GC-MS Assisted Determination of 26 Compounds in Phlomis stewartii Extract Exhibiting Antioxidant, Antifungal, and Antibacterial Properties.

Medicinal plants have long been studied for their therapeutic benifits. The present research aims to unveil complex phytochemical profile and therapeutic properties of ethyl acetate fraction of Phlomis stewartii, an important medicinal plant. In this context, the Gas Chromatography-Mass Spectrometry (GC-MS) analysis of the fraction identified 26 compounds. Additionally, the fraction exhibited concentration dependent antioxidant activity with an IC50 value lower than the standard antioxidant butylated hydroxytoluene. The antifungal activity of the fraction examined against F. oxysporum, A. alternate, and R. solani resulted in almost complete inhibition (>90%) of fungal growth. Furthermore, the fraction exhibited significant antibacterial potential against B. subtilus, S. aureus, E. coli, and S. dysenteriae, with inhibition zones of 18±0.22, 17±0.22, 12±0.11, and 10±0.12, respectively. Briefly, the plant extract was found to be highly potent, particularly in its antifungal action. Further studies, including natural products isolation coupled with bioassays, are recommended for promising drug candidates discovery.

Discovery of Cell-Permeable Allosteric Inhibitors of Liver Pyruvate Kinase: Design and Synthesis of Sulfone-Based Urolithins.

Metabolic dysfunction-associated fatty liver disease (MAFLD) presents a significant global health challenge, characterized by the accumulation of liver fat and impacting a considerable portion of the worldwide population. Despite its widespread occurrence, effective treatments for MAFLD are limited. The liver-specific isoform of pyruvate kinase (PKL) has been identified as a promising target for developing MAFLD therapies. Urolithin C, an allosteric inhibitor of PKL, has shown potential in preliminary studies. Expanding upon this groundwork, our study delved into delineating the structure-activity relationship of urolithin C via the synthesis of sulfone-based urolithin analogs. Our results highlight that incorporating a sulfone moiety leads to substantial PKL inhibition, with additional catechol moieties further enhancing this effect. Despite modest improvements in liver cell lines, there was a significant increase in inhibition observed in HepG2 cell lysates. Specifically, compounds 15d, 9d, 15e, 18a, 12d, and 15a displayed promising IC50 values ranging from 4.3 µM to 18.7 µM. Notably, compound 15e not only demonstrated a decrease in PKL activity and triacylglycerol (TAG) content but also showed efficient cellular uptake. These findings position compound 15e as a promising candidate for pharmacological MAFLD treatment, warranting further research and studies.

Design and synthesis of novel JNK inhibitors targeting liver pyruvate kinase for the treatment of non-alcoholic fatty liver disease and hepatocellular carcinoma.

Non-alcoholic fatty liver disease (NAFLD) comprises a broad range of liver disease including hepatocellular carcinoma (HCC) with is no FDA-approved drug. Liver pyruvate kinase (PKL) is a major regulator of metabolic flux and ATP generation in liver presenting a potential target for the treatment of NAFLD. Based on our recent finding of JNK-5A's effectiveness in inhibiting PKLR expression through a drug repositioning pipeline, this study aims to improve its efficacy further. We synthesized a series of JNK-5A analogues with targeted modifications, guided by molecular docking studies. These compounds were evaluated for their activities on PKL expression, cell viability, triacylglyceride (TAG) levels, and the expressions of steatosis-related proteins in the human HepG2 cell line. Subsequently, the efficacy of these compounds was assessed in reducing TAG level and toxicity. Compounds 40 (SET-151) and 41 (SET-152) proved to be the most efficient in reducing TAG levels (11.51 ± 0.90 % and 10.77 ± 0.67 %) and demonstrated lower toxicity (61.60 ± 5.00 % and 43.87 ± 1.42 %) in HepG2 cells. Additionally, all synthesized compounds were evaluated for their anti-cancer properties revealing that compound 74 (SET-171) exhibited the highest toxicity in cell viability with IC50 values of 8.82 µM and 2.97 µM in HepG2 and Huh7 cell lines, respectively. To summarize, compounds 40 (SET-151) and 41 (SET-152) show potential for treating NAFLD, while compound 74 (SET-171) holds potential for HCC therapy.

Ellagic Acid and Its Metabolites as Potent and Selective Allosteric Inhibitors of Liver Pyruvate Kinase.

