Effectiveness of spaced repetition for clinical problem solving amongst undergraduate medical students studying paediatrics in Pakistan.

BACKGROUND: Studies using spaced repetition for teaching and learning in undergraduate clinical rotations such as paediatrics are limited, even more so in the South Asian region. Therefore, this study aimed to identify the effectiveness of utilizing spaced repetition compared to traditional learning methods among undergraduate medical students during their paediatric rotation at a medical university in Pakistan. METHODS: Bahria University Medical and Dental College (BUMDC) conducted quasii-experimental research in Karachi. Four topics were identified from the Year 5 Pediatrics curriculum to be used in the study, using which the study content was developed along with 50 multiple choice questions (MCQs) for assessment. All BUMDC Year 5 medical students rotating in Pediatrics were included and randomly allocated to the control or intervention group. In the control group, they provided the students with traditional study methods consisting of books and lectures to learn topics. In the intervention group, we created an Anki flashcard deck of the same topics to enable learning via spaced repetition. The researchers conducted a pretest and post test assessment of the 50 MCQs in both groups at the beginning and after the four-week study interval. The data were analysed using SPSS 19. RESULTS: A total of 115 BUMDC medical students agreed to participate in the study; 70 (59.1%) were in the intervention group, and 45 (41.7%) were in the control group. The pretest mean score of the control group was 27.96 ± 3.70, and the posttest mean score was 27.22 ± 5.02, with no statistically significant difference at the 95% confidence level. The mean score of the pretest for the intervention group was 27.93 ± 4.53, and that of the posttest was 30.8 ± 4.56, with a statistically significant difference at the 95% confidence level. The intervention showed a significant effect size of 0.8. CONCLUSION: The use of spaced repetitions resulted in significantly greater scores for medical students studying paediatrics than for those using more traditional methods of learning, compromising medical books and lectures. Considering that medical students need to retain a vast amount of information, using spaced repetition through flashcards can be a more effective learning tool that is more cost-efficient and time-efficient than traditional learning methods.

Design of potent tyrosinase inhibiting N-arylated-4-yl-benzamides bearing 2-aminothiazole-triazole bi-heterocycles: mechanistic insight through enzyme inhibition, kinetics and computational studies.

By using a convergent methodology, a unique series of N-arylated 4-yl-benzamides containing a bi-heterocyclic thiazole-triazole core was synthesized and the structures of these hybrid molecules, 9a-k, were corroborated through spectral analyses. The in vitro studies of these multi-functional molecules demonstrated their potent mushroom tyrosinase inhibition relative to the standard used. The kinetics mechanism was exposed by lineweaver-burk plots which revealed that, 9c, inhibited mushroom tyrosinase non-competitively by forming an enzyme-inhibitor complex. The inhibition constant Ki calculated from Dixon plots for this compound was 0.016 µM. The computational study was also consistent with the experimental results and these molecules disclosed good results of all scoring functions and interactions, which suggested a good binding to mushroom tyrosinase. So, it was predicted from the inferred results that these molecules might be considered as promising medicinal scaffolds for the diseases associated with the over-expression of this enzyme.

Exploring chalcone-sulfonyl piperazine hybrids as anti-diabetes candidates: design, synthesis, biological evaluation, and molecular docking study.

To address the escalating rates of diabetes mellitus worldwide, there is a growing need for novel compounds. The demand for more affordable and efficient methods of managing diabetes is increasing due to the inevitable side effects associated with existing antidiabetic medications. In this present research, various chalcone-sulfonyl piperazine hybrid compounds (5a-k) were designed and synthesized to develop inhibitors against alpha-glucosidase and alpha-amylase. In addition, several spectroscopic methods, including FT-IR, 1H-NMR, 13C-NMR, and HRMS, were employed to confirm the exact structures of the synthesized derivatives. All synthesized compounds were evaluated for their ability to inhibit alpha-glucosidase and alpha-amylase in vitro using acarbose as the reference standard and they showed excellent to good inhibitory potentials. Compound 5k exhibited excellent inhibitory activity against alpha-glucosidase (IC50 = 0.31 ± 0.01 µM) and alpha-amylase (IC50 = 4.51 ± 1.15 µM), which is 27-fold more active against alpha-glucosidase and 7-fold more active against alpha-amylase compared to acarbose, which had IC50 values of 8.62 ± 1.66 µM for alpha-glucosidase and 30.97 ± 2.91 µM for alpha-amylase. It was discovered from the Lineweaver-Burk plot that 5k exhibited competitive inhibition against alpha-glucosidase. Furthermore, cytotoxicity screening assay results against human fibroblast HT1080 cells showed that all compounds had a good level of safety profile. To explore the binding interactions of the most potent compound (5k) with the active site of enzymes, molecular docking research was conducted, and the results obtained supported the experimental data.

