Design and construction of novel pyridine-pyrimidine hybrids as selective COX-2 suppressors: anti-inflammatory potential, ulcerogenic profile, molecular modeling and ADME/Tox studies.

NSAIDs represent a mainstay in pain and inflammation suppression, and their actions are mainly based on inhibiting COX-1 and COX-2 enzymes.Due to the adverse effects of these drugs, especially on the stomach and heart, scientists efforts have been directed to manufacture selective COX-2 without cardiovascular side effects and with minimal effects on the stomach. The cardiovascular side effects are thought to be related to the chemical composition rather than mechanism of action of these drugs.Novel pyridopyrimidines, 9a-j, were prepared and their chemical structures were confirmed by NMR, mass and IR Spectra, and elemental analysis. The effect of the 9a-j compounds on COX-1 and COX-2 was assessed and it was found that 2-hydrazino-5-(4-methoxyphenyl)-7-phenyl-3H-pyrido[2,3-d)pyrimidin-4-one (9d) was the most potent COX-2 inhibitor (IC50 = 0.54 uM) compared to celecoxib (IC50 = 1.11 uM) with selectivity indices of 6.56 and 5.12, respectively.The in vivo inhibition of paw edema of novel compounds 9a-j was measured using carrageenan-induced paw edema method, and that 2-hydrazino-5-(4-methoxyphenyl)-7-phenyl-3H-pyrido[2,3-d)pyrimidin-4-one (9d) showed the best inhibitory activity in comparison with the other compounds and celecoxib.The gastroprotective effect of the potent derivatives 9d, 9e, 9f, 9 g and 9h was investigated. 2-Hydrazino-5-(4-methoxyphenyl)-7-phenyl-3H-pyrido[2,3-d)pyrimidin-4-one (9d) and 7-(chlorophenyl)-hydrazino-5-(4-methoxyphenyl)-3H-pyrido[2,3-d)pyrimidin-4-one (9e) showed ulcer indices comparable to celecoxib (1 and 0.5 vs 0.5, respectively). Docking studies were carried out and they confirmed the mechanistic action of the designed compoundsCommunicated by Ramaswamy H. Sarma.

Evaluation of Outreach of Community Pharmacists in Public Health Services in Al-Jouf Region of Saudi Arabia: Findings and Implications.

BACKGROUND: Diversifying the conventional role of community pharmacists from dispensing to involvement in public health services could help in optimized patient care and ultimately good health practices. The current study aimed to ascertain the involvement of community pharmacists, barriers to involvement, their preparedness towards the provision of public health services in the future, and effective strategies to improve their existing role, especially in remote areas of the Kingdom of Saudi Arabia. METHODS: A cross-sectional study was conducted in the Al-Jouf region of Saudi Arabia (KSA), between January to April 2023. A convenient sampling technique was used to recruit community pharmacists (CPs). A self-designed and validated questionnaire was used for data collection. The relative importance index (RII) was utilized to rank the barriers to participation in public health services. Data were subjected to statistical analysis using SPSS. RESULTS: This study recruited 119 participants (mean age: 32.2 ± 7.9; male gender: 67.2%). Of these, 91.6% were involved in the provision of public health services at community pharmacies. Majority of CPs (n = 114/119, 95.8%) provided drug use-related written information to the patients, and the least practiced service was screening of dyslipidemia (n = 81; 68.1%). According to RII, the major barrier was the lack of time given by patients (RII: 0.812). Overall, the majority of the pharmacists (n = 94/119; 79%) were willing to provide public health services. Most of the CPs reported that empowerment through education and awareness (n = 100/119; 84%) is most effective strategy to enhance the involvement of pharmacists in public health services. CONCLUSIONS: Findings of the present study underscored the adequate participation of community pharmacists in public health activities. Further studies are required in other remote regions of KSA to get a clear insight into the overall participation of community pharmacists in public health services and generalize the findings.

Appraisal of anti-inflammatory and immunomodulatory potential of ramipril against Freund's adjuvant-provoked arthritic rat model.

Because of evident role of renin-angiotensin system in the etiology of rheumatoid arthritis, the current study's objective was to assess the anti-arthritic efficacy of ramipril through CFA-instigated arthritic model. The drug has been shown to have anti-inflammatory potential. CFA-instigated arthritic model assessed the anti-arthritic efficacy of ramipril by estimating different parameters, including paw volume, arthritic index scoring, haematological and biochemical attributes, histological and radiographic analyses, and various cytokines level. Ramipril significantly (p < 0.001) reduced paw volume and the arthritic index especially at the dose of 4mg/kg. The biochemical and haematological changes were likewise restored to normal by ramipril administration with an increase in anti-inflammatory cytokines while reducing pro-inflammatory cytokines level. Ramipril's ability to prevent arthritis by preserving the normal architecture of arthritis-induced joints is further supported by radiographic and histological investigation. The study's findings demonstrated ramipril's considerable anti-arthritic activity. To identify the precise mechanism of action, however, thorough mechanistic studies are still needed.