Liver pyruvate kinase (PKL) has recently emerged as a new target for non-alcoholic fatty liver disease (NAFLD), and inhibitors of this enzyme could represent a new therapeutic option. However, this breakthrough is complicated by selectivity issues since pyruvate kinase exists in four different isoforms. In this work, we report that ellagic acid (EA) and its derivatives, present in numerous fruits and vegetables, can inhibit PKL potently and selectively. Several polyphenolic analogues of EA were synthesized and tested to identify the chemical features responsible for the desired activity. Molecular modelling studies suggested that this inhibition is related to the stabilization of the PKL inactive state. This unique inhibition mechanism could potentially herald the development of new therapeutics for NAFLD.

The IDEAL approach to establish contemporary maternity care during labor.

Objectives: The objectives of this study were to assess the prevalence of abusive and disrespectful behavior from healthcare workers toward women during childbirth, to determine the type of abuse with the highest prevalence, and to assess the factors that contributed to the prevalence of abuse and disrespectful behavior. Methods: This is a quantitative observational cross-sectional study that was conducted among mothers who gave birth in a tertiary hospital in Riyadh, Saudi Arabia, from September 2019 to mid-March 2020, with a target sample size of 261. Descriptive statistics were described by frequencies and percentages, bivariate statistical analysis was carried out by using Chi-square test. Results: The overall prevalence of disrespect and abuse (D&A) was 62.5%, the non-consented category was the commonest type in this study. D&A was 2.8 times more prevalent in women whose newborn suffered complications during delivery. Likewise, mothers who delivered in a room with 5 or more caregivers were 2 times more likely to be disrespected than others. Mothers who underwent a natural delivery without episiotomy were 53% less likely to face the risk of being disrespected than others. Conclusion: This study reveals that the prevalence of disrespect and abuse towards women during labor in the chosen setting was high. The type of delivery, number of caregivers present, and complications that occurred during delivery were significantly associated with disrespect and abuse. Therefore, the authors of this study present an IDEAL approach as a way to upgrade the maternity care standards.

Discovery of therapeutic agents targeting PKLR for NAFLD using drug repositioning.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) encompasses a wide spectrum of liver pathologies. However, no medical treatment has been approved for the treatment of NAFLD. In our previous study, we found that PKLR could be a potential target for treatment of NALFD. Here, we investigated the effect of PKLR in in vivo model and performed drug repositioning to identify a drug candidate for treatment of NAFLD. METHODS: Tissue samples from liver, muscle, white adipose and heart were obtained from control and PKLR knockout mice fed with chow and high sucrose diets. Lipidomics as well as transcriptomics analyses were conducted using these tissue samples. In addition, a computational drug repositioning analysis was performed and drug candidates were identified. The drug candidates were both tested in in vitro and in vivo models to evaluate their toxicity and efficacy. FINDINGS: The Pklr KO reversed the increased hepatic triglyceride level in mice fed with high sucrose diet and partly recovered the transcriptomic changes in the liver as well as in other three tissues. Both liver and white adipose tissues exhibited dysregulated circadian transcriptomic profiles, and these dysregulations were reversed by hepatic knockout of Pklr. In addition, 10 small molecule drug candidates were identified as potential inhibitor of PKLR using our drug repositioning pipeline, and two of them significantly inhibited both the PKLR expression and triglyceride level in in vitro model. Finally, the two selected small molecule drugs were evaluated in in vivo rat models and we found that these drugs attenuate the hepatic steatosis without side effect on other tissues. INTERPRETATION: In conclusion, our study provided biological insights about the critical role of PKLR in NAFLD progression and proposed a treatment strategy for NAFLD patients, which has been validated in preclinical studies. FUNDING: ScandiEdge Therapeutics and Knut and Alice Wallenberg Foundation.

Suppression of COX-2/PGE2 levels by carbazole-linked triazoles via modulating methylglyoxal-AGEs and glucose-AGEs - induced ROS/NF-κB signaling in monocytes.

