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13 pages, 1218 KiB  
Article
Endothelial Protein Changes Indicative of Endometriosis in Unexplained Infertility, an Exploratory Study
by Heba Malik, Sirine Zamouri, Samir Akkawi, Siddh Mehra, Rana Mouaki, Thozhukat Sathyapalan, Manjula Nandakumar, Alexandra E. Butler and Stephen L. Atkin
Int. J. Mol. Sci. 2025, 26(13), 6485; https://doi.org/10.3390/ijms26136485 - 5 Jul 2025
Viewed by 481
Abstract
Previous research has linked both endothelial protein changes and vitamin D with infertility. This study was undertaken to investigate the association of proteins associated with endothelial function and vitamin D status in the luteal phase at day 21 in a group of non-obese [...] Read more.
Previous research has linked both endothelial protein changes and vitamin D with infertility. This study was undertaken to investigate the association of proteins associated with endothelial function and vitamin D status in the luteal phase at day 21 in a group of non-obese women prior to in vitro fertilization (IVF) with either unexplained infertility (UI) or male factor infertility (MFI). Twenty-five non-obese Caucasian women from a UK academic center with MFI (n = 14) and UI (n = 11) were recruited. Blood was withdrawn at day 21 of the menstrual cycle at the time of mock embryo transfer. Vitamin D parameters were measured by tandem mass spectroscopy. Off-rate Modified Aptamer (SOMA)-scan plasma protein measurement was undertaken for 20 protein markers of endothelial dysfunction. Baseline demographics did not differ between groups and parameters of response following IVF did not differ. Vitamins D2 and D3, and 1,25 Vitamin D3 did not differ between groups. In UI, markers of endothelial activation/dysfunction were investigated; vascular cell adhesion molecule 1 (VCAM-1) decreased and this is associated with endothelial stress; vascular endothelial growth factor (VEGF) decreased and this may suggest impaired endometrial angiogenesis; while intercellular adhesion molecule 1 (ICAM-3) increased (p < 0.05) and is associated with increased immunological activity. A marker of vascular integrity, angiopoietin-1, increased while soluble angiopoietin-1 receptor (sTie-2) decreased (p < 0.05), suggesting increased vascular development. Endothelial markers of inflammation, coagulation, and endothelial progenitor cells were unchanged. Vitamin D and its metabolites show no relationship to UI, but endothelial activation/dysfunction and vascular integrity changes in VCAM-1, VEGF, sICAM-3, angiopoietin-1, and sTie-2 may contribute to UI, though the mechanisms through which they work require further evaluation; however, these protein changes have been associated with endometriosis, raising the suggestion that subclinical/undiagnosed endometriosis may have contributed to UI in these subjects. Full article
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30 pages, 6137 KiB  
Article
Comprehensive Metabolomics Profiling and Bioactivity Study of Lycium shawii (Awsaj) Extracts with Particular Emphasis on Potential Anti-Malarial Properties
by Ruba Al-Nemi, Mutaz Akkawi, Khalid Sawalha, Siska Andrina Kusumastuti, Nuralih, Susi Kusumaningrum, Tia Okselni, Vania Chlarisa Situmorang, Abdi Wira Septama, Mariusz Jaremko and Abdul-Hamid Emwas
Metabolites 2025, 15(2), 84; https://doi.org/10.3390/metabo15020084 - 1 Feb 2025
Viewed by 2069
Abstract
Background/Objectives: Although malaria is one of the oldest known human diseases, it continues to be a major global health challenge. According to UNICEF, the global malaria mortality rate exceeded 600,000 annually in 2022, which includes more than 1000 children dying each day. This [...] Read more.
