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The present study was aimed at isolating endophytic fungi from the Algerian medicinal plant Salicornia arabica and analyzing its antifungal and antibacterial effects. The morphological analysis allowed us to identify endophyte isolates at the genus level as belonging to 8 different genera, Aureobasidium sp., Ulocladium sp., Acremonium sp., Stemphylium sp., Penicillium sp., Aspergillus sp., Phoma sp., and Chrysosporium sp. with frequency percentages 6.7%, 13.3%, 20%, 13.3%, 13.3%, 13.3%, 6.7%, 6.7%, respectively. The antimicrobial activity was caried out using the agar plug diffusion method. The three isolates of the genus Acremonium sp. were highly active against all tested bacteria except Enterococcus faecalis. Comparison of the means of inhibition zones of the active isolates showed that the three fungal isolates of Acremonium were the most active, followed by Chrysosporium sp., Penicillium sp.1, Aureobasidium sp., Stemphylium sp.1, Penicillium sp. .2, and Ulocladium sp.2. The widest zones of inhibition were 22.33 and 20.33mm for Acremonium sp.3, 18.33 and 15.33mm for Aureobasidium sp., 19.33mm for Penicillium sp.1, and 19 and 15mm for Stemphylium sp.1 obtained against Bacillus cereus and Staphylococcus aureus bacteria, respectively. Regarding the antifungal activity, the best inhibitory activity was 80 and 64.70% obtained with the isolate Penicillium sp.2 against Fusarium oxysporum f.sp. ciccri and Fusarium oxysporum f.sp. albedinis, respectively, and of 63.29 and 58% observed against Phytophthora infestans and Fusarium oxysporum f.sp. ciccri, respectively, with the endophytic isolate Aspergillus sp.2. These results indicated the possible prospect of endophytes fungi isolated from Salicornia arabica as a promising resource of antimicrobial compounds and in the quest for the potential starting points for the development of new antibiotics.

Unilateral right-sided varicocele is a rare and warning condition that should hint at a serious retroperitoneal disease such as renal cell neoplasm. Furthermore, its thrombosis is such an unusual entity that only a few cases have been described. We review the literature and report, to our knowledge, the second case of acute scrotal pain caused by unilateral right-sided varicocele thrombosis complicating an ipsilateral epididymo-orchitis, with no underlying coagulopathy or abdominal neoplasm, to illustrate the clinical, morphologic and therapeutic features of this entity.

Therapeutic drug monitoring is used to ensure that medications are prescribed and administered according to safe doseage advice and for the purpose of achieving the desired therapeutic effects in patients. Several methods are used to perform therapeutic drug monitoring. However, there is insufficient evidence to currently support therapeutic drug monitoring of Valproic acid using salivary samples. The aim of this paper is to determine the feasibility of using salivary samples as a substitute for plasma samples for therapeutic drug monitoring of Valproic acid. In this study a total of 23 patients participated, with the mean age of 33.39. Salivary and plasma samples were collected and analysed to determine the peak and trough concentrations of Valproic acid for comparison between the two methods. Calibrated LC- MS/ MS was used to measure Valproic acid levels. Statistical analyses were performed using ANOVA test and ethical approval was obtained prior to sample collection. The results showed that saliva Valproic acid levels were less than that of plasma levels. There was no significant correlation between saliva and plasma level of Valproic acid (P>0.05). However, there was a significant correlation between the area under the curve for both saliva and plasma Valproic acid (P<0.05). Creatinine clearance was significantly correlated with peak plasma levels of Valproic acid (P<0.05). Albumin was significantly correlated with plasma levels of Valproic acid. There was also a significantly positive and moderate relationship between Log Saliva Cmax and Log plasma free Valproic acid concentration (r=0.76, p<0.018). In conclusion, saliva samples can be used as a substitute for plasma samples in the therapeutic drug monitoring of Valproic acid., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Background: There is a scarcity of evidence regarding the real-world effectiveness of coronavirus disease 2019 (COVID-19) vaccines. This was the first study to evaluate the effectiveness of four types of vaccines against asymptomatic and symptomatic infection, and COVID-19 outcomes among the general population., Methods: This was a matched comparison group quasi-experimental study conducted in Jordan between 1 January and 29 August 2021. In the first part of the study, 1200 fully vaccinated individuals were matched with 1200 unvaccinated control participants. In order to measure vaccine effectiveness, the infection rates of both vaccinated and unvaccinated groups were calculated. The second part of the study included measuring specific anti-SARS CoV-2 immune cells and antibodies., Results: BNT162b2 (Pfizer, New York, NY, USA) showed a significantly higher effectiveness against asymptomatic COVID-19 infection (91.7%) and hospitalization (99.5%) than BBIBP-CorV (Sinopharm, Beijing, China) (88.4% and 98.7%, respectively) and ChAdOx1 nCoV-19 (AstraZeneca, Cambridge, UK) (84.3%, and 98.9%, respectively). The effectiveness rates of the Sputnik V (Gamaleya Research Institute, Moscow, Russia) vaccine against asymptomatic, symptomatic, and hospitalization were 100%, 100%, and 66.7%, respectively. The highest median anti-spike (S) IgG values were seen in individuals who received BNT162b2 (2.9 AU/mL) and ChAdOx1 nCoV-19 (2.8 AU/mL) vaccines. The levels of anti-S IgG were significantly decreased after 7 months of vaccination with BNT162b2 and BBIBP-CorV. There were significant decreases in the median number of neutralizing antibodies one month and seven months after receiving BNT162b2 (from 88.5 to 75.2 4 Bioequivalent Allergen Unit per milliliter/mL), BBIBP-CorV (from 69.5 to 51.5 BAU/mL), and ChAdOx1 nCoV-19 (from 69.2 to 58.BAU/mL) vaccines. The highest percentage of T cells specific to COVID-19 vaccine was found in individuals who received BNT162b2 (88.5%)., Conclusion: All four vaccines evaluated in this study showed effectiveness against asymptomatic COVID-19 infection, symptomatic infection, hospitalization, and death. Furthermore, BNT162b2, BBIBP-CorV, and ChAdOx1 nCoV-19 induced high levels of immunology markers within one month of vaccination.

