec. The splenic index demonstrated a sensitivity of 92.85% and diagnostic accuracy of 92.18% with a cutoff of 480 cm3. The splenic index followed by the CI is found to be a better predictor of esophageal varices (area under the curve of 96.8 and 96%, respectively). Conclusion: Ultrasonographic assessment of the portal vein and spleen is a reliable, noninvasive method for predicting gastroesophageal varices in liver cirrhosis. The splenic index and CI have high diagnostic accuracy.

Computed tomographic assessment of risk of anterior skull base injury of adult patients in tertiary care centre: a cross-sectional study.

Background and objectives: Functional endoscopic sinus surgery (FESS) carries the risk of anterior skull base injury. Understanding computed tomography of the paranasal sinuses (CT PNS) and anatomical variations is crucial before surgery. Several classifications, including Kero's, Gera's, and Thailand-Malaysia-Singapore (TMS), assess the risk of skull base injury. The objective was to determine the risk of anterior skull base injury using CT PNS in adult patients. Methods: A study of 188 patients with head and paranasal sinus pathologies used CT scans to measure olfactory fossa depth, the angle between lamina papyracea and horizontal plane, and the distance from the orbital rim to the cribriform plate. Variations were classified using Kero's, Gera's, and TMS classifications. Results: The study involved 188 individuals aged 18-85, with OF depths ranging from 0.1 to 0.52 cm. Kero's Class I was observed in 82.44% and 81.38% of individuals, while distances from orbital floor to cribriform plate and ethmoidal roof ranged from 1.37 to 2.93 cm. TMS Type I was observed in all individuals, and the angle between lateral lamella of the cribriform plate and cribriform plate ranged from 34° to 85°. Gera's Class II was observed in 77.12% and 84.57% of individuals. Conclusion: CT PNS provides important anatomical information for assessing the risk of skull base injury during FESS. Kero's, Gera's, and TMS classifications can be utilized to evaluate this risk. The study findings provide insights into the variations in olfactory fossa depth, distance measurements, and angle, which can aid in preoperative planning and reducing complications during FESS in Nepalese populations.

Prospective quantitative study: Doppler ultrasound in the evaluation of chronic renal allograft disease and correlation with histopathological finding.

Background and Objectives: Renal allograft biopsy is the gold standard for diagnosing chronic allograft nephropathy, but noninvasive methods are needed to avoid unnecessary biopsies. Doppler ultrasonography, particularly the resistive index (RI), correlates with renal allograft dysfunction. This study aims to assess the relationship between renal sonographic parameters and biochemical parameters in diagnosing graft interstitial fibrosis. Methods: The study evaluated 60 renal allograft recipients for sonographic renal morphological features and Doppler indices. The estimated glomerular filtration rate (eGFR) was calculated, and cortical fibrosis after the biopsy was determined using the Banff score. Continuous variables like mean and SD were calculated, and categorical variables were reported using frequencies and proportions. Associations were examined using independent sample t-tests, χ 2tests, and multivariate regression analysis. Results: The mean eGFR was 75.23±25.45 ml/min/1.73 m2. A significant correlation of eGFR with RI (r=0.341, P=0.008) was seen. A significant difference in mean RI (F=10.167; df=2,57; P<0.001) was seen among the histological grades of fibrosis. Among the histological grades of fibrosis, significant differences in RI among mild and moderate (S.E. 0.033, P=0.043), mild and severe (S.E. 0.026, P=0.001) as well as moderate and severe (S.E. 0.036, P=0.029) was seen. Conclusion: Doppler was able to noninvasively predict allograft fibrosis and could be used as a complementary imaging tool during the follow-up of renal allograft patients. Future research is needed to improve evidence, diagnostic criteria, guidelines, and long-term impact.

Metastatic Supraclavicular Lymph Nodes among Patients with Lung Carcinoma in a Tertiary Care Centre: A Descriptive Cross-sectional Study.