Background/Objectives: Although malaria is one of the oldest known human diseases, it continues to be a major global health challenge. According to UNICEF, the global malaria mortality rate exceeded 600,000 annually in 2022, which includes more than 1000 children dying each day. This study aimed to investigate the comprehensive chemical profile and biological activities, particularly the antimalarial activity, of Lycium shawii (Awsaj), a shrub traditionally used in the Arabian Peninsula, Middle East, India, and Africa to treat a myriad of ailments. Methods: Crude extracts of L. shawii were prepared using water, ethanol, methanol, and acetone. Nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS) were utilized to perform untargeted metabolomics to maximize metabolite detection and tentatively identify bioactive phytochemicals. The total phenolic content (TPC) was measured for each extract, and bioassays were conducted to evaluate their antimalarial, antibacterial, and anti-inflammatory activities, particularly those of the water extract, which is the traditional method of consumption in Arabian folk medicine. Results: A total of 148 metabolites were detected, 45 of which were classified as phytochemicals. The bioassays revealed that the water extract that is traditionally used showed promising antimalarial potential by significantly inhibiting β-hematin formation in vitro at 1 mg/mL (with an absorbance of 0.140 ± 0.027). This is likely due to the rich presence of quinoline in the aqueous extract among several other bioactive phytochemicals, such as phenylpropanoids, alkaloids, flavonoids, and benzenoids. However, their anti-inflammatory and antibacterial activities were found to be weak, with only a minor inhibition of nitric oxide (NO) production in LPS-induced RAW 264.7 cells at a concentration of 500 µg/mL and weak antibacterial effects against pathogens like P. aeruginosa, MRSA, A. baumannii, and K. pneumoniae with an MIC of 500 μg/mL. The results also revealed that the methanolic extract had the highest TPC at 26.265 ± 0.005 mg GAE/g. Conclusions: The findings support the traditional medicinal use of L. shawii and highlight its potential as a source of novel therapeutic compounds, particularly for treating malaria. This study encourages further research to isolate and develop effective plant-based anti-malarial agents. Full article
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12 pages, 549 KiB  
Article
Age Is a Predictor of In-Hospital Outcomes for Left Ventricular Assist Device Implantation: A Nationwide Analysis
by Abdul Rahman Akkawi, Akira Yamaguchi, Junichi Shimamura, Omar Chehab, Paulino Alvarez, Toshiki Kuno and Alexandros Briasoulis
J. Pers. Med. 2024, 14(3), 236; https://doi.org/10.3390/jpm14030236 - 22 Feb 2024
Viewed by 2109
Abstract
The 2018 heart allocation system has significantly influenced heart transplantation and left ventricular assist device (LVAD) utilization. Our study aims to investigate age-related outcomes following LVAD implantation in the post-allocation era. Using the National Inpatient Sample, we analyzed data from 7375 patients who [...] Read more.
The 2018 heart allocation system has significantly influenced heart transplantation and left ventricular assist device (LVAD) utilization. Our study aims to investigate age-related outcomes following LVAD implantation in the post-allocation era. Using the National Inpatient Sample, we analyzed data from 7375 patients who underwent LVAD implantation between 2019 and 2020. The primary endpoint was in-hospital mortality following LVAD implantation, stratified by age categories. The age groups were 18–49, 50–59, 60–69, and over 70. These represented 26%, 26%, 31%, and 17% of patients, respectively. Patients aged 60–69 and those over 70 exhibited higher in-hospital mortality rates of 12% and 17%, respectively, compared to younger age groups (7% for 18–49 and 6% for 50–59). The age groups 60–69 and over 70 were independent predictors of mortality, with adjusted odds ratios of 1.99 (p = 0.02; 95% confidence interval [CI], 1.12–3.57) and 2.88 (p = 0.002; 95% CI, 1.45–5.71), respectively. Additionally, a higher Charlson Comorbidity Index was associated with increased in-hospital mortality risk (adjusted odds ratio 1.39; p = 0.02; 95% CI, 1.05–1.84). Additionally, patients above 70 experienced a statistically shorter length of stay. Nonhome discharge was found to be significantly high across all age categories. However, the difference in hospitalization cost was not statistically significant across the age groups. Our study highlights that patients aged 60 and above face an increased risk of in-hospital mortality following LVAD implantation in the post-allocation era. This study sheds light on age-related outcomes and emphasizes the importance of considering age in LVAD patient selection and management strategies. Full article
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10 pages, 269 KiB  
Article
The Impact of Potentially Inappropriate Medications and Polypharmacy on 3-Month Hospital Readmission among Older Patients: A Retrospective Cohort Study from Malaysia
by Muhammad Eid Akkawi, Hani Hazirah Abd Aziz and Abdul Rahman Fata Nahas
Geriatrics 2023, 8(3), 49; https://doi.org/10.3390/geriatrics8030049 - 30 Apr 2023
Cited by 2 | Viewed by 2991
Abstract
Introduction: Potentially inappropriate medications (PIMs) use and polypharmacy are two issues that are commonly encountered among older people. They are associated with several negative outcomes including adverse drug reactions and medication-related hospitalization. There are insufficient studies regarding the impact of both PIMs and [...] Read more.
