Ashraf Abu-Seida

Despite the advances made in cancer therapeutics, their adverse effects remain a major concern, putting safer therapeutic options in high demand. Since chalcones, a group of flavonoids and isoflavonoids, act as promising anticancer agents, we aimed to evaluate the in vivo anticancer activity of a synthetic isoquinoline chalcone (CHE) in a mice model with Ehrlich solid carcinoma. Our in vivo pilot experiments revealed that the maximum tolerated body weight-adjusted CHE dose was 428 mg/kg. Female BALB/c mice were inoculated with Ehrlich ascites carcinoma cells and randomly assigned to three different CHE doses administered intraperitoneally (IP; 107, 214, and 321 mg/kg) twice a week for two consecutive weeks. A group injected with doxorubicin (DOX; 4 mg/kg IP) was used as a positive control. We found that in CHE-treated groups: (1) tumor weight was significantly decreased; (2) the total antioxidant concentration was substantially depleted in tumor tissues, resulting in elevated oxidative stress and DNA damage evidenced through DNA fragmentation and comet assays; (3) pro-apoptotic genes p53 and Bax, assessed via qPCR, were significantly upregulated. Interestingly, CHE treatment reduced immunohistochemical staining of the proliferative marker ki67, whereas BAX was increased. Notably, histopathological examination indicated that unlike DOX, CHE treatment had minimal toxicity on the liver and kidney. In conclusion, CHE exerts antitumor activity via induction of oxidative stress and DNA damage that lead to apoptosis, making CHE a promising candidate for solid tumor therapy.

Despite the advances made in cancer therapeutics, their adverse effects remain a major concern, putting safer therapeutic options in high demand. Since chalcones, a group of flavonoids and isoflavonoids, act as promising anticancer agents, we aimed to evaluate the in vivo anticancer activity of a synthetic isoquinoline chalcone (CHE) in a mice model with Ehrlich solid carcinoma. Our in vivo pilot experiments revealed that the maximum tolerated body weight-adjusted CHE dose was 428 mg/kg. Female BALB/c mice were inoculated with Ehrlich ascites carcinoma cells and randomly assigned to three different CHE doses administered intraperitoneally (IP; 107, 214, and 321 mg/kg) twice a week for two consecutive weeks. A group injected with doxorubicin (DOX; 4 mg/kg IP) was used as a positive control. We found that in CHE-treated groups: (1) tumor weight was significantly decreased; (2) the total antioxidant concentration was substantially depleted in tumor tissues, resulting in elevated oxidative stress and DNA damage evidenced through DNA fragmentation and comet assays; (3) pro-apoptotic genes p53 and Bax, assessed via qPCR, were significantly upregulated. Interestingly, CHE treatment reduced immunohistochemical staining of the proliferative marker ki67, whereas BAX was increased. Notably, histopathological examination indicated that unlike DOX, CHE treatment had minimal toxicity on the liver and kidney. In conclusion, CHE exerts antitumor activity via induction of oxidative stress and DNA damage that lead to apoptosis, making CHE a promising candidate for solid tumor therapy.

Background: Community pharmacists have the responsibilities of identifying and resolving medication-related problems (MRPs), thereby improving patient safety. Objectives: To deliver a series of clinical case scenarios using WhatsApp and assess the impact of this method on the ability of pharmacists to identify MRPs. Methods: This study was conducted in 104 community pharmacies in the United Arab Emirates (UAE) over a period of six months. Recruited pharmacies were randomly allocated to either intervention or control groups using a 1:1 allocation ratio. Senior experts in clinical pharmacy created a series of clinical case scenarios based on their clinical practice and based on previous published studies related to MRPs. WhatsApp®, a well-known messenger application, which has been proven to be an efficient platform to improve communication between learners and educators, was used to deliver clinical scenarios-based educational interventions to pharmacists. Then, pharmacists from both groups filled a standardized data reporting form. The clinical importance of pharmacist recommendations was assessed by a multidisciplinary expert panel. Results: The total number of patients with MRPs across the intervention and control groups was 492 versus 194 (p = 0.01). While the number of MRPs identified, the mean time needed to resolve MRPs for patients with major polypharmacy, and physicians' acceptance of pharmacist recommendations across the intervention and control groups were 492 versus 194, 1589 versus 255, 6.82 (±3.86) versus 10.78 (±6.38), and 1065/1284 (82.94%) versus 125/201 (62.18%), respectively, all with p < 0.05. Efficacy-related problems (27.56%) and safety-related problems (28.44%) were the most commonly identified MRPs by pharmacists in the intervention group. Clinically significance of pharmacist recommendations was a significant predictive factor for physicians' acceptance of pharmacist recommendations. Conclusion: Clinical case scenarios delivered by WhatsApp may be useful for improving the ability of pharmacists to identify MRPs and for shortening the mean time needed to resolve MRPs.