Biochemical association of regulatory variant of KLF14 genotype in the pathogenesis of cardiodiabetic patients.

Background and purpose: The study focuses on examining the relationship between a single nucleotide polymorphism (SNP) in KLF14 rs4731702 and risk of type 2 diabetes mellitus (T2DM) and dyslipidemia in different ethnic populations. The purpose of this study was to evaluate the association between KLF14 rs4731702 and serum lipid profile and to determine the frequency distribution of KLF14 rs4731702 among T2DM and cardiometabolic patients. Methods: A total of 300 volunteers were recruited, consisting of three groups: 100 healthy individuals, 100 individuals diagnosed with T2DM, and 100 individuals diagnosed with cardiometabolic disorders. Biochemical analysis of blood samples was conducted to assess various biomarkers related to glycemic control and lipid profile. This involved measuring levels of glucose, triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and ApoA1. Genotyping analysis was performed to investigate KLF14 rs4731702 polymorphism. The Tetra ARMS-PCR method was employed for genotyping analysis. Results: The results of biochemical profiling revealed a significant association between altered glycemic biomarkers and lipid profile in diseased patients compared to healthy participants. The frequencies of KLF14 rs4731702 alleles and genotypes were compared between the control group and T2DM group. A statistically significant difference was observed, indicating a potential association between KLF14 rs4731702 and T2DM. In the dominant inheritance model of KLF14 rs4731702 SNP, a statistically significant difference [odds ratio (95% confidence interval)] of 0.56 (0.34 -0.96) was found between the control and T2DM subjects. This suggests that the presence of certain genotypes influences the risk of T2DM. In T2DM patients, individuals carrying the C allele exhibited compromised insulin sensitivity, decreased HDL-C and ApoA1 levels, and increased serum glucose, TG, and LDL-C concentrations. Conversely, TT genotype carriers demonstrated increased levels of HDL-C and ApoA1, lower insulin resistance, serum glucose, LDL-C, and TG levels. Conclusion: The study's findings indicate that dyslipidemia in T2DM patients is associated with reduced KLF14 functionality due to CC and CT genotypes, leading to insulin resistance and an increased risk of cardiovascular diseases. Additionally, risk of KLF14 rs4731702 polymorphism was found to increase with age and was more prevalent in female than in male individuals. These insights contribute to understanding genetic factors influencing the development and progression of T2DM and dyslipidemia in different ethnic populations.

COVID-19 self-medication treatment: Media's adverse effect based on people's level of education.

OBJECTIVE: Self-medication has become a major concern among nonmedical professionals during the treatment of COVID-19. Such concerns have been attributed to the adverse effect of information shared via media outlets. Here, a survey was undertaken among nonhealthcare professionals to find out the adverse effect of media on self-medication for treating COVID-19. METHODS: A questionnaire-based survey was conducted electronically among nonmedical professionals (270 respondents). The questionnaire comprised three main components: demographic, education, and factor for self-medication. Statistical analysis of the data was made using analysis of variance to determine the degree of agreement between the response of participants with education below and above graduation. RESULTS AND CONCLUSION: Most of the respondents agreed that they get information about the COVID-19 medicines from different media. However, most of them do not visit the reliable source like World Health Organization (WHO) website to get information about COVID-19. The respondents were aware of the usage of medications such as Remdesvir, azithromycin, vitamins, herbal preparations, paracetamol, and cetirizine for COVID-19. The usage of herbal preparation may be due to their promotion in the media as over the counter drugs (OTC) products. It has been proposed to create more awareness and warning signs for the patients in and around pharmacy and hospital. Media campaign to create awareness for the prevention of COVID-19 spread should also be added with a caution line not to use any medication for treatment without prior consultation with physician. The matter of concern is that only a small fraction of the respondents follow WHO website to get information regarding COVID-19, which mandates to create awareness among the public regarding the role of WHO in healthcare. A significant agreement was noted between below graduates and post-graduates regarding questions such as visiting WHO website and the safety of taking medicine without consulting physician. Media is a contributing factor to self-medication, and measures of caution are highly imperative.

Biochemical Association of MTHFR C677T Polymorphism with Myocardial Infarction in the Presence of Diabetes Mellitus as a Risk Factor.