Introduction: Metastatic spread of lung cancer to supraclavicular lymph nodes is considered distant metastasis for treatment purposes. Detection of supraclavicular lymph node metastasis in patients with lung cancer serves for tissue diagnosis by itself and also helps avoid more invasive biopsy from the primary lung mass itself. Ultrasonography of the lower neck can detect supraclavicular lymph nodes before they are palpable and can also be used for safe sampling of these lymph nodes. The aim of this study was to find out the prevalence of metastatic supraclavicular lymph nodes among patients with lung carcinoma in a tertiary care centre. Methods: A descriptive cross-sectional study done in a tertiary care center, carried out from 15 September 2019 to 14 September 2020. Ethical approval was obtained from the Institutional Review Committee (Reference number: 84(611)E2/076/077). The study was done among 92 patients with biopsy-proven lung cancer (lung mass or supraclavicular lymph node biopsy) who were referred for evaluation, and/or percutaneous transthoracic biopsy. Convenience sampling method was used. Point estimate and 90% Confidence Interval were calculated. Results: Among 92 patients with proven lung cancer, metastatic supraclavicular lymph nodes were seen in 13 patients (14.10%) (8.17- 19.73, 90% Confidence Interval). Among 13 patients with metastatic lymph nodes, 9 (69.23%) had palpable supraclavicular lymph nodes. The majority 11 (84.61%) had round-shaped lymph nodes. All metastatic lymph nodes showed loss of echogenic fatty hilum. A total of 12 (92.30%) metastatic lymph nodes showed a peripheral disorganized pattern of vascularity. Conclusions: The prevalence of metastatic supraclavicular lymph nodes was lower than in similar studies done in international settings. Keywords: lung cancer; malignancy; ultrasonography.

Infection Prevalence at a Tertiary Hospital in Hail, Saudi Arabia: A Single-Center Study to Identify Strategies to Improve Antibiotic Usage.

Objective: Identifying the burden of disease and the condition of the Saudi population is in high demand from both a surveillance and analytical standpoint. The objective of this study was to determine the most prevalent infections among hospitalized patients (both community-acquired and hospital-acquired), the antibiotics prescribing pattern, and their relationship with patient characteristics like age and gender. Methods: A retrospective study was conducted comprising 2646 patients with infectious diseases or complications admitted to a tertiary hospital in the Hail region of Saudi Arabia. A standardized form was used to collect information from patient's medical records. Demographic data such as age, gender, prescribed antibiotics, and culture-sensitivity tests were included in the study. Results: Males represented about two-thirds (66.5%, n = 1760) of the patients. Most patients (45.9%) who suffered from infectious diseases were between the ages of 20 and 39. The most prevalent infectious ailment was respiratory tract infection (17.65%, n = 467). Furthermore, the most common multiple infectious diseases were gallbladder calculi with cholecystitis (40.3%, n = 69). Similarly, COVID-19 had the greatest impact on people over 60. Beta-lactam antibiotics were the most commonly prescribed (37.6%), followed by fluoroquinolones (26.26%) and macrolides (13.45%). But performing culture sensitivity tests were rather uncommon (3.8%, n = 101). For multiple infections, beta-lactam antibiotics (such as amoxicillin and cefuroxime) were the most commonly prescribed antibiotics (2.26%, n = 60), followed by macrolides (such as azithromycin and Clindamycin) and fluoroquinolones (eg, ciprofloxacin and levofloxacin). Conclusion: Respiratory tract infections are the most prevalent infectious disease among hospital patients, who are primarily in their 20s. The frequency of performing culture tests is low. Therefore, it is important to promote culture sensitivity testing in order to support the prudent use of antibiotics. Guidelines for anti-microbial stewardship programs are also highly recommended.

Vanillin-Based Indolin-2-one Derivative Bearing a Pyridyl Moiety as a Promising Anti-Breast Cancer Agent via Anti-Estrogenic Activity.

