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The impact of Engineered nanomaterials (ENMs) (i.e., Zinc Oxide nanoparticles (ZnO NPs)) on human health has been investigated at high and unrealistic exposure levels, overlooking the potential indirect harm of subtoxic and long exposures. Therefore, this study aimed to investigate the impacts of subtoxic concentrations of zinc oxide (ZnO NPs) on breast cancer cells' response to Doxorubicin. Zinc oxide nanoparticles caused a concentration-dependent reduction of cell viability in multiple breast cancer cell lines. A subtoxic concentration of 1.56 µg/mL (i.e., no observed adverse effect level) was used in subsequent mechanistic studies. Molecularly, miRNA profiling revealed significant downregulation of 13 oncogenic miRNAs (OncomiRs) in cells exposed to the sub-toxic dose of ZnO NPs followed by doxorubicin treatment. Our comprehensive bioinformatic analysis has identified 617 target genes enriched in ten pathways, mainly regulating gene expression and transcription, cell cycle, and apoptotic cell death. Several tumor suppressor genes emerged as validated direct targets of the 13 OncomiRs, including TFDP2, YWHAG, SMAD2, SMAD4, CDKN1A, CDKN1B, BCL2L11, and TGIF2. This study insinuates the importance of miRNAs in regulating the responsiveness of cancer cells to chemotherapy. Our findings further indicate that being exposed to environmental ENMs, even at levels below toxicity, might still modulate cancer cells' response to chemotherapy, which highlights the need to reestablish endpoints of ENM exposure and toxicity in cancer patients receiving chemotherapeutics., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Background: Fasting headaches frequently occur during the first few days of Ramadan, and treatment is challenging because of fasting., Objective: This study aimed to evaluate the effect of extended-release paracetamol on preventing fasting headaches., Methods: A randomized, open-label clinical trial investigated the efficacy of extended-release paracetamol at a daily dose of 1330 mg in preventing fasting headache. Adults aged 18 years and older were recruited through the Clinical Trial Unit at the King Saud University Medical City. The eligible participants in the study fasted 13.5 h daily during the first week of Ramadan. Participants in the treatment and control arms were followed up to investigate the occurrence, severity, and timing of headache symptoms via self-reporting using a standardized headache diary scale with a daily online link or phone call. The primary outcome was the frequency of headache episodes while fasting during the first week of Ramadan., Results: A total of 238 participants were enrolled and randomized. Of these, 173 followed the protocol (80 treated, 93 control) for at least the first day and were included in the analysis. Most participants were young and healthy, with a mean age of 32.2 ± 10.2 years. More men were included in the study (102/173; 59.0%), a small proportion of participants were smokers (31/173; 17.9%), and almost all participants reported being coffee drinkers (165/173; 95.4%); nonetheless, these characteristics were evenly distributed between the two groups in the study. The overall incidence of headache episodes was 33.0% (57/173) on day 1 and decreased to 11.3% (18/159) on day 7. On average over the 7 days, no significant effect was observed for the treatment on the incidence of headache, as the findings from the generalized estimating equation model indicated (β = -0.398, p = 0.084; odds ratio = 0.67, 95% confidence interval [CI] 0.42-1.06). Moreover, there was initially no significant difference in the incidence of headache episodes between the treatment and control groups. However, the treatment group had significantly fewer headache episodes during fasting than the control group on day 3 (4/72 [5.6%] vs. 15/91 [16.5%], p = 0.031; relative risk [RR] = 0.34, 95% CI 0.12-0.97) and day 6 (5/69 [7.2%] vs. 20/90 [22.2%], p = 0.010; RR = 0.33, 95% CI 0.13-0.82). No adverse effects were observed during the study period., Conclusion: No significant differences were observed in the occurrence of fasting headaches between the two groups on most days during the study period. Additional studies are required to address fasting headaches during the first week of Ramadan., (© 2024 American Headache Society.)

Background: Fasting-induced headaches (FIHs) have been shown to occur on the first day of Ramadan and clearly decline thereafter. Despite the wealth of knowledge about different types of headaches (e.g., migraine-, cluster-, and tension-type headaches), research on the mechanism underlying FIHs, as well as their treatment, remains scarce. Our study aimed to investigate any association between FIHs during the first day of Ramadan and potential headache-related biomarkers, including fasting blood glucose (FBG), C-reactive protein (CRP), magnesium, vitamin B9, vitamin B12, homocysteine, and calcitonin gene related peptide (CGRP), and to assess whether a prophylactic use of paracetamol may influence these biomarkers., Methods: As part of a randomized, open-label clinical trial that evaluated the effect of paracetamol as a prophylactic therapy for FIH, blood samples from stratified subjects in the prophylaxis and control groups were withdrawn while fasting after the 1st dose of paracetamol (in the prophylaxis group) and prior to reporting headache occurrence., Results: Plasma and serum were separated for 61 subjects; 31 and 30 subjects from the prophylaxis and control groups, respectively. Overall, no significant differences were found in the levels of FBG, CRP, magnesium, vitamin B9, and vitamin B12 in headache-suffering subjects compared to those without headache despite the use of paracetamol for prophylaxis. Homocysteine, however, was significantly reduced in all subjects who experienced FIH compared to those without headache (median 6.9 [1.6] vs. 7.7 [2.7] umol/L; p = 0.041). On the contrary, when the CGRP was measured using immunoassay, it was found to be significantly elevated in all headache-suffering subjects compared to those without headache (median 126.1 [17.7] vs. 105.8 [19.6] pg/mL; p ≤ 0.0001). This difference was maintained upon comparing the headache to non-headache subjects in both the prophylaxis (median 121.5 [15.4] vs. 105.8 [9.4] pg/mL; p < 0.01) and control groups (median 128.5 [28.3] vs. 105.8 [23.8] pg/mL; p < 0.01). Additionally, an elevated CGRP level was found to increase the odds of having a FIH [OR = 1.32; 95%CI 1.06-1.22]., Conclusions: Our findings revealed the role of CGRP in FIHs for the first time and suggest further investigation in signaling pathways downstream CGRP receptors. Furthermore, the modulation CGRP or CGRP receptors could have a clinical application in the prevention of FIHs., Trial Registration: This study was registered with the Saudi Food and Drug Authority in the Saudi Clinical Trials Registry (SCTR; No. 22122102)., (© 2024. The Author(s).)

Background: Immune checkpoint inhibitors (ICIs) offer a new treatment approach for cancer, with an improvement in patient survival. However, it remains unclear whether their use impacts the quality of life of treated patients. This study aims to compare the health-related quality of life (HRQoL) of patients treated with different anti-PD-1 and anti-PD-L1 drugs, including several single or combination therapies. Methods: This is a prospective observational study conducted with adult cancer patients who received at least one dose of anti-PD-1 or anti-PD-L1. The HRQoL of all adult patients was assessed using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 module (QLQ-C30), version 3, Arabic version. Results: A total of 199 patients were found to be eligible for this study. Of these, 93 patients (82 on a single medication and 11 on multiple ICIs) completed the questionnaire, with a response rate of 46.7%. The majority of patients were treated with pembrolizumab (39.8%), followed by a smaller number treated with nivolumab (35.5%). Most of the patients were diagnosed with solid and advanced malignancies-88.2% ( p = 0.023) and 87.1% ( p = 0.021), respectively-with a significant difference between treatment groups. The median functioning score was 84.7%, with no significant difference between treatment groups ( p = 0.752). Fatigue and pain were noted in >50% of patients, influencing the overall cohort's score related to these symptoms, with scores of 88.8% and 83.3%, respectively. Although a non-significant variation was found in the scores of all combined symptoms among all groups, ranging from 82.1% to 90.4% ( p = 0.931), patients receiving anti-PD-1 + anti-PD-L1 tended to more frequently complain about fatigue, pain, dyspnea, and constipation and hence, exhibited the worst, yet non-significant, scores compared to those of the other groups, with p = 0.234, p = 0.79, p = 0.704, and p = 0.86, respectively. All combined groups scored 83.3% on the global health scale. Nevertheless, the nivolumab-treated patients scored 75%, which was the worst global health score compared with those of the other groups, but this score was not statistically significant ( p = 0.809). Conclusions: Our findings revealed no significant difference in the impact of different ICIs on the HRQoL of cancer patients. However, a larger number of cases would be necessary to provide a robust analysis and to yield conclusive results.