Chronic hyperglycemia favours the formation of advanced glycation end products (AGEs) which are responsible of many diabetic vascular complications. Keeping in view the medicinal properties of the1,2,3-triazole-conjugated analogs, the present study was designed to evaluate the possible effect of carbazole-linked 1,2,3-triazoles 2-16 against glucose- and methylglyoxal-AGEs-induced inflammation in human THP-1 monocytes. In vitro antiglycation, and metabolic assays were used to determine antiglycation, and cytotoxicity activities. DCFH-DA, immunostaining, immunoblotting, and ELISA techniques were employed to study the ROS and levels of proinflammatory mediators in THP-1 monocytes. Among all the synthesized carbazole-linked 1,2,3 triazoles, compounds 2, 7, 8, and 11-16 showed antiglycation activity in glucose- and MGO-modified bovine serum albumin models, whereas parent compound 1 only exhibited activity in glucose-BSA model. The metabolic assay demonstrated the non-toxic profile of compounds 1-2, 11-13, and 15 up to 100 µM concentration in both HepG2 and THP-1 cell lines. We found that compounds 11-13, and 15 attenuated AGEs-induced ROS formation (P < 0.001), and halted NF-ĸB translocation (P < 0.001), likewise standard drugs, PDTC, rutin, and quercetin, in THP-1 monocytes. Among the derivatives, compounds 12, and 13 also suppressed the AGEs-induced elevation of COX-2 (P < 0.001) and PGE2 (P < 0.001). Our data show that the carbazole-linked triazoles 12, and 13 hampering the formation of glycation products, prevent the activation of AGEs-ROS-NF-κB signaling pathway, and limit the proinflammatory COX-2 protein, and PGE2 induction in human THP-1 monocytes. Both these compounds can thus serve as leads for further studies towards the treatment and prevention of diabetic vascular complications.

Physicians' Practice of the Non-Cosmetic Uses of Botulinum Toxin: A Cross-Sectional Study in Saudi Arabia.

Background Although botulinum toxin (BTX) has mainly been used cosmetically and therapeutically, its field of application is expanding. So far, BTX has shown promising outcomes in the management of a wide variety of medical conditions that are difficult to treat. Objectives We assessed physicians' knowledge and experience regarding the non-cosmetic use of BTX in different clinical settings. Methods This is a cross-sectional survey that was conducted in Riyadh, Saudi Arabia, and included physicians from different specialties, with different levels of training, and from different working hospitals. Data were collected by using a self-administered survey to assess physicians' knowledge, experience, current practice, and specific training in relation to Botox administration for non-cosmetic use. Results Most participants were residents (76.19%) and specialized in internal medicine (27.62%). The majority worked in governmental hospitals (76.19%). About 73% of our sample were aware of the non-cosmetic indications of BTX, but only 44% and 55% were aware of its contraindications and adverse effects, respectively. Less than one-third (31%) of respondents administered BTX injections in their clinical practice, and about 66% of respondents had two to five years of experience giving BTX injections. The most commonly treated conditions were spastic disorders, dystonia, and then migraine. Only 4.7% and 3.6% used validated scales or instruments for planning treatment with BTX, respectively, while about 36% opted for clinical evaluation only. More experience and training in giving BTX injections significantly predicted increased awareness of adverse effects and contraindications of non-cosmetic uses.  Conclusions The majority of specialty groups in our sample were aware of the non-cosmetic applications of botulinum toxin but did not use them to the same extent in their practice. Additionally, only a minority wished for further education on injection practices. The finding of insufficient knowledge about contraindications and the adverse effects of injections in a large number of participants, however, highlights the need for increased education, especially given the wide range of non-cosmetic applications and benefits that BTX can have for a variety of diseases.

Indole-linked 1,2,3-triazole derivatives efficiently modulate COX-2 protein and PGE2 levels in human THP-1 monocytes by suppressing AGE-ROS-NF-kß nexus.

