The impact of stressors on the learning outcome of high-fidelity patient simulation in undergraduate medical students.

INTRODUCTION: Simulation of the clinical setting incorporates an educational approach connecting a learner to a particular environment of learning. Undergraduate students in the health sector experience anxiety during simulation that influences their performance which ultimately affects their learning outcome. This study attempts to correlate the impact of stressors on learning outcome of high-fidelity patient simulation (HFPS) in undergraduate medical education. OBJECTIVE: This research is to analyze the impact of stressors and its relevance on the learning outcome of HFPS as a teaching-learning tool for the management of emergency surgical conditions including trauma. MATERIALS AND METHODS: This study is a Quasi-experimental time series design. A total number of 347 final-year undergraduate (MBBS) students of Melaka-Manipal Medical College, Malaysia. They were grouped and assessed individually by pre-test and post-tests on their knowledge, performance and associated stressor scores. The one-way repeated measure of Analysis of Variance (ANOVA) was used to determine the statistically significant differences in total score at pre-test simulation and post-test-simulation sessions. Friedman test was used for assessment of individual components of stressors. Pre-test and post-tests scores were compared to note progress in confidence and stress reduction. P value <0.001 was considered statistically significant. RESULTS: ANOVA with Bonferroni post hoc analysis showed a statistically significant (p <0.001) difference in stressor score over time. The drop-in stress was significant initially but flattened out later. CONCLUSION: Stress significantly decreased as the students were exposed to more sessions of HFPS which ultimately translated into better learning outcome.

Clinical, virological and epidemiological characterization of dengue outbreak in Myanmar, 2015.

Hospital-based surveillance was conducted at two widely separated regions in Myanmar during the 2015 dengue epidemic. Acute phase serum samples were collected from 332 clinically diagnosed dengue patients during the peak season of dengue cases. Viremia levels were measured by quantitative real-time PCR and plaque assays using FcγRIIA-expressing and non-FcγRIIA-expressing BHK cells to specifically determine the infectious virus particles. By serology and molecular techniques, 280/332 (84·3%) were confirmed as dengue patients. All four serotypes of dengue virus (DENV) were isolated from among 104 laboratory-confirmed patients including two cases infected with two DENV serotypes. High percentage of primary infection was noted among the severe dengue patients. Patients with primary infection or DENV IgM negative demonstrated significantly higher viral loads but there was no significant difference among the severity groups. Viremia levels among dengue patients were notably high for a long period which was assumed to support the spread of the virus by the mosquito vector during epidemic. Phylogenetic analyses of the envelope gene of the epidemic strains revealed close similarity with the strains previously isolated in Myanmar and neighboring countries. DENV-1 dominated the epidemic in 2015 and the serotype (except DENV-3) and genotype distributions were similar in both study sites.

Inducible expression of A Disintegrin and Metalloproteinase 8 in chronic periodontitis and gingival epithelial cells.

BACKGROUND AND OBJECTIVES: The expression of A Disintegrin and Metalloproteinase 8 (ADAM8) is associated with several inflammatory diseases. Elevated ADAM8 levels have been shown in gingival crevicular fluid of patients with chronic periodontitis. The objective of this study was to investigate ADAM8 expression in chronic periodontitis tissues compared with that in normal tissues. ADAM8 expression and its inductive mechanism were examined in human gingival epithelial cells (HGECs) and human gingival fibroblasts. MATERIAL AND METHODS: Total RNA and protein were extracted from gingival biopsies of 33 patients with chronic periodontitis and those of 23 healthy volunteers. ADAM8 mRNA and protein expression was analyzed by real-time polymerase chain reaction, immunoblotting and immunohistochemistry. ADAM8 expression in control and stimulated cells in the presence or absence of specific inhibitors for mitogen-activated protein kinase pathways was assayed by real-time polymerase chain reaction, immunoblotting, flow cytometry and immunofluorescence. RESULTS: ADAM8 mRNA and protein expression in chronic periodontitis tissues was significantly greater than that in normal tissues (p < 0.01). Significantly increased ADAM8 expression was detected in the gingival epithelium of chronic periodontitis tissues (p < 0.001). ADAM8 mRNA expression in HGECs, but not in human gingival fibroblasts, was significantly induced by stimulation with Fusobacterium nucleatum (p < 0.05), partially via the p44/42 mitogen-activated protein kinase pathway. ADAM8 expression in the cell lysates and on the surface of HGECs was induced by stimulation with F. nucleatum. CONCLUSION: ADAM8 expression is increased in inflamed chronic periodontitis tissues and localized within gingival epithelium, consistent with an upregulation of ADAM8 expression in F. nucleatum-stimulated HGECs, suggesting a possible role of ADAM8 in innate immunity of periodontal tissue.

