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Ghazwa B Korayem,1 Omar A Alshaya,2– 4 Sawsan M Kurdi,5 Lina I Alnajjar,1 Aisha F Badr,6 Amjaad Alfahed,1 Ameera Cluntun7 1Department of Pharmacy Practice, College of Pharmacy, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi Arabia; 2Department of Pharmacy Practice, College of Pharmacy, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia; 3Pharmaceutical Care Services, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia; 4King Abdullah International Medical Research Center, Riyadh, Saudi Arabia; 5Department of Pharmacy Practice, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia; 6Pharmacy Practice Department, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia; 7Curriculum and Training Department, Health Academy, Saudi Commission for Health Specialties, Riyadh, Saudi ArabiaCorrespondence: Amjaad Alfahed, Department of Pharmacy Practice, College of Pharmacy, Princess Nourah bint Abdulrahman University, 11564 King Khalid International Airport, P.O. Box: 84428, Riyadh, Saudi Arabia, Tel +966 564321410, Email Aabaniali@pnu.edu.sa; Amjaad.abd@hotmail.comAbstract: Simulation-based education (SBE) is a fundamental teaching method that complements traditional teaching modalities. SBE has improved students’ knowledge, understanding, and numerous essential skills within undergraduate pharmacy education, similar to traditional teaching methods. However, SBE has become crucial for developing students’ teamwork, decision-making, and communication skills. Even though the Accreditation Council for Pharmacy Education (ACPE) has acknowledged the benefit of SBE in interprofessional education (IPE) and the introductory pharmacy practice experience (IPPE). This article provides evidence that SBE can be effective beyond that. This narrative review is focused on the literature related to SBE modalities and the assessment methods of student learning outcomes in the undergraduate pharmacy curriculum. The review illustrates that SBE is an effective teaching method that could be utilized within the pharmacy curriculum. The review also could help pharmacy educators decide on the best modality and placement of integrating patient simulation within the pharmacy curriculum. Combining multiple simulation techniques may be the best way to achieve the desired student learning outcomes.Keywords: patient simulation, pharmacy, education, simulation-based education, pharmacy curriculum

Currently, statins, the β-hydroxy-β-methyl-glutaryl-CoA reductase (HMG-R) inhibitors, are widely used to lower cholesterol, nevertheless, they have several side effects. Consequently, the present study is designed to unravel the cardioprotective role of selected natural monoterpenoids (carvacrol and geraniol) via in-vitro targeting and molecular informatics study of HMG-R. Computational molecular informatics study revealed that carvacrol and geraniol efficiently occupies the catalytic site of HMG-R with the binding affinity (ΔG) of −4.60, and −1.99 Kcal/mol, respectively, and molecular mechanical-generalized Born surface area (MM-GBSA) free binding energy was depicted as −17.05 and −29.48 Kcal/mol, respectively. Further, molecular dynamics simulation was carried out for 100 ns. Carvacrol and geraniol potentially and competitively inhibit the in-vitro HMG-R activity with an IC50 value of 78.23 ± 2.21 µM, and 72.91 ± 2.92 µM, respectively. Thus, both carvacrol and geraniol exhibited significant anti-hypercholesterolemic activity while the molecular simulation studies depicted that the GR complex showed better stability than the carvacrol complex.

ABSTRACT Aims Lack of obstructive sleep apnea (OSA) awareness both directly and indirectly causes a medical and financial burden worldwide. The objective of this study is to provide new insights, focusing on type 2 diabetics and their knowledge levels about OSA in King Khalid University Hospital (KKUH), Riyadh, Saudi Arabia, and to recognize obesity as a common risk factor contributing to OSA in type 2 diabetes mellitus (T2DM) participants. Methods An analytical cross‐sectional study was conducted from July 2022 to December 2022 with a convenience sampling method of 386 participants (18 years old and above). The study was done face‐to‐face using an electronic questionnaire. The inclusion criterion was all T2DM patients at the waiting area of KKUH Diabetes Center in Riyadh, excluding participants with other metabolic disorders. Results Overall knowledge levels were poor, with 70.2% of participants not knowledgeable about the disease and 81.3% of participants having no knowledge concerning the bidirectional relationship between T2DM and OSA. Statistical significance was found between the risk of developing OSA symptoms and body mass index ≥30 (p ≤ 0.001). Conclusion The majority have very little to no knowledge regarding OSA and its bidirectional relationship with T2DM, indicating the need to put more effort into improving participant's awareness in this regard. Moreover, obesity should be considered as a common risk factor, recommending patients to practice healthier habits to minimize the risks and decrease mortality.

