Synthesis, In vitro and In silico Studies of Novel bis-triazolopyridopyrimidines from Curcumin Analogues as Potential Aromatase Agents.

This study aims to combat breast cancer, which is a significant health concern for women worldwide. By targeting aromatase, an enzyme crucial in estrogen synthesis, the research focuses on breast cancer cases, emphasizing the importance of hormonal therapy. The innovative approach of this study involves the synthesis of novel bis-triazolopyridopyrimidines, designed to amplify the combined pharmacological advantages of the pyridopyrimidine and 1,2,4-triazole structures known for their aromatase inhibition and anti-cancer capabilities. Through the synthesis and characterization of these compounds using 1H-NMR, 13C-NMR, and MS spectral analyses, and evaluating their anticancer efficacy with MTT assays against MCF-7 breast cancer cell lines in vitro, the research endeavors to develop potent aromatase inhibitors as viable anti-breast cancer agents. Identifying compounds with strong binding energies to aromatase through molecular docking analyses further supports their potential effectiveness in inhibiting aromatase activity, a key mechanism in breast cancer progression. The findings, particularly regarding compounds 5b, 5c, 10a, and 10b, which exhibited the strongest binding energies with aromatase, highlight promising candidates for further development and testing as potential therapeutic agents against breast cancer. This approach showcases the potential of these synthesized compounds in combating breast cancer by inhibiting aromatase activity.

Sitagliptin ameliorates L-arginine-induced acute pancreatitis via modulating inflammatory cytokines expression and combating oxidative stress.

Background: Acute pancreatitis (AP) is an inflammatory condition that resolves spontaneously, but occasionally, develops into systemic inflammation, organ failure and mortality. Oxidative stress and activation of inflammatory pathways represent major players in AP pathogenesis. Current management of AP relies on attenuating injuries to the pancreas and putting the inflammatory process under control. In this study, we investigated the role of sitagliptin in modulating L-arginine-induced AP in rats. Methods: Swiss rats were subdivided into a healthy control group, AP group (a single dose of L-arginine 250 mg/100 g, intraperitoneal), and sitagliptin + L-arginine-treated group (10 mg sitagliptin/kg body weight/day, orally). Sitagliptin treatment started 1 hour after L-arginine injection and continued for 3days. Biochemical and histopathological investigations were performed on serum and tissue samples collected from test animals. Results: L-arginine increased pancreatic meyloperoxidase and serum amylase- and lipase activities and serum levels of TNF-α, LT-α, IFN-γ, IL-1α/ß, IL-6, IL-10, IL-12, and IL-15. AP animals showed elevated MDA and NO and decreased GSH and serum calcium levels. Histopathological changes were observed by H&E staining. Sitagliptin treatment significantly ameliorated these biochemical and histological changes diminishing the signs of AP. Conclusion: Sitagliptin treatment was effective in ameliorating L-arginine-induced AP which can be regarded to its anti-inflammatory and antioxidant effect.

Fine-tuning Fluorescence of Amlodipine Adopting on Blocking of Photoinduced Electron Transfer (PET): Application in Human Plasma.

Assessing medication adherence through the determination of antihypertensive drugs in biological matrices holds significant importance. Amlodipine (AP), a potent antihypertensive medication extensively prescribed for hypertensive patients, is particularly noteworthy in this context. This article aims to introduce a rapid, simple, improved sensitivity, and reproducibility in detecting AP in its pure form, tablet formulation, and spiked human plasma than the other reported methods. The proposed method utilizes a fluorescence approach, relying on the inhibition of the intramolecular photoinduced electron transfer (PET) effect of the lone pair of the N-atom in the primary amino moiety of AP. This inhibition is achieved by acidifying the surrounding medium using 0.2 M acetic acid. By blocking PET, the target AP drug is sensitively detected, at [Formula: see text] 423 nm over a concentration range 25-500 ng mL- 1 showcasing an exceptionally low quantitation limit of 1.41 ng mL- 1. Notably, this innovative technique was successfully applied to detect AP in its solid dosage form and spiked human plasma. Remarkably, matrix interference was found to be insignificant, underscoring the robustness and applicability of the established approach. The combination of speed, sensitivity, and reproducibility makes this method particularly suitable for assessing medication adherence in patients prescribed AP for hypertension.