Tailor-made and designed micro- and nanocarriers can bring significant benefits over their traditional macroscopic counterparts in drug delivery applications. For the successful loading and subsequent release of bioactive compounds, carriers should present a high loading capacity, trigger release mechanisms, biodegradability and biocompatibility. Hydrophobic drug molecules can accumulate in fat tissues, resulting in drawbacks for the patient's recovery. To address these issues, we propose to combine the advantageous features of both host molecules (cyclodextrin) and calcium carbonate (CaCO 3 ) particles in order to load hydrophobic chemicals. Herein, hybrid cyclodextrin-CaCO 3 micro- to nano-particles have been fabricated by combining Na 2 CO 3 solution and CaCl 2 solution in the presence of an additive, namely poly (vinylsulfonic acid) (PVSA) or glycerol (gly). By investigating experimental parameters and keeping the Na 2 CO 3 and CaCl 2 concentrations constant (0.33 M), we have evidenced that the PVSA or gly concentration and mixing time have a direct impact on the final cyclodextrine-CaCO 3 particle size. Indeed, by increasing the concentration of PVSA (5 mM to 30 mM) or gly (0.7 mM to 4 mM) or the reaction time (from 10 min to 4 h), particles with a size of 200 nm could be reached. Interestingly, the vaterite or calcite form could also be selected, according to the experimental conditions. We hypothesised that the incorporation of PVSA or gly into the precipitation reaction might reduce the nucleation rate by sequestering Ca 2+ . The obtained particles have been found to keep their crystal structure and surface charge after storage in aqueous media for at least 6 months. In the context of improving the therapeutic benefit of hydrophobic drugs, the developed particles were used to load the hydrophobic drug tocopherol acetate. The resulting particles are biocompatible and highly stable in a physiological environment (pH 7.4, 0.15 M NaCl). A selective release of the cargo is observed in acidic media (pH lower than 5).