AIMS: AGEs augment inflammatory responses by activating inflammatory cascade in monocytes, and hence lead to vascular dysfunction. The current study aims to study a plausible role and mechanism of a new library of indole-tethered 1,2,3-triazoles 2-13 in AGEs-induced inflammation. MATERIAL AND METHODS: Initially, the analogs 2-13 were synthesized by cycloaddition reaction between prop-2-yn-1-yl-2-(1H-indol-3-yl) acetate (1) and azidoacetophenone (1a). In vitro glycation, and metabolic assays were employed to investigate antiglycation and cytotoxicity activities of new indole-triazoles. DCFH-DA, immunostaining, Western blotting, and ELISA techniques were used to study the reactive oxygen species (ROS), and pro-inflammatory mediators levels. KEY FINDINGS: Among all the synthesized indole-triazoles, compounds 1-3, and 9-13, and their precursor molecule 1 were found to be active against AGEs production in in vitro glucose- and methylglyoxal (MGO)-BSA models. Compounds 1-2, and 11-13 were also found to be nontoxic against HEPG2, and THP-1 cells. Our results show that pretreatment of THP-1 monocytes with selected lead compounds 1-2, and 11-13, particularly compounds 12, and 13, reduced glucose- and MGO-derived AGEs-mediated ROS production (P < 0.001), as compared to standards, PDTC, rutin, and quercetin. They also significantly (P < 0.001) suppressed NF-ĸB translocation in THP-1 monocytes. Moreover, compounds 12, and 13 attenuated the AGEs-induced COX-2 protein levels (P < 0.001), and PGE2 production (P < 0.001) in THP-1 monocytes. SIGNIFICANCE: Our data revealed that the indole-triazoles 12, and 13 can significantly attenuate the AGEs-induced proinflammatory COX-2 levels, and associated PGE2 production by suppressing AGE-ROS-NF-Kß nexus in THP-1 monocytes. These compounds can thus serve as leads for further evaluation as treatment to delay early onset of diabetic complications.

Association of High Immunohistochemical Expression of Minichromosome Maintenance 3 with Human Oral Squamous Cell Carcinoma-A Preliminary Study.

BACKGROUND: Oral squamous cell carcinoma (OSCC) may arise from premalignant oral lesions (PMOL) in most cases. Minichromosome maintenance 3 (MCM3) is a proliferative marker that has been investigated as a potential diagnostic biomarker in the diagnosis of oral cancer. OBJECTIVES: To evaluate the association of MCM3 expression, its clinicopathologic parameters and to identify snuff (also called naswar) as a potential risk factor for changes in MCM3 expression in PMOL and OSCC. METHODOLOGY: Immunohistochemistry (IHC) of MCM3 was performed on 32 PMOL, 32 OSCC and 16 normal controls after optimization of IHC methodology. Histoscore (0-300) was used as a scoring system and seven different cut-offs were identified for analyses. Data were analyzed using various statistical tests. RESULTS: Among the seven cutoffs, 40% strong positive cells were found to be a better cut-off as they were associated with many pathological variables (Broder's grade, Aneroth's grade, and mitotic activity). The differential MCM3 expression in oral lesions (PMOL and OSCC) was statistically significant (p = 0.03). Moreover, MCM3 expression is raised with increased duration and frequency of snuff use. CONCLUSION: High MCM3 expression is associated with disease progression and is a potential indicator of malignant transformations from PMOL to OSCC. Moreover, the use of snuff is associated with MCM3 over-expression.

Synthesis of 1,2,3,triazole modified analogues of hydrochlorothiazide via click chemistry approach and in-vitro α-glucosidase enzyme inhibition studies.

The current study was aimed to discover potent inhibitors of α-glucosidase enzyme. A 25 membered library of new 1,2,3-triazole derivatives of hydrochlorothiazide (1) (HCTZ, a diuretic drug also being used for the treatment of high blood pressure) was synthesized through click chemistry approach. The structures of all derivatives 2-26 were deduced by MS, IR, 1H-NMR, and 13C-NMR spectroscopic techniques. All the compounds were found to be new. Compounds 1-26 were evaluated for α-glucosidase enzyme inhibition activity. Among them, 18 compounds showed potent inhibitory activity against α-glucosidase with IC50 values between 24 and 379 µM. α-Glucosidase inhibitor drug acarbose (IC50 = 875.75 ± 2.08 µM) was used as the standard. Kinetics studies of compounds 6, 9, 11, 12, 15, 20, 23, and 24 revealed that only compound 15 as a mixed-type of inhibitor, while others were non-competitive inhibitors of α-glucosidase enzyme. All the compounds were found to be non-cytotoxic when checked against mouse fibroblast 3T3 cell line.

Prevalence of sleep disturbance and anxiety due to the COVID-19 pandemic in Saudi Arabia.