Context: Inappropriate prescribing of antibiotics can result in serious patient harm. Aims: To investigate the incidence, nature, clinical severity, and causes of antibiotic prescribing errors (APEs) in the emergency department (ED) of a large hospital in Jordan. Methods: A mixed-method approach was used to explore the incidence and types of APEs by direct observation of electronic prescriptions (EPS) of antibiotics over four weeks, and to identify causes of errors by semi-structured interviews with ED physicians. The clinical severity of APEs was rated by a committee of experts. SPSS V26 and NVivo 10 were used for the analysis of quantitative and qualitative data, respectively. Results: The incidence of APEs caused by the use of EPS was 4.3%. Wrong quantity (32.62%), wrong dose (15.25%), and duplicate drugs (13.55%) were identified as the most common types of APEs. More than one-third of APEs identified were deemed clinically significant, seven were serious, and one was lethal. Minor and significant antibiotic APEs across physicians who attended workshops on EPS and those who did not were 75.00% versus 46.77% (p = 0.001) and 18.75% versus 52.41% (p = 0.013), respectively. Three major causes of errors were identified: 1) System-related (system crash, drop-down menu), 2) user-related (lack of computer skills), and 3) workplace-related (overcrowding, inadequate staffing). Conclusions: APEs generated by the use of EPS were common in EDs in Jordan, clinically significant, and multifactorial. Further research is required to cover pharmacists' perspectives of this kind of errors.

Background: Although community pharmacists have been actively engaged in patient care, their role in deprescribing is still restricted. Objectives: This study aimed to assess the effectiveness of a new educational approach designed to catalyze deprescribing in community pharmacies. Methods: In this 4-month, randomized, controlled trial, 108 community pharmacies in Egypt were randomly and equally distributed to either the active or the control groups. Participants from the active group pharmacies received 31 deprescribing-related clinical case scenarios, designed according to the available deprescribing guideline and clinical experiences of an expert panel members, and delivered through WhatsApp. Then participants from both groups reported the incidence of potentially inappropriate medicines (PIMs), the frequency of deprescribing opportunities, and related pharmacist interventions. Results: Pharmacists from the active group reported a considerably higher incidence of PIMs (20.87%) than that reported by pharmacists from the control group (5.03%). In addition, they made 1326 deprescribing-related interventions, of which 1022 (77.07%) were accepted and 641 (48.34%) were significant interventions. The proportions of cessation of drug therapy, reducing the dose, and persuasion of patients to accept deprescribing pharmacist interventions in the active group were 37.85%, 22.09%, and 10.63%, respectively. In contrast, 150 of 268 deprescribing-related interventions (55.97%) in the active group were accepted. The clinical value and type of deprescribing decision were statistically significant determinants for the acceptance of deprescribing decisions. The mean time needed to persuade the patient about deprescribing and the cost saved per patient across the active and the control groups were 5.09 ± 3.54 minutes versus 10.03 ± 6.19 minutes and 17.88 ± 9.60 U.S. dollars versus 4.49 ± 2.44 U.S. dollars, respectively. Conclusion: The intervention proposed improved the frequency and clinical value of deprescribing decisions.