Evaluation of the MolecuTech® REBA MTB-XMDR kit for detection of pre-extensively drug-resistant TB.

BACKGROUND: Rapid diagnosis of drug-resistant TB is critical for early initiation of effective therapy. YD Diagnostics in South Korea recently developed the MolecuTech® REBA MTB-XMDR test to rapidly detect multidrug-resistant TB (MDR-TB), pre-extensively drug-resistant TB (pre-XDR-TB) and resistance to second-line injectable drugs (SLIDs) simultaneously using a fully automated test platform. This study aimed to evaluate the MolecuTech® test for the detection of MDR- and pre-XDR-TB, as well as SLID resistance.METHODS: A total of 151 clinical Mycobacterium tuberculosis isolates from South Korea were tested using the MolecuTech test, and the results were analysed by comparing these with phenotypic drug susceptibility testing (pDST) and sequencing.RESULTS: Compared to pDST, the MolecuTech test showed a sensitivity and specificity of respectively 97.7% and 100.0% for rifampicin (RIF), 82.4% and 100.0% for isoniazid (INH), 97.5% and 97.2% for fluoroquinolones (FQs), and 94.0% and 98.8% for SLIDs. Concordances with the sequencing results of each resistance determinant were 99.3% for RIF, 96.7% for INH, 98.7% for FQs and 99.3% for SLIDs.CONCLUSION: The MolecuTech test is an efficient and reliable rapid molecular diagnostic tool for the simultaneous screening of MDR- and pre-XDR-TB.

Noninvasive assessment of regulable transferred-p53 gene expression and evaluation of therapeutic response with FDG-PET in tumor model.

The use of tumor-suppressor gene p53 as an anticancer therapeutic has been vigorously investigated. However, progress has met with limited success to date. Some major drawbacks are the difficulty in achieving controllable and efficient gene transfer as well as in analyzing the transferred gene expression in real time and the treatment response in a timely manner. Thus, development of novel gene transfer vector with a regulative gene expression system coupled with the reporter gene, by which transgene can be monitored simultaneously, is critical. Moreover, noninvasive imaging-based assessment of the therapeutic response to exogenous wild-type p53 gene transfer is crucial for refining treatment protocols. In this study, as a simple preclinical model, we constructed a doxycycline-regulated bidirectional vector harboring a reporter gene encoding red fluorescence protein and p53. Then, we determined the controllable and simultaneously coordinated expression of both proteins and the p53-mediated anticancer effects in vitro and in vivo. Next, we observed that cells or tumors with induced p53 overexpression exhibited decreased uptake of [(14)C]FDG in cellular assay and [(18)F]FDG in positron emission tomography (PET) imaging. Thus, by coupling with bidirectional vector, controllable p53 transfer was achieved and the capability of fluoro-2-deoxy-D-glucose (FDG)-PET to assess the therapeutic response to p53 gene therapy was evidently confirmed, which may have an impact on the improvement of p53 gene therapy.

Visualization of in vivo electroporation-mediated transgene expression in experimental tumors by optical and magnetic resonance imaging.