Repaglinide-Solid Lipid Nanoparticles in Chitosan Patches for Transdermal Application: Box-Behnken Design, Characterization, and In Vivo Evaluation.

Background: Repaglinide (REP) is an antidiabetic drug with limited oral bioavailability attributable to its low solubility and considerable first-pass hepatic breakdown. This study aimed to develop a biodegradable chitosan-based system loaded with REP-solid lipid nanoparticles (REP-SLNs) for controlled release and bioavailability enhancement via transdermal delivery. Methods: REP-SLNs were fabricated by ultrasonic hot-melt emulsification. A Box-Behnken design (BBD) was employed to explore and optimize the impacts of processing variables (lipid content, surfactant concentration, and sonication amplitude) on particle size (PS), and entrapment efficiency (EE). The optimized REP-SLN formulation was then incorporated within a chitosan solution to develop a transdermal delivery system (REP-SLN-TDDS) and evaluated for physicochemical properties, drug release, and ex vivo permeation profiles. Pharmacokinetic and pharmacodynamic characteristics were assessed using experimental rats. Results: The optimized REP-SLNs had a PS of 249±9.8 nm and EE of 78%±2.3%. The developed REP-SLN-TDDS demonstrated acceptable characteristics without significant aggregation of REP-SLNs throughout the casting and drying processes. The REP-SLN-TDDS exhibited a biphasic release pattern, where around 36% of the drug load was released during the first 2 h, then the drug release was sustained at around 80% at 24 h. The computed flux across rat skin for the REP-SLN-TDDS was 2.481±0.22 µg/cm2/h in comparison to 0.696±0.07 µg/cm2/h for the unprocessed REP, with an enhancement ratio of 3.56. The REP-SLN-TDDS was capable of sustaining greater REP plasma levels over a 24 h period (p<0.05). The REP-SLN-TDDS also reduced blood glucose levels compared to unprocessed REP and commercial tablets (p<0.05) in experimental rats. Conclusion: Our REP-SLN-TDDS can be considered an efficient therapeutic option for REP administration.

Improving fluorescence emission of cyproheptadine by hindering its intramolecular photoinduced electron transfer (PET): Application to content uniformity testing and human plasma.

The ability to determine antihistaminic drugs in biological matrices is critical for the medication adherence assessment. Among these antihistaminic medications, cyproheptadine (CPD); that is acting as a potent first-generation antihistaminic drug that has been extensively prescribed for allergic patients. Most of the established approaches for CPD detection are not appropriate for this purpose owing to their weak sensitivity, lack of rapidity, and complicated experimental procedures. Herein, we present a very fast, highly sensitive, and reproducible approach for the detection of CPD in its pure form, tablet formulation, and spiked human plasma. The photoluminescence approach depends on hindering the intramolecular photoinduced electron transfer (PET) effect of the lone pair of the N-atom present on the piperidine ring of CPD by making the surrounding medium acidic using 1.0 M acetic acid. Based on blocking PET, the target CPD drug has been sensitively detected from 5.0 to 500 ng mL-1 with a very low detection and quantitation limit of 7.01 and 21.25 ng mL-1, respectively. Moreover, the established approach was used for checking the tablet content uniformity testing for each tablet and spiked human plasma, and noteworthy, the matrices interference was insignificant.

Migraine Management in Community Pharmacies: Knowledge, Attitude and Practice Patterns of Pharmacists in Saudi Arabia.