INTRODUCTION: In the COVID-19 pandemic, physical and psychological health are of immense concern for the governing bodies and health policymakers in the period of lockdown and self-isolation. An in-depth analysis is required to recognize the changes in mental health among the public of different geographical areas. OBJECTIVE: The study aimed to investigate the sleep quality and anxiety among the population in Saudi Arabia during the lockdown period from March to June 2020. MATERIAL AND METHODS: We conducted a cross-sectional study and surveyed the population in Saudi Arabia during the lockdown. We analyzed the anxiety and sleep quality in a population with variable socio-demographic profiles. We assessed anxiety using the self-rating anxiety scale (SAS) questionnaire and tested the sleep quality by using the Pittsburgh sleep quality index (PSQI) questionnaire. We analysed the questionnaire responses to determine the relationships between anxiety, stress, sleep disturbances by using SPSS, and considered the p-value<0.05 statistically significant. RESULTS: We collected 397 questionnaires from the participants. The respondents were mostly of youth age (19-24 years), 66.5% of respondents were male, while there were 33.5% females. Most of the participants did not contact any COVID-19 patients (75.1%, n=298). The finding revealed that most people did not consider associated anxiety as a worrying disorder as the vast majority were normal with only 12.6% had mild-to-moderate anxiety and almost 1% had moderate-to-severe anxiety. While correlating the sleep patterns disturbance in individuals who had contact with COVID-19 patients, there was a significant sleep disturbance. The disturbance of sleep was in having problems falling sleep (p-value=0.024), having bad/horrible dreams (p-value=0.017), feeling cold at sleeping (p-value=0.038), and difficulty staying active during eating or driving (p-value=0.012). There was a significant correlation with anxiety related to the COVID-19 contact and problems affecting the routine work (p-value=0.001). CONCLUSION: There is a significant correlation with anxiety related to the contact with COVID-19 positive patients and problems affecting the routine work among operational professionals. The sleep quality is poor due to the stay-at-home order, having a disorganized working schedule, and deprived lifestyle. The awareness regarding the publics' mental health related to the pandemic needs to be implemented and psychological guidelines ought to be available for the public. Health measures through the promotion of lifestyle modifications, mindful body practices, meditation, and home exercise can reduce stress and improve the quality of sleep.

Awareness about Vulvovaginal Aesthetics Procedures among Medical Students and Health Professionals in Saudi Arabia.

OBJECTIVE: The present study aimed to explore the opinion and ethical consideration of vulvovaginal aesthetics procedures (VVAPs) among health professionals and medical students in Saudi Arabia. METHODS: This is a cross-sectional study performed between January 2020 and April 2020. Data was collected through electronic media, WhatsApp, and emails. The results were analyzed by applying the Students t-test, and correlations were considered significant if they presented a p-value < 0.05. RESULTS: There is significant demand to educate doctors, health professionals, medical students, and gynecologists for the VVAPs to have a solid foundation, justified indications, and knowledge about various aesthetic options. Although female doctors, medical students, young doctors, and gynecologists have more knowledge about VVAPs, all health professionals ought to be aware of recent trends in vulvovaginal aesthetics (VVA). The present analysis determined that VVA should be under the domain of gynecologists, rather than under that of plastic surgeons, general surgeons, and cosmetologists. The majority of the participants considered that vaginal rejuvenation, "G-spot" augmentation, clitoral surgery, and hymenoplasty are not justifiable on medical grounds. CONCLUSION: The decision to opt for different techniques for vaginal tightening and revitalization should be taken very carefully, utilizing the shared decision-making approach. Ethical aspects and moral considerations are important key factors before embarking in the VVAPs purely for cosmetic reasons. Further research is required to determine the sexual, psychological, and body image outcomes for women who underwent elective VVAPs. Moreover, medical educators must consider VVAPs as part of the undergraduate and postgraduate medical curriculum.

Awareness about vulvovaginal aesthetics procedures among medical students and health professionals in saudi arabia