Background: Because COVID-19 patients are vulnerable to prescribing errors (PEs) and adverse drug events, designing and implementing a new approach to prevent prescribing errors (PEs) involving COVID-19 patients has become a priority in pharmacotherapy research. Objectives: To investigate whether using WhatsApp to deliver prescribing error (PE)-related clinical scenarios to community pharmacists could enhance their ability to detect PEs and conduct successful pharmaceutical interventions (PIs). Methods: In this study, 110 community pharmacies were recruited from different regions across Jordan and equally allocated to 2 groups. Over the course of 4 weeks, WhatsApp was used to send PEs-related clinical case scenarios to the active group. The second group was controlled with no clinical scenarios. After completion of the 4-week phase, pharmacists from both groups were asked to document PEs in COVID-19 patients and their interventions using a data-collection form. Results: The incidence of PEs in COVID-19 patients documented in the active group (18.54%) was higher than that reported in the control group (3.09%) (P =.001). Of the 6598 and 968 PIs conducted by participants working in the active and control group pharmacies, 6013 (91.13%) and 651 (67.25%) were accepted, respectively. The proportions of wrong drug (contraindication), wrong drug (unnecessary drug prescribed/no proof of its benefits), and omission of a drug between the active and control groups were 15.30% versus 7.21% (P =.001), 11.85% versus 6.29% (P =.03), and 17.78% versus 10.50% (0.01), respectively. Additionally, the proportions of lethal, serious, and significant errors were 0.74% versus 0.35% (P =.04), 10.52% versus 2.57% (0.002), and 47.88% versus 9.57% (0.001), respectively. Addition of drug therapy interventions (AOR = 0.62; 95% CI, 0.21-0.84) and errors with significant clinical seriousness (AOR = 0.32; 95% CI, 0.16-0.64). Conclusions PEs involving COVID-19 patients in community settings are common and clinically significant. The intervention assessed in this study could be promising for designing a feasible and time-efficient interventional tool to encourage pharmacists' involvement in identifying and correcting PEs in light of COVID-19.

Background: Because COVID-19 patients are vulnerable to prescribing errors (PEs) and adverse drug events, designing and implementing a new approach to prevent prescribing errors (PEs) involving COVID-19 patients has become a priority in pharmacotherapy research. Objectives: To investigate whether using WhatsApp to deliver prescribing error (PE)-related clinical scenarios to community pharmacists could enhance their ability to detect PEs and conduct successful pharmaceutical interventions (PIs). Methods: In this study, 110 community pharmacies were recruited from different regions across Jordan and equally allocated to 2 groups. Over the course of 4 weeks, WhatsApp was used to send PEs-related clinical case scenarios to the active group. The second group was controlled with no clinical scenarios. After completion of the 4-week phase, pharmacists from both groups were asked to document PEs in COVID-19 patients and their interventions using a data-collection form. Results: The incidence of PEs in COVID-19 patients documented in the active group (18.54%) was higher than that reported in the control group (3.09%) (P =.001). Of the 6598 and 968 PIs conducted by participants working in the active and control group pharmacies, 6013 (91.13%) and 651 (67.25%) were accepted, respectively. The proportions of wrong drug (contraindication), wrong drug (unnecessary drug prescribed/no proof of its benefits), and omission of a drug between the active and control groups were 15.30% versus 7.21% (P =.001), 11.85% versus 6.29% (P =.03), and 17.78% versus 10.50% (0.01), respectively. Additionally, the proportions of lethal, serious, and significant errors were 0.74% versus 0.35% (P =.04), 10.52% versus 2.57% (0.002), and 47.88% versus 9.57% (0.001), respectively. Addition of drug therapy interventions (AOR = 0.62; 95% CI, 0.21-0.84) and errors with significant clinical seriousness (AOR = 0.32; 95% CI, 0.16-0.64). Conclusions PEs involving COVID-19 patients in community settings are common and clinically significant. The intervention assessed in this study could be promising for designing a feasible and time-efficient interventional tool to encourage pharmacists' involvement in identifying and correcting PEs in light of COVID-19.