In Saudi Arabia, community pharmacies offer healthcare services for different conditions. However, clarity of the competence of pharmacists in managing migraines is lacking. This study aimed to explore the current knowledge, attitude, and practice patterns of community pharmacists concerning migraine management in the northwestern part of Saudi Arabia. A cross-sectional study was carried out between June and September 2022 among 215 Saudi community pharmacists. Data analysis was performed by descriptive and inferential statistics using SPSS version 27. Most community pharmacists (87.9%) feel that migraine management is essential to their practice, and 83.3% suggest between one and five over-the-counter (OTC) migraine products daily. Among the study pharmacists, 83.7% feel migraine patients should try OTC before prescription medications. Only 9.3% of the community pharmacists do not believe that migraine is a neurological disorder. The medications most prescribed for migraine were triptans, representing 52.1% of prescriptions. There were significant differences between the gender of the pharmacists and their knowledge, attitude, and practice overall score (p-value = 0.04). Male pharmacists exhibited higher knowledge, attitude, and practice scores than female pharmacists. Although many community pharmacists acknowledge their expertise and involvement in managing migraines, there is a requirement for further education and training to enhance their capacity to offer complete care to migraine patients. Pharmacists should also consider non-pharmacological interventions and complementary therapies when treating migraine symptoms.

The impact of CYP3A4 and CYP3A5 genetic variations on tacrolimus treatment of living-donor Egyptian kidney transplanted patients.

BACKGROUND: Tacrolimus (TAC) is the mainstay of immunosuppressive regimen for kidney transplantations. Its clinical use is complex due to high inter-individual variations which can be partially attributed to genetic variations at the metabolizing enzymes CYP3A4 and CYP3A5. Two single nucleotide polymorphisms (SNPs), CYP3A4*22 and CYP3A5*3, have been reported as important causes of differences in pharmacokinetics that can affect efficacy and/or toxicity of TAC. OBJECTIVE: Investigating the effect of CYP3A4*22 and CYP3A5*3 SNPs individually and in combination on the TAC concentration in Egyptian renal recipients. METHODS: Overall, 72 Egyptian kidney transplant recipients were genotyped for CYP3A4*22 G>A and CYP3A5*3 T>C. According to the functional defect associated with CYP3A variants, patients were clustered into: poor (PM) and non-poor metabolizers (Non-PM). The impact on dose adjusted through TAC concentrations (C0) and daily doses at different time points after transplantation was evaluated. RESULTS: Cyp3A4*1/*22 and PM groups require significantly lower dose of TAC (mg/kg) at different time points with significantly higher concentration/dose (C0/D) ratio at day 10 in comparison to Cyp3A4*1/*1 and Non-PM groups respectively. However, CyP3A5*3 heterozygous individuals did not show any significant difference in comparison to CyP3A5*1/*3 individuals. By comparing between PM and Non-PM, the PM group had a significantly lower rate of recipients not reaching target C0 at day 14. CONCLUSION: This is the first study on Egyptian population to investigate the impact of CYP3A4*22 and CYP3A5*3 SNPs individually and in combination on the TAC concentration. This study and future multicenter studies can contribute to the individualization of TAC dosing in Egyptian patients.

Assessment of risk factors associated with multidrug-resistant organism infections among patients admitted in a tertiary hospital - a retrospective study.

Background: Bacterial resistance has become a global health concern. To treat suspected multidrug resistant organisms (MDROs), physicians first use broad-spectrum antibiotics; however, this increases the chance of developing antimicrobial resistance. Thus, defining the risk factors for MDROs could aid in the selection of the ideal initial antimicrobial therapy and improve clinical outcomes. Objective: This study aimed to identify the common risk factors for MDRO infection among patients admitted to King Fahad Hospital (KFH) and to analyze the comorbidity factors associated with MDRO infections. Methods: This retrospective, observational, case-control study included adult patients ≥ 18 years old admitted to KFH between 1st of January to 31st of March 2021, with positive microbial culture. Pediatric patients, outpatients, or patients with only positive fungal cultures were excluded. Data were obtained from the KFH laboratory MDRO documenting database. Results: Two hundred and seventy patients were included in this study: 136 in the study group and 134 in the control group. Among patients, 167 (61.9 %) were males and 184 (68.1%) were 18 to 65 years old. The use of drugs such as cotrimoxazole, amikacin, and imipenem (OR = 4.331, C. I. of OR:1.728, 10.855, p = 0.002) were significantly associated with MDRO infections, whereas cefazolin was associated with a lower risk of MDRO infections (OR = 0.080, C.I. of OR:0.018, 0.347, p < 0.001). The intensive care unit showed higher odds of significant association with MDRO infections than those of the surgical unit (odds ratio [OR] = 8.717, 95% C.I. of OR: 3.040, 24.998, p < 0.001). Patients who previously consumed acid-suppressive medications showed higher odds of developing MDRO infections (OR = 5.333, C.I. of OR: 2.395, 11.877, p < 0.001). Conclusion: The most significant comorbidities were diabetes, hypertension, antibiotic use prior to hospitalization and the use of cotrimoxazole, amikacin and imipenem among other antibtiotics was mostly associated with MRDO infections. This study revealed an increasing trend of MDRO infections and a positive correlation with the incidence of strokes and mortality, which highlights the importance of understanding the risk factors for MDRO infections.