Abstract Background Recurrent pregnancy Loss (RPL) is common problem affecting many couples. A certain genetic variants link to increase the danger of this condition particularly HPA-1, HPA-3 and Human Factor XIII Val34Leu Mutation. The present study aims to find an association between RPL and the Factor XIII Val34Leu polymorphism, as well as HPA-1 and HPA-3 in Sudanese women with RPL. Methods This case-control study conducted between June 2022 and December 2022 included 216 women, with 103 cases having minimum three abortions in the past, and 113 healthy controls with at least two full-term births and no abortion history. DNA was isolated from whole blood and the status of three genetic polymorphisms (HPA-1, HPA-3, and factor XIII) was done using a polymerase chain reaction (PCR). Data was analysed using the SPSS version 24 software. Results The A/A genotype was found to be more prevalent in cases (79.6%) and controls (96.5%) regarding HPA-1. A significant difference was observed in overall allele frequency for B allele (97.0%) and expected frequency of A allele was (81.1%) using the Hardy-Weinberg distribution (p 0.05). Conclusion Our results indicate a link between Human Platelet Antigen-1 (HPA-1), Human Platelet Antigen-3 (HPA-3) and Factor XIII gene polymorphism with RPL.

Abstract Background Dexamethasone usually recommended for patients with severe coronavirus disease 2019 (COVID-19) to reduce short-term mortality. However, it is uncertain if another corticosteroid, such as methylprednisolone, may be utilized to obtain better clinical outcome. This study assessed dexamethasone’s clinical and safety outcomes compared to methylprednisolone. Methods A multicenter, retrospective cohort study was conducted between March 01, 2020, and July 31, 2021. It included adult COVID-19 patients who were initiated on either dexamethasone or methylprednisolone therapy within 24 h of intensive care unit (ICU) admission. The primary outcome was the progression of multiple organ dysfunction score (MODS) on day three of ICU admission. Propensity score (PS) matching was used (1:3 ratio) based on the patient’s age and MODS within 24 h of ICU admission. Results After Propensity Score (PS) matching, 264 patients were included; 198 received dexamethasone, while 66 patients received methylprednisolone within 24 h of ICU admission. In regression analysis, patients who received methylprednisolone had a higher MODS on day three of ICU admission than those who received dexamethasone (beta coefficient: 0.17 (95% CI 0.02, 0.32), P = 0.03). Moreover, hospital-acquired infection was higher in the methylprednisolone group (OR 2.17, 95% CI 1.01, 4.66; p = 0.04). On the other hand, the 30-day and the in-hospital mortality were not statistically significant different between the two groups. Conclusion Dexamethasone showed a lower MODS on day three of ICU admission compared to methylprednisolone, with no statistically significant difference in mortality.

