Implementing Formative Assessment in Human Anatomy Practical Sessions: Medical Students' Perception and Effect on Final Exam Performance.

Background: Formative assessment with feedback is part of the assessment program in medical education to improve students' learning. Limited research has focused on its application and impact on practical anatomy education. Methods: This study aimed to examine medical students' perceptions of formative assessment in practical anatomy sessions of body systems-based educational units and explore its influence on final practical exam performance. A descriptive, cross-sectional study was conducted. Data was collected from 173 Year 2 medical students through a survey that addressed their perception of process and importance of formative assessment and feedback. The survey employed a 5-point Likert scale. Two open-ended questions were appended at the end of the survey. Students' performance in Unit 3 (where formative assessment was conducted) was compared to their performance in Unit 2 (where no formative assessment was conducted) and with the performance of the previous academic year's students in Unit 3 (where no formative assessment was conducted). Descriptive statistics were used. The level of statistical significance was set at p-value < 0.05. Responses to open-ended questions (qualitative data) were counted, categorized as themes, and presented as frequencies and percentages. Results: The survey showed high internal consistency, and its validity was established through exploratory factor analysis. Results showed that the mean mark for the unit with formative assessment and feedback was significantly higher than for the units without formative assessment and feedback. Students showed positive perception of formative assessment and feedback conducted after practical anatomy sessions. They reported useful insights regarding the benefits they gained from formative assessment and feedback as well as constructive suggestions for future improvements. Conclusion: The study indicates that students positively perceived formative assessment and feedback sessions after practical anatomy sessions. Findings also refer to a positive effect of formative assessment on students' performance in summative practical assessment in anatomy.

Tofacitinib in Pediatric Ulcerative Colitis: A Retrospective Multicenter Experience.

BACKGROUND: Tofacitinib has recently been approved for treatment of moderate-to-severe ulcerative colitis (UC) in adults, yet pediatric data are limited. This international multicenter study describes the effectiveness and safety of tofacitinib in pediatric UC. METHODS: This is a retrospective review of children diagnosed with UC treated with tofacitinib from 16 pediatric centers internationally. The primary outcome was week 8 corticosteroid-free clinical remission (Pediatric Ulcerative Colitis Activity Index <10). Secondary outcomes were clinical response (≥20-point decrease in Pediatric Ulcerative Colitis Activity Index) at week 8, corticosteroid-free clinical remission at week 24, and colectomy rate and adverse safety events through to last follow-up. The primary outcome was calculated by the intention-to-treat principle. RESULTS: We included 101 children with a mean age at diagnosis of 12.8 ±â€…2.8 years and a median disease duration of 20 months (interquartile range [IQR], 10-39 months). All had treatment failure with at least 1 biologic agent, and 36 (36%) had treatment failure with 3 agents. Median follow-up was 24 weeks (IQR, 16-54 weeks). Sixteen (16%) children achieved corticosteroid-free clinical remission at week 8, and an additional 30 (30%) demonstrated clinical response. Twenty (23%) of 88 children achieved corticosteroid-free clinical remission at week 24. A total of 25 (25%) children underwent colectomy by median 86 days (IQR, 36-130 days). No serious drug-related adverse events were reported; there was 1 case of herpes zoster and 2 cases of minor blood test perturbations. CONCLUSIONS: In this largest real-life pediatric cohort to date, tofacitinib was effective in at least 16% of patients with highly refractory UC by week 8. Adverse events were minor and largely consistent with adult data.

Tofacitinib, widely reported in adult ulcerative colitis, has very limited pediatric data. This international collaboration is the largest pediatric study on the efficacy and safety of tofacitinib to date, providing important supportive data to clinicians and regulators.

Rare Case of Double Esophageal Web in a Two-Year-Old.

