Effects of early clinical and basic laboratory exposure program on premedical students: a questionnaire survey.

BACKGRUOUND: Because premed students do not take courses related to medicine during their first 2 years, they cannot establish their identity as students at medical schools, making it difficult for them to set goals as future doctors. We conducted an early clinical and basic laboratory exposure program for premed students and studied the effects of the program and student satisfaction levels. METHODS: We performed an early clinical and basic laboratory exposure program for premed students for 2 days and evaluated the effects of the program and student satisfaction with it. The program consisted of two types: type 1, where two to four students formed a group, which was assigned to a particular department to participate and make observations during ward rounds, outpatient clinics, examinations, procedures, and surgeries (in the case of basic laboratory work, the students partook in experimental observations); and type 2, where one student followed a medical school professor to observe the professor's day. After the program ended, an online survey was conducted to investigate the effects on students, their thoughts, and satisfaction levels. RESULTS: In total, 114 students (91.2%) responded to the survey. Approximately 94% of them were satisfied with the program. They found that the program would be useful for deciding on future career paths, gaining knowledge about a department of interest, studying for a medical program after premedical studies, and befriending residents and professors in certain departments. CONCLUSION: Early clinical and basic laboratory exposure programs are recommended for premedical students.

Cardiomyopathy in children: Can we rely on echocardiographic tricuspid regurgitation gradient estimates of right ventricular and pulmonary arterial pressure?

UNLABELLED: Introduction Agreement between echocardiography and right heart catheterisation-derived right ventricular systolic pressure is modest in the adult heart failure population, but is unknown in the paediatric cardiomyopathy population. METHODS: All patients at a single centre from 2001 to 2012 with a diagnosis of cardiomyopathy who underwent echocardiography and catheterisation within 30 days were included in this study. The correlation between tricuspid regurgitation gradient and catheterisation-derived right ventricular systolic pressure and mean pulmonary artery pressure was determined. Agreement between echocardiography and catheterisation-derived right ventricular systolic pressure was assessed using Bland-Altman plots. Analysis was repeated for patients who underwent both procedures within 7 days. Haemodynamic data from those with poor agreement and good agreement between echocardiography and catheterisation were compared. RESULTS: A total of 37 patients who underwent 48 catheterisation procedures were included in our study. The median age was 11.8 (0.1-20.6 years) with 22 males (58% total). There was a modest correlation (r=0.65) between echocardiography and catheterisation-derived right ventricular systolic pressure, but agreement was poor. Agreement between tricuspid regurgitation gradient and right ventricular systolic pressure showed wide 95% limits of agreement. There was a modest correlation between the tricuspid regurgitation gradient and mean pulmonary artery pressure (r=0.6). Shorter time interval between the two studies did not improve agreement. Those with poor agreement between echocardiography and catheterisation had higher right heart pressures, but this difference became insignificant after accounting for right atrial pressure. CONCLUSION: Transthoracic echocardiography estimation of right ventricular systolic pressure shows modest correlation with right heart pressures, but has limited agreement and may underestimate the degree of pulmonary hypertension in paediatric cardiomyopathy patients.

Efficacy and safety of PG201 (Layla(®)) and celecoxib in the treatment of symptomatic knee osteoarthritis: a double-blinded, randomized, multi-center, active drug comparative, parallel-group, non-inferiority, phase III study.

The objectives of the study are to demonstrate the non-inferiority of PG201 (Layla(®)) 600 mg in comparison with celecoxib 200 mg for the treatment of symptomatic knee osteoarthritis (OA). In total, 309 patients were randomly assigned to receive either the test drug, PG201 600 mg (n = 154) or celecoxib 200 mg (n = 155). The primary efficacy variable was improvement in mean 100-mm pain VAS score from baseline to the final visit (week 8), and this value was compared between the 2 treatment groups. Secondary outcome variables included changes from baseline in the Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain VAS score and subscale score, patient's global assessment of disease status quality of life (short form-36) and responder index at weeks 4 and 8. For safety assessment, adverse events were recorded at each clinical visit. At weeks 8, the 100-mm pain VAS scores were significantly decreased in patients receiving both PG201 600 mg (p < 0.0001) and celecoxib 200 mg (p < 0.0001) as compared to the baseline scores; however, no statistically significant differences in these values were noted between the groups (p = 0.312). These results met pre-specified criteria for non-inferiority for both the intent-to-treat and per-protocol populations. PG201 600 mg and celecoxib 200 mg were both well tolerated and no statistically significant differences in the tolerability profile between the groups. PG201 600 mg was as effective and safe as celecoxib 200 mg in the treatment of symptomatic knee OA and might be a useful new medication for the treatment of symptomatic knee OA.