Pakistan's HIV high-risk populations: Critical appraisal of failure to curtail spread beyond key populations.

Pakistan has been a hub of several HIV outbreaks over the last 2 decades, with four major outbreaks being registered since 2018. There has been a recent rise in HIV infections, especially in high-risk populations, mainly consisting of people who inject drugs, men who have sex with men, prisoners, the transgender women community, and female sex workers. Consistently poor infection control practices, unregulated unsafe blood transfusion, questionable ethical practices by healthcare providers, and a general lack of awareness are the main drivers of recent HIV outbreaks, with these issues exacerbated by the presence of untrained health care providers. To stop the spread of HIV systemically and sustainably, aggressive measures need to be taken at all levels by all concerned stakeholders that not only deal with building up testing, tracing, and treatment capabilities but also address underlying grassroots problems that have largely been ignored to date.

Pathways to prevention: insights on stemming HIV outbreaks in Larkana, Pakistan.

In the past two decades, Pakistan has faced multiple human immunodeficiency virus outbreaks, with Larkana appearing to be the hub of such outbreaks. While the previous Larkana outbreaks happened in high-risk populations, the alarming outbreak in 2019 occurred in a low-risk paediatric population, raising several concerning questions. Human immunodeficiency virus infections spilling into the general population is indicative of a steady increase in the number of cases, and the failure of control strategies to stem the concentrated epidemic from evolving. Although several causative factors have been identified from previous outbreaks, the one that occurred in 2019 may have been influenced by an additional, hitherto unexplored factor; child sexual abuse. The current narrative review was planned to summarise human immunodeficiency virus risk factors and causes identified in previous Larkana epidemics, to explore potential reasons for the outbreaks in children, and to discuss possible steps needed for stemming human immunodeficiency virus outbreaks in Pakistan.

Effectiveness of blended pedagogy for radiographic interpretation skills in operative dentistry - a comparison of test scores and student experiences at an undergraduate dental school in Pakistan.

BACKGROUND: Utilizing Blended pedagogy (BP) in radiographic skills may prove to be an effective teaching strategy. However, studies on the use of BP in dentistry are quite limited in Pakistan, where teaching has mostly been via traditional Didactic Lectures (DL); and radiographic interpretation skills of undergraduate dental students are suboptimal. Therefore, this study aims to assess whether utilizing BP to teach radiographic interpretation skills is an effective teaching methodology in Pakistan. METHODS: This mixed-method study was conducted on final year dental students at Jinnah Medical and Dental College (JMDC). Two groups of students were utilized for this study, one taught by traditional DL and the other taught by BP for the same module. BP was conducted over six weeks. A post-module test was conducted in both groups. Additionally, the BP group completed a modified Community of Inquiry (CoI) survey tool and volunteered to discuss their experiences through a focused group discussion (FGD). Descriptive statistics were computed and independent sample t-test was used to analyse the difference between the scores of the two groups. Thematic analysis was performed for the qualitative data. RESULTS: The mean post-test scores were found to be significantly higher in the BP group (61.0 ± 10.2) compared to the DL group (44.4 ± 12.3) (p = < 0.001, CI = 95%, Cronbach Alpha > 0.8). The mean scores for the modified CoI instrument were 4.0 ± 0.29 for the whole instrument; 4.25 ± 0.22 for Teaching Presence, 3.71 ± 0.23 for Social Presence and 3.97 ± 0.16 Cognitive Presence, with all three having a Cronbach's alpha > 0.75. Thematic analysis revealed that BP students mutually agreed that BP method was beneficial with the appreciation of strong support from the facilitator. However, challenges like interrupted power supply and increased effort requirement from students were pointed out. CONCLUSION: Students taught radiographic interpretation skills with BP in comparison to DL had higher test scores and expressed a positive experience demonstrated via a modified CoI survey and FGD. Considering the encouraging results found, dental schools should incorporate BP in their teaching methodology and follow-up studies are needed to further support the use of BP as an effective teaching methodology in Dentistry.