Abstract Objective The present study aimed to explore the opinion and ethical consideration of vulvovaginal aesthetics procedures (VVAPs) among health professionals and medical students in Saudi Arabia. Methods This is a cross-sectional study performed between January 2020 and April 2020. Data was collected through electronic media, WhatsApp, and emails. The results were analyzed by applying the Students t-test, and correlations were considered significant if they presented a p-value<0.05. Results There is significant demand to educate doctors, health professionals, medical students, and gynecologists for the VVAPs to have a solid foundation, justified indications, and knowledge about various aesthetic options. Although female doctors, medical students, young doctors, and gynecologists have more knowledge about VVAPs, all health professionals ought to be aware of recent trends in vulvovaginal aesthetics (VVA). The present analysis determined that VVA should be under the domain of gynecologists, rather than under that of plastic surgeons, general surgeons, and cosmetologists. Themajority of the participants considered that vaginal rejuvenation, "G-spot" augmentation, clitoral surgery, and hymenoplasty are not justifiable on medical grounds. Conclusion The decision to opt for different techniques for vaginal tightening and revitalization should be taken very carefully, utilizing the shared decision-making approach. Ethical aspects and moral considerations are important key factors before embarking in the VVAPs purely for cosmetic reasons. Further research is required to determine the sexual, psychological, and body image outcomes for women who underwent elective VVAPs. Moreover, medical educators must consider VVAPs as part of the undergraduate and postgraduate medical curriculum.

Virulent and multidrug-resistant Klebsiella pneumoniae from clinical samples in Balochistan.

Klebsiella pneumoniae is an important pathogen causing hospital-acquired infections in human beings. Samples from suspected patients of K pneumoniae associated with respiratory and urinary tract infections were collected at Bolan Medical Complex, Quetta, Balochistan. Clinical samples (n = 107) of urine and sputum were collected and processed for K pneumoniae isolation using selective culture media. Initially, 30 of 107 isolates resembling Klebsiella spp. were processed for biochemical profiling and molecular detection using gyrase A (gyrA) gene for conformation. The K pneumoniae isolates were analysed for the presence of drug resistance and virulence genes in their genomes. The 21 of 107 (19.6%) isolates were finally confirmed as K pneumoniae pathogens. An antibiogram study conducted against 17 different antibiotics showed that a majority of the isolates are multidrug resistant. All the isolates (100%) were resistant to amoxicillin, cefixime, amoxicillin-clavulanic acid, cefotaxime, and ceftriaxone followed by tetracycline (95.2%), ciprofloxacin and gentamicin (76.2%), sulphamethoxazol (66.7%), nalidixic acid (61.9%), norfloxacine (42.9%), piperacillin-tazobactam (23.8%), cefoperazone-sulbactam (19%), and cefotaxime-clavulanic acid (33.3%), whereas all the isolates showed sensitivity to amikacin, chloramphenicol, and imipenem. The presence of tetracycline, sulphamethoxazol-resistant genes, and extended-spectrum beta-lactamase was reconfirmed using different specific genes. The presence of virulence genes fimH1 and EntB responsible for adherence and enterobactin production was confirmed in the isolates. The high virulence and drug resistance potential of these Klebsiella isolates are of high public health concern. Multidrug resistance and virulence potential in K. pneumoniae are converting these nosocomial pathogens into superbugs and making its management harder.

Audience response system (ARS); A way to foster formative assessment and motivation among medical students.

This article was migrated. The article was marked as recommended. Using an audience response system (ARS) is very effective to improve learning through active participation and enhanced interaction among medical students. Although the validity of ARS in engagement during the learning process is clear, we know little about its impact on self-motivation. Aim: This study aimed to investigate the effectiveness of ARS as compared to other used methods such as quizzes on paper/verbal questioning and analyzed how ARS nurture motivation among medical students. Methods: This is mixed-method research and assessed the medical student's perceptions about the use of ARS and its role in the augmentation of motivation for learning. We used a google doc questionnaire for data collection and the qualitative part of the study we conducted by semi-structured focused group discussions to explore the impact on self-motivation. For data analysis, we applied students paired t-test, and a p-value of less than 0.05 determined the significant correlation between ARS and other methods of formative assessment (quiz on paper/verbal questions). We coded the focused group discussions and identified themes based on the grounded theory. Results: There is a significant correlation (P value= 0.008) for the comfort level of the formative assessment methods with ARS as compared to quizzes on paper/verbal response. ARS helped significantly to enhance the self-evaluation and self-motivation through instant comparisons of the results with the rest of the audience with P-value=0.027 and 0.021 respectively. ARS is a validated and proficient tool to assess student's learning and generating self-motivation. Conclusion: In medical education, ARS enhances the opportunity to recognize the knowledge gaps and encouraged conceptual learning. It provided students with a powerful insight into the learning of key concepts and self-assessment. Using ARS triggers not only motivation but also generates novel ideas and lifelong learning skills.