The structure-based design introduced indoles as an essential motif in designing new selective estrogen receptor modulators employed for treating breast cancer. Therefore, here, a series of synthesized vanillin-substituted indolin-2-ones were screened against the NCI-60 cancer cell panel followed by in vivo, in vitro, and in silico studies. Physicochemical parameters were evaluated with HPLC and SwissADME tools. The compounds demonstrated promising anti-cancer activity for the MCF-7 breast cancer cell line (GI = 6-63%). The compound with the highest activity (6j) was selective for the MCF-7 breast cancer cell line (IC50 = 17.01 µM) with no effect on the MCF-12A normal breast cell line supported by real-time cell analysis. A morphological examination of the used cell lines confirmed a cytostatic effect of compound 6j. It inhibited both in vivo and in vitro estrogenic activity, triggering a 38% reduction in uterine weight induced by estrogen in an immature rat model and hindering 62% of ER-α receptors in in vitro settings. In silico molecular docking and molecular dynamics simulation studies supported the stability of the ER-α and compound 6j protein-ligand complex. Herein, we report that indolin-2-one derivative 6j is a promising lead compound for further pharmaceutical formulations as a potential anti-breast cancer drug.

Synthesis, Molecular Docking, and Dynamic Simulation Targeting Main Protease (Mpro) of New, Thiazole Clubbed Pyridine Scaffolds as Potential COVID-19 Inhibitors.

Many biological activities of pyridine and thiazole derivatives have been reported, including antiviral activity and, more recently, as COVID-19 inhibitors. Thus, in this paper, we designed, synthesized, and characterized a novel series of N-aminothiazole-hydrazineethyl-pyridines, beginning with a N'-(1-(pyridine-3-yl)ethylidene)hydrazinecarbothiohydrazide derivative and various hydrazonoyl chlorides and phenacyl bromides. Their Schiff bases were prepared from the condensation of N-aminothiazole derivatives with 4-methoxybenzaldehyde. FTIR, MS, NMR, and elemental studies were used to identify new products. The binding energy for non-bonding interactions between the ligand (studied compounds) and receptor was determined using molecular docking against the SARS-CoV-2 main protease (PDB code: 6LU7). Finally, the best docked pose with highest binding energy (8a = -8.6 kcal/mol) was selected for further molecular dynamics (MD) simulation studies to verify the outcomes and comprehend the thermodynamic properties of the binding. Through additional in vitro and in vivo research on the newly synthesized chemicals, it is envisaged that the achieved results will represent a significant advancement in the fight against COVID-19.

Multifaced Assessment of Antioxidant Power, Phytochemical Metabolomics, In-Vitro Biological Potential and In-Silico Studies of Neurada procumbens L.: An Important Medicinal Plant.

This work was undertaken to explore the phytochemical composition, antioxidant, and enzyme-inhibiting properties of Neurada procumbens L. extracts/fractions of varying polarity (methanol extract and its fractions including n-hexane, chloroform, n-butanol, and aqueous fractions). A preliminary phytochemical study of all extracts/fractions, HPLC-PDA polyphenolic quantification, and GC-MS analysis of the n-hexane fraction were used to identify the phytochemical makeup. Antioxidant (DPPH), enzyme inhibition (against xanthine oxidase, carbonic anhydrase, and urease enzymes), and antibacterial activities against seven bacterial strains were performed for biological investigation. The GC-MS analysis revealed the tentative identification of 22 distinct phytochemicals in the n-hexane fraction, the majority of which belonged to the phenol, flavonoid, sesquiterpenoid, terpene, fatty acid, sterol, and triterpenoid classes of secondary metabolites. HPLC-PDA analysis quantified syringic acid, 3-OH benzoic acid, t-ferullic acid, naringin, and epicatechin in a significant amount. All of the studied extracts/fractions displayed significant antioxidant capability, with methanol extract exhibiting the highest radical-scavenging activity, as measured by an inhibitory percentage of 81.4 ± 0.7 and an IC50 value of 1.3 ± 0.3. For enzyme inhibition experiments, the n-hexane fraction was shown to be highly potent against xanthine oxidase and urease enzymes, with respective IC50 values of 2.3 ± 0.5 and 1.1 ± 0.4 mg/mL. Similarly, the methanol extract demonstrated the strongest activity against the carbonic anhydrase enzyme, with an IC50 value of 2.2 ± 0.4 mg/mL. Moreover, all the studied extracts/fractions presented moderate antibacterial potential against seven bacterial strains. Molecular docking of the five molecules ß-amyrin, campesterol, ergosta-4,6,22-trien-3ß-ol, stigmasterol, and caryophyllene revealed the interaction of these ligands with the investigated enzyme (xanthine oxidase). The results of the present study suggested that the N. procumbens plant may be evaluated as a possible source of bioactive compounds with multifunctional therapeutic applications.