Introduction: Potentially inappropriate medications (PIMs) use and polypharmacy are two issues that are commonly encountered among older people. They are associated with several negative outcomes including adverse drug reactions and medication-related hospitalization. There are insufficient studies regarding the impact of both PIMs and polypharmacy on hospital readmission, especially in Malaysia. Aim: To investigate the possible association between polypharmacy and prescribing PIMs at discharge and 3-month hospital readmission among older patients. Materials and method: A retrospective cohort study involved 600 patients ≥60 years discharged from the general medical wards in a Malaysian teaching hospital. The patients were divided into two equal groups: patients with or without PIMs. The main outcome was any readmission during the 3-month follow-up. The discharged medications were assessed for polypharmacy (≥five medications) and PIMs (using 2019 Beers’ criteria). Chi-square test, Mann–Whitney test, and a multiple logistic regression were conducted to study the impact of PIMs/polypharmacy on 3-month hospital readmission. Results: The median number for discharge medications were six and five for PIMs and non-PIMs patients, respectively. The most frequently prescribed PIMs was aspirin as primary prevention of cardiovascular diseases (33.43%) followed by tramadol (13.25%). The number of medications at discharge and polypharmacy status were significantly associated with PIMs use. Overall, 152 (25.3%) patients were re-admitted. Polypharmacy and PIMs at discharge did not significantly impact the hospital readmission. After applying the logistic regression, only male gender was a predictor for 3-month hospital readmission (OR: 2.07, 95% CI: 1.022–4.225). Conclusion: About one-quarter of the patients were admitted again within three months of discharge. PIMs and polypharmacy were not significantly associated with 3-month hospital readmissions while male gender was found to be an independent risk factor for readmission. Full article
(This article belongs to the Section Geriatric Public Health)
20 pages, 3846 KiB  
Article
Sex Modulates Response to Renal-Tubule-Targeted Insulin Receptor Deletion in Mice
by Soha Sohail, Gabriella Akkawi, Taylor Rechter, Maurice B. Fluitt and Carolyn M. Ecelbarger
Int. J. Mol. Sci. 2023, 24(9), 8056; https://doi.org/10.3390/ijms24098056 - 29 Apr 2023
Viewed by 2312
Abstract
Insulin facilitates renal sodium reabsorption and attenuates gluconeogenesis. Sex differences in this regulation have not been well characterized. Using tetracycline-inducible Cre-lox recombination, we knocked out (KO) the insulin receptor (InsR) from the renal tubule in adult male (M) and female (F) mice (C57Bl6 [...] Read more.