Background: Despite the growing literature, the effectiveness of liraglutide in weight management among individuals with prediabetes and in preventing the disease remains controversial. This study aims to critically evaluate the extent of liraglutide's impact on weight management in this population and assess the heterogeneity among extant studies., Methods: A systematic literature search was conducted across MEDLINE, Embase, ClinicalTrials.gov, and the reference list of retrieved studies to identify eligible English language randomized controlled trials evaluating liraglutide's effect on weight in individuals with pre-diabetes. Non-randomized studies, studies not reporting relevant outcomes, and those conducted on patients with type 2 diabetes were excluded from this review. Outcomes included a change from baseline in absolute body weight in kg, body mass index (BMI), waist circumference, glycosylated hemoglobin (HbA1c), and low-density lipoprotein cholesterol levels. Additional safety outcomes were also reported. Data were analyzed using R statistical software version 4.3.1. A fixed-effect model was used when pooling crude numbers for study outcomes. Moreover, a sensitivity analysis using random-effect model was performed and heterogeneity was assessed using I 2 statistics., Results: Five eligible studies were included, with a total of 1604 subjects in the liraglutide arm and 859 subjects in the control arm. Participants exposed to liraglutide showed a decrease in body weight (mean difference [MD] = -4.95 kg; 95% CI -5.16, -4.73; I 2  = 93%), BMI (MD = -2.06 kg/m 2 ; 95%CI -2.22, -1.89; I 2  = 97%), waist circumference (MD = -4.61 cm; 95% CI -4.79, -4.43; I 2  = 82%), HbA1c (MD = -0.33%; 95%CI -0.34, -0.31; I 2  = 100%), and low-density lipoprotein cholesterol levels (MD = -0.36 mmol/L; 95% CI -0.39, -0.33; I 2  = 99%). The overall effect size remained similar when using a random-effects model for all outcomes. In addition, the rate of adverse events was higher with liraglutide when compared to the control; however, the dropout rates were relatively lower in the former arm., Conclusion: While our meta-analysis suggests that liraglutide can reduce body weight, BMI, waist circumference, and HbA1c levels in individuals with pre-diabetes, the findings should be interpreted cautiously due to limitations such as the small number of trials and their short duration, and variability in dosages. Further randomized controlled trials examining long-term outcomes are essential to validate these findings and address the high heterogeneity among the studies included in this analysis., Competing Interests: Disclosure The authors have no multiplicity of interest to disclose., (Copyright © 2024 AACE. Published by Elsevier Inc. All rights reserved.)

Background: New multiple myeloma (MM) medications have revolutionized the treatment landscape, but they are also associated with a range of adverse events (AEs). This study aims to provide a comprehensive overview of AEs reported for four new MM medications: daratumumab, ixazomib, elotuzumab, and panobinostat., Methods: This study uses a descriptive retrospective approach to analyze the FDA Adverse Event Reporting System (FAERS) from 2015 to 2022. It includes variables like medication names, report details, patient demographics, adverse events, and reporter types. The initial dataset consists of over 3700 adverse events, which are categorized into 21 groups for clarity and comparison., Results: The FAERS database revealed 367,756 adverse events (AEs) associated with novel multiple myeloma drugs from 2015-2022. Ixazomib had the highest number of reported AEs with 206,243 reports, followed by daratumumab with 98,872 reports, then elotuzumab with 26,193 AEs. Ixazomib's AE reports increased dramatically over the study period, rising approximately 51-fold from 1183 in 2015 to 60,835 in 2022. Of the medications studied, ixazomib also recorded the highest number of deaths (24,206), followed by daratumumab (11,624), panobinostat (7227), and elotuzumab (3349). The majority of AEs occurred in patients aged 55-64 and 65-74 years., Conclusions: Ixazomib, a new MM medication, had the highest number of AEs reported. Also, it has the highest rate of reported deaths compared to other new MM medications. Clinicians should be aware of the potential AEs associated with this medication and further research is needed to understand the reasons for the high number of AEs and to develop mitigation strategies. More attention should also be paid to the safety of new multiple myeloma medications in younger patients.

Understanding the pharmacokinetics of gentamicin is essential in special populations, such as pediatric patients with acute lymphoblastic leukemia (ALL), in light of previous studies indicating that ALL patients have a lower volume of distribution than non-ALL patients. Furthermore, validation of such results is needed to ensure their clinical application. Accordingly, this single-center, retrospective, cross-sectional study compares the pharmacokinetic parameters of volume of distribution and clearance (Cl) of gentamicin between ALL and non-ALL patients. Inclusion criteria were pediatric patients aged between 1 and 14 years with or without ALL and receiving intravenous gentamicin for treatment courses > 72 h. Patients' characteristics, such as age, sex, height, serum albumin, diagnosis, serum creatinine (Scr) concentration, dosing, and pharmacokinetic information, including peak and trough concentrations, were retrieved. The study scrutinized a total of 115 pediatric patients, comprising toddlers (15.7 %), children (76.5 %), and adolescents (7.8 %). All patients received gentamicin every 8 h, with an average dose of 2.50 (0.64) mg/kg. Patients were divided into two groups based on disease state, with 45.2 % (n = 52) in the non-ALL group and 54.8 % (n = 63) in the ALL group. Both groups had similar characteristics in terms of gender, weight, body surface area, and dose. The only significant covariates identified were weight and creatinine clearance (Cl cr ) for volume of distribution (V d ). A significant difference was found in Scr, Cl cr , and blood urea nitrogen (BUN); however, no significant difference between ALL and non-ALL patients emerged in the volume of distribution or Cl. In conclusion, the study findings indicate that dosing requirements were similar between the two groups. Further prospective studies with larger sample sizes are warranted., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier B.V. on behalf of King Saud University.)

Background: Quetiapine is commonly prescribed off-label to manage delirium in intensive care unit (ICU) patients. However, limited studies comparing its efficacy and safety to those of other antipsychotics exist in the literature. Method: A retrospective, single-center chart review study was conducted on adults admitted to the ICU between January 2017 and August 2022, who were diagnosed with delirium and treated with a single antipsychotic and had no neurological medical conditions, active alcohol withdrawal, or prior use of antipsychotics. Data were analyzed using SPSS software version 28, with p -values of <0.05 indicating statistical significance. Results: In total, 47 patients were included, of whom 22 (46.8%), 19 (40.4%), 4 (8.5%), and 2 (4.3%) were on quetiapine, haloperidol, risperidone, and olanzapine, respectively. The median number of hours needed to resolve delirium were 12 (21.5), 23 (28), 13 (13.75), and 36 (10) ( p = 0.115) for quetiapine, haloperidol, risperidone, and olanzapine, respectively, with haloperidol being used for a significantly shorter median number of days than quetiapine (3 (2.5) days vs. 7.5 (11.5) days; p = 0.007). Of the medication groups, only quetiapine-treated patients received a significantly higher median maintenance compared to the initiation dose (50 (50) mg vs. 50 (43.75) mg; p = 0.039). For the length of stay in the ICU and hospital, delirium-free days, % of ICU time spent in delirium, ventilator-free days, the difference between the highest and baseline QTc intervals, and ICU and hospital mortalities, no significant difference was observed between the groups. Conclusions: Overall, the use of quetiapine in our retrospective study seems to not be advantageous over the other drugs in terms of efficacy and safety outcomes.

The solubility and solution thermodynamics of isotretinoin (ITN) (3) in numerous {dimethyl sulfoxide (DMSO) (1) + water (H 2 O) (2)} combinations were studied at 298.2-318.2 K under fixed atmospheric pressure of 101.1 kPa. A shake flask methodology was used to determine ITN solubility, and correlations were made using the "van't Hoff, Apelblat, Buchowski-Ksiazczak λh , Yalkowsky-Roseman, Jouyban-Acree, and Jouyban-Acree-van't Hoff models". In mixtures of {(DMSO (1) + H 2 O (2)}, the solubility of ITN in mole fractions was enhanced with the temperature and DMSO mass fraction. The mole fraction solubility of ITN was highest in neat DMSO (1.02 × 10 -1 at 318.2 K) and lowest in pure H 2 O (3.14 × 10 -7 at 298.2 K). The output of computational models revealed good relationships between the solubility data from the experiments. The dissolution of ITN was "endothermic and entropy-driven" in all of the {(DMSO (1) + H 2 O (2)} mixtures examined, according to the positive values of measured thermodynamic parameters. Enthalpy was discovered to be the driving force behind ITN solvation in {(DMSO (1) + H 2 O (2)} combinations. ITN-DMSO displayed the highest molecular interactions when compared to ITN-H 2 O. The outcomes of this study suggest that DMSO has a great potential for solubilizing ITN in H 2 O.