Combination of Niclosamide and Pirfenidone Alleviates Pulmonary Fibrosis by Inhibiting Oxidative Stress and MAPK/Nf-κB and STATs Regulated Genes.

The pathogenesis of pulmonary fibrosis (PF) is extremely complex and involves numerous intersecting pathways. The successful management of PF may require combining multiple agents. There is a growing body of evidence that suggests the potential benefits of niclosamide (NCL), an FDA-approved anthelminthic drug, in targeting different fibrogenesis molecules. This study aimed at investigating the anti-fibrotic potential of NCL alone and in combination with pirfenidone (PRF), an approved drug for PF, in a bleomycin (BLM) induced PF experimental model. PF was induced in rats by intratracheal BLM administration. The effect of NCL and PRF individually and in combination on different histological and biochemical parameters of fibrosis was investigated. Results revealed that NCL and PRF individually and in combination alleviated the histopathological changes, extracellular matrix deposition and myofibroblastic activation induced by BLM. NCL and PRF either individually or in combination inhibited the oxidative stress and subsequent pathways. They modulated the process of fibrogenesis by inhibiting MAPK/NF-κB and downstream cytokines. They inhibited STATs and downstream survival-related genes including BCL-2, VEGF, HIF-α and IL-6. Combining both drugs showed significant improvement in the tested markers in comparison to the monotherapy. NCL, therefore, has a potential synergistic effect with PRF in reducing the severity of PF.

IL-6 at the center of cytokine storm: Circulating inflammation mediators as biomarkers in hospitalized COVID-19 patients.

INTRODUCTION: The management of hospitalized COVID-19 patients depends largely on controlling the intensified inflammatory response known as the cytokine storm. Candidate inflammatory cytokines can serve as new biomarkers for the management of hospitalized COVID-19 patients. METHODS: Patients (80) were recruited into three groups: room air (RA), oxygen (OX) and mechanical ventilator (MV). Blood analysis was performed for RBC, WBC, Hb, Platelets, serum albumin and creatinine, INR, PTT, and hematocrit. ELISA was used to quantify a panel of inflammatory mediators including GM-SCF, IFN-α, IFNγ, IL-1ß, IL-1R, IL-2, IL-2Ra, IL-6, IL-8, IL-10, IL-12p70, IL-13, MCP-1, MIP-1a, and TNF-α. Correlations between laboratory results and the levels of circulating inflammation mediators were investigated. RESULTS: Patients on MV had low RBC, Hb, albumin, and HCT and high WBC count, PTT, and INR when compared to RA and OX groups. A statistical positive correlation was found between WBC and the levels of IL-6 and MCP-1. RBCs correlated negatively with IL-6 and IL-10 and positively with IL-8. Higher TNF-α correlated with lower platelet counts while higher levels of IL-1Rα and IL-10 were associated with lower Hb levels. Increases in IFN-γ and TNF-α were indicative of compromised kidney functions as creatinine levels increased significantly. Most significant correlations were found between IL-6 and lab results, showing positive correlation with WBC and INR, and negative correlation with RBC, albumin, and HCT. CONCLUSIONS: Having the most significant correlations, IL-6 high levels in mechanically ventilated patients were shown to affect laboratory results, and, therefore, is suggested as a severity biomarker of COVID-19.