A comparative study between a single-dose and 24-hour multiple-dose antibiotic prophylaxis for elective hysterectomy.

INTRODUCTION: Surgical site infections (SSIs) are a major health issue in surgical specialties in terms of health care costs and patients' clinical outcomes. At the level of the patient, prolonged hospital stays or readmissions for SSIs, can affect the patient's quality of life. At the level of the health care system, it exhausts the hospital's resources and increases the burden on the medical staff due to the need for continuous wound care, microbiological cultures, laboratory tests and medications. In this study, we assessed the effectiveness of two antibiotic prophylaxis regimens for the prevention of SSIs in patients undergoing elective hysterectomy surgeries. METHODOLOGY: A retrospective cohort, analyzing 141 patients, was conducted between November 2016 and January 2019 at a university hospital. We compared the efficacy of a single dose vs. 24-hour multiple doses of Cefazolin in patients who underwent elective hysterectomy for benign or malignant indications. The secondary objective was to identify potential risk factors associated with SSIs. RESULTS: There was no statistically significant difference between both groups (p = 0.872). Obesity and a laparotomy surgical approach are risk factors to the development of SSIs (p = 0.001 and 0.014, respectively). Other potential risk factors include the duration of hospital stay, the duration of the surgery and the amount of blood loss. CONCLUSIONS: Although the rate of SSIs is not significantly different between both groups, risk stratification can be done after screening patients and the prophylactic regimen must be tailored for each patient in a cost-effective manner and using a multidisciplinary approach.

Chemical constituents from Parrotia persica- Structural derivatization and their potential prolyl endopeptidase inhibition activity.

The current study was aimed to evaluate the prolyl endopeptidase (PEP) inhibitory activity of glutinol (1), azadiradione (2), quercetin 3-O-ß-d-glactopyranoside (3), catechin (4), quercetin (5), naringenin (6) isolated from Parrotia persica C. A. Mey. Naringenin (6) was further derivatized into 7-O-propargylnaringenin (7), 4',6',4″-O-propargylchalcone (8), and 4',4″-O-propargylchalcone (9). All compounds 1-9 were evaluated for their PEP inhibition activity. PEP is associated with several diseases, including dementia, and Alzheimer's disease (AD). Azadiradione (2) was less active with IC50 = 356.80 ± 2.9 µM, whereas quercetin (5) showed a potent activity with IC50 = 37.12 ± 2.2 µM, as compared to IC50 = 125.00 ± 1.5 µM of standard drug bacitracin. Naringenin (6) was found to be inactive, whereas its new analogues 7-9 were identified as potent inhibitors of PEP with IC50 = 35.20, 41.20, and 29.60 µM, respectively. Kinetic studies of active compounds indicated their modes of inhibition. Compounds 7-9 were found to be mixed-type inhibitors, while compound 5 was found to be non-competitive inhibitor.

A CREATIVE approach to designing a contemporary medical curriculum.

This article was migrated. The article was marked as recommended. In medical education, Outcome-based Education (OBE) is facing many challenges due to the rapid proliferation in biomedical sciences; technology-enhanced learning; globalization of health system, and the availability of various pedagogical techniques. A steady stream of evidence-based developments challenges those who are responsible for sustaining and improving their medical curricula. Curriculum reform is a dynamic process and there is no explicit approach that can serve as a guide for a curriculum reviewer while making amendments in the OBE integrated curriculum. This study took place in a medical college in Saudi Arabia and it highlights the key components to be considered while reviewing the Bachelor in Medicine and Surgery (MBBS) course specifications and curriculum. It suggests the importance of course reports as the main driving force for curriculum reforms. Delineating major and minor changes in the curriculum and frequency of amendments in course specifications also remains a questionable task and requires established institutional guidelines. Furthermore, based on practical experience in the periodic curriculum review process, the authors suggest some best practice. We present a "CREATIVE" way forward which we have found invaluable, both for curriculum developers and for engaging with our stakeholders. This mnemonic spells out the key factors to consider while revisiting the curriculum from various angles. These factors are: Course Report recommendations, Evaluation tools (internal and external), Alignment of pedagogical strategies with assessment, Technology, Innovation, Variations in the learning environment, and Establishment of institutional guidelines. Application of these fundamental elements allowed us the development of a curriculum that meets the standards for international accreditation and helped the institution to form a cohesive team of educationalists.