Safety profile of COVID-19 vaccines, preventive strategies, and patient management.

INTRODUCTION: Fast-track approval has led to serious concerns on the perception of COVID-19 vaccines' safety among the public. Common adverse drug reactions (ADRs) of COVID-19 vaccines are minor localized reactions, while systemic ADRs have been reported rarely. The serious ADRs include anaphylaxis, vaccine-induced immune thrombotic thrombocytopenia syndrome (VITTS), and reactions related to the pharmaceutical excipients present in the vaccine. A comprehensive review on the safety of COVID-19 vaccines would help in early identification and better management of ADRs. This literature review was conducted using PubMed, Google Scholar, COVID-19 Vaccine package inserts, and UpToDate. AREAS COVERED: This article provides various aspects of COVID-19 vaccine safety and offers strategies to prevent and clinically manage suspected ADRs related to COVID-19 vaccines. EXPERT OPINION: A careful consideration of contraindications and patient education on early identification of serious ADRs are the cornerstones in tackling safety concerns associated with COVID-19 vaccines. Most of the mild ADR cases are manageable with over-the-counter medications, while the serious ones may require physician oversight and hospitalization. It is also mandatory to report all ADRs to the local pharmacovigilance centers, with a higher priority given to the moe significant ones, in order to improve vaccine safety data.

Generic Medicine and Generic Prescribing in Nepal: An Implication for Policymakers.

Generic medicines are being promoted in many countries for their added benefits over branded drugs, such as reduced price, therapeutic equivalence, and convenience to the patients. However, generic prescribing is still not up to the optimum level in Nepal to assure access to cost-effective, quality medicines to the public and to reduce the overall economic burden and practice-related errors of medications. This review aimed to discuss the current scenario of generic medicine, generic prescribing, hurdles on the one hand, and potentials ways in promoting generic medicine usage and generic prescribing in Nepal on the other. Extensive literature on generic medicine usage and generic prescribing practice in Nepal was reviewed. This review found some of the major challenges to be addressed for the proper implementation of generic medicine prescribing, and utilization. These challenges include lack of facilities and competency to assure therapeutic equivalence of different brand-name medicines, lack of understanding about generic medicines among health care providers (HCPs) and the public, and lack of stringent regulation towards promoting generic medicines. Rational pharmaceutical promotion and awareness about generic medication to the medical students are also inevitable towards promoting the practice of generic medicines. The practice of generic medicine and generic prescribing is not possible without the assurance of therapeutically equivalent generic alternatives. The study recommended the prompt effort of the regulatory authority to enforce the generic prescribing and generic substitution policy through strengthening policies, procedures and laboratory testing to assure citizens' right to access to cost-effective, and affordable quality medicine, as the Nepal's National Health and Drug Policy mandated.

Assessment of the Quality of Saudi Patient Information Leaflets (PILs) Based on the Accuracy of Physical Description and Frequency of Solid Dosage Forms.

The physical description of dosage forms is one of the most important considerations in avoiding patient confusion and minimizing medication errors. This study aimed to determine the quality and accuracy of the physical descriptions in patient information leaflets (PILs). This cross-sectional study constituted a total of 200 drugs and PILs that were randomly selected, by pharmacy students, from Al-Dawaa community pharmacies in the Hail region of Saudi Arabia, from January 2021 to July 2021. The drugs and PILs were thoroughly evaluated in accordance with the Gulf Cooperation Council (GCC) guidelines for PILs. The accuracy screening of the total solid dosage forms (capsules + tablets) revealed that 45% showed complete accuracy and compliance, 1.5% showed poor accuracy and compliance, and 53% showed no accuracy and no compliance with the GCC guidelines and the Saudi Food and Drug Authority (SFDA) guidelines. In the frequency test, color, shape, and imprints accounted for 95.6%, 79.1%, and 73.6%, respectively. However, the size of the dosage form was the least (2.2%) used physical description feature. These findings recommend pharmaceutical companies to pay more attention to the written physical description in their PILs. Additionally, the process of PIL approval should be optimized, evaluated, and updated systematically to ensure that they contain the essential information.