Population genetic analysis and origin discrimination of snow crab (Chionoecetes opilio) using microsatellite markers.

Major habitats for the snow crab Chionoecetes opilio are mostly found within the northwest Atlantic and North Pacific Oceans. However, the East Sea populations of C. opilio, along with its relative the red snow crab (C. japonicas), are two of the most important commercial crustacean species for fisheries on the east coast of the Korean Peninsula. The East Sea populations of C. opilio are facing declining resources due to overfishing and global climate change. Thus, an analysis of population structure is necessary for future management. Five Korean and one Russian group of C. opilio were analyzed using nine microsatellite markers that were recently developed using next-generation sequencing. No linkage disequilibrium was found between any pair of loci, indicating that the markers were independent. The number of alleles per locus varied from 4 to 18 with a mean of 12, and allelic richness per locus ranged from 4.0 to 17.1 across all populations with a mean of 9.7. The Hardy-Weinberg equilibrium test revealed significant deviation in three out of nine loci in some populations after sequential Bonferroni correction and all of them had higher expected heterozygosity than observed heterozygosity. Null alleles were presumed in four loci, which explained the homozygosity in three loci. The pairwise fixation index (F ST ) values among the five Korean snow crab populations did not differ significantly, but all of the pairwise F ST values between each of the Korean snow crab populations and the Russian snow crab population differed significantly. An UPGMA dendrogram revealed clear separation of the Russian snow crab population from the Korean snow crab populations. Assignment tests based on the allele distribution discriminated between Korean and Russian origins with 93 % accuracy. Therefore, the snow crab populations around the Korean Peninsula need to be managed separately from the populations in Bering Sea in global scale resource management. Also, this information can be used for identification of snow crab origin which is problematic in worldwide crab trade.

A proline-hinge alters the characteristics of the amphipathic α-helical AMPs.

HP (2-20) is a 19-aa, amphipathic, α-helical peptide with antimicrobial properties that was derived from the N-terminus of Helicobacter pylori ribosomal protein L1. We previously showed that increasing the net hydrophobicity of HP (2-20) by substituting Trp for Gln(17) and Asp(19) (Anal 3) increased the peptide's antimicrobial activity. In hydrophobic medium, Anal 3 forms an amphipathic structure consisting of an N-terminal random coil region (residues 2-5) and an extended helical region (residues 6-20). To investigate the structure-activity relationship of Anal 3, we substituted Pro for Glu(9) (Anal 3-Pro) and then examined the new peptide's three-dimensional structure, antimicrobial activity and mechanism of action. Anal 3-Pro had an α-helical structure in the presence of trifluoroethanol (TFE) and sodium dodecyl sulfate (SDS). NMR spectroscopic analysis of Anal 3-Pro's tertiary structure in SDS micelles confirmed that the kink potential introduced by Pro(10) was responsible for the helix distortion. We also found that Anal 3-Pro exhibited about 4 times greater antimicrobial activity than Anal 3. Fluorescence activated flow cytometry and confocal fluorescence microscopy showed that incorporating a Pro-hinge into Anal 3 markedly reduced its membrane permeability so that it accumulated in the cytoplasm without remaining in the cell membrane. To investigate the translocation mechanism, we assessed its ability to release of FITC-dextran. The result showed Anal 3-Pro created a pore <1.8 nm in diameter, which is similar to buforin II. Notably, scanning electron microscopic observation of Candida albicans revealed that Anal 3-Pro and buforin II exert similar effects on cell membranes, whereas magainin 2 exerts a different, more damaging, effect. In addition, Anal 3-Pro assumed a helix-hinge-helix structure in the presence of biological membranes and formed micropores in both bacterial and fungal membranes, through which it entered the cytoplasm and tightly bound to DNA. These results indicate that the bending region of Anal 3- Pro peptide is prerequisite for effective antibiotic activity and may facilitate easy penetration of the lipid bilayers of the cell membrane.