Review of sepsis in Pakistan: how far have we come?

Pakistan is a low-middle-income country (LMIC) with a high burden of sepsis, yet there is a profound dearth of data regarding sepsis with no comprehensive review. In Pakistan, access to competent healthcare services is delayed and in places, often not available. Patients may present with sepsis after common community-acquired infections; the commonest sources of sepsis are the respiratory tract followed by the urinary tract. Gram-negative organisms are responsible for a large majority of cases of sepsis. Unfortunately, compliance with sepsis guidelines remains poor, and sepsis-related statistics do not seem to be improving significantly. Adult sepsis presents a significant burden on healthcare services, particularly in LMICs, and is a leading cause of morbidity and mortality. Many factors which affect outcomes and cost of care are amenable to prompt interventions. Consequently, there is a dire need to make concentrated efforts in implementing simple, cost-effective, and context-specific guidelines and monitoring strategies regarding the diagnosis and management of sepsis. The collection and analysis of information on sepsis in Pakistan hence remains imperative, in order to prospectively assess the effects of guideline compliance on outcomes and to formulate and refine new schemata to address emerging problems.

Recent Development on Sensing Strategies for Small Molecules Detections.

Sensors play a critical role in the detection and monitoring of various substances present in our environment, providing us with valuable information about the world around us. Within the field of sensor development, one area that holds particular importance is the detection of small molecules. Small molecules encompass a wide range of organic or inorganic compounds with low molecular weight, typically below 900 Daltons including gases, volatile organic compounds, solvents, pesticides, drugs, biomarkers, toxins, and pollutants. The accurate and efficient detection of these small molecules has attracted significant interest from the scientific community due to its relevance in diverse fields such as environmental pollutants monitoring, medical diagnostics, industrial optimization, healthcare remedies, food safety, ecosystems, and aquatic and terrestrial life preservation. To meet the demand for precise and efficient monitoring of small molecules, this summary aims to provide an overview of recent advancements in sensing and quantification strategies for various organic small molecules including Hydrazine, Glucose, Morpholine, Ethanol amine, Nitrosamine, Oxygen, Nitro-aromatics, Phospholipids, Carbohydrates, Antibiotics, Pesticides, Drugs, Adenosine Triphosphate, Aromatic Amine, Glutathione, Hydrogen Peroxide, Acetone, Methyl Parathion, and Thiophenol. The focus is on understanding the receptor sensing mechanism, along with the electrical, optical, and electrochemical response. Additionally, the variations in UV-visible spectral properties of the ligands upon treatment with the receptor, fluorescence and absorption titration analysis for limit of detection (LOD) determination, and bioimaging analysis are discussed wherever applicable. It is anticipated that the information gathered from this literature survey will be helpful for the perusal of innovation regarding sensing strategies.

Synthesis and Computational Exploration of Morpholine Bearing Halogenated Sulfonamides as Potential Tyrosinase Inhibitors.

In the presented work, a new series of three different 4-((3,5-dichloro-2-[(2/4-halobenzyl)oxy]phenyl)sulfonyl)morpholines was synthesized and the structure of these compounds were corroborated by 1 H-NMR & 13 C-NMR studies. The in vitro results established all the three compounds as potent tyrosinase inhibitors relative to the standard. The Kinetics mechanism plots established that compound 8 inhibited the enzyme non-competitively. The inhibition constants Ki calculated from Dixon plots for this compound was 0.0025 µM. Additionally, computational techniques were used to explore electronic structures of synthesized compounds. Fully optimized geometries were further docked with tyrosinase enzyme for inhibition studies. Reasonably good binding/interaction energies and intermolecular interactions were obtained. Finally, drug likeness was also predicted using the rule of five (RO5) and Chemical absorption, distribution, metabolism, excretion, and toxicity (ADMET) characteristics. It is anticipated that current experimental and computational investigations will evoke the scientific interest of the research community for the above-entitled compounds.

Synthesis and Molecular Docking Studies of Novel Biheterocyclic Propanamides as Antidiabetic Agents Having Mild Cytotoxicity.