Purpose: We aimed to assess the family caregivers' level of knowledge and attitudes about Parkison's disease (PD), identify factors affecting their knowledge, evaluate their quality of life (QoL) and factors influencing it and to define the effect of PD on activities of daily living (ADLs) of PD patients., Method: We developed and validated a questionnaire to assess the level of knowledge and attitudes of family caregivers toward PD, effects of PD on caregivers' QoL as well as its effects on activities of daily living (ADLs) of patients from the caregivers' perspective. A scoring system was utilized and SPSS was used to evaluate the differences in responses between the groups; p < 0.05 indicated statistical significance., Results: 69 caregivers and their corresponding patients were included in the study. Family caregivers had a low level of knowledge, as reflected by a mean score of 3.45 out of 8. However, 62.3% were aware of all medications used by their patients. Additionally, the level of knowledge was associated with caregivers' gender as 57.1% of the female caregivers had medium PD knowledge scores while 58.5% of the male had low scores (p = 0.038). The level of knowledge was also associated with daily caregiving hours as only 44.5% of caregivers whom spending 0-5 h/day had medium and high knowledge scores while greater proportions with same scoring levels were found among those providing care > 5 h/day (75.0% in > 5-10 hrs; 52.4% in > 10-24 hrs; p = 0.024). Most caregivers confirmed their QoL had declined, yet the male caregivers had better QoL than females (p = 0.026). Longer caregiving time was associated with decline (p = 0.016) and severe effect on QoL of caregivers (p = 0.04)., Conclusion: Caregivers of PD patients had a low level of knowledge. Female caregivers had significantly higher level of PD knowledge than their male counterparts. Low level of PD knowledge was significantly associated with shorter caregiving time per day. Longer caregiving time was significantly associated with a decline in caregivers' QoL. Increasing awareness and knowledge among caregivers is necessary to ensure better treatment outcomes and improve the QoL of both caregivers and patients., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

In this study, an environmentally friendly "high-performance liquid chromatography (HPLC)" assay to quantify isotretinoin (ITN) in commercial products and solubility samples is designed and verified. A Nucleodur reverse-phase C 18 column was used as the stationary phase to identify ITN. The ecologically friendly mobile phase was composed of ethyl acetate and ethanol (50:50 v/v), and it was delivered at a flow rate of 1.0 mL/min. ITN was measured at 354 nm in wavelength. The current HPLC method had a determination coefficient of 0.9994 and was linear in the 0.2-80 μg/g range. The current protocol for ITN measurement was also rapid (retention time = 2.78 min), accurate (%recoveries = 98.60-101.52), precise (% uncertainties = 0.71-0.98), and sensitive. According to the AGREE methodology, the current procedure received an outstanding greenness profile with an AGREE score of 0.76. By determining ITN in commercial products and solubility samples, the applicability of the current approach was proven. ITN was discovered to be present in 98.43% and 100.84%, respectively, of commercial capsule brands A and B. The ITN's solubility in numerous eco-friendly solvents was successfully measured. Under different stress conditions, the current approach was able to distinguish between its degradation products, demonstrating its stability-indicating characteristics. These findings indicated that ITN in procured capsules and solubility samples might be regularly tested by the suggested approach., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Introduction: Isotretinoin is a synthetic vitamin A derivative, administered off-label as maintenance therapy for neuroblastoma. This report addresses the challenge of administering isotretinoin to children, given its availability as soft gelatin capsules only., Case Report: A 3-year-old boy diagnosed with stage IV neuroblastoma has undergone multimodal therapy, including six cycles of chemotherapy, followed by tumor resection and radiotherapy. Later, he was initiated on immunotherapy and prescribed isotretinoin 50 mg orally twice daily for two weeks, before each immunotherapy cycle. Isotretinoin is not available in liquid formulation and the patient could not swallow isotretinoin capsules. Therefore, pharmacist counseling was required to ensure appropriate administration of the drug., Management and Outcomes: The patient's parents were instructed to pierce prescribed capsules, and empty and dilute their contents into a small glass containing olive oil after taking safety measures. Isotretinoin's stability in olive oil for 72 h was compared using high-performance liquid chromatography to its stability in soybean oil. The recovery rates were 98.62% and 98.3%, respectively. Drug miscibility was not an issue as isotretinoin is lipophilic. Therefore, it could be administered easily without considerable remaining on the interior wall of the glass., Discussion: To the best of our knowledge, this is the first report that suggests a practical method for administering isotretinoin in liquid form, particularly in pediatric oncology patients. Isotretinoin was noted to be stable in olive oil and its exposure to light and oxygen would not be an issue given the short time from preparation to administration and the low emphasis on exposure by the manufacturer when such a method is recommended.

Introduction: Devastating cancer-related events are not uncommon, and these events have weakened communication performance and induced stress among health care providers (HCPs), particularly physicians. This study aimed to investigate the perspective of HCPs emotionally affected by poor clinical outcomes due to the failure of cancer therapy., Methods: A cross-sectional, online survey was conducted over 3 months among HCPs practicing in the field of oncology in Saudi Arabia, comprising physicians, pharmacists, and nurses. Data were analyzed using Statistical Package for Social Sciences version 26.0. A P -value <.05 was considered statistically significant., Results: This study demonstrated a positive correlation between HCPs' length of experience and emotional impact of treatment failure, albeit this was not statistically significant (P = .071). Analysis of their perspective toward failure of cancer therapies revealed a significant impact of occupation and sex (P = .014 and P = .047, respectively). Moreover, occupation played a significant role in shaping the viewpoint of HCPs toward the need for conducing further research to test the appropriateness of treatment protocols on local patients (P = .022). Despite the emotional responses of HCPs to suboptimal clinical outcomes, factors such as work burnout, lack of concentration and patience, work or personal problems, and under appreciation were frequently identified as triggers of such outcomes., Conclusion: Our results revealed that poor clinical outcomes observed among cancer patients are emotional triggers for HCPs practicing in the oncology field. The emotional response is often perceived negatively, and can potentially lead to a decline in the quality of care provided to these patients.

Purpose: Despite the effectiveness of androgen deprivation therapy in advanced prostate cancer, serious neuropsychiatric consequences in androgen deprivation therapy (ADT)-treated patients, mainly depression, have been concerning and gained more attention recently. This narrative review aims to shed light on the risk and pharmacological management of ADT-induced depression in PCa patients. Methods: We searched PubMed, Scopus and Google Scholar databases using MESH keywords "Prostate cancer OR prostate neoplasm" AND "Depression" AND "Androgen Deprivation Therapy" AND "antidepressants". Search was limited to English and studies conducted on humans. Studies' titles and abstracts were screened, and further information were obtained from the text, if necessary, to decide whether studies are to be included in this review. Results: Our review revealed 23 studies confirming the occurrence and worsening of depressive symptoms in ADT-treated patients, which frequently require pharmacological interventions; whereas 10 studies indicated otherwise. All studies were prospective, retrospective, cross-sectional or case reports. Based on the incidence of depression provided by the observational studies, the average among ADT-treated patients was 18.23% (range: 2.1-46.9%), while it was 8.42% (range: 1.4-23.3%) in the non-ADT patients. Although several treatments have been used for depression in cancer patients, current knowledge lacks observational and controlled studies as well as clinical guidelines that demonstrate efficacy and safety of antidepressants and guide clinicians to the appropriate treatment in these patients, respectively. On the other side, a few clinical studies have been published regarding the efficacy of selective serotonin reuptake inhibitors, selective serotonin and norepinephrine reuptake inhibitors and/or saftey on other ADT associated adverse effects. Conclusions: Our work supports the recent attention towards mood issues as an adverse effect of ADT, and that greater awareness of this is warranted among clinicians. Clinical studies published regarding the use of antidepressants for other ADT associated adverse effects established the foundation that can be adopted to examine these therapies on ADT-induced depression.

The solubilization and thermodynamic analysis of isotretinoin (ITN) in eleven distinct green solvents, such as water, methyl alcohol (MeOH), ethyl alcohol (EtOH), 1-butyl alcohol (1-BuOH), 2-butyl alcohol (2-BuOH), ethane-1,2-diol (EG), propane-1,2-diol (PG), polyethylene glycol-400 (PEG-400), ethyl acetate (EA), Transcutol-HP (THP), and dimethyl sulfoxide (DMSO) was studied at several temperatures and a fixed atmospheric pressure. The equilibrium approach was used to measure the solubility of ITN, and the Apelblat, van’t Hoff, and Buchowski−Ksiazczak λh models were used to correlate the results. The overall uncertainties were less than 5.0% for all the models examined. The highest ITN mole fraction solubility was achieved as 1.01 × 10−1 in DMSO at 318.2 K; however, the least was achieved as 3.16 × 10−7 in water at 298.2 K. ITN solubility was found to be enhanced with an increase in temperature and the order in which it was soluble in several green solvents at 318.2 K was as follows: DMSO (1.01 × 10−1) > EA (1.73 × 10−2) > PEG-400 (1.66 × 10−2) > THP (1.59 × 10−2) > 2-BuOH (6.32 × 10−3) > 1-BuOH (5.88 × 10−3) > PG (4.83 × 10−3) > EtOH (3.51 × 10−3) > EG (3.49 × 10−3) > MeOH (2.10 × 10−3) > water (1.38 × 10−6). ITN−DMSO showed the strongest solute−solvent interactions when compared to the other ITN and green solvent combinations. According to thermodynamic studies, ITN dissolution was endothermic and entropy-driven in all of the green solvents tested. The obtained outcomes suggested that DMSO appears to be the best green solvent for ITN solubilization.