In vivo electroporation (EP) is an efficient method for effective gene transfer and is highly expected for application in anticancer gene therapy. Non-invasive monitoring of gene transfer/expression is critical for optimal gene therapy. Here we report in vivo optical and high-field magnetic resonance imaging (MRI) of EP-mediated transgene expression in a tumor model. Initially, we observed spatio-temporal change in in vivo EP-mediated transgene expression by optical imaging using red fluorescence protein (RFP) as a reporter gene. Next, we constructed a dual-reporter plasmid carrying a gene-encoding MRI reporter ferritin heavy chain and RFP gene to visualize the intratumoral transgene expression by dual modality. Cells transfected with this plasmid showed lower signal intensity on in vitro T(2)-weighted cellular MRI and quantitatively increased the transverse relaxation rate (1/T(2)) compared with control cells. After conducting in vivo EP in an experimental tumor, the plasmid-injected region showed both fluorescent emissions in optical imaging and detectably lowered signal on T(2)-weighted MRI. The correlative immunohistological findings confirmed that both the reporter transgenes were co-expressed in this region. Thus, our strategy provides a platform for evaluating EP-mediated cancer gene therapy easily and safely without administering contrast agent or substrate.

Extensively drug-resistant tuberculosis in Myanmar: burden and mutations causing second-line drug resistance.

SETTING: Two tuberculosis (TB) reference laboratories in Myanmar. OBJECTIVES: To determine the proportion of extensively drug-resistant TB (XDR-TB) cases among multidrug-resistant TB (MDR-TB) cases and the mutations that cause resistance to second-line drugs in Myanmar. DESIGN: This was a cross-sectional, retrospective study. Multidrug-resistant Mycobacterium tuberculosis isolates were collected during 2015-2016. Phenotypic drug susceptibility testing (DST) was performed and drug-resistant mutations identified by sequencing. Genotypes were determined to explain relationships between drug resistance patterns and genotypes. RESULTS: Of 89 MDR-TB isolates, 12 were XDR-TB and 24 were pre-XDR-TB, with 21 resistant to fluoroquinolones (FQs) and 3 to second-line injectable agents (SLIDs). High rates of cross-resistance among second-line drugs were observed. Correlations between phenotypic and molecular DST against FQs and SLIDs were 91% in both cases. The most frequent mutation in FQ-resistant isolates was D94G (8/21) in gyrA and A1401G (11/15) in rrs in those resistant to SLIDs. The dominant genotype was the Beijing type (76/89). CONCLUSION: There were high proportions of XDR-TB and pre-XDR-TB among MDR-TB cases; cross-resistance among second-line drugs was high, with various types of genetic mutations. These data suggest that resistance to second-line anti-tuberculosis drugs should be monitored intensively, and molecular DST should be employed.

Antiapoptotic activity is dispensable for insulin-like growth factor I receptor-mediated clonogenic radioresistance after gamma-irradiation.

PURPOSE: The purpose of this study was to evaluate the relationship between apoptotic activity and clonogenic radiosensitivity in vitro using an insulin-like growth factor I receptor (IGF-IR) signaling model, which is known to exert tumorigenic and antiapoptotic effects. EXPERIMENTAL DESIGN: We used mouse embryo fibroblast cell lines expressing either human IGF-IR [R+(Wt) and R+] or the marker gene alone [R-(puro)]; these cell lines were derived from R- cells, which are deficient in IGF-IR. After gamma-irradiation, apoptotic activity was determined by the presence of DNA fragmentation and caspase-3-, -8-, and -9-like activities. Clonogenic radiosensitivity was determined by a colony-forming assay. RESULTS: R+(Wt) and R+ cells expressed similar levels of IGF-IR, transducing phosphorylation signals to major downstream substrates on insulin-like growth factor I stimulation. R+ cells were resistant to the induction of apoptosis after gamma-irradiation; however, both R+(Wt) and R-(puro) cells demonstrated significant DNA fragmentation and increase in caspase-3-, -8-, and -9-like activities. Both R+(Wt) and R+ cells were radioresistant (to a similar extent) compared with R-(puro) cells as measured by a colony-forming assay. Clonogenic radioresistance was not influenced by the inhibition of Akt/protein kinase B through treatment with wortmannin at low concentrations specifically inhibiting phosphatidylinositol 3'-kinase. CONCLUSIONS: Our findings indicate that apoptotic activity does not necessarily predict clonogenic survival after exposure to ionizing radiation. This study provides clinical implications in the evaluation of apoptotic activities observed during the course of radiotherapy to predict accurate tumor response or local control.