Myocardial infarction (MI) is a cardiovascular disease that occurs due to the blockage of the coronary artery. Subsequently, cardiac muscles receive a lower oxygen supply, which leads to the death of cardiac muscles. The etiology of MI is linked to various environmental, occupational, and genetic factors. Various studies have been conducted on the polymorphism of genes involved in MI. Previous studies have shown that different variants of the methylene tetrahydrofolate reductase (MTHFR) gene are involved in causing MI by altering the metabolism of folate and homocysteine. However, the genetic polymorphism of MTHFR C677T (rs1801133) and its association with MI in the presence of diabetes mellitus (DM) as a risk factor still needs to be investigated. This study recruited 300 participants who were divided into three groups, i.e., the control, MI, and MI-DM. The blood samples collected from the study participants were subjected to various biochemical tests and their clinical parameters were monitored. MTHFR C677T (rs1801133) genotyping was performed by Tetra ARMS PCR using predetermined primers. The MTHFR C677T (rs1801133) polymorphism was associated with MI in the presence of DM as a risk factor among the participants. The MTHFR C677T (rs1801133) T/T homozygous genotype was found to be significant among MI patients in the presence of DM as a risk factor.

The anticancer and EGFR-TK/CDK-9 dual inhibitory potentials of new synthetic pyranopyrazole and pyrazolone derivatives: X-ray crystallography, in vitro, and in silico mechanistic investigations.

Treatment options for the management of breast cancer are still inadequate. This inadequacy is attributed to the lack of effective targeted medications, often resulting in the recurrence of metastatic disorders. Cumulative evidence suggests that epidermal growth factor receptor (EGFR-TK) and cyclin-dependent kinases-9 (CDK-9) overexpression correlates with worse overall survival in breast cancer patients. Pyranopyrazole and pyrazolone are privileged options for the development of anticancer agents. Inspired by this proven scientific fact, we report here the synthesis of two new series of suggested anticancer molecules incorporating both heterocycles together with their characterization by IR, 1H NMR, 13C NMR, 13C NMR-DEPT, and X-ray diffraction methods. An attempt to get the pyranopyrazole-gold complexes was conducted but unexpectedly yielded benzylidene-2,4-dihydro-3H-pyrazol-3-one instead. This unexpected result was confirmed by X-ray crystallographic analysis. All newly synthesized compounds were assessed for their anti-proliferative activity against two different human breast cancer cells, and the obtained results were compared with the reference drug Staurosporine. The target compounds revealed variable cytotoxicity with IC50 at a low micromolar range with superior selectivity indices. Target enzyme EGFR-TK and CDK-9 assays showed that compounds 22 and 23 effectively inhibited both biological targets with IC50 values of 0.143 and 0.121 µM, respectively. Molecular docking experiments and molecular dynamics simulation were also conducted to further rationalize the in vitro obtained results.Communicated by Ramaswamy H. Sarma.

Surveillance of Side Effects after Two Doses of COVID-19 Vaccines among Patients with Comorbid Conditions: A Sub-Cohort Analysis from Saudi Arabia.

Background: Individuals with underlying chronic illnesses have demonstrated considerable hesitancy towards COVID-19 vaccines. These concerns are primarily attributed to their concerns over the safety profile. Real-world data on the safety profile among COVID-19 vaccinees with comorbid conditions are scarce. This study aimed to ascertain the side-effects profile after two doses of COVID-19 vaccines among chronic-disease patients. Methodology: A cross-sectional questionnaire-based study was conducted among faculty members with comorbid conditions at a public educational institute in Saudi Arabia. A 20-item questionnaire recorded the demographics and side effects after the two doses of COVID-19 vaccines. The frequency of side effects was recorded following each dose of vaccine, and the association of the side-effects score with the demographics was ascertained through appropriate statistics. Results: A total of 204 patients with at least one comorbid condition were included in this study. A total of 24 side effects were reported after the first dose and 22 after second dose of the COVID-19 vaccine. The incidence of at least one side effect was 88.7% and 95.1% after the first and second doses of the vaccine, respectively. The frequent side effects after the first dose were pain at the injection site (63.2%), fatigue (58.8%), fever (47.5%), muscle and joint pain (38.7%), and headache (36.3%). However, pain at the injection site (71.1%), muscle and joint pain (62.7%), headache (49.5%), fever (45.6%), and stress (33.3%) were frequent after the second dose. The average side-effects score was 4.41 ± 4.18 (median: 3, IQR: 1, 6) and 4.79 ± 3.54 (median 4, IQR: 2, 6) after the first and second dose, respectively. Female gender, diabetes mellitus, hypertension, hyperlipidemia, comorbidity > 2, family history of COVID-19, and the AstraZeneca vaccine were significantly associated with higher side-effect scores. Only 35.8% of study participants were satisfied with the safety of COVID-19 vaccines. Conclusions: Our analysis showed a high proportion of transient and short-lived side effects of Pfizer and AstraZeneca vaccines among individuals with chronic illnesses. However, the side-effects profile was comparable with the safety reports of phase 3 clinical trials of these vaccines. The frequency of side effects was found to be associated with certain demographics, necessitating the need for further investigations to establish a causal relationship. The current study's findings will help instill confidence in the COVID-19 vaccines among people living with chronic conditions, overcome vaccine hesitancy, and increase vaccine coverage in this population.