Background/Objectives: PRKACA alterations have clear diagnostic and biological roles in the fibrolamellar variant of hepatocellular carcinoma and a potential predictive role in that cancer type. However, the roles of PRKACA have not been comprehensively examined in gastric and colorectal cancers (GC and CRC). This study, therefore, sought to investigate the roles of PRKACA expression in GC and CRC. Methods: The clinico-genomic data of 441 GC and 629 CRC cases were analyzed for therapeutic, clinicopathological, and biological correlates using appropriate bioinformatics and statistical tools. Furthermore, the deregulation of PRKACA expression in GC and CRC was investigated using correlative and regression analyses. Results: The results showed that PRKACA expression subsets were enriched for gene targets of chemotherapeutics, tyrosine kinase, and β-adrenergic inhibitors. Moreover, high PRKACA expression was associated with adverse clinicopathological and genomic features of GC and CRC. Gene Ontology Enrichment Analysis also showed that PRKACA-high subsets of the GI cancers were enriched for the biological and molecular functions that are associated with cell motility, invasion, and metastasis but not cell proliferation. Finally, multiple regression analyses identified multiple methylation loci, transcription factors, miRNA species, and PRKACA copy number changes that deregulated PRKACA expression in GC and CRC. Conclusions: This study has identified potential predictive and clinicopathological roles for PRKACA expression in GI cancers and has added to the growing body of knowledge on the deregulation of PRKACA in cancer.

The migration–proliferation dichotomy (MPD) has long been observed in cultured cancer cells. This phenomenon is not only relevant to tumour progression but may also have therapeutic significance in clinical cancer. However, MPD has rarely been investigated in primary cancer. This study aimed to either confirm or disprove the existence of MPD in primary cancer. Using primary gastric, colorectal and prostate cancer (GC, CRC and PCa) cohorts from the Cancer Genome Atlas and Memorial Sloan Kettering Cancer Center, this study interrogated the MPD phenomenon by utilising RNA–Seq-based proliferation (CIN70 signature) and migration (epithelial-mesenchymal transition) indices, as well as gene set enrichment analyses (GSEA). Alternative hypothetical migration–proliferation models—The simultaneous migration–proliferation (SMP) and phenotype–refractory (PR) models—were compared to the MPD model by probing the migration–proliferation relationships within cancer stages and between early- and late-stage diseases using chi-square and independent T tests, z-score statistics and GSEA. The results revealed an inverse relationship between migration and proliferation signatures overall in the GC, CRC and PCa cohorts, as well as in early- and late-stage diseases. Additionally, a shift in proliferation- to migration dominance was observed from early- to late-stage diseases in the GC and CRC cohorts but not in the PCa cohorts, which showed enhanced proliferation dominance in metastatic tumours compared to primary cancers. The above features exhibited by the cancer cohorts are in keeping with the MPD model of the migration–proliferation relationship at the cellular level and exclude the SMP and PR migration–proliferation models.

The protein kinase TAOK3, belongs to the MAP kinase family, is one of three closely related members, namely TAOK1, TAOK2, and TAOK3. We performed a pan-cancer investigation of TAOK3 across different cancer types, including uterine carcinosarcoma, adenocarcinoma of the stomach and pancreas, and endometrial carcinoma of the uterus, to better understand TAOK3′s role in cancer. In at least 16 types of cancer, our findings indicate that TAOK3 expression levels differ considerably between normal and tumor tissues. In addition, our study is the first to identify the oncogenic role of TAOK3 locus S331 and S471 in renal clear cell carcinoma, Glioblastoma Multiforme, hepatocellular carcinoma, Lung adenocarcinoma, and Pancreatic adenocarcinoma, indicating their involvement in cancer progression. In addition, our data analysis indicates that copy number variation is the most prevalent form of mutation in the TAOK3 gene, and that there is a negative correlation between TAOK3 mRNA and DNA promoter methylation. Moreover, our analysis suggests that TAOK3 may serve as a prognostic marker for several kinds of cancer, including Colon adenocarcinoma, renal clear cell carcinoma, Lower Grade Glioma, Lung adenocarcinoma, Mesothelioma, and hepatocellular carcinoma. In addition, our research on signature cancer genes has uncovered a positive association between TAOK3 and SMAD2, SMAD4, and RNF168 in most of the malignancies we have examined. TAOK3 is also correlated with the frequency of mutations and microsatellite instability in four types of cancer. Numerous immune-related genes are closely associated with TAOK3 levels in numerous malignancies. TAOK3 expression is positively correlated with immune infiltrates, which include activated CD4 T cells, CD8 T cells, and type 2T helper cells. Our pan-cancer analysis of TAOK3 provides vital insight into its potential role across a variety of cancer types.