The aim of this work was to bring forth some new hybrid molecules having pharmacologically potent indole and 1,3,4-oxadiazole heterocyclic moieties unified with a propanamide entity. The synthetic methodology was initiated by esterification of 2-(1H-indol-3-yl)acetic acid (1) in a catalytic amount of sulfuric acid and ethanol in excess, to form ethyl 2-(1H-indol-3-yl)acetate (2), which was converted to 2-(1H-indol-3-yl)acetohydrazide (3) and further transformed to 5-(1H-indole-3-yl-methyl)-1,3,4-oxadiazole-2-thiol (4). 3-Bromopropanoyl chloride (5) was reacted with various amines (6a-s) in aqueous alkaline medium to generate a series of electrophiles, 3-bromo-N-(substituted)propanamides (7a-s), and these were further reacted with nucleophile 4 in DMF and NaH base to yield the targeted N-(substituted)-3-{(5-(1H-indol-3-ylmethyl)-1,3,4-oxadiazol-2-yl)sulfanyl}propanamides (8a-s). The chemical structures of these biheterocyclic propanamides were confirmed by IR, 1H NMR, 13C NMR, and EI-MS spectral techniques. These compounds were evaluated for their enzyme inhibitory potentials against the α-glucosidase enzyme, where the compound 8l showed promising enzyme inhibitory potential with an IC50 value less than that of the standard acarbose. Molecular docking results of these molecules were coherent with the results of their enzyme inhibitory potentials. Cytotoxicity was assessed by the percentage of hemolytic activity method, and these compounds generally exhibited very low values as compared to the reference standard, Triton-X. Hence, some of these biheterocyclic propanamides might be considered as salient therapeutic agents in further stages of antidiabetic drug development.

γ-Glutamyltranspeptidase (GGT) Sensitive Fluorescence Probes for Cancer Diagnosis; Brief Review.

Millions of deaths occur each year due to the late diagnosis of abnormal cellular growth within the body. However, the devastating impact of this can be significantly reduced if cancer metastasis is detected early through the use of enzymatic biomarkers. Among several biomarkers, γ-glutamyltranspeptidase (GGT) stands out as a member of the aminopeptidase family. It is primarily found on the surface of cancer cells such as glioma, ovarian, lung, and prostate cancer, without being overexpressed in normal cells or tissues. Recent years have witnessed significant progress in the field of cancer monitoring and imaging. Fluorescence sensing techniques have been employed, utilizing organic small molecular probes with enzyme-specific recognition sites. These probes emit a fluorescent signal upon interacting with GGT, enabling the imaging, identification, and differentiation of normal and cancerous cells, tissues, and organs. This review article presents a concise overview of recent progress in fluorescent probes developed for the selective detection of GGT, focusing on their applications in cancer imaging. It highlights the observed alterations in the fluorescence and absorption spectra of the probes before and after interaction with GGT. Additionally, the study investigates the changes in the probe molecule's structure following enzyme treatment, evaluates the sensor's detection limit, and consolidated imaging studies conducted using confocal fluorescence analysis. This comprehensive survey is expected to contribute to the advancement of sensing techniques for biomarker detection and cancer imaging, providing valuable insights for refining methodologies and inspiring future developments in this field.

Convergent synthesis, kinetics insight and allosteric computational ascriptions of thiazole-(5-aryl)oxadiazole hybrids embraced with propanamides as alkaline phosphatase inhibitors.

Considering the varied pharmacological prominence of thiazole and oxadiazole heterocyclic moieties, a unique series of bi-heterocyclic hybrids, 8a-h, was synthesized in a convergent manner. The structures of newly synthesized compounds were characterized by 1H-NMR, 13C-NMR, and IR spectral studies. The structure-activity relationship of these compounds was predicted by examining their inhibitory effects against alkaline phosphatase, whereby all these molecules exhibited superb inhibitory potentials relative to the standard used. The kinetics mechanism was determined by Lineweaver-Burk plots which revealed that 8g inhibited the studied enzyme non-competitively by forming an enzyme-inhibitor complex. The inhibition constant Ki calculated from Dixon plots for this compound was 0.42 µM. The allosteric computational study was coherent with the experimental records and these ligands exhibited good binding energy values (kcal mol-1). The hemolytic analysis revealed their mild cytotoxicity towards red blood cell membranes and hence, these molecules have potential to be nontoxic medicinal scaffolds for the treatment of alkaline phosphate-associated ailments.