Alpha-Mangostin ameliorates acute kidney injury via modifying levels of circulating TNF-α and IL-6 in glycerol-induced rhabdomyolysis animal model.

Alpha mangostin (AM), isolated from G. mangostana, showed beneficial effects in several disorders due to its antioxidant and anti-inflammatory properties. Acute kidney injury (AKI) due to different etiologies can develop into severe complications, resulting in high mortality rates. In this work, AM is tested for its ability to alleviate AKI in glycerol-induced AKI rat model, where 30 Male Sprague-Dawley rats were assigned to a healthy group, glycerol-treated group and AM-treated group. Glycerol- and AM groups received a single dose of glycerol (per IM, 50% glycerol in saline, 8 ml/kg), whereas control group was injected with saline. AM treatment (a single daily dose, per IP, 175mg/kg) was accomplished for three days. Animals were executed to collect blood samples and kidney tissue for biochemical and histological examination. It was found that glycerol induced increase in serum creatinine, blood urea nitrogen (BUN), lipid peroxidation, serum magnesium, TNF-α and IL-6. It also induced renal edema and hypocalcemia along with histopathological renal damage. AM treatment improved renal histological features and alleviated increase in serum creatinine, BUN, serum magnesium, TNF-α and IL-6 levels, as well as renal edema and lipid peroxidation but did not affect serum calcium levels. This suggests AM as a potential therapeutic agent for treating AKI mainly via its antioxidant and anti-inflammatory properties.

Alpha-Mangostin as a New Therapeutic Candidate for Concanavalin A-Induced Autoimmune Hepatitis: Impact on the SIRT1/Nrf2 and NF-κB Crosstalk.

Alpha-mangostin (α-MN) is a xanthone obtained from Garcinia mangostana that has diverse anti-oxidative and anti-inflammatory potentials. However, its pharmacological activity against autoimmune hepatitis (AIH) has not been investigated before. Concanavalin A (Con A) was injected into mice to induce AIH and two doses of α-MN were tested for their protective effects against Con A-induced AIH. The results demonstrated the potent hepatoprotective activity of α-MN evidenced by a remarkable decrease of serum indices of the hepatic injury and amendment of the histological lesions. α-MN significantly attenuated the level and immuno-expression of myeloperoxidase (MPO) indicating a decrease in the neutrophil infiltration into the liver. Additionally, the recruitment of the CD4+ T cell was suppressed in the α-MN pre-treated animals. α-MN showed a potent ability to repress the Con A-induced oxidative stress evident by the reduced levels of malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), and protein carbonyl (PC), as well as the enhanced levels of antioxidants as the reduced glutathione (GSH), superoxide dismutase (SOD), and total antioxidant capacity (TAC). The ELISA, RT-PCR, and IHC analyses revealed that α-MN enhanced the sirtuin1/nuclear factor erythroid 2 related factor-2 (SIRT1/Nrf2) signaling and its downstream cascade genes concurrently with the inhibition of the nuclear factor kappa B (NF-κB) and the inflammatory cytokines (tumor necrosis factor-alpha and interleukine-6) signaling. Taken together, these results inferred that the hepatoprotective activity of α-MN could prevent Con A-induced AIH through the modulation of the SIRT1/Nrf2/NF-κB signaling. Hence, α-MN may be considered as a promising candidate for AIH therapy.

Incremental Concentrations of Tacrolimus Eye Drops as a Strategy for the Management of Severe Vernal Keratoconjunctivitis.