The goal of our study was to determine the expression and phosphorylation of PTEN at residues Ser380/Thr382/383, as well as the nuclear expression of p53 in Sudanese patients with breast cancer (BC) in association with clinicopathological aspects of BC. Methods and Results: This retrospective, descriptive study was carried out in Wad-Madani, Gezira state in Sudan, from January 2015 to August 2016. A total of 179 biopsies were taken at random from patients with breast lesions. Two blocks were obtained for each patient. One came from a malignant lesion (Group A), whereas the other came from the margin adjacent to healthy tissue (Group B). Immunohistochemistry and immunofluorescent histochemistry were performed on two separate slides. We found a statistically significant difference in the frequency of immunohistochemical expression of p53 and phosphorylation of PTEN between the cancerous breast tissue and adjacent normal tissue. P53 and PTEN exhibited a significant relationship with each other and the grade of tumor, indicating their importance in the aggressiveness of breast lesions. It should also be emphasized that there is an association between p53 expression and lymph node metastasis, which indicates the involvement of p53 mutation in the metastasis of BC.

Simple Summary: Migration–proliferation dichotomy (MPD) is a characteristic that has been observed in cancer cells growing in artificial culture media. The MPD principle states that when cells begin to grow in number (cell proliferation), their ability to migrate from one point to another (cell migration) is paused, and vice versa. This phenomenon has been used to study cancer advancement in cancer cells growing in culture, and is proposed to be responsible for the adverse therapeutic outcomes observed in patients with cancer. However, MPD has not been comprehensively investigated in cancer tissues obtained directly from patients. This study investigated MPD in stomach and bowel cancers using gene expression signatures of natural cancers. The overall findings confirm that cell proliferation and migration occur in the reverse direction in cancer cells, which is in keeping with the features that have long been observed in artificially grown cancer cells. These results also provide a basis for further investigation of MPD in natural cancers. The migration–proliferation dichotomy (MPD) has long been observed in cultured cancer cells. This phenomenon is not only relevant to tumour progression but may also have therapeutic significance in clinical cancer. However, MPD has rarely been investigated in primary cancer. This study aimed to either confirm or disprove the existence of MPD in primary cancer. Using primary gastric, colorectal and prostate cancer (GC, CRC and PCa) cohorts from the Cancer Genome Atlas and Memorial Sloan Kettering Cancer Center, this study interrogated the MPD phenomenon by utilising RNA–Seq-based proliferation (CIN70 signature) and migration (epithelial-mesenchymal transition) indices, as well as gene set enrichment analyses (GSEA). Alternative hypothetical migration–proliferation models—The simultaneous migration–proliferation (SMP) and phenotype–refractory (PR) models—were compared to the MPD model by probing the migration–proliferation relationships within cancer stages and between early- and late-stage diseases using chi-square and independent T tests, z-score statistics and GSEA. The results revealed an inverse relationship between migration and proliferation signatures overall in the GC, CRC and PCa cohorts, as well as in early- and late-stage diseases. Additionally, a shift in proliferation- to migration dominance was observed from early- to late-stage diseases in the GC and CRC cohorts but not in the PCa cohorts, which showed enhanced proliferation dominance in metastatic tumours compared to primary cancers. The above features exhibited by the cancer cohorts are in keeping with the MPD model of the migration–proliferation relationship at the cellular level and exclude the SMP and PR migration–proliferation models. [ABSTRACT FROM AUTHOR]

