An XYZ-axis Matrix Approach for the Integration of Neuroscience and Neuroethics

The recent, unprecedented advancement in neuroscience has led to new discoveries about the human brain and its function. Yet at the same time, it has spurred novel ethical and regulatory issues, and the field of neuroethics has emerged as an interdisciplinary endeavor to address these issues.Across the globe, extensive efforts have been underway to achieve the integration of neuroscience and Neuroethics, with active engagement not only from academia but also from the government, the public, and industry. However, in some countries, integrating neuroscience and neuroethics has proved to be a particularly challenging task. For example, in South Korea, the government has primarily driven the integration effort, and only a small group of researchers is properly trained for conducting an interdisciplinary evaluation of ethical, legal, social, and cultural implications (ELSCI) of neurotechnology. On the basis of the last few years of experience pursuing a government-funded neuroethics project in South Korea, we developed a new operational framework to provide practical guidance on ELSCI research. This framework consists of the X, Y, and Z axes; the X-axis represents a target neurotechnology, the Y-axis represents different developmental stages of the technology, and the Z-axis represents ELSCI issues that may arise from the development and use of the neurotechnology. Here we also present a step-by-step workflow to apply this matrix framework, from organizing a panel for a target neurotechnology to facilitating stakeholder discussion through public hearings. This framework will enable meaningful integration of neuroscience and neuroethics to promote responsible innovation in neuroscience and neurotechnology.

A Caring Program for Health Promotion among Women Who Have Experienced Trauma: A QuasiExperimental Pilot Study

Purpose@#Women are more vulnerable to post-traumatic stress (PTS) than men, causing several health problems. Nurses should understand and work with women who have experienced trauma and provide interventions to promote their physical, social, and mental health. @*Methods@#This quasi-experimental pilot study used a one-group pre-test/post-test design. Data were collected from 14 women recruited between December 2019 and May 2020 from a self-sufficiency support center in South Korea for sexually-exploited women who had experienced trauma. The program consisted of six one-on-one intervention sessions per week for six weeks. Each session averaged 60~120 minutes. Participants were assessed at pre-test, post-test, and one-month follow-up. Changes in outcome variables over time were analyzed using the Wilcoxon signed-rank and Friedman tests. @*Results@#The caring program for health promotion was divided into six sessions: understanding the self, sharing traumatic events and negative emotions, reframing the meaning of traumatic events, identifying thoughts and physical and emotional responses, developing health promotion activities, and maintaining a positive attitude during the process of change. As a result of the caring program, PTS (F = 36.33, p < .001), depression (F = 24.45, p < .001), health-promoting behaviors (F = 7.06, p = .004), and self-esteem (F = 19.74, p < .001) among the participants differed significantly at pre-test, post-test, and follow-up. @*Conclusion@#This study provides foundational information for the implementation of a theory-driven program by nurses in clinical and community settings to provide comprehensive care for women who have experienced trauma.

Evaluating a shared decision-making intervention regarding dialysis modality: development and validationof self-assessment items for patients with chronic kidney disease

Shared decision-making is a two-way symmetrical communication process in which clinicians and patients work together to achieve the best outcome. This study aimed to develop self-assessment items as a decision aid for choosing a dialysis modality in patients with chronic kidney disease (CKD) and to assess the construct validity of the newly developed items. Methods: Five focus group interviews were performed to extract specific self-assessment items regarding patient values in choosing a dialysis modality. After survey items were refined, a survey of 330 patients, consisting of 152 hemodialysis (HD) and 178 peritoneal dialysis (PD) patients, was performed to validate the self-assessment items. Results: The self-assessment for the decision aid was refined to 35 items. The structure of the final items appeared to have three dimensions of factors; health, lifestyle, and dialysis environment. The health factor consisted of 12 subscales (α = 0.724), the lifestyle factor contained 11 subscales (α = 0.624), and the dialysis environment factor was represented by 12 subscales (α = 0.694). A structural equation model analysis showed that the relationship between the decision aid factors (health, lifestyle, and dialysis environment), patients’ CKD perception, and cognition of shared decision-making differed between HD patients and PD patients. Conclusion: We developed and validated self-assessment items as part of a decision aid to help patients with CKD. This attempt may assist CKD patients in making informed and shared decisions closely aligned with their values when considering dialysis modality.

Spatiotemporal Profile and Morphological Changes of NG2 Glia in the CA1 Region of the Rat Hippocampus after Transient Forebrain Ischemia