Study of quantitative oral radioactivity in salivary gland scintigraphy and determination of the clinical stage of Sjögren's syndrome.

UNLABELLED: In this study, the oral radioactivity seen in salivary gland scintigraphy, which was established entirely on the basis of radioactive saliva secreted by the parotid and submandibular glands, was evaluated quantitatively in healthy volunteers and in patients with Sjögren's syndrome. METHODS: Salivary gland scintigraphy and labial biopsy were performed on 70 patients with Sjögren's syndrome. After intravenous administration of 99mTc-sodium pertechnetate, dynamic scintigraphy was performed and time-activity curves for the oral cavity and four major salivary glands were generated. Lemon juice stimulation was delivered at 40 min. The prestimulatory oral activity index, poststimulatory oral activity index, and time interval between the vascular perfusion peak and the prestimulated maximum oral activity point were calculated to quantify the oral activity. Other glandular functional parameters-namely, maximum accumulation (MA), maximum secretion, secretion velocity, time at maximum count, time interval from stimulation to minimum count, and uptake ratio (UR) of the parotid and submandibular glands-were also calculated. Salivary gland scintigraphy was also performed on 21 healthy subjects with no evidence of salivary gland malfunction. RESULTS: Histopathologic grade 1 or 2 was found in 29 patients and grade 3 or 4 was found in 41 patients, and they were regarded as being in the early and advanced stages of Sjögren's syndrome, respectively. After overall analysis, all of the oral activity indices and the MA and UR of the submandibular gland clearly decreased as clinical severity progressed, and statistically significant differences were observed. CONCLUSION: New oral activity indices correlated with the stage of Sjögren's syndrome, and these quantitative oral indices together with certain glandular parameters (mainly MA and UR of the submandibular gland) were found to be sensitive enough to distinguish the disease severity of Sjögren's syndrome.

Sjögren's syndrome: comparison of assessments with quantitative salivary gland scintigraphy and contrast sialography.

UNLABELLED: This study compared the quantitative parameters of salivary gland scintigraphy and the sialographic stages in patients with Sjögren's syndrome. METHODS: One hundred sixteen patients suspected of having Sjögren's syndrome were examined with salivary gland scintigraphy and contrast sialography. When contrast sialography was used as the gold standard, Sjögren's syndrome was diagnosed in 50 of these 116 patients; Sjögren's syndrome was not seen in the other 66 patients. After injection of 370 MBq 99mTc-sodium pertechnetate, dynamic salivary gland scintigraphy with lemon juice stimulation was performed for 50 min. Functional parameters for the parotid and submandibular glands were calculated, and scintigraphic and sialographic results were compared. RESULTS: With the progression of sialographic stages from 0 to 4, the quantity of tracer accumulation decreased in the submandibular gland (P < 0.0001), and the quantity of tracer secretion decreased in the parotid gland (P < 0.0001). The sialographic stage in patients with Sjögren's syndrome was correlated with these scintigraphic parameters (P < 0.0001): sialographic stage = 3.243 - 0.337 x (submandibular gland uptake ratio) - 0.026 x (parotid gland maximum secretion). CONCLUSION: The decreased accumulation in the submandibular gland and the decreased secretion in the parotid gland were highly sensitive indicators of salivary gland disease in Sjögren's syndrome. The sialographic stage was correlated with these scintigraphic parameters.