Aims: Lack of obstructive sleep apnea (OSA) awareness both directly and indirectly causes a medical and financial burden worldwide. The objective of this study is to provide new insights, focusing on type 2 diabetics and their knowledge levels about OSA in King Khalid University Hospital (KKUH), Riyadh, Saudi Arabia, and to recognize obesity as a common risk factor contributing to OSA in type 2 diabetes mellitus (T2DM) participants. Methods: An analytical cross‐sectional study was conducted from July 2022 to December 2022 with a convenience sampling method of 386 participants (18 years old and above). The study was done face‐to‐face using an electronic questionnaire. The inclusion criterion was all T2DM patients at the waiting area of KKUH Diabetes Center in Riyadh, excluding participants with other metabolic disorders. Results: Overall knowledge levels were poor, with 70.2% of participants not knowledgeable about the disease and 81.3% of participants having no knowledge concerning the bidirectional relationship between T2DM and OSA. Statistical significance was found between the risk of developing OSA symptoms and body mass index ≥30 (p ≤ 0.001). Conclusion: The majority have very little to no knowledge regarding OSA and its bidirectional relationship with T2DM, indicating the need to put more effort into improving participant's awareness in this regard. Moreover, obesity should be considered as a common risk factor, recommending patients to practice healthier habits to minimize the risks and decrease mortality. [ABSTRACT FROM AUTHOR]

Background/Objectives: PRKACA alterations have clear diagnostic and biological roles in the fibrolamellar variant of hepatocellular carcinoma and a potential predictive role in that cancer type. However, the roles of PRKACA have not been comprehensively examined in gastric and colorectal cancers (GC and CRC). This study, therefore, sought to investigate the roles of PRKACA expression in GC and CRC. Methods: The clinico-genomic data of 441 GC and 629 CRC cases were analyzed for therapeutic, clinicopathological, and biological correlates using appropriate bioinformatics and statistical tools. Furthermore, the deregulation of PRKACA expression in GC and CRC was investigated using correlative and regression analyses. Results: The results showed that PRKACA expression subsets were enriched for gene targets of chemotherapeutics, tyrosine kinase, and β-adrenergic inhibitors. Moreover, high PRKACA expression was associated with adverse clinicopathological and genomic features of GC and CRC. Gene Ontology Enrichment Analysis also showed that PRKACA-high subsets of the GI cancers were enriched for the biological and molecular functions that are associated with cell motility, invasion, and metastasis but not cell proliferation. Finally, multiple regression analyses identified multiple methylation loci, transcription factors, miRNA species, and PRKACA copy number changes that deregulated PRKACA expression in GC and CRC. Conclusions: This study has identified potential predictive and clinicopathological roles for PRKACA expression in GI cancers and has added to the growing body of knowledge on the deregulation of PRKACA in cancer. [ABSTRACT FROM AUTHOR]

BACKGROUND: Premarital screening (PMS) is a mandatory laboratory examination before marriage to identify genetic blood and some infectious diseases. Sickle cell anemia (SCA) and thalassemia are genetic disorders caused by errors in the hemoglobin genes and are prevalent in Saudi Arabia OBJECTIVE: This study assessed the knowledge and response of the Al-Madinah community regarding PMS program. METHODOLOGY: This cross-sectional study assessed the knowledge and attitude of Al-Madinah community regarding hereditary blood disorders. Thirty-seven interviewers conducted direct and electronic interviews from October 2016 to January 2017. RESULTS: The total number of respondents was 2554, among the participants, 61% noted that PMS can diagnose SCA, 5.3% noted that PMS cannot diagnose SCA, and 33.4% answered “I don't know.” Regarding thalassemia, 50.2% answered that PMS can diagnose thalassemia, 7.4% answered “no,” and 42% answered “I don't know.” Furthermore, 76.4% of the participants answered that PMS can prevent SCA, whereas 71% of the participants answered that PMS can prevent thalassemia. Approximately 88.6% of the participants agreed to undergo elective PMS, 78.2% of them will not marry someone who has SCA or thalassemia, and 79.5% of them will not marry someone with a genetic trait if they themselves have a trait. In terms of raising the community's awareness on various hereditary blood disorders, 95.9%, 93.9%, and 92.5% agreed on the importance of media, medical education in school, and seminars, respectively. CONCLUSION: As half of the population were unaware about the screened diseases, it is necessary to raise the community's awareness on the importance of PMS.