Purpose: To assess the effect of different concentrations of tacrolimus eye suspension on the epithelium and stromal keratocytes of human corneas and investigate whether it can be safely used for severe cases of vernal keratoconjunctivitis (VKC). Methods: Tacrolimus eye suspension was prepared in a range of concentrations of 0.005%, 0.01%, 0.05%, 0.1%, and 0.2%. Molecular analysis was performed ex vivo on human corneas (n = 18), obtained from the eye bank. Transparency and thickness of each cornea were measured while live/dead staining was performed using a triple labeling assay. An incremental concentration approach was then tested on three severe cases of VKC. Results: All tested tacrolimus concentrations showed no significant changes in corneal thickness or transparency. In corneas treated with 0.1%, rare scattered dead cells were observed, while the folds of corneal surfaces were mostly viable, unlike concentrations higher than 0.1% and lower than 0.05%. Stromal cell densities were highest in the 0.1% tacrolimus treatment condition. Incremental concentrations of tacrolimus suspension were shown to significantly improve VKC cases, where the concentration used for each case depended on the severity of the case. Conclusions: Topical administration of tacrolimus was not toxic to human corneal cells at all tested concentrations, and the 0.1% concentration has shown the best viability of the corneal tissue. Tacrolimus eye suspension was shown to be safe and effective for use in severe VKC and is proposed as a topical ocular immunosuppressant drug enabling clinicians to incrementally increase the drug concentration according to the clinical severity of the disease to achieve the optimal therapeutic response.

Prognostic factors for predicting severity and mortality in hospitalized COVID-19 patients.

BACKGROUND: Coronavirus disease 2019, COVID-19, has reached all the corners of the world and was declared by the WHO as a global pandemic and public health emergency of international concern on the January 31, 2020. Allocating quick and specific biomarkers to predict the disease severity upon admission to hospital became a crucial need. This study, therefore, aimed at exploring the relationship between laboratory results in COVID-19 patients admitted to hospital and the final outcome in these patients. METHODS: Retrospective analysis was performed on the medical records of 310 COVID-19-positive patients admitted to Uhod Hospital, the referral hospital in the area of Madinah, Kingdom of Saudi Arabia, between the April 13 and the July 29, 2020. The association of laboratory results with the survival/mortality outcomes was studied. RESULTS: It was demonstrated that lymphopenia, prolonged aPTT, high INR, high D. dimer and high CK are valuable prognostic predictors of the severity of the disease at early stages that can determine the outcome. Based on the results of the multiple logistic regression, the variables that are associated with death outcome are aPTT, HR, RR, ALT and CK level CONCLUSION: It is proposed to perform these tests on admission to hospital for moderate to severe COVID-19 patients to improve the management of those cases and reduce mortality.

Impact of narrow-band ultraviolet B radiation therapy on the quality of life of patients with vitiligo.

OBJECTIVES: Patients with vitiligo experience emotional and psychological stress as they undergo long-term therapy. The debilitating psychosocial effects of this disease on patients' quality of life is well-documented. This study evaluates the effect of the introduction of narrow-band ultraviolet-B (NB-UVB) therapy on the quality of life of patients with vitiligo in Almadinah Almunawwarah, KSA. METHODS: Thirty-eight patients from the main dermatology center of Ohud Hospital, Almadinah Almunawwarah, were interviewed between June 2017 and March 2019 using the Dermatology Life Quality Index (DLQI) questionnaire. The interviews were conducted before and one year after the course of NB-UVB therapy, which was added as a new treatment modality to the basic therapeutic regimen of topical medications. RESULTS: The patients' response to vitiligo therapy was positive. The overall patient satisfaction score regarding the NB-UVB therapy was as high as 9.1 out of 10. The initial overall DLQI score (5.67 ± 0.90) markedly decreased after the NB-UVB therapy (3.08 ± 0.56), indicating a significant improvement. The patients' adherence to the follow-up visits also improved. CONCLUSION: NB-UVB therapy is effective in alleviating psychological stress and improving the quality of life of patients with vitiligo.

Design of molecular hybrids of phthalimide-triazole agents with potent selective MCF-7/HepG2 cytotoxicity: Synthesis, EGFR inhibitory effect, and metabolic stability.