Design and synthesis of thiadiazole-oxadiazole-acetamide derivatives: Elastase inhibition, cytotoxicity, kinetic mechanism, and computational studies.

Considering the biological significance of 1,3,4-thiadiazole/oxadiazole heterocyclic scaffolds, a novel series of 1,3,4-thiadiazole-1,3,4-oxadiazole-acetamide derivatives (7a-j) was designed and synthesized using molecular hybridization. The inhibitory effects of the target compounds on elastase were evaluated, and all of these molecules were found to be potent inhibitors compared to the standard reference oleanolic acid. Compound 7f exhibited the excellent inhibitory activity (IC50 = 0.06 ± 0.02 µM), which is 214-fold more active than oleanolic acid (IC50 = 12.84 ± 0.45 µM). Kinetic analysis was also performed on the most potent compound (7f) to determine the mode of binding with the target enzyme, and it was discovered that 7f inhibits the enzyme in a competitive manner. Furthermore, the MTT assay method was used to assess their toxicity on the viability of B16F10 melanoma cell lines, and all compounds did not display any toxic effect on the cells even at high concentrations. The molecular docking studies of all compounds also justified with their good docking score and among them, compound 7f had a good conformational state with hydrogen bond interactions within the receptor binding pocket, which is consistent with the experimental inhibition studies.

Assessing Risk Factors for Prolonged Intensive Care Unit Stay After Surgery for Adult Congenital Heart Disease: A Study From a Lower-Middle-Income Country.

Background Prolonged post-surgery intensive care unit (ICU) stay for congenital heart disease (CHD) has been explored in the pediatric population. However, there is limited data for adult CHD (ACHD), also called grown-up congenital heart (GUCH) disease, especially in low-resource countries where intensive care beds are scarce. This study identifies factors associated with prolonged ICU stay following surgery for ACHD in Pakistan, a lower-middle-income country (LMIC). Methods This retrospective study included all adult patients (⩾18 years) who underwent cardiac surgery with cardiopulmonary bypass for their CHD from 2011-2016 at a tertiary-care private hospital in Pakistan. Prolonged ICU stay was defined as stay >6 days (75th percentile). Regression analysis was used to explore risk factors of prolonged ICU stay. Results A total of 166 patients (53.6% males) with a mean age of 32.05 ± 12.11 years were included. Atrial septal defect repair was the most common surgery (42.2%). Most patients were categorized as Risk Adjustment for Congenital Heart Surgery 1 (RACHS-1) Category 1 (51.8%) and Category 2 (30.1%). Forty-three of 166 patients (25.9%) experienced prolonged ICU stay. Complications occurred in 38.6% of patients postoperatively, with the most common being acute kidney injury (29.5%). On multivariable logistic regression adjusted for age, gender, and RACHS-1 categories, intraoperative inotrope score, cardiopulmonary bypass time, aortic cross-clamp time duration of mechanical ventilation, and postoperative acute kidney injury (AKI) were associated with prolonged ICU stay. Conclusion Surgeons managing ACHD in LMICs must strive for shorter operative durations and the judicious use of intraoperative inotropes in addition to anticipating and promptly managing postoperative complications such as AKI, to minimize ICU stay in countries where intensive care beds are a scarce resource.

Synthesis and discovery of potential tyrosinase inhibitor of new coumarin-based thiophenyl-pyrazolylthiazole nuclei: In vitro evaluation, cytotoxicity, kinetic, and computational studies.

A well-known key enzyme in melanogenesis and hyperpigmentation is tyrosinase. The present study introduces a novel series of thiophenyl-pyrazolylthiazole-coumarin hybrids (6a-6h) as tyrosinase inhibitors. The in-vitro tyrosinase inhibition results indicated that all compounds have strong tyrosinase inhibitory activity, particularly compound 6g (IC50  = 0.043 ± 0.006 µM), was identified as the most active compound compared to the positive control (kojic acid, IC50  = 18.521 ± 1.162 µM). Lineweaver-Burk plots were employed to analyze the kinetic mechanism, and compound 6g formed an enzyme-inhibitor complex by inhibiting tyrosinase non-competitively. Furthermore, all compounds demonstrated excellent antioxidant activity against DPPH. MTT assay was used to screen the cytotoxicity of all compounds on B16F10 melanoma cells, and they had no toxic effect on the cells. The binding affinity of compounds with tyrosinase was also investigated using molecular docking, and the ligands displayed good binding energy values. These molecules could be a promising lead for skin pigmentation and associated diseases as nontoxic pharmacological scaffolds.

