Antimalarial drugs are an urgently need and crucial tool in the campaign against malaria, which can threaten public health. In this study, we examined the cytotoxicity of the 9 antimalarial compounds chemically synthesized using SKM13-2HCl. Except for SKM13-2HCl, the 5 newly synthesized compounds had a 50% cytotoxic concentration (CC50) > 100 µM, indicating that they would be less cytotoxic than SKM13-2HCl. Among the 5 compounds, only SAM13-2HCl outperformed SKM13-2HCl for antimalarial activity, showing a 3- and 1.3-fold greater selective index (SI) (CC50/IC50) than SKM13-2HCl in vitro against both chloroquine-sensitive (3D7) and chloroquine -resistant (K1) Plasmodium falciparum strains, respectively. Thus, the presence of morpholine amide may help to effectively suppress human-infectious P. falciparum parasites. However, the antimalarial activity of SAM13-2HCl was inferior to that of the SKM13-2HCl template compound in the P. berghei NK65-infected mouse model, possibly because SAM13-2HCl had a lower polarity and less efficient pharmacokinetics than SKM13-2HCl. SAM13-2HCl was more toxic in the rodent model. Consequently, SAM13-2HCl containing morpholine was selected from screening a combination of pharmacologically significant structures as being the most effective in vitro against human-infectious P. falciparum but was less efficient in vivo in a P. berghei-infected animal model when compared with SKM13-2HCl. Therefore, SAM13-2HCl containing morpholine could be considered a promising compound to treat chloroquine-resistant P. falciparum infections, although further optimization is crucial to maintain antimalarial activity while reducing toxicity in animals.

Purpose: Longitudinal integrated clerkships (LICs) have been introduced in medical schools, as learning relationships with clinical faculty or peers are important components of medical education. The purpose of this study was to investigate the characteristics of student-faculty and student-student interactions in the LIC and to identify other factors related to whether students understood and acquired the program’s main outcomes. Methods: The study was conducted among the 149 third-year students who participated in the LIC in 2019. We divided the students into groups of eight. These groups were organized into corresponding discussion classes, during which students had discussions with clinical faculty members and peers and received feedback. Clinical faculty members and students were matched through an e-portfolio, where records were approved and feedback was given. A course evaluation questionnaire was completed and analysed. Results: A total of 144 valid questionnaires were returned. Logistic regression analysis showed that relevant feedback in discussion classes (adjusted odds ratio [AOR], 5.071; p<0.001), frequency of e-portfolio feedback (AOR, 1.813; p=0.012), and motivation by e-portfolio feedback (AOR, 1.790; p=0.026) predicted a greater likelihood of understanding the continuity of the patient’s medical experience. Relevant feedback from faculty members in discussion classes (AOR, 3.455; p<0.001) and frequency of e-portfolio feedback (AOR, 2.232; p<0.001) also predicted a greater likelihood of understanding the concept of patient-centered care. Conclusion Student-faculty interactions, including relevant feedback in discusstion classes, frequency of e-portfolio feedback, and motivation by e-portfolio feedback were found to be important factors in the LIC program.

PURPOSE: To evaluate clinical outcomes of idiopathic epiretinal membrane removal in patients ≥ 80 years of age.METHODS: A retrospective review of medical records was performed with 56 patients who underwent vitrectomy and removal of idiopathic epiretinal membrane. In the ≥ 80 years of age group (n = 28), the best-corrected visual acuity (BCVA) and central macular thickness (CMT) before surgery were compared with those at the final follow-up. The amount of change in the BCVA after surgery was also compared between the ≥ 80 years of age group and the < 80 years of age group (n = 28).RESULTS: In the ≥ 80 years of age group, the mean follow-up period was 19.1 ± 17.0 months. Before surgery, 11 eyes were pseudophakic and 17 eyes were phakic. Combined cataract surgery was performed with epiretinal membrane removal in all 17 phakic eyes. The mean logarithm of the minimal angle of resolution BCVA was 0.75 ± 0.30 before surgery, which improved to 0.50 ± 0.30 at the final follow-up (p < 0.001). The CMT was 458.0 ± 79.7 µm before surgery, which decreased to 367.2 ± 83.4 µm at the final follow-up (p < 0.001). There was no significant difference in the amount of change in the BCVA after the surgery between the ≥ 80 years of age group and the < 80 years of age group (p = 0.547).CONCLUSIONS: In patients with idiopathic epiretinal membrane who were ≥ 80 years of age, the visual acuity was improved or maintained, and was accompanied with anatomical improvement after epiretinal membrane removal with or without cataract surgery. These results suggest the usefulness of epiretinal membrane removal in older patients.
Cataract ; Epiretinal Membrane ; Follow-Up Studies ; Humans ; Medical Records ; Retrospective Studies ; Visual Acuity ; Vitrectomy

Objective: This study estimated the incidence of driving-related adverse events and examined the association of cognitive function with the risk of future driving-related adverse events in the elderly Korean male population. Methods: We analyzed 1,172 male drivers aged 60 years or older in the Korean Longitudinal Study on Cognitive Aging and Dementia (KLOSCAD). Using the data from Korean National Police Agency, we classified the participants into three groups: safe driving (drove for 2 years after baseline without a traffic accident or repeated violations), driving cessation (stopped driving), and risky driving (one or more traffic accidents or repeated violations). We estimated the incidences of driving cessation and risky driving, and examined the effect of cognitive function on their risks. Results: The incidence of driving cessation and risky driving in the Korean male drivers aged 60 years or older was 19.3 and 69.9 per 1,000 person-years respectively and increased in the late 80s. Drivers with better baseline Word List Memory Test scores showed less risky driving (OR=0.94, p=0.039). Conclusion Driving-related adverse events increased in late 80s, and better memory function was protective against these events.