Congenital esophageal stenosis (CES) is an uncommon condition that poses diagnostic and therapeutic challenges due to its rarity and clinical presentation similar to other esophageal disorders. Symptoms typically start with dysphagia around the introduction of solid foods. A broad range of potential differential diagnoses contributes to a delay in obtaining a definitive diagnosis and administering the proper treatment. We report a two-year-old boy who presented with difficulty swallowing solid foods since 11 months of age, manifesting as choking and gagging. Initial evaluation revealed a double esophageal web, with proximal stenosis detected in an esophagram. Despite two endoscopic dilations and cauterization of the proximal web, a second web in the middle third of the esophagus was found. Subsequent dilatation successfully improved symptoms, and the child began tolerating table foods. This case report aims to contribute to the limited existing literature on CES and to add to the clinical practice in the diagnosis and treatment of this uncommon congenital anomaly.

Human ACE2 orthologous peptide sequences show better binding affinity to SARS-CoV-2 RBD domain: Implications for drug design.

Computational methods coupled with experimental validation play a critical role in the identification of novel inhibitory peptides that interact with viral antigenic determinants. The interaction between the receptor binding domain (RBD) of SARS-CoV-2 spike protein and the helical peptide of human angiotensin-converting enzyme-2 (ACE2) is a necessity for the initiation of viral infection. Herein, natural orthologs of human ACE2 helical peptide were evaluated for competitive inhibitory binding to the viral RBD by use of a computational approach, which was experimentally validated. A total of 624 natural ACE2 orthologous 32-amino acid long peptides were identified through a similarity search. Molecular docking was used to virtually screen and rank the peptides based on binding affinity metrics, benchmarked against human ACE2 peptide docked to the RBD. Molecular dynamics (MD) simulations were done for the human reference and the Nipponia nippon peptide as it exhibited the highest binding affinity (Gibbs free energy; -14 kcal/mol) predicted from the docking results. The MD simulation confirmed the stability of the assessed peptide in the complex (-12.3 kcal/mol). The top three docked-peptides (from Chitinophaga sancti, Nipponia nippon, and Mus musculus) and the human reference were experimentally validated by use of surface plasmon resonance technology. The human reference exhibited the weakest binding affinity (Kd of 318-441 pM) among the peptides tested, in agreement with the docking prediction, while the peptide from Nipponia nippon was the best, with 267-538-fold higher affinity than the reference. The validated peptides merit further investigation. This work showcases that the approach herein can aid in the identification of inhibitory biosimilar peptides for other viruses.

The Evolving Effectiveness of Biologics in Avoiding Surgery in Children With Ulcerative Colitis: At what Nutritional Cost?

BACKGROUND: Pediatric ulcerative colitis (UC) treatment has changed dramatically with the introduction of multiple biologics. The goal of this study was to determine the effectiveness of these new biologics on achieving remission, nutritional impact, and eventual need for surgery in children. METHODS: We retrospectively analyzed hospital records of UC patients (ages 1-19) seen at a pediatric gastroenterology clinic between January 2012 andAugust 2020. Patients were divided into groups: 1) medically without biologics or surgery; 2) patients treated with one biologic; and 3) patients treated with multiple biologics 4)patients that underwent colectomy. RESULTS: There were 115 UC patients with a mean follow-up of 5.9 ± 3.7 years (1 month-15.3 years). PUCAI score at diagnosis was mild in 52 patients (45%), moderate in 25 (21%), and severe in 5 (4.3%). PUCAI score for 33 patients (29%) could not be calculated. There were 48 (41.3%) in group 1 with 58% remission, 34 (29.6%) in group 2 with 71% remission, 24 (20.8%) in group 3 with 29% remission, and only 9 (7.8%) in group 4 with 100% remission. The majority (55%) of surgical patients had colectomy within the first year of diagnosis. BMI improved after surgery (P = 0.001). The change from one biologic to others did not improve nutrition over time. DISCUSSION: New biologics are changing the landscape in maintaining remission from UC. The current need for surgery is much lower than previously published studies. In medically refractive UC, nutritional status only improved after surgery. Addition of another biologic for medically refractory ulcerative colitis in order to avoid surgery must take into account the positive impact surgery has on nutrition and disease remission.

Caffeine protects against hippocampal alterations in type 2 diabetic rats via modulation of gliosis, inflammation and apoptosis.