A vast majority of studies evaluated pregnant women's knowledge and attitudes towards using medications during their pregnancy, with few global and lack of regional studies conducted to spot obstetrician-gynecologists practices in this regard. This study aims to assess Obstetrician-gynecologists' knowledge of medication teratogenicity potential, their frequently used resources, and their residency training contribution to medication use during pregnancy. This is a cross-sectional, survey-based study targeting licensed Obstetrician-gynecologists who are practicing in Saudi Arabia using a validated self-administered web-based questionnaire developed by the American College of Obstetricians and Gynecologists. A total of 60 obstetrician-gynecologists were included in the study. Most participants were female (72%) with median age and clinical experience of 42 and 13 years, respectively. The majority (87%) agreed that Isotretinoin is contraindicated, while around 60% of respondents were unsure about the safety of herbal remedies use. Online databases (e.g., Lexi-Comp and Micromedex) were chosen as the top utilized medication resources (45%). Around 48% strongly agreed that liability is a concern if there were adverse pregnancy outcomes following the use of medications. Regarding their training assessment, obstetrician-gynecologists who had been in practice for more than 15 years were significantly more likely to rate themselves as well qualified (P value < .05). The majority adequately and significantly rated their training on prescribed medications (58.3%), OTC medications (45%) and dietary supplements or herbal remedies (32%) (P value < .05). Obstetrician-gynecologists showed a different level of knowledge about the risks and safety of medications when used during pregnancy. More efforts are needed to optimize medication selection, herbal avoidance, and training performance., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background and Objective: Numeracy is the branch of mathematics involved in understanding basic calculations, quantitation, estimation, reasoning, and execution of multistep operations. It is very imperative that pharmacists understand and apply numeracy skills in their routine work in the interest of their profession and patient care. This observational study was designed to assess the pharmacy student's perceptions of numeracy., Methods: A prospective observational study was conducted by the Department of Pharmacy, King Saud University, Kingdom of Saudi Arabia, between December 2021 and February 2022. All the enrolled subjects pursued a 5-year Pharma degree course at the university using a 9-item instrument, which accessed the perception of students toward numeracy. The data were analyzed using the statistical software statistical package for social science (SPSS) version 26.0 (SPSS Inc., Chicago, IL, USA). Chi-square and Fisher's exact test were used to derive an association between various parameters of the study subjects. A P -value of < 0.05 was taken as statistically significant., Results: A total of 550 pharmacy students were approached in this study, out of which 21 (3.8%) students were excluded due to incompleteness of the responses; thereupon, 529 students were included in the study. We learned that almost 90.0% of students had excellent and/or good mathematical ability, but at the same time, they were frequent users of calculators. Most of the students endorsed the importance of numeracy and showed their interest in attaining more knowledge of numeracy. Similarly rating the perceptions of mathematical ability is significantly associated with the frequency of use of a calculator for calculations ( p = 0.0001)., Conclusion: Pharmacy students showed interest in numeracy and correspondingly showed excellent perceptions toward mathematical ability. Although the role of numeracy has been well accepted, inciting changes in teaching-learning practices through mathematically focused teaching approaches throughout the pharmacy program will increase its applicability in healthcare., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Alrabiah, Arafah, Rehman, Syed, Babelghaith, Alwhaibi, Alghadeer, Alhossan and Al Arifi.)

Background: Health care professionals have an important role in increasing awareness about smoking harms and serving as role models. This study aims to assess knowledge, attitude and perception toward electronic cigarettes (ECs) as well as prevalence of ECs use among male health colleges students., Method: This is a cross-sectional survey-based study conducted among students in the male campus of five different health colleges over a 4-month period from February 2020 to May 2020. Descriptive analysis was used to assess the knowledge, perception and attitude, and inferential testing was used to evaluate the association of different participant's variables and knowledge toward ECs usage using SPSS., Results: A total of 333 students were included in the analysis. Most of students ( n = 205; 61.6%) had never used ECs, while 22.8 and 15.6% used them for recreational and smoking cessation purposes, respectively. Focusing on ECs users from each college individually, medical students had the highest prevalence followed by dental, pharmacy and nursing students (47.4, 40.7, 34.5, and 32%, respectively). Many students had misconceptions and a low level of knowledge about ECs, such as recognizing them as smoking-cessation tools and not knowing whether toxic and carcinogenic components levels in ECs are similar to conventional cigarettes, respectively. Medical students had significantly higher knowledge compared to dental students [3 (2) vs. 2 (1); p = 0.033]. Moreover, smokers were less knowledgeable than non-smokers [2.5 (1) vs. 2.1 (1), p = 0.027]. At least 62.8% of students perceived using ECs as a fashionable alternative smoking method and 59.2% believed that they may become a gateway for smoking addiction. Only 120 (36.0%) health colleges students were confidently able to advise smokers regarding ECs., Conclusion: Our study highlights an increased trend of ECs use accompanied with insufficient knowledge and several misconceptions about ECs among health colleges students. This was associated with a negative influence on their attitude toward ECs use, which would potentially lead to negative consequences on public health., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Alsanea, Alrabiah, Samreen, Syed, Bin Khunayn, Al-Arifi, Alenazi, Alghadeer, Alhossan, Alwhaibi and Al-Arifi.)

Objective: The impact of pharmaceutical services on public health especially in regards to smoking cessation counseling can influence the rate of smoking cessation. The present study aims to evaluate prevalence, beliefs, and attitude of pharmacy students toward smoking habit and SC methods., Methods: An online cross-sectional survey was conducted among pharmacy students at King Saud University, Riyadh, Saudi Arabia over 4-month period from May to August 2021. The survey consisted of 22-items focused on evaluating the prevalence, belief, and attitude toward smoking habits and smoking cessation methods. Data was descriptively analyzed using a statistical package for social science version 26 (SPSS)., Results: A total of 675 students completed the survey, among which 78.7 % were non-smokers and only 31.7% received education on the dangers of smoking. The most common methods of smoking cessation they heard of were consultation (58.6%), followed by use of electronic cigarettes (41.92 %) and Nicotine patch (40.7%). One-third of the surveyed students (36.8 %) agreed that specialized smoking cessation clinics enhance the efficacy of smoking cessation methods. The majority of students (80.6%) agreed to ban smoking in public places and 92.2% believed that tobacco sales to adolescents should be forbidden. Health professionals should actively participate and advise their patients to quit smoking as 89.8 % students agreed on that. Age and gender of students had significantly influenced the prevalence of smoking, history of smoking, frequency of smoking, efforts to quit smoking among smokers ( p = 0.0001)., Conclusion: The prevalence of non-smokers among pharmacy students is encouraging, yet level of awareness about and usefulness of smoking cessation methods is unsatisfactory. Therefore, the study clearly highlights a great need for integrating smoking cessation programs in their academic curricula to prepare them for real-world practice., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Alwhaibi, Wajid, Alenezi, Salami, Alhaydan, Samreen, Alhossan and Al-Arifi.)

Akt1 suppression in advanced cancers has been indicated to promote metastasis. Our understanding of how Akt1 orchestrates this is incomplete. Using the NanoString ® -based miRNA and mRNA profiling of PC3 and DU145 cells, and subsequent data analysis using the DIANA-mirPath, dbEMT, nCounter, and Ingenuity ® databases, we identified the miRNAs and associated genes responsible for Akt1-mediated prostate cancer (PCa) epithelial-to-mesenchymal transition (EMT). Akt1 loss in PC3 and DU145 cells primarily induced changes in the miRNAs and mRNAs regulating EMT genes. These include increased miR-199a-5p and decreased let-7a-5p expression associated with increased TGFβ-R1 expression. Treatment with locked nucleic acid (LNA) miR-199a-5p inhibitor and/or let-7a-5p mimic induced expression changes in EMT genes correlating to their anticipated effects on PC3 and DU145 cell motility, invasion, and TGFβ-R1 expression. A correlation between increased miR-199a-5p and TGFβ-R1 expression with reduced let-7a-5p was also observed in high Gleason score PCa patients in the cBioportal database analysis. Collectively, our studies show the effect of Akt1 suppression in advanced PCa on EMT modulating miRNA and mRNA expression changes and highlight the potential benefits of miR-199a-5p and let-7a-5p in therapy and/or early screening of mPCa.