Objective: Cardiovascular diseases are representative risk factors for the onset of cognitive decline. The purpose of this study was to confirm the relationship between diastolic blood pressure and cognitive function in elderly people in Korea. Methods: Data from subjects who were enrolled in the prospective Korean Longitudinal Study on Cognitive Aging and Dementia were used in this study. Data from 701 subjects whose diastolic blood pressure range did not change (≤79 mm Hg or ≥80 mm Hg) over 2 years were analyzed. To analyze the differences in cognitive function between the groups at the 2-year follow-up, an analysis of covariance was performed with covariates, which were significantly different between the two groups, and the baseline cognitive function. Results: Significant differences were observed between the two groups, and the mean scores on the constructional praxis (η2=0.010) and word list recall tests (η2=0.018) in the diastolic blood pressure ≥80 mm Hg group were higher than those in the diastolic blood pressure ≤79 mm Hg group at the 2-year follow-up. Conclusion These results indicate that maintaining a DBP below 79 mm Hg presents a greater risk of cognitive decline in Korean elderly people.

Transient receptor potential canonical 4 (TRPC4) channel is a nonselective calcium-permeable cation channels. In intestinal smooth muscle cells, TRPC4 currents contribute more than 80% to muscarinic cationic current (mIcat). With its inward-rectifying current-voltage relationship and high calcium permeability, TRPC4 channels permit calcium influx once the channel is opened by muscarinic receptor stimulation. Polyamines are known to inhibit nonselective cation channels that mediate the generation of mIcat. Moreover, it is reported that TRPC4 channels are blocked by the intracellular spermine through electrostatic interaction with glutamate residues (E728, E729). Here, we investigated the correlation between the magnitude of channel inactivation by spermine and the magnitude of channel conductance. We also found additional spermine binding sites in TRPC4. We evaluated channel activity with electrophysiological recordings and revalidated structural significance based on Cryo-EM structure, which was resolved recently. We found that there is no correlation between magnitude of inhibitory action of spermine and magnitude of maximum current of the channel. In intracellular region, TRPC4 attracts spermine at channel periphery by reducing access resistance, and acidic residues contribute to blocking action of intracellular spermine; channel periphery, E649; cytosolic space, D629, D649, and E687.
Amino Acids ; Binding Sites ; Calcium ; Cytosol ; Glutamic Acid ; Myocytes, Smooth Muscle ; Permeability ; Polyamines ; Receptors, Muscarinic ; Spermine ; Transient Receptor Potential Channels

Purpose: This study was conducted to investigate the factors affecting the discrimination of the elderly using welfare centers. Methods: A cross-sectional study was conducted with 217 elderly people from a welfare center in D city. Data were collected using a self-administered questionnaire survey consisting of ageism experience, social participation attitude, social support, and empowerment. For data analysis, descriptive statistics, t-test, one-way ANOVA, Pearson correlation coefficients, and multiple regression were performed using SPSS/WIN 21.0 program. Results: As a result of analyzing the correlations among the variables, the discrimination experience of the elderly showed negative correlations in social participation attitude and child relationship support. The factors affecting the discrimination experience of the elderly include gender, job, smartphone use, and child relationship support had a significant effect. The explanatory power of the discrimination experience of these factors was 15.4%. Conclusion This study found that gender, job, social support, and smartphone use were factors influencing the discrimination experience of the elderly. It is hoped that public relations and policy measures should be considered.

Background: Longitudinal integrated clerkships (LICs) have been adopted by medical schools to overcome the limitations of traditional block clerkship rotations and to promote continuity of care. In 2018, Seoul National University College of Medicine introduced a patient-centered LIC program as part of a new curriculum in parallel with traditional block rotation clerkships. The purpose of this study was to present the patient-centered LIC program and to investigate its educational effects. Methods: In 2018 and 2019, a total of 298 third-year medical students participated in the LIC program. We divided the students into groups of eight, which were organized into corresponding discussion classes. Throughout the academic year, students followed up patients by interviewing them at the hospital or reviewing their electric medical records.Discussion classes on set topics were held seven times per year with facilitators and clinical faculties. Students completed a course evaluation questionnaire at the end of the academic year. The questionnaire included 22 items measured on a 5-point scale and two open-ended questions asking about the benefits and limitations of the program. The items covered three domains: student experience, satisfaction, and self-assessment. Final reflective essays were collected as both student assessments and data for qualitative analysis. Results: During the study period, the overall experience of the students improved. We increased the number of faculty members and patients and decreased the number of students in each discussion class. We also provided additional feedback through an e-portfolio.Students' satisfaction changed positively. Compared to the rotational clerkship, students answered that the LIC provided additional help in learning the two core competencies.During the first 2 years of the program, the percentage of students who answered that the program was more helpful than the rotational clerkship increased from 23.7% to 46.4% for continuity of care (P < 0.001), and from 20.5% to 50.7% for patient-centered care (P < 0.001). Conclusion Our patient-centered LIC, in parallel with traditional block rotation clerkships, had a positive effect on students' experience of continuity of care and patient-centered care.