Soil contamination with indium (In) oxide nanoparticles (In2O3-NPs) threatens plant growth and development. However, their toxicity in plants under ambient (aCO2) and elevated (eCO2) conditions is scarcely studied. To this end, this study was conducted to investigate In2O3-NPs toxicity in the young and old leaves of C3 (barley) and C4 (maize) plants and to understand the mechanisms underlying the stress mitigating impact of eCO2. Treatment of C3 and C4 plants with In2O3-NPs significantly reduced growth and photosynthesis, induced oxidative damage (H2O2, lipid peroxidation), and impaired P and Fe homeostasis, particularly in the young leaves of C4 plants. On the other hand, this phytotoxic hazard was mitigated by eCO2 which improved both C3 and C4 growth, decreased In accumulation and increased phosphorus (P) and iron (Fe) uptake, particularly in the young leaves of C4 plants. Moreover, the improved photosynthesis by eCO2 accordingly enhanced carbon availability under the challenge of In2O3-NPs that were directed to the elevated production of metabolites involved in antioxidant and detoxification systems. Our physiological and biochemical analyses implicated the role of the antioxidant defenses, including superoxide dismutase (SOD) in stress mitigation under eCO2. This was validated by studying the effect of In2O3-stress on a transgenic maize line (TG) constitutively overexpressing the AtFeSOD gene and its wild type (WT). Although it did not alter In accumulation, the TG plants showed improved growth and photosynthesis and reduced oxidative damage. Overall, this work demonstrated that C3 was more sensitive to In2O3-NPs stress; however, C4 plants were more responsive to eCO2. Moreover, it demonstrated the role of SOD in determining the hazardous effect of In2O3-NPs.

The risk of vacuum loss in linear solar heat collection elements (HCEs) is one of the major practical challenges that are facing the parabolic trough solar concentrator (PTSC) systems in concentrating solar power (CSP) plants. Despite the long-life span of CSP systems, HCEs are frequently replaced due to permeated hydrogen (due to saturation of getters) or leaked air (due to failures in end metal-to-glass welding or cracked glass shells). This study proposes a low-tech solution for boosting the performance of PTSCs with partial or lost vacuum through rotating the HCEs. A carefully validated integrated 3D optical-thermal model is developed and used to quantify the energetic and exergetic performances of PTSCs with rotated and fixed HCEs for both cases of lost and maintained vacuum. Both steady and unsteady simulations are reported using high-precision ground measurements of direct irradiance and meteorological parameters. As the rotational speed increases from 0 to 20 rad/s, the energy efficiency of PTSCs with new and damaged HCEs is improved by ∼47 and 52{%}, respectively, at a Reynolds number of 4000 and an inlet temperature of 350 °C. By rotating a damaged HCE at only 10 rad/s, maximum improvements of ∼26 and 53{%} in the useful heat gain are obtained, compared to non-rotating evacuated and non-rotating damaged HCEs, respectively, at the same operating conditions. Overall, the advantage of the proposed concept is more pronounced when the PTSC is operating at relatively low flow rates, high temperatures, or under high irradiance levels.

The risk of vacuum loss in linear solar heat collection elements (HCEs) is one of the major practical challenges that are facing the parabolic trough solar concentrator (PTSC) systems in concentrating solar power (CSP) plants. Despite the long-life span of CSP systems, HCEs are frequently replaced due to permeated hydrogen (due to saturation of getters) or leaked air (due to failures in end metal-to-glass welding or cracked glass shells). This study proposes a low-tech solution for boosting the performance of PTSCs with partial or lost vacuum through rotating the HCEs. A carefully validated integrated 3D optical-thermal model is developed and used to quantify the energetic and exergetic performances of PTSCs with rotated and fixed HCEs for both cases of lost and maintained vacuum. Both steady and unsteady simulations are reported using high-precision ground measurements of direct irradiance and meteorological parameters. As the rotational speed increases from 0 to 20 rad/s, the energy efficiency of PTSCs with new and damaged HCEs is improved by ∼47 and 52%, respectively, at a Reynolds number of 4000 and an inlet temperature of 350 °C. By rotating a damaged HCE at only 10 rad/s, maximum improvements of ∼26 and 53% in the useful heat gain are obtained, compared to non-rotating evacuated and non-rotating damaged HCEs, respectively, at the same operating conditions. Overall, the advantage of the proposed concept is more pronounced when the PTSC is operating at relatively low flow rates, high temperatures, or under high irradiance levels.