Barriers and facilitators of childhood COVID-19 vaccination among parents: A systematic review.

Background: The acceptance of vaccination against COVID-19 among parents of young children plays a significant role in controlling the current pandemic. A wide range of factors that influence vaccine hesitancy in adults has been reported worldwide, but less attention has been given to COVID-19 vaccination among children. Vaccine hesitancy is considered a major challenge in achieving herd immunity, and it is more challenging among parents as they remain deeply concerned about their child's health. In this context, a systematic review of the current literature is inevitable to assess vaccine hesitancy among parents of young children to ensure a successful ongoing vaccination program. Method: A systematic search of peer-reviewed English literature indexed in Google Scholar, PubMed, Embase, and Web of science was performed using developed keywords between 1 January 2020 and August 2022. This systematic review included only those studies that focused on parental concerns about COVID-19 vaccines in children up to 12 years without a diagnosis of COVID-19. Following PRISMA guidelines, a total of 108 studies were included. The quality appraisal of the study was performed by Newcastle-Ottawa Scale (NOS). Results: The results of 108 studies depict that vaccine hesitancy rates differed globally with a considerably large number of factors associated with it. The highest vaccine hesitancy rates among parents were reported in a study from the USA (86.1%) and two studies from Saudi Arabia (>85%) and Turkey (89.6%). Conversely, the lowest vaccine hesitancy rates ranging from 0.69 and 2% were found in two studies from South Africa and Switzerland, respectively. The largest study (n = 227,740) was conducted in Switzerland while the smallest sample size (n = 12) was represented by a study conducted in the USA. The most commonly reported barriers to childhood vaccination were mothers' lower education level (N = 46/108, 43%), followed by financial instability (N = 19/108, 18%), low confidence in new vaccines (N = 13/108, 12%), and unmonitored social media platforms (N = 5/108, 4.6%). These factors were significantly associated with vaccine refusal among parents. However, the potential facilitators for vaccine uptake among respondents who intended to have their children vaccinated include higher education level (N = 12/108, 11%), followed by information obtained through healthcare professionals (N = 9/108, 8.3%) and strong confidence in preventive measures taken by the government (N = 5/81, 4.6%). Conclusion: This review underscores that parents around the globe are hesitant to vaccinate their kids against COVID-19. The spectrum of factors associated with vaccine hesitancy and uptake varies across the globe. There is a dire need to address vaccine hesitancy concerns regarding the efficacy and safety of approved vaccines. Local context is inevitable to take into account while developing programs to reduce vaccine hesitancy. There is a dire need to devise strategies to address vaccine hesitancy among parents through the identification of attributing factors.

Estimation of Psychological Impairment and Coping Strategies during COVID-19 Pandemic among University Students in Saudi Arabia: A Large Regional Analysis.

BACKGROUND: The COVID-19 pandemic and associated restrictive measures have substantially affected educational processes around the globe, resulting in psychological distress among students. The mental health of students in higher education is of paramount importance, and the COVID-19 pandemic has brought this vulnerable population into renewed focus. In this context, the evaluation of students' mental health at educational institutes has gained invaluable popularity during the COVID-19 pandemic. This study aimed to ascertain the psychological health and coping strategies among students from a higher education institute in Saudi Arabia. METHODS: An online study instrument was used to assess anxiety (Generalized Anxiety Disorder-7, GAD-7), depression (Patient Health Questionnaire-9, PHQ-9), post-traumatic stress disorder-PTSD (Impact of Event Scale-Revised, IES-R) and coping strategies (Brief-COPE). The severity of the psychological distress was classified as per the scoring criteria and correlated with demographics using appropriate statistical methods. RESULTS: Of 1074 students (age 21.1 ± 2.1 years), 12.9% and 9.7% had severe anxiety and depression, respectively. The mean anxiety and depression scores were 7.50 ± 5.51 and 9.31 ± 6.72, respectively. About one-third (32%) of students reported suicidal ideation, with 8.4% students having such thoughts nearly every day. The average PTSD score was 21.64 ± 17.63, where avoidance scored higher (8.10 ± 6.94) than intrusion and hyperarousal. There was no association of anxiety, depression and PTSD score with the demographics of the study participants. Religious/spiritual coping (5.43 ± 2.15) was the most adoptive coping mechanism, followed by acceptance (5.15 ± 2.10). Male students were significantly (p < 0.05) associated with active copings, instrumental support, planning, humor, acceptance and religious coping. Substance use was the least adopted coping strategy but practiced by a considerable number of students. CONCLUSIONS: The long-lasting pandemic situation, onerous protective measures and uncertainties in educational procedures have resulted in a high prevalence of psychological ailments among university students, as indicated in this study. These findings accentuate the urgent need for telepsychiatry and appropriate population-specific mental health services to assess the extent of psychological impairment and to leverage positive coping behaviors among students.