This study reports an efficient and convenient click chemistry synthesis of a novel series of phthalimide scaffold linked to 1,2,3 triazole ring and terminal lipophilic fragments. Structures of newly synthesized compounds were well characterized by different spectroscopic tools. In vitro MTT cytotoxicity assay was performed comparing the cytotoxic effects of newly synthesized compounds to staurosporine using three different types: human liver cancer cell line (HepG2), Michigan cancer foundation-7 (MCF-7) and human colorectal carcinoma cell line (HCT116). The initial screening showed excellent to moderate anticancer activity for these newly synthesized compounds with high degree of cell line selectivity with micromolar (µM) half maximal inhibitory concentration (IC50) values against tumor cells. The SAR analysis of these derivatives confirmed the role of molecular fragments including phthalimide, linker, triazole, and terminal tails in correlation to activity. In addition, enzymatic inhibitory assay against wild type EGFR was performed for the most active compounds to get more details about their mechanism of action. In order to further explore their binding affinities, molecular docking simulation was studied against EGFR site. The results obtained from molecular docking study and those obtained from cytotoxic screening were correlated. One of the most prominent analogs is (6f) with terminal disubstituted ring and amide linker showed selective MCF-7 cytotoxicity profile with IC50 0.22 µM and 79 nM to EGFR target. Extensive structure activity relationship (SAR) analyses were also carried out. The pharmacokinetic profile of (6f) was studied showing good metabolic stability and long duration behavior. This design offered a potent selective anticancer phthalimide-triazole leads for further optimization in cancer drug discovery.

Prevalence of dry eye syndrome in association with the use of contact lenses in Saudi Arabia.

BACKGROUND: Dry eye disease is a tear film disorder which can cause discomfort to patients and negatively affect vision acuity. A number of risk factors has been reported to affect the incidence and severity of dry eye syndrome (DES). The aim is to study the prevalence of DES in Saudi Arabia and the factors affecting the severity of DES in relation to the use of contact lenses. METHODS: A cross-sectional questionnaire-based study was conducted on 310 participants using the ocular surface disease index (OSDI) questionnaire and the eye dryness part from contact lens questionnaire-8 (CLDEQ-8). Dry eye OSDI scores were compared across different epidemiological and risk factors with focus on the use of contact lenses. Pearson and Spearman's correlation coefficients were used to analyze the frequency of contact lenses usage in relation to OSDI scores. Student's t-test and one-way analysis of variance (ANOVA) tests were used to compare means of two or more than two groups, respectively. RESULTS: Forty eight (15.5%) of participants did not have any degree of DES, achieving an OSDI score between 0 and 12. Forty participants (12.9%) scored from 13 to 22, (mild DES), 44 (14.2%) were moderate, scoring 23-32 on the OSDI, while those who scored above 33 were 178 (57.4%) had severe DES. The mean score for all participants was 37.8. A high percentage of participants (84.5%) had some degree of DES. There was a strong positive correlation between OSDI score and the frequency of the feeling of dry eye and a moderate positive correlation between OSDI score and the intensity of dryness feeling. Out of 310 participants, 136 (43.9%) indicated using contact lenses. There was no significant association between the use of contact lenses per se and DES, however, those who used contact lenses more frequently had significantly higher OSDI scores. CONCLUSIONS: Dry eye syndrome is a widespread, underdiagnosed condition in Saudi Arabia. The frequency of contact lenses use may contribute to the incidence of DES.

The detection of SARS-CoV-2 in outpatient clinics and public facilities during the COVID-19 pandemic.