Edible sprouts are rich in flavonoids and other polyphenols, as well as proteins, minerals, and vitamins. Increasing sprout consumption necessitates improving their quality, palatability, and bioactivity. The purpose of this study was to test how KNO3 priming affects the sprouting process species on three Medicago species (Medicago indicus, Medicago interexta, and Medicago polymorpha) and their nutritional values. Targeted species of Medicago were primed with KNO3, and the levels of different primary and secondary metabolites were determined. KNO3 induced biomass accumulation in the sprouts of the three species, accompanied by an increased content of total mineral nutrients, pigments, vitamins, and essential amino acids. Besides, our results showed that KNO3 enhanced the activity of nitrate reductase (NR), glutamate dehydrogenase (GDH), and glutamine synthetase (GS) enzymes, which are involved in the nitrogen metabolism and GOGAT cycle, which, in turn, increase the nitrogen and protein production. KNO3 treatment improved the bioactive compound activities of Medicago sprouts by increasing total phenolic and flavonoid contents and enhancing the antioxidant and antidiabetic activities. Furthermore, species-specific responses toward KNO3 priming were noticeable, where Medicago interexta showed the highest antioxidant and antidiabetic activities, followed by Medicago polymorpha. Overall, this study sheds the light on the physiological and biochemical bases of growth, metabolism, and tissue quality improvement impact of KNO3 on Medicago sprouts.

Arbuscular mycorrhizal fungi (AMF) are beneficial for the plant growth under heavy metal stress. Such beneficial effect is improved by elevated CO2 (eCO2). However, the mechanisms by which eCO2 improves AMF symbiotic associations under arsenite (AsIII) toxicity are hardly studied. Herein, we compared these regulatory mechanisms in species from two agronomical important plant families – grasses (wheat) and legumes (soybean). AsIII decreased plant growth (i.e., 53.75 and 60.29% of wheat and soybean, respectively) and photosynthesis. It also increased photorespiration and oxidative injury in both species, but soybean was more sensitive to oxidative stress as indicated by higher H2O2 accumulation and oxidation of protein and lipid. eCO2 significantly improved AMF colonization by increasing auxin levels, which induced high carotenoid cleavage dioxygenase (CCDs) activity, particularly in soybean roots. The improved sugar metabolism in plant shoots by co-application of eCO2 and AsIII allocated more sugars to roots sequentially. Sugar accumulation in plant roots is further induced by AMF, resulting in more C skeletons to produce organic acids, which are effectively exudated into the soil to reduce AsIII uptake. Exposure to eCO2 reduced oxidative damage and this mitigation was stronger in soybean. This could be attributed to a greater reduction in photorespiration as well as a stronger antioxidant and detoxification defence systems. The grass/legume-specificity was supported by principal component analysis, which revealed that soybean was more affected by AsIII stress and more responsive to AMF and eCO2. This study provided a mechanistic understanding of the impact of AMF, eCO2 and their interaction on As-stressed grass and legume plants, allowing better practical strategies to mitigate AsIII phytotoxicity.

The sequestration of elevated atmospheric CO2 levels in seawater results in increasing acidification of oceans and it is unclear what the consequences of this will be on seaweed ecophysiology and ecological services they provide in the coastal ecosystem. In the present study, we examined the physiological and biochemical response of intertidal green seaweed Ulva compressa to elevated pCO2 induced acidification. The green seaweed was exposed to control (pH 8.1) and acidified (pH 7.7) conditions for 2 weeks following which net primary productivity, pigment content, oxidative status and antioxidant enzymes, primary and secondary metabolites, and mineral content were assessed. We observed an increase in primary productivity of the acidified samples, which was associated with increased levels of photosynthetic pigments. Consequently, primary metabolites levels were increased in the thalli grown under lowered pH conditions. There was also richness in various minerals and polyunsaturated fatty acids, indicating that the low pH elevated the nutritional quality of U. compressa. We found that low pH reduced malondialdehyde (MDA) content, suggesting reduced oxidative stress. Consistently we found reduced total antioxidant capacity and a general reduction in the majority of enzymatic and non-enzymatic antioxidants in the thalli grown under acidified conditions. Our results indicate that U. compressa will benefit from seawater acidification by improving productivity. Biochemical changes will affect its nutritional qualities, which may impact the food chain/food web under future acidified ocean conditions.