Incidence, risk factors and outcomes of acute kidney injury among COVID-19 patients: A systematic review of systematic reviews.

The COVID-19 associated acute kidney injury (CAKI) has emerged as a potential intricacy during the management of patients. Navigating the rapidly growing body of scientific literature on CAKI is challenging, and ongoing critical appraisal of this complication is essential. This study aimed to summarize and critically appraise the systematic reviews (SRs) on CAKI to inform the healthcare providers about its prevalence, risk factors and outcomes. All the SRs were searched in major databases (PubMed, EMBASE, Web of Science) from inception date to December 2021. This study followed SR of SRs methodology, all the records were screened, extracted and subjected to quality assessment by assessing the methodological quality of systematic reviews (AMSTAR-2). The extracted data were qualitatively synthesized and tabulated. This review protocol was registered in PROSPERO (CRD42022299444). Of 3,833 records identified; 42 SRs were included in this overview. The quality appraisal of the studies showed that 17 SRs were of low quality, while 8 moderate and 17 were of high-quality SRs. The incidence of CAKI ranged from 4.3% to 36.4% in overall COVID-19 patients, 36%-50% in kidney transplant recipients (KTRs), and up to 53% in severe or critical illness. Old age, male gender, cardiovascular disease, chronic kidney disease, diabetes mellitus and hypertension were frequently reported risk factors of CAKI. The need of renal replacement therapy (RRT) was up to 26.4% in overall COVID-19 patients, and 39% among those having CAKI. The occurrence of acute kidney injury (AKI) was found independent predictor of death, where mortality rate among CAKI patients ranged from 50% to 93%. This overview of SRs underscores that CAKI occurs frequently among COVID-19 patients and associated with high mortality, need of RRT and adverse outcomes. However, the confidence of these results is moderate to low which warrants the need of more SRs having established methodological standards. Systematic review registration: [https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=299444], identifier [CRD42022299444].

Evaluation of Conspiracy Beliefs, Vaccine Hesitancy, and Willingness to Pay towards COVID-19 Vaccines in Six Countries from Asian and African Regions: A Large Multinational Analysis.

Vaccination protects people from serious illness and associated complications. Conspiracy theories and misinformation on vaccines have been rampant during the COVID-19 pandemic and are considered significant drivers of vaccine hesitancy. Since vaccine hesitancy can undermine efforts to immunize the population against COVID-19 and interferes with the vaccination rate, this study aimed to ascertain the COVID-19-vaccine-related conspiracy beliefs, vaccine hesitancy, views regarding vaccine mandates, and willingness to pay for vaccines among the general population. A web-based, cross-sectional survey was conducted (April−August 2021) among the adult population in six countries (Pakistan, Saudi Arabia, India, Malaysia, Sudan, and Egypt). Participants were recruited using an exponential, non-discriminate snowball sampling method. A validated self-completed electronic questionnaire was used for the data collection. All the participants responded to questions on various domains of the study instrument, including conspiracy beliefs, vaccine hesitancy, and willingness to pay. The responses were scored according to predefined criteria and stratified into various groups. All data were entered and analyzed using SPSS version 22. A total of 2481 responses were included in the study (Pakistan 24.1%, Saudi Arabia 19.5%, India 11.6%, Malaysia 8.1%, Sudan 19.3%, and Egypt 17.3%). There was a preponderance of participants ≤40 years old (18−25 years: 55.8%, 26−40 years: 28.5%) and females (57.1%). The average score of the COVID-19 vaccine conspiracy belief scale (C19V-CBS) was 2.30 ± 2.12 (median 2; range 0−7). Our analysis showed that 30% of the respondents were found to achieve the ideal score of zero, indicating no conspiracy belief. The mean score of the COVID-19 vaccine hesitancy scale (C19V-HS) was 25.93 ± 8.11 (range: 10−50). The majority (45.7%) had C19V-HA scores of 21−30 and nearly 28% achieved a score greater than 30, indicating a higher degree of hesitancy. There was a significant positive correlation between conspiracy beliefs and vaccine hesitancy (Spearman's rho = 0.547, p < 0.001). Half of the study population were against the vaccine mandate. Respondents in favor of governmental enforcement of COVID-19 vaccines had significantly (p < 0.001) lower scores on the C19V-CBS and C19V-HS scale. Nearly 52% reported that they would only take vaccine if it were free, and only 24% were willing to pay for COVID-19 vaccines. A high prevalence of conspiracy beliefs and vaccine hesitancy was observed in the targeted countries. Our findings highlight the dire need for aggressive measures to counter the conspiracy beliefs and factors underlying this vaccine hesitancy.