The transmission of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can occur through an airborne route, in addition to contaminated surfaces and objects. In hospitals, it has been confirmed by several studies that SARS-CoV-2 can contaminate surfaces and medical equipment especially in hospitals dedicated to coronavirus disease 2019 (COVID-19) patients. The aim of this study was to detect the contamination of hands, objects, and surfaces in isolation rooms and also in outpatients' clinics in hospitals and polyclinics. Environmental contamination of public high-touch surfaces in public facilities was also investigated during an active COVID-19 pandemic. Random swabs were also taken from public shops, pharmacies, bakeries, groceries, banknotes, and automated teller machines (ATMs). Samples were analyzed for SARS-CoV-2 positivity using real-time polymerase chain reaction. In the COVID-19 regional reference hospital, only 3 out of 20 samples were positive for SARS-CoV-2 RNA. Hand swabs from SARS-CoV-2-positive patients in isolation rooms were occasionally positive for viral RNA. In outpatients' clinics, door handles were the most contaminated surfaces. Dental chairs, sinks, keyboards, ophthalmoscopes, and laboratory equipment were also contaminated. Although no positive swabs were found in shops and public facilities, random ATM swabs returned a positive result for SARS-CoV-2. Although there is no longer a focus on COVID-19 wards and isolation hospitals, more attention is required to decontaminate frequently touched surfaces in health-care facilities used by patients not diagnosed with COVID-19. Additionally, high-touch public surfaces such as ATMs require further disinfection procedures to limit the transmission of the infection.

Enhancement of atorvastatin oral bioavailability via encapsulation in polymeric nanoparticles.

Despite the fact that atrovastatin (At) is being one of the bestselling statins used to prevent complicated cardiovascular diseases, its low oral bioavailability decreases its clinical relevance. Herein, incorporation of At into ethylcellulose nanoparticles (At-NPs) was executed to test if it would enhance its oral bioavailability. The emulsification-evaporation method was used to prepare the At-NPs. The prepared nanoparticles were characterized by measuring the particle size, zeta potential as well as using FTIR, DSC, and XRD examination. The entrapment efficiency, drug content, and the in vitro release behavior of At-NPs were also examined. The in vivo oral bioavailability of the selected At-NPs formula was tested after being given orally to New Zealand rabbits. The nanoparticles obtained had a high drug content and a distinct spherical shape but with varying sizes. No physical or chemical interactions were detected between At and the nanoparticles as confirmed by FTIR, DSC, and XRD. The in vitro release study of At from the prepared At-NPs has shown nanoparticles size-dependent release behavior. The in vivo oral absorption testing confirmed the bioavailability of the prepared At-NPs to be as follows: (Cmax = 940 ng/ml and AUC0-12 = 8759 ng.h/ml) > Lipitor® (Cmax = 635 ng/ml and AUC0-12 = 4367 ng.h/ml) > At (Cmax = 515 ng/ml and AUC0-12 = 2517 ng.h/ml). These results revealed that the oral formula of At-NPs increases the bioavailability of At 3.87 times. This makes ethylcellulose nanoparticles an esteemed candidate nano-vehicle for At, increasing its bioavailability and thus improving its clinical relevance.

Generation of Combinatorial Lentiviral Vectors Expressing Multiple Anti-Hepatitis C Virus shRNAs and Their Validation on a Novel HCV Replicon Double Reporter Cell Line.

Despite the introduction of directly acting antivirals (DAAs), for the treatment of hepatitis C virus (HCV) infection, their cost, patient compliance, and viral resistance are still important issues to be considered. Here, we describe the generation of a novel JFH1-based HCV subgenomic replicon double reporter cell line suitable for testing different antiviral drugs and therapeutic interventions. This cells line allowed a rapid and accurate quantification of cell growth/viability and HCV RNA replication, thus discriminating specific from unspecific antiviral effects caused by DAAs or cytotoxic compounds, respectively. By correlating cell number and virus replication, we could confirm the inhibitory effect on the latter of cell over confluency and characterize an array of lentiviral vectors expressing single, double, or triple cassettes containing different combinations of short hairpin (sh)RNAs, targeting both highly conserved viral genome sequences and cellular factors crucial for HCV replication. While all vectors were effective in reducing HCV replication, the ones targeting viral sequences displayed a stronger antiviral effect, without significant cytopathic effects. Such combinatorial platforms as well as the developed double reporter cell line might find application both in setting-up anti-HCV gene therapy approaches and in studies aimed at further dissecting the viral biology/pathogenesis of infection.