Type 2 diabetes (T2D) is implicated in the injury of several organs, including the brain resulting in neuronal damage, which may lead to cognitive impairment and dementia. Additionally, it is linked to inflammation, cytokine release, apoptosis and various degenerative conditions. Astrocytes and microglia might have a role in mediating these processes. Caffeine, a psychoactive beverage, has been shown to reduce the risk of cognitive and memory impairment. This study proposes anti-inflammatory and anti-apoptotic role of caffeine, which can be mediated via microglia/astrocyte activation and overexpression of pro-inflammatory molecules. T2D was induced in rats by feeding with high fat high sugar diet and injecting a single low dose streptozotocin (STZ) intraperitoneally. Other diabetic rats were given caffeine orally (in two doses) for 5 weeks, starting 1 week before STZ injection. Measurement of plasma cytokines, TNFα and IL6, was performed using enzyme-linked immunosorbent assay (ELISA) technique. After sacrificing animals, brains were obtained and processed for histological evaluation. Immunohistochemistry was also performed using the following primary antibodies, anti-astrocyte marker GFAP, anti-microglia marker CD11b and apoptotic marker (anti-cleaved caspase-3). There was upregulation of IL6 and TNF-α in diabetic rats. Additionally, histological evaluation of the hippocampus of diabetic rats revealed cellular degeneration. There was increased immunostaining of GFAP, CD11b and cleaved caspase-3 in diabetic rats. Pretreatment with caffeine to diabetic rats, resulted in improvement of structural changes and decrease in cytokine levels and immuno-markers, expression, and this was in a dose-dependent manner. In conclusion, caffeine had an ameliorative role in enhancing hippocampal degenerative changes in T2D.

Computational design and characterization of a multiepitope vaccine against carbapenemase-producing Klebsiella pneumoniae strains, derived from antigens identified through reverse vaccinology.

Klebsiella pneumoniae is a Gram-negative pathogen of clinical relevance, which can provoke serious urinary and blood infections and pneumonia. This bacterium is a major public health threat due to its resistance to several antibiotic classes. Using a reverse vaccinology approach, 7 potential antigens were identified, of which 4 were present in most of the sequences of Italian carbapenem-resistant K. pneumoniae clinical isolates. Bioinformatics tools demonstrated the antigenic potential of these bacterial proteins and allowed for the identification of T and B cell epitopes. This led to a rational design and in silico characterization of a multiepitope vaccine against carbapenem-resistant K. pneumoniae strains. As adjuvant, the mycobacterial heparin-binding hemagglutinin adhesin (HBHA), which is a Toll-like receptor 4 (TLR-4) agonist, was included, to increase the immunogenicity of the construct. The multiepitope vaccine candidate was analyzed by bioinformatics tools to assess its antigenicity, solubility, allergenicity, toxicity, physical and chemical parameters, and secondary and tertiary structures. Molecular docking binding energies to TLR-2 and TLR-4, two important innate immunity receptors involved in the immune response against K. pneumoniae infections, and molecular dynamics simulations of such complexes supported active interactions. A codon optimized multiepitope sequence cloning strategy is proposed, for production of recombinant vaccine in classical bacterial vectors. Finally, a 3 dose-immunization simulation with the multiepitope construct induced both cellular and humoral immune responses. These results suggest that this multiepitope construct has potential as a vaccination strategy against carbapenem-resistant K. pneumoniae and deserves further validation.

Comparative analysis of an anthraquinone and chalcone derivatives-based virtual combinatorial library. A cheminformatics "proof-of-concept" study.