Gastrointestinal haemorrhage from a jejunal gangliocytic paraganglioma.

A case of jejunal gangliocytic paraganglioma is reported in a 54 year old woman who presented with brisk melaena. The tumour was not encapsulated, involved the mucosa and submucosa, and was composed of epithelial nests, spindle cells, and ganglion cells. These cells were mixed, giving carcinoid-like, paraganglioma-like, and ganglioneuroma-like patterns in different areas of the tumour. The lesion was excised locally and recovery was uneventful. Only four previous cases have been reported at this site.

Diffuse large cell lymphoma of B-cell type associated with reactive hemophagocytosis.

Some lymphomas, virtually all phenotypically of the T-cell type, have been associated with the phenomenon of hemophagocytosis. Only two B-cell lymphomas, one T-cell-rich and the other an angiocentric lymphoma, have been observed to exhibit this phenomenon. A case is reported of a diffuse large cell lymphoma of the B-cell type associated with reactive hemophagocytosis. Cytokines or other humoral factors produced by the lymphoma are a possible cause, and their effect is probably systemic. There is some evidence suggesting correlation of hemophagocytosis with tumor aggressiveness.

Comparison of lung perfusion scintigraphic findings in pulmonary thromboembolism in systemic lupus erythematosus, SLE plus antiphospholipid syndrome, and primary antiphospholipid syndrome.

In this study, we compared and reviewed the findings on lung perfusion scans performed in patients with systemic lupus erythematosus (SLE), systemic lupus erythematosus with associated antiphospholipid syndrome (SLE + APS), and primary antiphospholipid syndrome (PAPS), to evaluate the prevalence of pulmonary embolism in restricted samples of the patient groups. Lung perfusion scintigraphy with 99Tc(m)-macroaggregated albumin was performed in 31 patients (SLE = 7; SLE + APS = 14; PAPS = 10). The seven patients with SLE alone and the 10 patients with PAPS had normal perfusion lung scans. Six of the 14 SLE + APS patients showed a segmental uptake defect on multi-view perfusion scans. Thus, the SLE + APS patients were found to have a higher risk of pulmonary thromboembolism than the SLE alone and primary APS patients (P<0.05). The results of our study suggest that lung perfusion scintigraphy should be performed routinely in these patients, even in the absence of pulmonary clinical manifestations, to obtain baseline data for disease outcome and management.

Stability of Russell's viper venom toxoid (lyophilized form) on storage.

A previously developed Russell's viper venom toxoid in Myanmar is in a liquid form that shows reversion in the form of a reduced number of formaldehyde linkages and toxicity during storage at 37 degrees C and at room temperature. In order to have a safe, potent and stable toxoid, a lyophilized form was prepared in the present study from the liquid toxoid through the use of a freeze dryer. Both the liquid and lyophilized forms were then stored at 4 degrees C and at room temperature, and in addition to safety and immunogenicity tests, biochemical parameters such as the protein content, the activity of venom enzymes (proteinase, phospholipase A, phosphodiesterase, and arginine esterase), and the released free formalin amounts were assessed at 3-month intervals over a period of 1 year. The results indicate that under both conditions, the lyophilized toxoid shows minimum changes in enzyme activity, a reduced tendency toward formaldehyde linkage, no toxicity, and more immunogenicity in comparison with the respective liquid toxoids. It could therefore be hypothesized that Russell's viper venom toxoid in a lyophilized form is more promising in terms of efficacy and stability for prophylactic use in human immunization than the conventional toxoid in a liquid form.

Relationship of breast-feeding and hand-washing with dehydration in infants with diarrhoea due to Escherichia coli.