Vancomycin is a commonly used antibiotic for multi-drug resistant gram-positive infections treatment, especially methicillin-resistant Staphylococcus aureus (MRSA). Despite that, it has wide individual pharmacokinetic variability and nephrotoxic effect. Vancomycin trough concentrations for 57 Jordanian patients were measured in plasma and saliva through immunoassay and liquid chromatography-mass spectrometry (LC-MS/MS), respectively. Plasma levels were within accepted normal range, with exception of 6 patients who showed trough levels of more than 20 μg/ml and vancomycin was discontinued. Bayesian dose-optimizing software was used for patient-specific pharmacokinetics prediction and AUC/MIC calculation. Physiological-based pharmacokinetic (PBPK) vancomycin model was built and validated through GastroPlus™ 9.8 using in-house plasma data. A weak correlation coefficient of 0.2478 (P=0.1049) was found between plasma and saliva concentrations. The suggested normal saliva trough range of vancomycin is 0.01906 to 0.028589 (μg/ml). Analysis of variance showed significant statistical effects of creatinine clearance and albumin concentration on dose-normalized Cmin plasma and saliva levels respectively, which is in agreement with PBPKmodeling. It can be concluded that saliva is not a suitable matrix for TDM of vancomycin. Trough levels in plasma matrix should always be monitored for the safety of patients., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Background: Tissue damage caused by COVID-19 could be detected by several clinical indicators including hematological, immunological, biochemical, and inflammatory markers. This study was to detect these clinical parameters to reveal the correlation between the factors and their roles in the development of COVID-19, to explore the hazard factors in severe cases., Materials and Methods: A total of 200 participants of both sexes were included in the study, with an age range of (25-72) years, categorized into three main groups: 50 healthy individuals, 62 mild infected patients, and 88 severe infected patients with pneumonia. Different hematological and clinical parameters were included in the analysis (Basrah city, Iraq). Serum levels of interleukin-6 (IL-6), ferritin, and high-sensitivity C -reactive protein (hs-CRP) were assessed for all participants using an enzyme-linked immunosorbent assay (ELISA). The liver, renal, and cardiac functions were assessed by clinical chemistry testing., Results: COVID-19 patients had leukocytosis, with an increased number of neutrophils and a decreased lymphocyte count, according to our findings. In regard to inflammatory parameters, both ESR and hs-CRP showed significant differences between the two groups, whereas IL-6 was significantly higher in the total severe group compared to the other two groups. Biochemical results revealed that each lactate dehydrogenase (LDH), ferritin, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) had significant changes in the total severe group. Among pneumonic with an O2 requirement and pneumonic without an O2 requirement, there were significant differences in immunological and inflammatory markers ( p > 0.05). The neutrophils-lymphocytes ratio (NLR) was highly elevated in severe who required O2. Moreover, IL-6, lymphocytes, and neutrophils were possible risk factors for COVID-19 infection, with the strongest influence of IL-6 with a high odds ratio (OR: 24.138, 95% CI: 8.437-30.65, p < 0.01). Furthermore, there were significant correlations among the indicators., Conclusion: Each of IL-6, lymphocytes, and neutrophils might represent major factors in the severity of COVID-19 and IL-6 plays the main role in inducing the inflammatory and pathophysiology process that is known as the cytokine storm., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Eman T. Ali et al.)

Biologicals are crucial targeted therapeutic agents in oncological, immunological, and inflammatory diseases, and their use in clinical practice is broadening. In recent years, the spread of Personalized Precision Medicine has facilitated a proliferation of new treatment options, especially biologicals. Consequently, biologicals are now among the drugs that most frequently cause hypersensitivity reactions (HSRs). Patients can develop HSRs to these agents during the first-lifetime exposure or after repeated exposure, and these HSRs can be potentially life-threatening or limit therapeutic options. Despite the relatively high prevalence, the underlying mechanisms of these HSRs remain obscure, and the optimal management pathways are still a matter of discussion. In this Position Paper, the authors will provide evidence-based recommendations for diagnosing and managing HSRs to biologicals. Additionally, the document defines unmet needs as an opportunity to shape future research., (© 2021 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: Clinical pharmacists have a vital role in intercepting prescribing errors (PEs) but their impact within a Jordanian hospital emergency department (ED) has never been studied. Objective: To evaluate the impact of clinical pharmacy services on PEs and assess predictors of physicians' acceptance of clinical pharmacists' interventions. Setting: This study was conducted in the ED of the largest governmental hospital in Jordan. Method: This was a pre-post study conducted in October and November 2019 using a disguised observational method. There were 2 phases: control phase (P0) with no clinical interventions, and active phase (P1) where clinical pharmacists prospectively intervened upon errors. The clinical significance of errors was determined by a multidisciplinary committee. The SPSS software version 24 was used for data analysis. Main Outcome Measure: PEs incidence, type, severity, and predictors for physicians' acceptance. Results: Of 18003 patients, 8732 were included in P0 and 9271 in P1. PEs incidence decreased from 24.6% to 5.4%. Contraindication, drug selection, and dosage form error types were significantly reduced from 32.6%, 9.1%, and 3.7% (P0) to 12.6%, 0.0%, and 0.0% (P1), respectively. Albeit not statistically significant, drug-drug interaction, drug frequency, and allergy error types were reduced from 4.9%, 3.1%, and 0.1% to 4.5%, 2.5%, and 0.0%, respectively. Significant and serious errors were significantly reduced from 68.7% and 3.0% (P0) to 8.9% and 1.8% (P1), respectively. During P1, most errors were minor (89.3%, 1574/1763), and lethal errors ceased. Predictors for physicians' acceptance were: significant errors (OR 3.1; 95% CI 2.6-4.3; P = 0.03) and non-busy physicians (OR 2.1; 95% CI 1.6-2.7; P = 0.04). Conclusion: Clinical pharmacists significantly reduced PEs in the ED by 76%; most of interventions were significant. Policymakers are advised to implement active clinical pharmacy in the ED., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2020.)