Background: Teachers play a central role in successful education. Due to the COVID-19 pandemic, regular in-person attendance in classes at all levels of education has been disrupted for more than 1 year in many countries. These lockdowns, which include the discontinuation of in person learning at schools and universities has presented a significant challenge for teachers to adapt to online teaching. Given this rapid format change, occupational anxiety levels among educators has increased., Objective: The primary objective of this study was to assess the prevalence of anxiety among teachers in Saudi Arabia. A secondary objective was to explore characteristics of teachers associated with the level of anxiety level during the period of lockdown., Methods: An anonymous, online cross-sectional study was carried for 3 months (February 2021 through April 2021). The questionnaire consisted of four sections and included the Generalized Anxiety Disorder instrument (GAD-7). Chi-square tests were completed for categorical comparisons while binary logistic regressions were used for associative relationship exploration. The IRB at King Saudi University Medical City, Saudi Arabia approved this study., Results: A total of 742 respondents completed the survey yielding an anxiety prevalence of 58.2 % among teachers. Medium degree of statistically significant differences identified as marital status ( p = 0.046). women had higher anxiety (65.3%) than men (34.7%) but gender with anxiety was low degree of statistical significance compared with non-anxiety status ( p = 0.697). The odds of anxiety among middle teachers was twice (OR = 2.01) as high as the odds of anxiety among other levels of teacher ( p = 0.01, 95% CI 0.94-4.26)., Conclusions: This study identified that many teachers experienced anxiety during the lockdown, especially women and middle school teachers. Future studies should identify contributing factors to estimate the magnitude of the exposure to anxiety between different types of teachers to help establish better preventive measures based on the workplace environment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Alhazmi, Alghadeer, Al-Arifi, Alamer, Mubarak, Alwhaibi, Alfayez and Alsubaie.)

Pharmacists are considered among the most accessible healthcare workers in fundamental positions to implement new clinical initiatives, such as pharmacogenomics services. The scope of pharmacogenomics in improving health outcomes and the quality of health care is well-known. Implementation of such initiatives requires adequate knowledge, perception, and positive attitudes among pharmacists. A study was conducted on pharmacy students at King Saud University in Riyadh to analyze their attitudes, knowledge, and perceptions concerning pharmacogenomics to explore the feasibility of establishing full-time pharmacogenomics instruction and services. A cross-sectional study was carried out in one of the significant pharmacy schools of Saudi Arabia, using a simple questionnaire-based survey in pharmacy students pursuing Bpharm and PharmD courses to obtain preliminary information about pharmacogenomics among the surveyed population. The study's secondary objective was to determine the perceived belief about pharmacogenomics implementation in clinical practice. Out of the total of 552 participants, 41.8% correctly defined pharmacogenomics and 81.3% understood that genetic change could lead to adverse reactions. More than half of the participants agreed that the FDA recommends pharmacogenomics testing for certain drugs. The knowledge about a year of use of pharmacogenomics in clinical practice was found to be very low; only 15.2% could correctly answer. Only 60% of students agreed on pharmacogenomics testing for selecting the therapy with the most negligible adverse effects. Due to the limited knowledge about and understanding of pharmacogenomics, there is a lack of interest among pharmacy students in implementing pharmacogenomics testing in clinical practice. Our study highlights the need for improving pharmacy students' knowledge about pharmacogenomics and pharmacogenetics so that the implementation of pharmacogenomics testing in clinical practice will become easier. There is a need to introduce an up-to-date curriculum for pharmacy courses other pharmacogenomics-based health education programs in Saudi Arabia.

Background and Objectives: Neural tube defects are congenital anomalies which canlead to infant death and serious disability. They are initiated during embryogenesis, between the 23rd and 27th day of fetal life, and can be prevented by the administration of folic acid. Therefore, this study aims to evaluate the knowledge and practice of Saudi women at childbearing age regarding NTDs and FA supplementation., Methodology: This is a cross-sectional study on Saudi women of reproductive age who were asked to complete an online survey to examine their knowledge and practice regarding folic acid supplementation and neural tube defects. Descriptive and simple linear regression analyses were conducted using SPSS v.26 (SPSS Inc., Chicago, IL, USA)., Results: A total of 613 women have completed the questionnaire, from which the majority (46.7%) were aged between 36 and 40 years. About 94% of women heard about folic acid and 80% indicated that its deficiency has some relation to neural tube defects. Approximately 37%, 25.3%, and 23.2% of women reported the proper time for folic acid intake to be during first trimester of pregnancy, before pregnancy, or throughout pregnancy, respectively. Linear regression analysis revealed that increase age and education were significantly correlated with a decrease in folic acid administration ( p = 0.008) and ( p = 0.001), respectively. However, there was no association between time of folic acid administration and income or number of parities., Conclusion: Despite the acceptable level of awareness about the relation of folic acid and neural tube defects, our results revealed that more education is required towards the proper time of supplementation among Saudi childbearing women.

Introduction: When it comes to non-communicable diseases like diabetes, inadequate knowledge, attitude, and practice are often linked to poor health outcomes. This study aims to assess the patients' knowledge, attitude, and practice (KAP) of diabetes in the outpatient department of a university teaching hospital in Saudi Arabia., Methodology: In this cross-sectional study, diabetes type 2 patients attending outpatient departments at a university teaching hospital, Riyadh, were assessed regarding their knowledge, attitude, and practice toward diabetes using a validated KAP scale. Descriptive and inferential analysis was done to determine the factors associated with KAP score using SPSS version 26.0 software (SPSS Inc., Chicago, IL, U.S.)., Results: Males made up 69.7% of the sample (n = 165), while 56.9% were between the ages of 41 and 75. The level of knowledge and practice had "good" in 37.6%, and 47.9%, respectively, but level of attitude had "positive" in 30.9% of patients. The association between knowledge tier and gender (p0.014) and insurance status (p0.008), respectively, was shown to be significant. However, the attitude tier was only significantly associated with gender ( P = .003). The practice tier also showed a significant age association ( P = .049). As regards, the mean scores for diabetes-related knowledge were higher only among insured participants ( P = .03) than for other participants' sociodemographic factors. Meanwhile, the mean attitude scores were also higher among males ( P = .006) than for other sociodemographic characteristics. A comparison of the participants' sociodemographic characteristics found no statistically significant variations in practice scores., Conclusion: Unfortunately, this study found that outpatient diabetes patients had insufficient knowledge, practice, and a negative attitude toward diabetes type 2. This imposes a great burden on healthcare workers and hence the healthcare system to improve patient scores via diabetes education programs or pharmacist-led patient counseling initiatives.

Aim: 1) To investigate the pharmacokinetic profile of sildenafil citrate in Middle Eastern males and, 2) To highlight the impact of ethnicity on its pharmacokinetics parameters through comparing Middle Eastern data to the data estimated from different ethnic groups., Method: The study was conducted on 24 Middle Eastern healthy male volunteers. Pharmacokinetic data including C max , T max , t 1/2 , AUC 0-t , AUC 0-∞ were estimated from blood samples collected at several time points within 24 h post-administration of a single 100-mg tablet of sildenafil citrate (Viagra®). Pharmacokinetic data of sildenafil generic 100-mg tablet (product B) was determined in the volunteers using the same analytical method. Pharmacokinetic data of other studies published on different ethnicities were obtained and compared to our Viagra®-related data., Results: Analysis of Middle Eastern data (mean ± SD) revealed C max  = 398.9 ± 107.7 ng/ml; T max  = 1.84 ± 0.22 h; t 1/2  = 2.66 ± 0.97 h; AUC 0-24  = 1475 ± 515.3 ng.h/ml; AUC 0-∞ = 1556 ± 567.58 ng.h/ml. There was no significant difference between Viagra® and product B, confirming the bioequivalence of the two preparation as well as the reliability of utilized analytical method. Data comparisons between Middle Eastern and other ethnicities indicated that Iranian, Mexican, and Thai would potentially have twice the effect observed in Arabs and Caucasians, considering the same prescribed drug formulation and dose., Conclusion: There is a considerable difference in the pharmacokinetic profile of sildenafil citrate between Middle Eastern and other ethnic groups. Ethnicity may predispose individuals to unwanted prolonged activity of sildenafil and adverse events. Thus, it should be taken in consideration by clinicians when recommending sildenafil dose., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 King Saud University.)