A Laplacian scoring algorithm for gene selection and the Gini coefficient to identify the genes whose expression varied least across a large set of samples were the state-of-the-art methods used here. These methods have not been trialed for their feasibility in cheminformatics. This was a maiden attempt to investigate a complete comparative analysis of an anthraquinone and chalcone derivatives-based virtual combinatorial library. This computational "proof-of-concept" study illustrated the combinatorial approach used to explain how the structure of the selected natural products (NPs) undergoes molecular diversity analysis. A virtual combinatorial library (1.6 M) based on 20 anthraquinones and 24 chalcones was enumerated. The resulting compounds were optimized to the near drug-likeness properties, and the physicochemical descriptors were calculated for all datasets including FDA, Non-FDA, and NPs from ZINC 15. UMAP and PCA were applied to compare and represent the chemical space coverage of each dataset. Subsequently, the Laplacian score and Gini coefficient were applied to delineate feature selection and selectivity among properties, respectively. Finally, we demonstrated the diversity between the datasets by employing Murcko's and the central scaffolds systems, calculating three fingerprint descriptors and analyzing their diversity by PCA and SOM. The optimized enumeration resulted in 1,610,268 compounds with NP-Likeness, and synthetic feasibility mean scores close to FDA, Non-FDA, and NPs datasets. The overlap between the chemical space of the 1.6 M database was more prominent than with the NPs dataset. A Laplacian score prioritized NP-likeness and hydrogen bond acceptor properties (1.0 and 0.923), respectively, while the Gini coefficient showed that all properties have selective effects on datasets (0.81-0.93). Scaffold and fingerprint diversity indicated that the descending order for the tested datasets was FDA, Non-FDA, NPs and 1.6 M. Virtual combinatorial libraries based on NPs can be considered as a source of the combinatorial compound with NP-likeness properties. Furthermore, measuring molecular diversity is supposed to be performed by different methods to allow for comparison and better judgment.

Evaluation of Catechin Synergistic and Antibacterial Efficacy on Biofilm Formation and acrA Gene Expression of Uropathogenic E. coli Clinical Isolates.

Uropathogenic Escherichia coli has a propensity to build biofilms to resist host defense and antimicrobials. Recurrent urinary tract infection (UTI) caused by multidrug-resistant, biofilm-forming E. coli is a significant public health problem. Consequently, searching for alternative medications has become essential. This study was undertaken to investigate the antibacterial, synergistic, and antibiofilm activities of catechin isolated from Canarium patentinervium Miq. against three E. coli ATCC reference strains (ATCC 25922, ATCC 8739, and ATCC 43895) and fifteen clinical isolates collected from UTI patients in Baghdad, Iraq. In addition, the expression of the biofilm-related gene, acrA, was evaluated with and without catechin treatment. Molecular docking was performed to evaluate the binding mode between catechin and the target protein using Autodock Vina 1.2.0 software. Catechin demonstrated significant bactericidal activity with a minimum inhibitory concentration (MIC) range of 1-2 mg/mL and a minimum bactericidal concentration (MBC) range of 2-4 mg/mL and strong synergy when combined with tetracycline at the MBC value. In addition, catechin substantially reduced E. coli biofilm by downregulating the acrA gene with a reduction percent ≥ 60%. In silico analysis revealed that catechin bound with high affinity (∆G = -8.2 kcal/mol) to AcrB protein (PDB-ID: 5ENT), one of the key AcrAB-TolC efflux pump proteins suggesting that catechin might inhibit the acrA gene indirectly by docking at the active site of AcrB protein.

Isolation and Characterization of Werneria Chromene and Dihydroxyacidissimol from Burkillanthus malaccensis (Ridl.) Swingle

The secondary metabolites of endemic plants from the Rutaceae family, such as Burkillanthusmalaccensis (Ridl.) Swingle from the rainforest of Malaysia, has not been studied. Burkillanthusmalaccensis (Ridl.) Swingle may produce antibacterial and antibiotic-potentiating secondary metabolites. Hexane, chloroform, and methanol extracts of leaves, bark, wood, pericarps, and endocarps were tested against bacteria by broth microdilution assay and their antibiotic-potentiating activities. Chromatographic separations of hexane extracts of seeds were conducted to investigate effective phytochemicals and their antibacterial activities. Molecular docking studies of werneria chromene and dihydroxyacidissiminol against SARS-CoV-2 virus infection were conducted using AutoDock Vina. The methanol extract of bark inhibited the growth of Staphylococcusaureus, Escherichiacoli, and Pseudomonasaeruginosa with the minimum inhibitory concentration of 250, 500, and 250 µg/mL, respectively. The chloroform extract of endocarps potentiated the activity of imipenem against imipenem-resistant Acinetobacterbaumannii. The hexane extract of seeds increased the sensitivity of P. aeruginosa against ciprofloxacin and levofloxacin. The hexane extract of seeds and chloroform extract of endocarps were chromatographed, yielding werneria chromene and dihydroxyacidissiminol. Werneria chromene was bacteriostatic for P.aeruginosa and P.putida, with MIC/MBC values of 1000 > 1000 µg/mL. Dihydroxyacidissiminol showed the predicted binding energies of −8.1, −7.6, −7.0, and −7.5 kcal/mol with cathepsin L, nsp13 helicase, SARS-CoV-2 main protease, and SARS-CoV-2 spike protein receptor-binding domain S-RBD. Burkillanthusmalaccensis (Ridl.) Swingle can be a potential source of natural products with antibiotic-potentiating activity and that are anti-SARS-CoV-2.