The SARS-CoV-2 mutations versus vaccine effectiveness: New opportunities to new challenges.

BACKGROUND: The SARS-CoV-2 coronavirus epidemic is hastening the discovery of the most efficient vaccines. The development of cost-effective vaccines seems to be the only solution to terminate this pandemic. However, the vaccines' effectiveness has been questioned due to recurrent mutations in the SARS-CoV-2 genome. Most of the mutations are associated with the spike protein, a vital target for several marketed vaccines. Many countries were highly affected by the 2nd wave of the SARS-CoV-2, like the UK, India, Brazil and France. Experts are also alarming the further COVID-19 wave with the emergence of Omicron, which is highly affecting the South African populations. This review encompasses the detailed description of all vaccine candidates and COVID-19 mutants that will add value to design further studies to combat the COVID-19 pandemic. METHODS: The information was generated using various search engines like google scholar, PubMed, clinicaltrial.gov.in, WHO database, ScienceDirect, and news portals by using keywords SARS-CoV-2 mutants, COVID-19 vaccines, efficacy of SARS-CoV-2 vaccines, COVID-19 waves. RESULTS: This review has highlighted the evolution of SARS-CoV-2 variants and the vaccine efficacy. Currently, various vaccine candidates are undergoing several phases of development. Their efficacy still needs to check for newly emerged variants. We have focused on the evolution, multiple mutants, waves of the SARS-CoV-2, and different marketed vaccines undergoing various clinical trials and the design of the trials to determine vaccine efficacy. CONCLUSION: Various mutants of SARS-CoV-2 arrived, mainly concerned with the spike protein, a key component to design the vaccine candidates. Various vaccines are undergoing clinical trial and show impressive results, but their efficacy still needs to be checked in different SARS-CoV-2 mutants. We discussed all mutants of SARS-CoV-2 and the vaccine's efficacy against them. The safety concern of these vaccines is also discussed. It is important to understand how coronavirus gets mutated to design better new vaccines, providing long-term protection and neutralizing broad mutant variants. A proper study approach also needs to be considered while designing the vaccine efficacy trials, which further improved the study outcomes. Taking preventive measures to protect from the virus is also equally important, like vaccine development.

Assessment of Parents' Perceptions of Childhood Immunization: A Cross-Sectional Study from Pakistan.

Immunization is one of the most cost-effective public health interventions, with considerable impacts on people's health. Parents' perception of their knowledge, attitude, and satisfaction is an important factor, as they may be targeted by interventions for better immunization coverage. Therefore, this study aimed to assess parents' perceptions in terms of their knowledge, attitude, and satisfaction of the immunization of their children aged less than two years of age, in two cities of Pakistan. A descriptive cross-sectional study was conducted in the vicinity of Rawalpindi and Islamabad from March to August 2019. A semi-structured questionnaire was used for the data collection on a convenient sample of parents. The questionnaire was hand-delivered to the parents by data collectors. Descriptive and inferential statistics were used for data analysis via SPSS version 22. A total of n = 382 respondents were included in the data analysis. Statistically significant differences were found between the parents' knowledge scores and their education levels and monthly incomes (p < 0.05). Parents with master's education degrees and low monthly incomes had significantly better knowledge (p < 0.05). Additionally, 96.85% of the respondents believed that child immunization was important. In addition, more than half of the respondents (57.58%) thought that the affordability of vaccines was a principal factor for delays in immunization. Although the parents' knowledge regarding the immunization of their children was not adequate, they had positive perceptions toward it.

Fabrication and Characterization of Paclitaxel and Resveratrol Loaded Soluplus Polymeric Nanoparticles for Improved BBB Penetration for Glioma Management.