Aim: Warfarin is commonly used in patients with thrombotic diseases. This study aimed to evaluate the impact of Ramadan fasting on warfarin efficacy by investigating international normalised ratio (INR) stability in medically stable patients., Methods: A retrospective observational study was conducted at King Khalid University Hospital during Ramadan 2016 on fasting adult patients aged above 18 years and receiving warfarin. The INR values during pre-Ramadan, Ramadan and post-Ramadan periods were collected after satisfying the inclusion criteria. Time within the therapeutic range (TTR) during the whole period was estimated using the conventional method., Results: In total, 101 patients were included in the study. The mean age (SD) was 55.8 ± 15.5 years, and 52.4% were females. The target INR range for 62.4% was 2-3, while 37.6% had a target INR range of 2.5-3.5. An upward trend in the proportion of patients with therapeutic INR was noticed during Ramadan (59.4%) as compared to pre- (56.4%) and post-Ramadan periods (53.5%) respectively. Additionally, the proportions of patients with supratherapeutic and sub-therapeutic INR were the highest and lowest, 23% and 24% respectively post-Ramadan as compared to other periods. Based on target INR categorisation, achieving therapeutic INR during Ramadan was more feasible with the low INR (2-3) compared to the high INR (2.5-3.5) target patients, 63.5% vs 52.6% respectively. TTR estimation revealed 62.4% and 37.6% of the patients had good and poor, respectively, anticoagulation status throughout the study period., Conclusion: Despite the changes in mean INR and proportion of patients with therapeutic INR during Ramadan compared to other non-fasting months, our results confirmed that short-term fasting during Ramadan has no significant influence on INR stability and, consequently, therapeutic efficacy in warfarin-treated medically stable patients., (© 2021 John Wiley & Sons Ltd.)

Background and Aim: During the Coronavirus 2019 (COVID-19) crisis, there has been a huge demand for medications and unprecedented utilization of intensive care unit (ICU) services that subsequently and profoundly impacted the quality of medical care provided to COVID-19 patients. This study aimed to shed light on the role of pharmacists on the health care provided to critically ill COVID-19 patients., Methods: A retrospective study, was conducted in Diriyah hospital in Riyadh, Saudi Arabia on all COVID-19 patients admitted to the ICU between June 27th and August 15th, 2020 until patients were transferred to the medical ward, discharged, or deceased. All medication related interventions performed by pharmacists have been documented electronically, collected and subsequently categorized and analyzed., Results: The mean age of patients was 58.8 years (±12.98 SD), with age of >64 years in approximately 37%. Four hundred and seventy interventions (470) were made by pharmacists of which 32%, 11.7%, 4%, 2.6%, 2.1% were due to error in dosing regimens, drug duplication, missing drug information, drugs requiring prior authorization, and missing critical information, respectively; while 40.6% were due to medication shortage of which 40.3% were substituted with alternative medications. Based on the analysis of drugs involved in interventions, medication groups that were mainly associated with interventions included antibiotics (16.8%), electrolytes/minerals (11.7%) and vitamins (9.4%)., Conclusion: During health crises such as COVID-19 pandemic, the role of pharmacists in the ICU services becomes extremely crucial for providing better patients' outcomes. Further studies should be conducted to follow up these findings in the context of COVID-19 pandemic., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Author(s).)

Objective: The present study examined pharmacists' knowledge and practices towards prescribed medications for hemodialysis patients. The impact of a pharmacist's current positions and years of experience on practices and knowledge was also assessed., Methods: A cross-sectional survey was distributed to pharmacists working at King Abdul-Aziz Medical City-Central Region over a period of 4 months from July to October in 2015., Results: Of the 85 approached pharmacists, 66 pharmacists completed the questionnaire, among which 45 (68.2%), 9 (13.6%), and 12 (18.2%) of them were outpatient hospital pharmacists, discharge counselling pharmacists, and pharmacy practice residents, respectively. In total, 47 (55.3%) of the pharmacists sought drug information resources for newly prescribed medications to hemodialysis patients. Among the surveyed pharmacists, around two-thirds of them (63.6%) were completely confident during counselling hemodialysis patients, while 32% were moderately confident, and only 4.5% were not confident. All of the participating pharmacists checked each patient's allergic status before dispensing hemodialysis medications. The majority of the outpatient hospital pharmacists (35; 77.8%), discharge pharmacists (8; 88.9%), and the pharmacy practice residents (11; 91.7%) agreed that oral ciprofloxacin should be given after dialysis session on the same dialysis days, while 18 (40%), 5 (55.6%), and 9 (75%) of the outpatient hospital pharmacists, discharge pharmacists, and pharmacy practice residents agreed that IV route is preferred for hemodialysis patients to administer epoetin alfa, respectively. Sixty-six percent of discharge pharmacists ( n = 6), 91.7% ( n = 11) of the pharmacy practice residents, and 55.6% ( n = 25) of the outpatient hospital pharmacists checked patient laboratory results prior to dispensing medications ( p = 0.001)., Conclusions: Despite the limited knowledge regarding some prescribed medications, most of the hospital pharmacists showed good practices toward dialysis patients.

Objective: Fever alone can lead to rare serious complications in children, such as febrile seizures. The aim of this study is to assess the knowledge, beliefs, and behavior of parents toward fever and its management., Methods: A cross-sectional study using an online questionnaire was applied over a period of 3 months, from January to March 2018, to parents who were living in Saudi Arabia. The inclusion criteria were a parent who is a resident of Saudi Arabia, with at least one child aged 6 years or less, while incomplete questionnaires, having a child aged more than 6 years, or parents who were not living in Saudi Arabia were excluded., Results: A total of 656 parents completed the questionnaire. More than two-thirds of the subjects were female, the majority of whom were aged between 25-33 years old. The best-reported place to measure the temperature of children was the armpit (46%), followed by the ear (28%) and the mouth (10.7%). More than half of the parents considered their children feverish at a temperature of 38 °C. The majority of parents (79.7%) reported that the most serious side effects of fever were seizure, brain damage (39.3%), coma (29.9%), dehydration (29.7%), and death (25%). The most common method used to measure a child's temperature was an electronic thermometer (62.3%). The most common antipyretic was paracetamol (84.5%)., Conclusions: Our study demonstrates the good knowledge of parents in identifying a feverish temperature using the recommended route and tools for measuring body temperature.

Purpose: The aim of the study was to evaluate physicians' perception of the concept of pharmacokinetics and therapeutic drug monitoring (PK/TDM) and their use in clinical practice., Methods: A novel, structured, self-administered questionnaire was designed, validated and distributed to physicians in 3 major cities in Saudi Arabia (Riyadh, Jeddah, Dammam) during a 4-month period. Data were collected on demographics, knowledge and practice of PK/TDM. Attitudes toward integrating these skills into daily clinical practice were also investigated., Results: A total of 724 physicians completed the survey and included in the study. European and North American physicians were found to be more exposed to PK/TDM than other physicians. About 70% of the participants stated that they have applied PK/TDM in their practice, at least, once and most of these were consultants. Only 4.3% of respondents had never checked organ function prior to prescribing narrow therapeutic index drugs. Although the majority (78.4%) perceived PK/TDM as very important to their practice, only 35.3% have tried to calculate drug PK parameters for their patients when necessary., Conclusion: The result of this study showed that the knowledge of physicians about PK/TDM was inadequate. Moreover, the utilization of competent clinical pharmacists trained in PK/TDM was low. An interdisciplinary educational program between the physicians and pharmacist in PK/TDM will lead to a better health care outcome., Competing Interests: The authors declared that there are no conflicts of interest in this work., (© 2021 Alrabiah et al.)

This study evaluates the knowledge, attitude of Saudi mothers towards diarrhea in their children and its management at home. Online cross-sectional validated online surveys, targeting Saudi mothers who are living in Saudi Arabia, are used to collect data from the beginning of March to the end of April 2019. Our results show that a total of 1140 mothers (52.1% of them were housewives) participated in the study. Approximately 40.3% of participating mothers believed that childhood diarrhea is a major problem in the Saudi community; however, almost 23% of the participants were unable to identify any critical sign of severe diarrhea, and around 66% falsely stated that diarrhea is caused by teething. Although 62% of our participating mothers knew about oral rehydration therapy (ORS), only 23.5% of them used it for their children. Adequate knowledge about the critical signs, causes, transmission, prevention, and management of childhood diarrhea should be applied in simple language to communicate the health-related information clearly.