Draft Genome Sequence of the Marine Bioluminescent Bacterium Aliivibrio fischeri ATCC 7744.

The Gram-negative marine bioluminescent bacterium Aliivibrio fischeri is commonly used as a bioreporter in drug inhibition studies. Its bioluminescence is regulated by the gene expression of the luxI-luxR quorum-sensing system. Here, we report the draft genome sequence of A. fischeri ATCC 7744, including identification of the putative lux operon.

A Flare of Systemic Lupus Erythematosus Disease After COVID-19 Infection: A Case of Lupus Cerebritis.

The association between coronavirus disease 19 (COVID-19) and autoimmune disease has been mounting, and literature on COVID-19-induced flare-up of systemic lupus erythematosus (SLE) disease is lacking. We describe a case of lupus cerebritis triggered by COVID-19 in a young female with SLE, who presented with fluctuated mentation, psychomotor retardation, slow speech, and intermittent choreiform movement in the upper part of the body. She had a history of COVID-19 infection three weeks back. Her serum immunoglobulin G antibodies were positive against COVID-19. On examination, she had psychomotor agitation, intermittent choreiform movements of upper limbs, and poor speech. Brain magnetic resonance imaging revealed hyperintense signals in the white matter of both hemispheres, suggestive of lupus cerebritis secondary to COVID-19 infection and lack of any other identifiable risk factor. Management included methylprednisolone, prednisone, and olanzapine. The patient was also placed on monthly intravenous cyclophosphamide, and her condition started improving gradually.

Review on the Antibacterial Mechanism of Plant-Derived Compounds against Multidrug-Resistant Bacteria (MDR).

Microbial resistance has progressed rapidly and is becoming the leading cause of death globally. The spread of antibiotic-resistant microorganisms has been a significant threat to the successful therapy against microbial infections. Scientists have become more concerned about the possibility of a return to the pre-antibiotic era. Thus, searching for alternatives to fight microorganisms has become a necessity. Some bacteria are naturally resistant to antibiotics, while others acquire resistance mainly by the misuse of antibiotics and the emergence of new resistant variants through mutation. Since ancient times, plants represent the leading source of drugs and alternative medicine for fighting against diseases. Plants are rich sources of valuable secondary metabolites, such as alkaloids, quinones, tannins, terpenoids, flavonoids, and polyphenols. Many studies focus on plant secondary metabolites as a potential source for antibiotic discovery. They have the required structural properties and can act by different mechanisms. This review analyses the antibiotic resistance strategies produced by multidrug-resistant bacteria and explores the phytochemicals from different classes with documented antimicrobial action against resistant bacteria, either alone or in combination with traditional antibiotics.

Antiviral activity of Embelia ribes Burm. f. against influenza virus in vitro.

Viral respiratory infections are raising serious concern globally. Asian medicinal plants could be useful in improving the current treatment strategies for influenza. The present study examines the activity of five plants from Bangladesh against influenza virus. MDCK cells infected with influenza virus A/Puerto Rico/8/34 (H1N1) were treated with increasing concentrations of ethyl acetate extracts, and their cytotoxicity (CC50), virus-inhibiting activity (IC50), and selectivity index (SI) were calculated. The ethyl acetate extract of fruits of Embelia ribes Burm. f. (Myrsinaceae) had the highest antiviral activity, with an IC50 of 0.2 µg/mL and a SI of 32. Its major constituent, embelin, was further isolated and tested against the same virus. Embelin demonstrated antiviral activity, with an IC50 of 0.3 µM and an SI of 10. Time-of-addition experiments revealed that embelin was most effective when added at early stages of the viral life cycle (0-1 h postinfection). Embelin was further evaluated against a panel of influenza viruses including influenza A and B viruses that were susceptible or resistant to rimantadine and oseltamivir. Among the viruses tested, avian influenza virus A/mallard/Pennsylvania/10218/84 (H5N2) was the most susceptible to embelin (SI = 31), while A/Aichi/2/68 (H3N2) virus was the most resistant (SI = 5). In silico molecular docking showed that the binding site for embelin is located in the receptor-binding domain of the viral hemagglutinin. The results of this study provide evidence that E. ribes can be used for development of a novel alternative anti-influenza plant-based agent.