Insulin facilitates renal sodium reabsorption and attenuates gluconeogenesis. Sex differences in this regulation have not been well characterized. Using tetracycline-inducible Cre-lox recombination, we knocked out (KO) the insulin receptor (InsR) from the renal tubule in adult male (M) and female (F) mice (C57Bl6 background) with a paired box 8 (PAX8) promoter. Body weights were not affected by the KO, but mean kidney weights were reduced in the KO mice (13 and 3%, in M and F, respectively, relative to wild-type (WT) mice). A microscopic analysis revealed 25 and 19% reductions in the proximal tubule (PT) and cortical collecting duct cell heights, respectively, in KOMs relative to WTMs. The reductions were 5 and 11% for KOFs. Western blotting of renal cortex homogenates showed decreased protein levels for the β and γ subunits of the epithelial sodium channel (ENaC) and the sodium-potassium-2-chloride cotransporter type 2 (NKCC2) in both sexes of KO mice; however, α-ENaC was upregulated in KOMs and downregulated in KOFs. Both sexes of KO mice cleared exogenously administered glucose faster than the WT mice and had lower semi-fasted, anesthetized blood glucose levels. However, KOMs (but not KOFs) demonstrated evidence of enhanced renal gluconeogenesis, including higher levels of renal glucose-6-phosphatase, the PT’s production of glucose, post-prandial blood glucose, and plasma insulin, whereas KOFs exhibited downregulation of renal high-capacity sodium glucose cotransporter (SGLT2) and upregulation of SGLT1; these changes appeared to be absent in the KOM. Overall, these findings suggest a sex-differential reliance on intact renal tubular InsR signaling which may be translationally important in type 2 diabetes, obesity, or insulin resistance when renal insulin signaling is reduced. Full article
(This article belongs to the Special Issue Insulin Resistance and Metabolic Syndrome)
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17 pages, 1463 KiB  
Article
Assessment of the Microbiological Acceptability of White Cheese (Akkawi) in Lebanon and the Antimicrobial Resistance Profiles of Associated Escherichia coli
by Nasri Daher Hussein, Jouman W. Hassan, Marwan Osman, Khaled El-Omari, Samer A. Kharroubi, Imad Toufeili and Issmat I. Kassem
Antibiotics 2023, 12(3), 610; https://doi.org/10.3390/antibiotics12030610 - 19 Mar 2023
Cited by 10 | Viewed by 4222
Abstract
Dairy foods are a staple in Lebanon, a low- and middle-income country that has been experiencing serious challenges to food safety and antimicrobial stewardship among other issues. The microbiological acceptability of dairy products has been of increasing concern. This is partially due to [...] Read more.
Dairy foods are a staple in Lebanon, a low- and middle-income country that has been experiencing serious challenges to food safety and antimicrobial stewardship among other issues. The microbiological acceptability of dairy products has been of increasing concern. This is partially due to the failing economy and prolonged power outages that affect the quality of raw material and disrupt the dairy cold chain, respectively. Therefore, we assessed the microbiological acceptability of Akkawi, a popular white-brined cheese in Lebanon. For this purpose, we quantified the densities of Escherichia coli (a fecal indicator) and Staphylococcus aureus in cheeses collected from Lebanese retail stores. Additionally, we evaluated the antibiotic resistance profiles of the E. coli isolated from the cheese. E. coli and S. aureus were detected in 40 (80%) and 16 (32%) of the 50 cheese samples, respectively. Notably, 40 (80%) and 16 (32%) of the samples exceeded the maximum permissible limit of E. coli and S. aureus, respectively. A high percentage of the 118 E. coli isolated from the cheeses showed resistance to clinically and agriculturally important antibiotics, while 89 (75%) isolates were classified as multidrug-resistant (MDR). Given that Akkawi can be consumed without cooking, our findings highlight serious food safety and antimicrobial resistance problems that require immediate interventions. Full article
(This article belongs to the Special Issue Non-antibiotic Approaches to Control Food-Borne Pathogens)
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11 pages, 686 KiB  
Article
Evaluation of Antibiotic Prescribing Pattern and Appropriateness among Hospitalized Pediatric Patients: Findings from a Malaysian Teaching Hospital
by Muhammad Eid Akkawi, Randa Mahmoud Taffour and Abdulkareem Mohammed AL-Shami
Infect. Dis. Rep. 2022, 14(6), 889-899; https://doi.org/10.3390/idr14060089 - 17 Nov 2022
Cited by 5 | Viewed by 4279
Abstract
Background: Antibiotics are commonly prescribed for hospitalized children. However, only a limited number of studies have evaluated antibiotic use in this population. The current work assessed the indication, prescribing pattern and appropriateness of antibiotics among pediatric inpatients. Methods: A retrospective cross-sectional [...] Read more.