Evaluation of knowledge and barriers of influenza vaccine uptake among university students in Saudi Arabia; a cross-sectional analysis.

Background: Influenza vaccine hesitancy is a significant threat to global maneuvers for reducing the burden of seasonal and pandemic influenza. This study estimated the vaccine uptake, barriers, and willingness for influenza vaccines among university students in Saudi Arabia. Methods: A cross-sectional survey was conducted among health science (HS) and non-health science (NHS) university students. A 31-item questionnaire was used to ascertain the vaccination rate, barriers, and willingness for the flu vaccine. Results: This study included 790 students (mean age: 21.40 ± 1.94 years), 246 (31.1%) from HS and 544 (68.9%) from NHS disciplines. About 70% did not take flu shots before the arrival of the winter. The mean knowledge score was 7.81 ± 1.96, where 20.4%, 67.6%, and 12% of respondents had good, moderate, and poor knowledge regarding flu vaccines. The relative importance index (RII) analysis showed a lack of recommendation from physicians (51.5%, RI ranked: 1) was a top-ranked barrier to vaccine uptake, followed by negative perceptions and accessibility issues. Only 36.6% of the participants were willing to get vaccinated every year, 70% were willing to receive a vaccine on their doctor's recommendations, and 46% agreed to vaccinate if vaccines were freely available in the university. The knowledge, barriers, and willingness widely varied across students from two disciplines. Conclusions: Our analysis underscored low flu vaccine uptake among university students. In addition, the study participants' knowledge was unsatisfactory, and they were less inclined to receive the flu vaccine in the future. Lack of recommendation from the physicians, negative perceptions towards the flu vaccine, and difficult accessibility were found as significant barriers to the vaccine uptake. A multidimensional approach at educational institutes to cover the knowledge gap and address the barriers curtailing the vaccination rate among students is recommended.

Evaluation of Impact of a Pharmacist-Led Educational Campaign on Disease Knowledge, Practices and Medication Adherence for Type-2 Diabetic Patients: A Prospective Pre- and Post-Analysis.

Type 2 Diabetes mellitus is a major public health concern with an alarming global growth rate. According to the World Health Organization (WHO), Saudi Arabia ranks seventh in the world and second in the Middle East for the largest estimated burden of diabetic cases. Evidence shows that pharmacist-led care programs can be beneficial for the effective treatment of diabetes mellitus. Current study was aimed to evaluate the impact of Pharmacist-Based Diabetic Intervention (PDIM) for Type 2 Diabetes patients on knowledge of the disease, adherence to medications and self-care practices during the first wave of COVID-19. A multi-arm pre-post study was conducted among type 2 diabetic patients from April to October 2021 in Sakaka, Saudi Arabia. Patients were randomly divided into an intervention and a control group. The intervention group received the PDIM, whereas the control group only received the usual care. The pharmacist-based diabetes intervention model consisted of a diabetic educational module and medication improvement strategies. Furthermore, the intervention group also received specific telepharmacy services (calls, messages or emails) to address their medication-related problems, inquire about medication adherence and follow-up. At the end of six months, disease knowledge, self-care practices, and medication adherence score were analyzed. Furthermore, HbA1c and lipid profile were also compared. A total of 109 patients were included in the study. A significant difference was observed in the knowledge score between the intervention and control group (16.89 ± 2.01 versus 15.24 ± 2.03, p-value < 0.001). Similarly, self-care practices also improved in the intervention group as compared to the control group (4.39 ± 1.10 versus 3.16 ± 0.97, p-value < 0.001). Furthermore, the medication adherence and HbA1c significantly improved during between the group analysis (p < 0.05). Our study demonstrates that pharmacist-based diabetes intervention model is effective in improving patients' knowledge of diabetes, self-care practices, medication adherence and glycemic control.

Assessment of Knowledge Regarding Safety Profile, Use, and Boxed Warnings of Fluoroquinolones Among Healthcare Professionals in Saudi Arabia: A Potential Implication for Drug Regulatory Authorities.