In Silico Investigation of Flavonoids as Potential Trypanosomal Nucleoside Hydrolase Inhibitors.

Human African Trypanosomiasis is endemic to 37 countries of sub-Saharan Africa. It is caused by two related species of Trypanosoma brucei. Current therapies suffer from resistance and public accessibility of expensive medicines. Finding safer and effective therapies of natural origin is being extensively explored worldwide. Pentamidine is the only available therapy for inhibiting the P2 adenosine transporter involved in the purine salvage pathway of the trypanosomatids. The objective of the present study is to use computational studies for the investigation of the probable trypanocidal mechanism of flavonoids. Docking experiments were carried out on eight flavonoids of varying level of hydroxylation, namely, flavone, 5-hydroxyflavone, 7-hydroxyflavone, chrysin, apigenin, kaempferol, fisetin, and quercetin. Using AutoDock 4.2, these compounds were tested for their affinity towards inosine-adenosine-guanosine nucleoside hydrolase and the inosine-guanosine nucleoside hydrolase, the major enzymes of the purine salvage pathway. Our results showed that all of the eight tested flavonoids showed high affinities for both hydrolases (lowest free binding energy ranging from -10.23 to -7.14 kcal/mol). These compounds, especially the hydroxylated derivatives, could be further studied as potential inhibitors of the nucleoside hydrolases.

Isoprenyl caffeate, a major compound in manuka propolis, is a quorum-sensing inhibitor in Chromobacterium violaceum.

The emergence of antibiotic-resistant bacterial pathogens, especially Gram-negative bacteria, has driven investigations into suppressing bacterial virulence via quorum sensing (QS) inhibition strategies instead of bactericidal and bacteriostatic approaches. Here, we investigated several bee products for potential compound(s) that exhibit significant QS inhibitory (QSI) properties at the phenotypic and molecular levels in Chromobacterium violaceum ATCC 12472 as a model organism. Manuka propolis produced the strongest violacein inhibition on C. violaceum lawn agar, while bee pollen had no detectable QSI activity and honey had bactericidal activity. Fractionated manuka propolis (pooled fraction 5 or PF5) exhibited the largest violacein inhibition zone (24.5 ± 2.5 mm) at 1 mg dry weight per disc. In C. violaceum liquid cultures, at least 450 µg/ml of manuka propolis PF5 completely inhibited violacein production. Gene expression studies of the vioABCDE operon, involved in violacein biosynthesis, showed significant (≥two-fold) down-regulation of vioA, vioD and vioE in response to manuka propolis PF5. A potential QSI compound identified in manuka propolis PF5 is a hydroxycinnamic acid-derivative, isoprenyl caffeate, with a [M-H] of 247. Complete violacein inhibition in C. violaceum liquid cultures was achieved with at least 50 µg/ml of commercial isoprenyl caffeate. In silico docking experiments suggest that isoprenyl caffeate may act as an inhibitor of the violacein biosynthetic pathway by acting as a competitor for the FAD-binding pockets of VioD and VioA. Further studies on these compounds are warranted toward the development of anti-pathogenic drugs as adjuvants to conventional antibiotic treatments, especially in antibiotic-resistant bacterial infections.

Binding mode analysis of zerumbone to key signal proteins in the tumor necrosis factor pathway.