Background: Antibiotics are commonly prescribed for hospitalized children. However, only a limited number of studies have evaluated antibiotic use in this population. The current work assessed the indication, prescribing pattern and appropriateness of antibiotics among pediatric inpatients. Methods: A retrospective cross-sectional study was conducted at the pediatric wards of a teaching hospital in Malaysia. Electronic charts of inpatients (≤12 years old) admitted in 2019 were reviewed. Antibiotic indication, selection, dosing regimen, route of administration and duration of treatment were evaluated using the national antibiotic guidelines (NAG). A binomial logistic regression was applied to test potential predictors of inappropriate antibiotic prescribing (IAP) incidence. Results: Out of 702 pediatric inpatients, 292 (41.6%) patients were given antibiotics and met the inclusion criteria. More than half of the patients (57.9%) were males, with a median age of 2.5 years. A total of 385 and 285 antibiotics were prescribed during hospitalization and at discharge, respectively. Azithromycin, co-amoxiclav and cefuroxime were the top three prescribed agents. Out of 670 prescriptions, IAP was identified in 187 (28%) prescriptions that were issued for 169 (57.9%) out of the 292 patients included in the study. Improper antibiotic selection, wrong dose and unnecessary antibiotic prescribing accounted for 41%, 34% and 10% of the identified IAP, respectively. Giving lower-than-recommended doses (28%) was more prevalent than prescribing higher doses (5%). The use of two antibiotics and treating upper respiratory tract infections were independent risk factors for IAP incidence. Conclusions: Prescribers did not adhere to the NAG in more than one quarter of the prescriptions. This may increase the risk of treatment failure, adverse drug reactions and the development of antibiotic resistance. Full article
(This article belongs to the Section Bacterial Diseases)
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14 pages, 647 KiB  
Article
Chemical Markers and Pharmacological Characters of Pelargonium graveolens Essential Oil from Palestine
by Nidal Jaradat, Mohammed Hawash, Mohammad Qadi, Murad Abualhasan, Aseel Odetallah, Ghfran Qasim, Reem Awayssa, Amna Akkawi, Ibtesam Abdullah and Nawaf Al-Maharik
Molecules 2022, 27(17), 5721; https://doi.org/10.3390/molecules27175721 - 5 Sep 2022
Cited by 30 | Viewed by 3982
Abstract
Pelargonium graveolens leaves are widely used in traditional medicine for relieving some cardiovascular, dental, gastrointestinal, and respiratory disorders. They are also used as food and tea additives in Palestine and many other countries. Consequently, this investigation aimed to describe the chemical markers, cytotoxic, [...] Read more.
Pelargonium graveolens leaves are widely used in traditional medicine for relieving some cardiovascular, dental, gastrointestinal, and respiratory disorders. They are also used as food and tea additives in Palestine and many other countries. Consequently, this investigation aimed to describe the chemical markers, cytotoxic, antioxidant, antimicrobial, metabolic, and cyclooxygenase (COX) enzymes inhibitory characteristics of P. graveolens essential oil (PGEO) from Palestine utilizing reference methods. There were 70 chemicals found in the GCMS analysis, and oxygenated terpenoids were the most abundant group of the total PGEO. Citronellol (24.44%), citronellyl formate (15.63%), γ-eudesmol (7.60%), and iso-menthone (7.66%) were the dominant chemical markers. The EO displayed strong antioxidant activity (IC50 = 3.88 ± 0.45 µg/mL) and weak lipase and α-amylase suppressant effects. Notably, the PGEO displayed high α-glucosidase inhibitory efficacy compared with Acarbose, with IC50 doses of 52.44 ± 0.29 and 37.15 ± 0.33 µg/mL, respectively. PGEO remarkably repressed the growth of methicillin-resistant Staphylococcus aureus (MRSA), even more than Ampicillin and Ciprofloxacin, and strongly inhibited Candida albicans compared with Fluconazole. The highest cytotoxic effect of the PGEO was noticed against MCF-7, followed by Hep3B and HeLa cancer cells, with IC50 doses of 32.71 ± 1.25, 40.71 ± 1.89, and 315.19 ± 20.5 µg/mL, respectively, compared with doxorubicin. Moreover, the screened EO demonstrated selective inhibitory activity against COX-1 (IC50 = 14.03 µg/mL). Additionally, PGEO showed a weak suppressant effect on COX-2 (IC50 = 275.97 µg/mL). The current research can be considered the most comprehensive investigation of the chemical and pharmacological characterization of the PGEO. The results obtained in this study demonstrate, without doubt, that this plant represents a rich source of bioactive substances that can be further investigated and authenticated for their medicinal potential. Full article
(This article belongs to the Special Issue Essential Oils II)
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