Background: Despite a series of "boxed warnings" (BWs) issued by the US Food and Drug Administration (FDA), fluoroquinolones (FQs) are among the most prescribed antibiotics across the world. Moreover, few studies demonstrated that BW of FQs had less or no impact on prescribing patterns among healthcare professionals (HCPs), which might be attributed to the lack of knowledge toward such warnings. Since FQs contribute to a major proportion of antimicrobial prescriptions in the Kingdom of Saudi Arabia (KSA), this study aimed to ascertain the extent of knowledge toward safety profile, use, and BW of FQs among HCPs working in the KSA. Methods: This cross-sectional study (May-August 2021) was conducted among HCPs working in KSA through a validated questionnaire. The HCPs were requested to identify the indications, adverse effects (AEs), and BW of FQs. The knowledge score (out of 40) was estimated among participants, and its association with demographics was ascertained through the chi-square test, Student's t-test, or Mann-Whitney U-test and one-way ANOVA, or Kruskal-Wallis test, where appropriate. Results: Of the 573 participants (age: 36.1 ± 10.6 years, men: 59.7%), 262 (45.8%) were prescribers reporting frequent use of ciprofloxacin, levofloxacin, and ofloxacin. One-fourth (25.6%) of the prescribers did not recognize nalidixic acid as an agent from FQs class. About 60% of participants correctly identified the mechanism of action of FQs. The average knowledge score was 14.8 ± 6.4, where only 21.5% of respondents scored ≥50%. The average knowledge score for indications, AEs, and BW domains was 5.29 ± 3.05, 6.17 ± 4.05, and 2.3 ± 1.5, respectively. Only 75 (13.1%) participants recognized half of the BW, and 38.6% of participants identified at least one warning. The HCPs aged >40 years (p = 0.043), having non-Saudi's nationality (p < 0.001), working in Riyadh and Eastern regions (p < 0.001), having pharmacy and medicine disciplines (p < 0.001), practicing in public sectors (p = 0.004), and having more than 10 years of experience (p < 0.001) were significantly associated with high knowledge score. Conclusion: This study demonstrates the unsatisfactory knowledge toward safety profile, use, and BW of FQs among HCPs which may put patients at increased risks of AEs. The knowledge score differed among various socio-demographic groups. There is a dire need to initiate the antimicrobial-focused educational campaigns among HCPs regardless of their specialties and methods to improve education and disseminate FDA warnings in practice.

Chitosan Silver and Gold Nanoparticle Formation Using Endophytic Fungi as Powerful Antimicrobial and Anti-Biofilm Potentialities.

Nanotechnology is emerging as a new technology with encouraging innovations. Global antibiotic use has grown enormously, with antibiotic resistance increasing by about 80 percent. In view of this alarming situation, intensive research has been carried out into biogenic nanoparticles and their antibacterial, antifungal, and antitumor activities. Many methods are available to enhance stability and dispersion via peroration of conjugate with a polymer, such as chitosan, and other bioactive natural products. Two marine fungi were isolated and identified as Aspergillus sp. and Alternaria sp. via sequencing of the 16S rRNA gene. In this work, these strains were used to form the conjugation of biogenic silver nanoparticles (AgNPs) from Aspergillus sp. Silv2 extract and gold nanoparticles (AuNPs) from Alternaria sp. Gol2 extracts with chitosan to prepare chitosan-AgNPs and chitosan-AuNP conjugates. A variety of imaging and analytical methods, such as UV-vis, X-ray powder diffraction (XRD), FTIR spectroscopy, transmission electron microscopy (TEM), and scanning electron microscopy (SEM) were utilized to characterize biogenic nanoparticles and conjugates. The biosynthesized Ag and Au nanoparticles along with the prepared conjugates were evaluated for their antimicrobial effects on Gram-negative and Gram-positive bacterial isolates, including Escherichia coli and Staphylococcus aureus. Both chitosan-AgNP and AuNP showed powerful antimicrobial activities compared to the control. On the other hand, chitosan-AgNP conjugation had better antibacterial ctivity than chitosan-AuNPs, which exhibited moderate activity against S. aureus and very low activity against E. coli. Furthermore, the antibiofilm potentials of the prepared conjugates were tested against four biofilm-forming bacteria, including P. aeruginosa, B. subtilis, E. coli, and S. aureus. The obtained results indicate that the chitosan-AgNP showed a promising anti-biofilm activities on all strains, especially S. aureus, while chitosan-AuNP conjugates showed moderate anti-biofilm against B. subtilis and weak activities against the other three strains. These results showed the superiority of chitosan-AgNP as a promising antibacterial as well as biofilm formation inhibitors.

A meta-analysis showing the effect of surgical site wound infections and associated risk factors in neonatal surgeries.