This prospective cohort study was carried out in the neonatal unit of the Yangon Children Hospital, Myanmar, to gather more information on the types of feedings and hand-washing practices of mothers as the determinant of severe dehydration in infants with acute diarrhoea due to Escherichia coli. The study subjects included 100 infants with diarrhoea, aged less than 4 months, admitted to the hospital from June 1997 to May 1998. Data on isolation of E. coli from rectal swab samples, types of feedings, hand-washing practices, and dehydration status were collected. Of the 100 cases, E. coli was isolated from rectal swab samples of 48 infants. Of these 48 cases, 28 had some dehydration and 20 had severe dehydration. Exclusive breast-feeding was observed only in the age group < 1 and > 1-2 month(s). The association of the severity of dehydration with other types of feedings compared to exclusive breast-feeding was not statistically significant. In this study, most mothers washed their hands with water only after cleansing their children's defaecation, and before and after feeding their children. The severity of dehydration was statistically significant in hand-washing practices when compared to washing with water only and washing with soap and water. This study has shown the association between types of feedings and hand-washing practices with dehydration in infants with acute diarrhoea due to E. coli. The results of the study suggest that there is a need for appropriate intervention programmes to promote exclusive breast-feeding and hand-washing practices with soap and water after cleansing children's defaecation, and before and after feeding children.

Smooth muscle tumour of the pharynx: a rare tumour presenting with globus pharyngeus symptoms.

A rare case of a smooth muscle tumour in the pharynx is reported, together with histopathological findings. The patient's psychiatric background and recurrent complaint of a sensation of a lump in the throat all pointed to a psychogenic aetiology, and diagnosis was delayed. The importance of mirror or endoscopic examination of the pharynx is stressed in patients with globus pharyngeus symptoms.

Improved method of direct microscopy for detection of acid-fast bacilli in sputum.

Microscopy of direct smears for acid-fast bacilli (AFB) is the most commonly used method for diagnosis of tuberculosis. However, direct microscopy of sputum, though rapid, has low sensitivity and there is a need for improved methods. Sputum samples were collected from patients attending the Union Tuberculosis Institute, Yangon. The microscopy of smears made directly from sputum were compared with the microscopy after liquefaction of sputum with household bleach (NaOCl) and concentration of bacteria by centrifugation. Out of 948 samples, 248 samples (26.2%) were positive for acid-fast bacilli by direct microscopy and 293 samples (30.9%) were positive for acid-fast bacilli by the household bleach method. There was a significant increase in the number of acid-fast bacilli positive samples by the house-hold bleach method (p<0.05). The method is simple and cheap. As a disinfectant, household bleach has the advantage of lowering the risk of laboratory infection.

Diffusion coefficients in abdominal organs and hepatic lesions: evaluation with intravoxel incoherent motion echo-planar MR imaging.

PURPOSE: To determine the true diffusion coefficients of abdominal organs and hepatic lesions with intravoxel incoherent motion (IVIM) echo-planar magnetic resonance (MR) imaging. MATERIALS AND METHODS: Seventy-eight patients suspected of having hepatic lesions were examined with IVIM echo-planar MR imaging at 1.5 T. There were 77 hepatic masses (27 hepatocellular carcinomas, 10 metastatic tumors, eight hemangiomas, and 32 cysts) in the 78 patients. The true diffusion coefficient D and the perfusion fraction f were calculated and compared with the apparent diffusion coefficient (ADC). RESULTS: Specific values of D were found for abdominal organs (liver, 0.72 x 10(-3) mm2/sec; spleen, 0.80 x 10(-3) mm2/sec; kidney, 1.38 x 10(-3) mm2/sec; gallbladder, 2.82 x 10(-3) mm2/sec) and for hepatic lesions (hepatocellular carcinoma, 1.02 x 10(-3) mm2/sec; metastasis, 1.16 x 10(-3) mm2/sec; hemangioma, 1.31 x 10(-3) mm2/sec; cysts, 3.03 x 10(-3) mm2/sec). The ADCs of solid organs and solid lesions were significantly higher than their D values, indicating a high contribution of perfusion to the ADCs. CONCLUSION: Perfusion contributes to the ADCs of abdominal organs and hepatic lesions. The D and f values are useful for the characterization of hepatic lesions.