Currently, statins, the β-hydroxy-β-methyl-glutaryl-CoA reductase (HMG-R) inhibitors, are widely used to lower cholesterol, nevertheless, they have several side effects. Consequently, the present study is designed to unravel the cardioprotective role of selected natural monoterpenoids (carvacrol and geraniol) via in-vitro targeting and molecular informatics study of HMG-R. Computational molecular informatics study revealed that carvacrol and geraniol efficiently occupies the catalytic site of HMG-R with the binding affinity (ΔG) of −4.60, and −1.99 Kcal/mol, respectively, and molecular mechanical-generalized Born surface area (MM-GBSA) free binding energy was depicted as −17.05 and −29.48 Kcal/mol, respectively. Further, molecular dynamics simulation was carried out for 100 ns. Carvacrol and geraniol potentially and competitively inhibit the in-vitro HMG-R activity with an IC50 value of 78.23 ± 2.21 μM, and 72.91 ± 2.92 μM, respectively. Thus, both carvacrol and geraniol exhibited significant anti-hypercholesterolemic activity while the molecular simulation studies depicted that the GR complex showed better stability than the carvacrol complex. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) is a severe and infectious respiratory condition caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). This case-control study aimed to evaluate serum levels of various immunological markers in patients with COVID-19 compared to those with bacterial pneumonia and a healthy control group. Serum samples were collected from adult participants across various COVID-19 isolation centers, including Kassala State and Ahmed Gasim Hospital, between April and June 2021. The study included 70 patients diagnosed with COVID-19, 30 with bacterial pneumonia, and 50 healthy controls. Serum levels of C-reactive protein (CRP), complement components C3 and C4, and cytokines IL-8, IL-10, IL-12, TNF-α, and IFN-γ were measured using standard reagent kits. Serum level of CRP was significantly elevated in both bacterial pneumonia and COVID-19 but significantly higher among patients with bacterial pneumonia. C3 and C4 were also increased in both patient groups, with C3 significantly higher in bacterial pneumonia. IL-8, IL-10, IL-12, TNF-α, and IFN-γ were significantly increased in bacterial pneumonia and SARS-Cov-2 compared to healthy controls. However, IFN-γ was significantly increased among patients with COVID-19 than patients with bacterial pneumonia. This study highlights the potential significant impact of COVID-19 on the immunological biomarkers investigated. [ABSTRACT FROM AUTHOR]

Background: A genetic polymorphism that causes abnormal folate metabolism may lead to genomic instability and increase susceptibility to malignancies such as Acute Lymphoblastic leukemia (ALL). The purpose of this research is to identify methylene tetrahydrofolate reductase (MTHFR C677T) (NCBI ID: 4524) mutation in ALL patients. Methods: The study was a descriptive case-control hospital-based study with one hundred Sudanese participants divided equally into fifty (50) Sudanese ALL diagnosed patients as cases and fifty (50) Sudanese individuals as controls. The MTHFR C677T mutant allele was detected using conventional PCR, with the primer sequence of MTHFR C677T F-TGAAGGAAGGTGTCTGCGGGA RAGGACGGTGCGGTGAGAGTG. The study was conducted from January to March 2023, and samples were collected from the Radiation and Isotops Center at Khartoum Hospital. Results: The investigation revealed that 12 of the 50 patients in the case group (24%) had the MTHFR C677T mutant allele, and the study also revealed that there is significant correlation with the control group. There is no significant relationship between socio-demographic variables and MTHFR mutation detection in ALL patients. Also, the sociodemographic variables predictors of MTHFR mutation among ALL patients adjusted for smoking habit revealed no significant relationship. Conclusion: According to the findings of this study, the mutant allele of the Methylene Tetra Hydro Folate Reductase C677T was detected and demonstrated varying degrees of significance. It was concluded that the MTHFR C677T gene mutation was associated with acute lymphoblastic leukemia in Sudanese patients. [ABSTRACT FROM AUTHOR]