Novel microsatellite markers of Meretrix petechialis and cross-species amplification in related Taxa (Bivalvia: Veneroida).

The Asian hard clam, Meretrix petechialis, is an economically important bivalve, but its catch and population sizes are decreasing rapidly, owing to many factors, including large-scale reclamation of its natural habitat on the western coast of the Korean peninsula. Attempts to restore the resources and production of this species require genetic structure and diversity information. In this study, we developed 15 microsatellite markers from a partial genomic library enriched in GT repeats. Nine of these markers were polymorphic, with an average allele number of six, and six were monomorphic in 95 tested individuals. No linkage disequilibrium was found between any pair of loci (p > 0.05), and deviations from the Hardy-Weinberg equilibrium (HWE) test showing excess of heterozygotes was observed in only one of nine loci. In addition, no null alleles or genetic differentiation between two tested populations were detected. A cross-species amplification in 12 species of four families resulted in two M. petechialis-specific loci and three possible universal markers. This information will be useful in the future development of high-quality artificial seedlings and sustainable resource management.

Induction of apoptosis by the overexpression of an alternative splicing variant of mitochondrial thioredoxin reductase.

Mammalian cells harbor two forms of thioredoxin reductase (TrxR), cytosolic TrxR1 and mitochondrial TrxR2, both of which are involved in the redox regulation of cell growth and apoptosis. Furthermore, several alternative splicing variants of TrxR1 and TrxR2 have been identified. However, little remains known with regard to their functions in cells. Here, we report an alternative splicing variant of TrxR2 (TrxR2A), which displays a 3-bp deletion in the coding region and an insertion of 1228 bp in the 3'-UTR, between the stop codon and the SECIS element, of the TrxR2 cDNA. In order to determine the cellular function of TrxR2A, we established TrxR2A-inducible HeLa cell lines in which TrxR2A transcription was regulated via a Tet-off expression system. We observed that the induction of TrxR2A resulted in increased apoptosis, due to the reduction of NADPH and alterations in cellular ROS levels. These results suggest that TrxR2A may play a vital role in the regulation of TrxR2 and may confer functional complexity onto the thioredoxin system.

Ventricular septal flattening at end systole falsely predicts right ventricular hypertension in patients with ostium primum atrial septal defects.

PURPOSE: To assess the reliability of ventricular septal position in predicting elevated right ventricular pressure (RVP) in patients with ostium primum atrial septal defects (ASD 1). METHODS: Echocardiograms of 4 groups were retrospectively analyzed: Patients with ASD 1 and low RVP, patients with ASD 1 and high RVP, and 2 age-matched control groups: one with isolated ostium secundum atrial septal defects (ASD 2), and 1 with normal cardiac findings. End-systolic left ventricular sectional diameters along the midmitral diameter (D1) and a diameter orthogonal to it (D2) were measured off-line by a blinded observer. The ratio D2/D1, the eccentricity index (EI), was calculated; a higher index represents greater septal flattening. RESULTS: The mean EI in the ASD 1 with low RVP group was significantly higher than both the group with ASD 2 and the healthy control group. The mean EI of the ASD 1 group with high RVP was significantly higher than the mean EI of the ASD 1 group with low RVP, although there was a poor correlation between EI and RVP in this group, r = 0.54. CONCLUSION: The ventricular septum is flatter in the ASD 1 patients with low RVP than in an age-matched control group with ASD 2 and compared with an age-matched control group of healthy subjects, giving a false impression of elevated RVP in the ASD 1 group. Although the mean EI is significantly higher in the ASD 1 group with high RVP than in the group with low RVP, there is a poor correlation between EI and RVP, which limits the reliability of this index.