Background and Aim: Dyspepsia is one of the gastrointestinal diseases that is very common worldwide. Despite its prevalence globally, which ranges between 1.8% and 57%, no study has assessed the prevalence in Saudi Arabia. This study was aimed to investigate the prevalence and severity of dyspepsia in the general population of Saudi Arabia., Methods: A modified Short-Form Leeds Dyspepsia Questionnaire (SF-LDQ) was utilized to conduct our study. The questionnaire score ranges between 0 and 32, where zero indicated no dyspepsia, a score of 1-8 indicated mild dyspepsia, a score of 9-15 indicated moderate dyspepsia and a score of higher than 15 represented severe dyspepsia. Socio-demographic data of the participants including age, gender, marital status, BMI, job description, insurance, and education level were collected. Using Statistical Package for Social Sciences version 21.0 (SPSS), a univariate analysis was performed to assess the association of participants characteristics with the prevalence of dyspepsia, whereas logistic regression analysis was used to correlate their characteristics with the severity of dyspepsia., Results: During a period of one month, March 1st to 31st 2019, a total of 778 participants have completed the survey. Most of them were females accounting for 68% of the population, married (63.9%), middle aged (range 34-51 years old) and literate with high school education (72.3%). Ninety two percent (92%) of the study population were found to experience dyspepsia. However, there is no significant association between socio-demographic characteristics and dyspepsia or its severity as well., Conclusion: The prevalence of dyspepsia in Saudi Arabia is the highest in the gulf region which would potentially lead to more GI complications, and associate to poor health and economic outcomes. Education programs are essential to raise the people awareness of dyspepsia and the appropriate ways to prevent it., Competing Interests: The authors disclose no conflicts., (© 2020 The Author(s).)

Metastatic prostate cancer (PCa) has high mortality and a poor 5-year survival rate primarily due to the lack of effective treatments. Bone is the primary site of PCa metastasis in humans and the development of reliable therapeutic options for bone metastatic PCa will make a huge impact in reducing the mortality among these patients. Although P21 activated kinases (PAKs) have been studied in the past for their role in cancer, the efficacy of targeting PAKs to treat lung and bone metastatic PCa has not been tested yet. In the current study, we report that targeting PAK1 using IPA-3, an allosteric inhibitor of PAK1 kinase activity, significantly inhibits the murine metastatic PCa (RM1) cell proliferation and motility in vitro, and metastasis to the lungs in vivo. More importantly, we demonstrate for the first time that treatment with IPA-3 can blunt metastatic PCa-induced bone remodeling in vivo as analyzed by the 3-dimensional microcomputer tomography analysis. Our study has identified IPA-3 as a potential drug to treat bone metastatic PCa., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The adaptive immune response could play a major role in the resolution of lung injury. Although regulatory T cells (Tregs) have been implicated in promoting the resolution of lung injury, therapeutic strategies to enhance Treg quantity and activity at the site of injury need further exploration. In the current study, Akt inhibition using triciribine (TCBN), given 48 h after lipopolysaccharide (LPS) administration, increased Tregs-promoted resolution of acute lung injury (ALI). TCBN treatment enhanced the resolution of LPS-induced ALI on day 7 by reducing pulmonary edema and neutrophil activity associated with an increased number of CD4 + /FoxP3 + /CD103 + and CTLA4 + effector Tregs, specifically in the injured lungs and not in the spleen. Treatment of EL-4 T-lymphocytes with two Akt inhibitors (TCBN and MK-2206) for 72 h resulted in increased FoxP3 expression in vitro. On the other end, Treg-specific PTEN knockout (PTEN Treg KO) mice that have a higher Akt activity in its Tregs exhibited a significant impairment in ALI resolution, increased edema, and neutrophil activity associated with a reduced number of CD4 + /FoxP3 + /CD103 + and CTLA4 + effector Tregs as compared with the control group. In conclusion, our study identifies a potential target for the treatment of late-stage ALI by promoting resolution through effector Treg-mediated suppression of inflammation.

Several studies have unraveled the negative role of Akt1 in advanced cancers, including metastatic prostate cancer (mPCa). Hence, understanding the consequences of targeting Akt1 in the mPCa and identifying its downstream novel targets is essential. We studied how Akt1 deletion in PC3 and DU145 cells activates the Nodal pathway and promotes PCa epithelial-to-mesenchymal transition (EMT) and metastasis. Here we show that Akt1 loss increases Nodal expression in PCa cells accompanied by activation of FoxO1/3a, and EMT markers Snail and N-cadherin as well as loss of epithelial marker E-cadherin. Treatment with FoxO inhibitor AS1842856 abrogated the Nodal expression in Akt1 deleted PCa cells. Akt1 deficient PCa cells exhibited enhanced cell migration and invasion in vitro and lung metastasis in vivo, which were attenuated by treatment with Nodal pathway inhibitor SB505124. Interestingly, Nodal mRNA analysis from two genomic studies in cBioportal showed a positive correlation between Nodal expression and Gleason score indicating the positive role of Nodal in human mPCa. Collectively, our data demonstrate Akt1-FoxO3a-Nodal pathway as an important mediator of PCa metastasis and present Nodal as a potential target to treat mPCa patients., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Aims/hypothesis: Breakdown of the inner blood-retinal barrier (BRB) is an early event in the pathogenesis of diabetic macular oedema, that eventually leads to vision loss. We have previously shown that diabetes causes an imbalance of nerve growth factor (NGF) isoforms resulting in accumulation of its precursor proNGF and upregulation of the p75 neurotrophin receptor (p75 NTR ), with consequent increases in the activation of Ras homologue gene family, member A (RhoA). We also showed that genetic deletion of p75 NTR in diabetes preserved the BRB and prevented inflammatory mediators in retinas. This study aims to examine the therapeutic potential of LM11A-31, a small-molecule p75 NTR modulator and proNGF antagonist, in preventing diabetes-induced BRB breakdown. The study also examined the role of p75 NTR /RhoA downstream signalling in mediating cell permeability., Methods: Male C57BL/6 J mice were rendered diabetic using streptozotocin injection. After 2 weeks of diabetes, mice received oral gavage of LM11A-31 (50 mg kg -1  day -1 ) or saline (NaCl 154 mmol/l) for an additional 4 weeks. BRB breakdown was assessed by extravasation of BSA-AlexaFluor-488. Direct effects of proNGF were examined in human retinal endothelial (HRE) cells in the presence or absence of LM11A-31 or the Rho kinase inhibitor Y-27632., Results: Diabetes triggered BRB breakdown and caused significant increases in circulatory and retinal TNF-α and IL-1β levels. These effects coincided with significant decreases in retinal NGF and increases in vascular endothelial growth factor and proNGF expression, as well as activation of RhoA. Interventional modulation of p75 NTR activity through treatment of mouse models of diabetes with LM11A-31 significantly mitigated proNGF accumulation and preserved BRB integrity. In HRE cells, treatment with mutant proNGF (10 ng/ml) triggered increased cell permeability with marked reduction of expression of tight junction proteins, zona occludens-1 (ZO-1) and claudin-5, compared with control, independent of inflammatory mediators or cell death. Modulating p75 NTR significantly inhibited proNGF-mediated RhoA activation, occludin phosphorylation (at serine 490) and cell permeability. ProNGF induced redistribution of ZO-1 in the cell wall and formation of F-actin stress fibres; these effects were mitigated by LM11A-31., Conclusions/interpretation: Targeting p75 NTR signalling using LM11A-31, an orally bioavailable receptor modulator, may offer an effective, safe and non-invasive therapeutic strategy for treating macular oedema, a major cause of blindness in diabetes.

Recent studies conducted in the mouse and cellular models suggest a stage-specific, differential effect of Akt activity modulation on tumor growth and metastasis in various cancers. In prostate cancer (PCa), although the deletion of Akt1 gene in a neuroendocrine model of TRansgenic Adenocarcinoma of the Mouse Prostate (TRAMP) blunted oncogenic transformation and tumor growth, Akt1 suppression in the advanced PCa resulted in the activation of transforming growth factor-β pathway and enhanced metastasis to the lungs. Such a dual role for the Akt isoforms and its signaling partners has not been investigated in human PCa. In the current study, we performed genomic database analysis of Akt isoforms and associated pathway molecules in human prostate adenocarcinoma, castration-resistant PCa, neuroendocrine PCa and metastatic PCa for mutations, genetic alterations, mRNA and protein expressions and activating phosphorylations from cBioportal. Results from the protein data analysis from the cBioportal were compared to the results of our data on human PCa tissue analysis and the cellular effects of Akt1 suppression using MK-2206 on PCa cell aggressiveness. Our study indicates the existence of a dual role for Akt1 in PCa and warrants a large-scale analysis of the early and advanced stage PCa clinical samples for further clarity., Competing Interests: CONFLICTS OF INTEREST Authors declare that there are no financial or conflicts of interests exist.