Diagnostic value of bronchoscopy in Sars-Cov-2 infection: A systematic review.

OBJECTIVE: To investigate the diagnostic performance of bronchoscopy in patients with coronavirus disease 2019 infection. METHODS: The systematic review was conducted in April 2021 and comprised search of published articles and preprint servers for original articles assessing diagnostic performance of bronchoscopy in patients with suspected coronavirus disease 2019 infection. The primary outcome of interest was diagnostic sensitivity of bronchoalveolar lavage in the patients. The quality of each study was assessed using the Quality Assessment, Data Abstraction and Synthesis-2 tool. RESULTS: Of the 29 full-text articles assessed for eligibility, 4(13.8%) were included collectively comprising 209 patients who had undergone bronchoalveolar lavage. Mean sensitivity of bronchoalveolar lavage was 83.5% ± 10.63 (range: 68.2-940%). Overall, the 4 studies had an unclear or low risk of bias. CONCLUSIONS: Limited data suggested that bronchoscopy with bronchoalveolar lavage did not have reliably higher diagnostic sensitivity than that reported for either nasopharyngeal or oropharyngeal swabs.

2-Aminothiazole-Oxadiazole Bearing N-Arylated Butanamides: Convergent Synthesis, Tyrosinase Inhibition, Kinetics, Structure-Activity Relationship, and Binding Conformations.

A multi-step synthesis of novel bi-heterocyclic N-arylated butanamides was consummated through a convergent strategy and the structures of these medicinal scaffolds, 7a-h, were corroborated using spectral techniques. The in vitro analysis of these hybrid molecules revealed their potent tyrosinase inhibition as compared to the standard used. The kinetics mechanism was investigated through Lineweaver-Burk plots which exposed that, 7f, inhibited tyrosinase enzyme non-competitively by forming the enzyme-inhibitor complex. The inhibition constants Ki calculated from Dixon plots for this compound was 0.025 µM. Their binding conformations were ascertained by in silico computational studies whereby these molecules disclosed good binding energy values (kcal/mol). So, it was anticipated from the current research that these bi-heterocyclic butanamides might be probed as imperative therapeutic agents for melanogenesis.

Synthesis, kinetic studies and in-silico investigations of novel quinolinyl-iminothiazolines as alkaline phosphatase inhibitors.

Deposition of hydroxyapatite (HA) or alkaline phosphate crystals on soft tissues causes the pathological calcification diseases comprising of end-stage osteoarthritis (OA), ankylosing spondylitis (AS), medial artery calcification and tumour calcification. The pathological calcification is symbolised by increased concentration of tissue non-specific alkaline phosphatase (TNAP). An efficient therapeutic strategy to eradicate these diseases is required, and for this the alkaline phosphatase inhibitors can play a potential role. In this context a series of novel quinolinyl iminothiazolines was synthesised and evaluated for alkaline phosphatase inhibition potential. All the compounds were subjected to DFT studies where N-benzamide quinolinyl iminothiazoline (6g), N-dichlorobenzamide quinolinyl iminothiazoline (6i) and N-nitrobenzamide quinolinyl iminothiazoline (6j) were found as the most reactive compounds. Then during the in-vitro testing, the compound N-benzamide quinolinyl iminothiazoline (6g) exhibited the maximum alkaline phosphatase inhibitory effect (IC50 = 0.337 ± 0.015 µM) as compared to other analogues and standard KH2PO4 (IC50 = 5.245 ± 0.477 µM). The results were supported by the molecular docking studies, molecular dynamics simulations and kinetic analysis which also revealed the inhibitory potential of compound N-benzamide quinolinyl iminothiazoline (6g) against alkaline phosphatase. This compound can be act as lead molecule for the synthesis of more effective inhibitors and can be suggested to test at the molecular level.