Gliomas are one of the prominent cancers of the central nervous system with limited therapeutic modalities. The present investigation evaluated the synergistic effect of paclitaxel (PAX) and resveratrol (RESV)-loaded Soluplus polymeric nanoparticles (PNPs) against glioma cell lines along with in vivo pharmacokinetics and brain distribution study. PAX-RESV-loaded PNPs were prepared by the thin film hydration technique and optimized for different dependent and independent variables by using DoE (Design-Expert) software. The in vitro physiochemical characterization of prepared PAX-RESV-loaded PNPs exhibited appropriate particle size, PDI and % encapsulation efficiency. Cytotoxicity assay revealed that PTX-RESV loaded PNPs had a synergistic antitumor efficacy against C6 glioma cells compared with single and combined pure drugs. Finally, the pharmacokinetic and brain distribution studies in mice demonstrated that the PNPs significantly enhanced the bioavailability of PTX-RESV PNPs than pure PAX and RESV. Thus, the study concluded that PAX-RESV PNPs combination could significantly enhance anti-glioma activity, and this could be developed into a potential glioma treatment strategy.

Current Status of Brain Tumor in the Kingdom of Saudi Arabia and Application of Nanobiotechnology for Its Treatment: A Comprehensive Review.

OBJECTIVE: Brain tumors are the most challenging of all tumors and accounts for about 3% of all cancer allied deaths. The aim of the present review is to examine the brain tumor prevalence and treatment modalities available in the Kingdom of Saudi Arabia. It also provides a comprehensive analysis of the application of various nanotechnology-based products for brain cancer treatments along with their prospective future advancements. METHODS: A literature review was performed to identify and summarize the current status of brain cancer in Saudi Arabia and the scope of nanobiotechnology in its treatment. RESULTS: Depending upon the study population data analysis, gliomas, astrocytoma, meningioma, and metastatic cancer have a higher incidence rate in Saudi Arabia than in other countries, and are mostly treated in accordance with conventional treatment modalities for brain cancer. Due to the poor prognosis of cancer, it has an average survival rate of 2 years. Conventional therapy includes surgery, radiotherapy, chemotherapy, and a combination thereof, but these do not control the disease's recurrence. Among the various nanomaterials discussed, liposomes and polymeric nanoformulations have demonstrated encouraging outcomes for facilitated brain cancer treatment. CONCLUSIONS: Nanomaterials possess the capacity to overcome the shortcomings of conventional therapies. Polymer-based nanomaterials have shown encouraging outcomes against brain cancer when amalgamated with other nano-based therapies. Nonetheless, nanomaterials could be devised that possess minimal toxicity towards normal cells or that specifically target tumor cells. In addition, rigorous clinical investigations are warranted to prepare them as an efficient and safe modality for brain cancer therapy.

Mutagenesis, Hydrogen-Deuterium Exchange, and Molecular Docking Investigations Establish the Dimeric Interface of Human Platelet-Type 12-Lipoxygenase.

It was previously shown that human platelet 12S-lipoxygenase (h12-LOX) exists as a dimer; however, the specific structure is unknown. In this study, we create a model of the dimer through a combination of computational methods, experimental mutagenesis, and hydrogen-deuterium exchange (HDX) investigations. Initially, Leu183 and Leu187 were replaced by negatively charged glutamate residues and neighboring aromatic residues were replaced with alanine residues (F174A/W176A/L183E/L187E/Y191A). This quintuple mutant disrupted both the hydrophobic and π-π interactions, generating an h12-LOX monomer. To refine the determinants for dimer formation further, the L183E/L187E mutant was generated and the equilibrium shifted mostly toward the monomer. We then submitted the predicted monomeric structure to protein-protein docking to create a model of the dimeric complex. A total of nine of the top 10 most energetically favorable docking conformations predict a TOP-to-TOP dimeric arrangement of h12-LOX, with the α-helices containing a Leu-rich region (L172, L183, L187, and L194), corroborating our experimental results showing the importance of these hydrophobic interactions for dimerization. This model was supported by HDX investigations that demonstrated the stabilization of four, non-overlapping peptides within helix α2 of the TOP subdomain for wt-h12-LOX, consistent with the dimer interface. Most importantly, our data reveal that the dimer and monomer of h12-LOX have distinct biochemical properties, suggesting that the structural changes due to dimerization have allosteric effects on active site catalysis and inhibitor binding.