Decades of research have elucidated the critical role of Akt isoforms in cancer as pro-tumorigenic and metastatic regulators through their specific effects on the cancer cells, tumor endothelial cells and the stromal cells. The pro-cancerous role of Akt isoforms through enhanced cell proliferation and suppression of apoptosis in cancer cells and the cells in the tumor microenvironment is considered a dogma. Intriguingly, studies also indicate that the Akt pathway is essential to protect the endothelial-barrier and prevent aberrant vascular permeability, which is also integral to tumor perfusion and metastasis. To complicate this further, a flurry of recent reports strongly indicates the metastasis suppressive role of Akt, Akt1 in particular in various cancer types. These reports emanated from different laboratories have elegantly demonstrated the paradoxical effect of Akt1 on cancer cell epithelial-to-mesenchymal transition, invasion, tumor endothelial-barrier disruption, and cancer metastasis. Here, we emphasize on the specific role of Akt1 in mediating tumor cell-vasculature reciprocity during the advanced stages of cancers and discuss how Akt1 differentially regulates cancer metastasis through mechanisms distinct from its pro-tumorigenic effects. Since Akt is integral for insulin signaling, endothelial function, and metabolic regulation, we also attempt to shed some light on the specific effects of diabetes in modulating Akt pathway in the promotion of tumor growth and metastasis., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The angiotensin II type 2 receptor (AT 2 R) agonist, compound 21 (C21), has been shown to be neurovascularly protective after ischemic stroke in male rats. In the current study, we aim to study the impact of C21 treatment on female rats. Young female Wistar rats were subjected to different durations of middle cerebral artery occlusion (MCAO) (3 h, 2 h, and 1 h) using a silicone-coated monofilament, treated at reperfusion with 0.03 mg/kg ip of C21 and followed up for different times (1, 3, and 14 days) after stroke. Behavioral tests were performed (Bederson, paw grasp, beam walk, and rotarod), and animals were euthanized for infarct size analysis and Western blot analysis. In vitro, primary male and female brain microvascular endothelial cells (ECs) were grown in culture, and the expression of the AT 2 R was compared between males and females. At 1 day, C21 treatment resulted in an improvement in Bederson scores. However, at 3 days and 14 days, the impact of C21 on stroke outcomes was less robust. In vitro, the expression of the AT 2 R was significantly higher in female ECs compared with male ECs. In conclusion, C21 improves Bederson scores after stroke in female rats when administered early at reperfusion. The ability of C21 to exert its neuroprotective effects might be affected by fluctuating levels of female hormones. NEW & NOTEWORTHY The present study shows the neuroprotective impact of C21 on ischemic stroke in female rats and how the protective effects of C21 can be influenced by the hormonal status of female rodents.

Enhanced vascular permeability is associated with inflammation and edema in alveoli during the exudative phase of acute respiratory distress syndrome (ARDS). Mechanisms leading to the endothelial contribution on the early exudative stage of ARDS are not precise. We hypothesized that modulation of endothelial stromelysin1 expression and activity by Akt1-forkhead box-O transcription factors 1/3a (FoxO1/3a) pathway could play a significant role in regulating pulmonary edema during the initial stages of acute lung injury (ALI). We utilized lipopolysaccharide (LPS)-induced mouse ALI model in vivo and endothelial barrier resistance measurements in vitro to determine the specific role of the endothelial Akt1-FoxO1/3a-stromelysin1 pathway in ALI. LPS treatment of human pulmonary endothelial cells resulted in increased stromelysin1 and reduced tight junction claudin5 involving FoxO1/3a, associated with decreased trans-endothelial barrier resistance as determined by electric cell-substrate impedance sensing technology. In vivo, LPS-induced lung edema was significantly higher in endothelial Akt1 knockdown (EC-Akt1 -/- ) compared to wild-type mice, which was reversed upon treatment with FoxO inhibitor (AS1842856), stromelysin1 inhibitor (UK356618) or with shRNA-mediated FoxO1/3a depletion in the mouse lungs. Overall, our study provides the hope that targeting FoxO and styromelysin1 could be beneficial in the treatment of ALI., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Recent studies indicate a stage-specific, differential role for the oncogene Akt on various cancers. In prostate cancer (PCa), suppression of Akt activity in the advanced stages promoted transforming growth factor-β (TGFβ) pathway-mediated epithelial-to-mesenchymal transition (EMT) and metastasis to the lungs. In the current study, we performed Affymetrix analysis to compare the expression profile of microRNAs in the mouse prostate tissues collected at the prostatic inter-epithelial neoplasia (PIN) stage from Transgenic adenocarcinoma of the mouse (TRAMP)/Akt1 +/+ versus TRAMP/Akt1 -/- prostate tumors express a set of miRNAs responsible for regulating cancer cell survival, proliferation, and tumor growth, whereas, in the advanced stages, a different set of miRNAs that promote EMT and cancer metastasis is expressed. Our study has identified novel Akt-regulated signature microRNAs in the early and advanced PCa and demonstrates their differential effects on PCa growth and metastasis.TRAMP/Akt1 +/+ mice treated with triciribine (Akt inhibitor) versus DMSO-treated control. Our analysis demonstrates that in the early stage, Akt1 in the TRAMP prostate tumors express a set of miRNAs responsible for regulating cancer cell survival, proliferation, and tumor growth, whereas, in the advanced stages, a different set of miRNAs that promote EMT and cancer metastasis is expressed. Our study has identified novel Akt-regulated signature microRNAs in the early and advanced PCa and demonstrates their differential effects on PCa growth and metastasis.

Background: Cancer research, in general, is focused on targeting tumour cells to limit tumour growth. These studies, however, do not account for the specific effects of chemotherapy on tumour endothelium, in turn, affecting metastasis., Methods: We determined how endothelial deletion of Akt1 promotes prostate cancer cell invasion in vitro and metastasis to the lungs in vivo in endothelial-specific Akt1 knockdown mice., Results: Here we show that metastatic human PC3 and DU145 prostate cancer cells invade through Akt1-deficient human lung endothelial cell (HLEC) monolayer with higher efficiency compared to control HLEC. Although the endothelial Akt1 loss in mice had no significant effect on RM1 tumour xenograft growth in vivo, it promoted metastasis to the lungs compared to the wild-type mice. Mechanistically, Akt1-deficient endothelial cells exhibited increased phosphorylation and nuclear translocation of phosphorylated β-catenin, and reduced expression of tight-junction proteins claudin-5, ZO-1 and ZO-2. Pharmacological inhibition of β-catenin nuclear translocation using compounds ICG001 and IWR-1 restored HLEC tight-junction integrity and inhibited prostate cancer cell transendothelial migration in vitro and lung metastasis in vivo., Conclusions: Here we show for the first time that endothelial-specific loss of Akt1 promotes cancer metastasis in vivo involving β-catenin pathway.

Akt1 is essential for the oncogenic transformation and tumor growth in various cancers. However, the precise role of Akt1 in advanced cancers is conflicting. Using a neuroendocrine TRansgenic Adenocarcinoma of the Mouse Prostate (TRAMP) model, we first show that the genetic ablation or pharmacological inhibition of Akt1 in mice blunts oncogenic transformation and prostate cancer (PCa) growth. Intriguingly, triciribine (TCBN)-mediated Akt inhibition in 25-week old, tumor-bearing TRAMP mice and Akt1 gene silencing in aggressive PCa cells enhanced epithelial to mesenchymal transition (EMT) and promoted metastasis to the lungs. Mechanistically, Akt1 suppression leads to increased expression of EMT markers such as Snail1 and N-cadherin and decreased expression of epithelial marker E-cadherin in TRAMP prostate, and in PC3 and DU145 cells. Next, we identified that Akt1 knockdown in PCa cells results in increased production of TGFβ1 and its receptor TGFβ RII, associated with a decreased expression of β-catenin. Furthermore, treatment of PCa cells with ICG001 that blocks nuclear translocation of β-catenin promoted EMT and N-cadherin expression. Together, our study demonstrates a novel role of the Akt1-β-catenin-TGFβ1 pathway in advanced PCa., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Isoform specific expression, intracellular localization and function of Akt in bladder cancer are not known. In the current study, we identified Akt1, followed by Akt2 and Akt3 as the predominant Akt isoform in human T24 and UM-UC-3 metastatic bladder cancer cells. Whereas Akt1 is localized at the membrane, cytoplasm and nucleus, Akt2 is solely cytoplasmic and Akt3 is mostly localized in the nucleus in T24 cells. ShRNA-mediated Akt1 knockdown resulted in impaired T24 cell survival, proliferation, colony formation, migration and microinvasion. Whereas pharmacological inhibition of Akt1 resulted in impaired T24 and UM-UC-3 cell motility, viability and proliferation, effect of pharmacological inhibition by Akt2 inhibitor was limited to proliferation in T24, but not UM-UC-3 cells. Our data provide important clues on the therapeutic benefits of targeting Akt1 for bladder cancer therapy., (Copyright © 2015 Elsevier B.V. All rights reserved.)