A meta-analysis was performed to assess the effect of surgical site wound infections and risk factors in neonates undergoing surgery. A systematic literature search up to January 2022 incorporated 17 trials involving 645 neonates who underwent surgery at the beginning of the trial; 198 of them had surgical site wound infections, and 447 were control for neonates. The statistical tools like the dichotomous or continuous method used within a random or fixed-influence model to establish the odds ratio (OR) and mean difference (MD) with 95% confidence intervals (CIs) to evaluate the risk factors and influence of surgical site wound infections in neonates undergoing surgery. Surgical site wound infections had significantly higher mortality with OR value 2.03 at 95% CI 1.40-2.95 with P-value <0.001, the longer length of hospital stay (MD, 31.88; 95% CI, 18.17-45.59, P < 0.001), and lower birthweight of neonates (MD, -0.30; 95% CI, -0.53 to -0.07, P = 0.01) compared with neonates with no surgical site wound infections undergoing surgery. However, no remarkable change was observed with surgical site wound infections in the gestational age at birth of neonates (MD, -0.70; 95% CI, -1.46 to 0.05, P = 0.07), and the preoperative antibiotic prophylaxis (OR, 1.28; 95% CI, 0.57-2.87, P = 0.55) compared with no surgical site wound infections for neonates undergoing surgery. Surgical site wound infections had significantly higher mortality, a longer length of hospital stay, and lower birthweight of neonates. However, they had no statistically significant difference in the gestational age at birth of neonates and the preoperative antibiotic prophylaxis compared with no surgical site wound infections for neonates undergoing surgery. Furthermore, evidence is needed to confirm the outcomes.

Pharmacological evaluation of cardioprotective potential of Berberis orthobotrys Bien.ex Aitch.

The resurgence of scrutiny in plant-based medicine is mainly due to the current widespread belief that "green medicine" is safe and more dependable than the expensive synthetic drugs. The current study was focused to evaluate the anti-myocardial ischemic potential of Berberis orthobotrys Bien ex Aitch against chemically induced myocardial ischemia in animal models. Myocardial ischemia was instigated in Sprague Dawley rats of either sex (250-450g) by administration of Isoproterenol (ISO) and doxorubicin (DOX) at doses of 25mg/kg b.w and 15mg/kg b.w. respectively. The protective effect of the plant extract was explored by pretreating a group of animals with aqueous methanolic extract of Berberis orthobotrys roots at a dose of 50mg/kg b.w. (orally) for 10 days in ISO-ischemic model while for doxorubicin ischemic model; the study was conducted for 14 days. The findings of the study revealed that serum levels of cardiac marker enzymes were significantly increased (p<0.0001) followed by the administration of Isoproterenol and doxorubicin whereas the pretreatment with aqueous methanolic plant extract had significantly (p<0.0001) prevented the rise in the same, as compared to both intoxicated groups. The statistical analysis of the study led to the conclusion that Berberis orthobotrys possesses cardio protective potential against chemically induced myocardial ischemia.

Pharmacological exploration of anti-arthritic potential of terbutaline through in-vitro and in-vivo experimental models.

Terbutaline have been reported to have anti-inflammatory activity. Present study aimed to check the anti-arthritic activity of terbutaline. The drug was tested using in vitro models (bovine serum albumin denaturation, egg albumin denaturation and HRBC membrane stabilization) and in vivo (formaldehyde induced arthritis). Results of bovine serum albumin denaturation assay illustrated that terbutaline inhibited 89.54±0.46% denaturation at 6400µg/ml concentration. Terbutaline resulted in dose dependent impediment of protein denaturation in egg albumin denaturation assay with 74.40±0.72% inhibition at concentration of 6400µg/ml. Terbutaline also showed protection of HRBC membrane against hypotonic stress in a dose dependent manner, with maximum 76.45±0.62% prevention at 6400µg/ml concentration. Results of formaldehyde induced arthritis model showed that paw volume was significantly declined by terbutaline with maximum percentage inhibition at 10th day of study period which implies immune inhibitory potential of terbutaline. Findings of present study concluded that terbutaline has arthritis reducing potential possible through inhibitory effects on synthesis and release of inflammatory mediators as well as limiting the formation of autoantigen. Thus, terbutaline might be the potential candidate for use in treatment of arthritis.

Cardioprotective potential of Thymus linearis Benth.

In developing countries, myocardial ischemia and the resulting impairments in heart function are the leading cause of illness and mortality. Thymus linearis Benth has been used as an antibiotic, antioxidant, and antihypertensive agent for centuries. The goal of this investigation was to see if Thymus linearis could protect isoproterenol and doxorubicin-induced myocardial ischemia in vivo at doses of 25 mg/kg s.c. and 15 mg/kg i.p., respectively. The level of cardiac enzymes (CK-MB, LDH, and AST) in the serum isolated from the experimental animal's blood was used to determine myocardial ischemia. The anti-ischemic potential was assessed by comparing the levels of the aforementioned cardiac biomarkers in the intoxicated and treated animal groups. The study found substantial increase (p0.0001) in the serum levels of CK-MB, LDH, AST when compared to intoxicated groups, while pretreatment of animals with crude extract of Thymus linearis significantly reduced the rise in serum cardiac indicators. The findings of the study indicated that the aqueous methanolic Thymus linearis crude extract has cardioprotective potential against Isoproterenol and Doxorubicin-induced cardiac necrosis in rats.