Breast cancer is the second most common cancer among women worldwide. Several signaling pathways have been implicated as causative and progression agents. The tumor necrosis factor (TNF) α protein plays a dual role in promoting and inhibiting cancer depending largely on the pathway initiated by the binding of the protein to its receptor. Zerumbone, an active constituent of Zingiber zerumbet, Smith, is known to act on the tumor necrosis factor pathway upregulating tumour necrosis factor related apoptosis inducing ligand (TRAIL) death receptors and inducing apoptosis in cancer cells. Zerumbone is a sesquiterpene that is able to penetrate into the hydrophobic pockets of proteins to exert its inhibiting activity with several proteins. We found a good binding with the tumor necrosis factor, kinase κB (IKKß) and the Nuclear factor κB (NF-κB) component proteins along the TNF pathway. Our results suggest that zerumbone can exert its apoptotic activities by inhibiting the cytoplasmic proteins. It inhibits the IKKß kinase that activates the NF-κB and also binds to the NF-κB complex in the TNF pathway. Blocking both proteins can lead to inhibition of cell proliferating proteins to be downregulated and possibly ultimate induction of apoptosis.

In Silico Screening of Mutated K-Ras Inhibitors from Malaysian Typhonium flagelliforme for Non-Small Cell Lung Cancer.

K-ras is an oncogenic GTPase responsible for at least 15-25% of all non-small cell lung cancer cases worldwide. Lung cancer of both types is increasing with an alarming rate due to smoking habits in Malaysia among men and women. Natural products always offer alternate treatment therapies that are safe and effective. Typhonium flagelliforme or Keladi Tikus is a local plant known to possess anticancer properties. The whole extract is considered more potent than individual constituents. Since K-ras is the key protein in lung cancer, our aim was to identify the constituents of the plant that could target the mutated K-ras. Using docking strategies, reported potentially active compounds of Typhonium flagelliforme were docked into the allosteric surface pockets and switch regions of the K-ras protein to identify possible inhibitors. The selected ligands were found to have a high binding affinity for the switch II and the interphase region of the ras-SOS binding surface.

Pneumatosis intestinalis associated with Henoch-Schönlein purpura.

Henoch-Schönlein purpura (HSP) is the most common vasculitis in children. It is a disorder of the inflammatory cascade leading to immunoglobulin A deposition and leukocytoclastic vasculitis of small vessels of skin, kidneys, joints, and gastrointestinal (GI) tract. A wide variety of GI manifestations are seen in ∼50% to 75% of patients with HSP. Diffuse colicky abdominal pain is the most common GI symptom. The small bowel is the most frequently involved GI site. Intussusception is rare but is the most common surgical complication. We report the case of a 2-year-old girl with a 5-day history of abdominal pain followed by a palpable purpuric rash. Her urinalysis, complete blood cell count, and tests of renal function were normal. An acute abdominal series was unremarkable initially, and abdominal ultrasound imaging showed ascites and thickened small bowel loops. She was diagnosed with HSP. The abdominal pain worsened, and an abdominal computed tomography scan demonstrated distal small bowel wall thickening and pneumatosis intestinalis in the descending colon. She was started on total parenteral nutrition and antibiotics and placed on bowel rest. She was given 2 mg/kg of intravenous immunoglobulin. Her abdominal pain gradually improved over the next week, and a repeat computed tomography scan showed significant improvement of the small bowel wall thickening and pneumatosis. The purpuric rash improved, and her abdominal pain resolved. We report a case of HSP and pneumatosis intestinalis, an association that has not been reported previously.

NKT cell immune responses to viral infection.

BACKGROUND: Natural killer T (NKT) cells are a heterogeneous population of innate T cells that have attracted interest because of their potential to regulate immune responses to a variety of pathogens. The most widely studied NKT cell subset is the invariant (i)NKT cells that recognize glycolipids in the context of the CD1d molecule. The multifaceted methods of activation iNKT cells possess and their ability to produce regulatory cytokines has made them a primary target for studies. OBJECTIVE/METHODS: To give insights into the roles of iNKT cells during infectious diseases, particularly viral infections. We also highlight mechanisms leading to iNKT cell activation in response to pathogens. CONCLUSIONS: iNKT cell's versatility allows them to detect and respond to several viruses. Therapeutic approaches to specifically target iNKT cells will require additional research. Notably, the roles of non-invariant NKT cells in response to pathogens warrant further investigation.