Neuron-glial antigen-2 (NG2) glia undergo proliferation and morphological changes following brain insults. Here, we show that NG2 glia is activated in a characteristic time- and layer-specific manner in the ischemia-vulnerable CA1 region of the rat hippocampus. Resting NG2 glia of the pyramidal cell layer (somatic region) shared morphological features with those of the neighboring dendritic stratum radiatum. During the postischemic period, reactive NG2 glia of the pyramidal cell layer exhibited shortened, scarcely branched processes, while those of the stratum radiatum had multiple branching processes with their arborization being almost indiscernible 7~14 days after reperfusion. Immunoelectron microscopy demonstrated that NG2 immunoreactivity was specifically associated with the plasma membrane and the adjacent extracellular matrix of NG2 glia in the stratum radiatum at 14 days. NG2 glia also exhibited differences in their numbers and proliferation profiles in the two examined hippocampal strata after ischemia. In addition, induced NG2 expression in activated microglia/macrophages exhibited a characteristic strata-dependent pattern in the ischemic CA1 hippocampus. NG2 induction was prominent in macrophage-like phenotypes which were predominantly localized in the pyramidal cell layer, compared with activated stellate microglial cells in the stratum radiatum. Thus, our data demonstrate that activation of NG2 glia and the induction of NG2 expression in activated microglia/macrophages occur in a distinct time- and layer-specific manner in the ischemic CA1 hippocampus. These characteristic profiles of reactive NG2 glia could be secondary to the degeneration processes occurring in the cell bodies or dendritic domains of hippocampal CA1 pyramidal neurons after ischemic insults.

Long Commute Time and Sleep Problems with Gender Difference in Work–Life Balance: A Cross-sectional Study of More than 25,000 Workers

BACKGROUND: There is a lack of statistical analysis investigating the relationship between sleep problems and commute time in Korea. We aimed to analyze the association between representative health symptoms, sleep disturbances, and commute time according to working hours in Korea.METHODS: The 4th Korean Working Conditions Survey data were used for analysis, and unpaid family workers and workers who work fewer than three days in a week were excluded. Commute time, working hours, and sleep hours were assessed using self-reported questionnaires. Odds ratios (ORs) with 95% confidence intervals (CIs) for sleep problems were calculated using a multivariate logistic regression model with ≤10 min commute time as the reference group.RESULTS: Among a total of 28,804 workers (men = 14,945, women = 13,859), 2.6% of men and 3.2% of women experienced sleep problems. In both sexes, long commute time (51–60 minutes and >60 minutes) showed an increased OR [men, 2.03 (CI = 1.32–3.13) and 2.05 (CI = 1.33–3.17); women, 1.58 (CI = 1.05–2.39) and 1.63 (CI = 1.06–2.50), respectively]. In stratification analysis of working hours, long commute time (51–60 and > 60 minutes) showed an increased OR in men working >40 hours/week [2.08 (CI = 1.16–3.71) and 1.92 (CI = 1.08–3.41), respectively]. Furthermore, long commute time (41–50, 51–60, and >60 minutes) showed an increased OR in women working >40 hours/week [2.40 (CI = 1.27–4.55), 2.28 (CI = 1.25–4.16), and 2.19 (CI = 1.17–4.16), respectively]. Moreover, commute time >60 minutes showed an increased OR in women working ≤40 hours/week [1.96 (CI = 1.06–3.62)].CONCLUSION: This large cross-sectional study highlights that long commute time is related to sleep problems in both sexes. Shorter commute times and decreased working hours are needed to prevent sleep problems in workers.

Clinical Findings of Menkes Disease and the Treatment of Epilepsy / 대한소아신경학회지

Menkes disease (also known as kinky hair disease) is an X-linked recessive neurodegenerative disorder caused by diverse mutations in a copper-transport gene, ATP7A. Affected patients are characterized by kinky hair, hypotonia, and generalized myoclonic seizures. Here, we report a case of Menkes disease in which the patient presented with progressive hypotonia and intractable seizures. A 4-month-old male infant visited our pediatric clinic for focal seizures with blinking eyes. He was generally hypotonic and suffered from malnutrition. The focal seizures became more frequent, and the patient became intractable to anti-seizure medications. An electroencephalogram (EEG) indicated diffuse cerebral dysfunction with focal seizure, and a brain magnetic resonance imaging (MRI) showed tortuous and ectatic intracranial arteries, as well as several ischemic lesions. A genetic analysis was performed, and a c.2473_2474del (p.Leu825fsX1) of the ATP7A gene was detected.

TLR5 Activation through NF-κB Is a Neuroprotective Mechanism of Postconditioning after Cerebral Ischemia in Mice

Postconditioning has been shown to protect the mouse brain from ischemic injury. However, the neuroprotective mechanisms of postconditioning remain elusive. We have found that toll-like receptor 5 (TLR5) plays an integral role in postconditioning-induced neuroprotection through Akt/nuclear factor kappa B (NF-κB) activation in cerebral ischemia. Compared to animals that received 30 min of transient middle cerebral artery occlusion (tMCAO) group, animals that also underwent postconditioning showed a significant reduction of up to 60.51% in infarct volume. Postconditioning increased phospho-Akt (p-Akt) levels and NF-κB translocation to the nucleus as early as 1 h after tMCAO and oxygen-glucose deprivation. Furthermore, inhibition of Akt by Akt inhibitor IV decreased NF-κB promoter activity after postconditioning. Immunoprecipitation showed that interactions between TLR5, MyD88, and p-Akt were increased from postconditioning both in vivo and in vitro. Similar to postconditioning, flagellin, an agonist of TLR5, increased NF-κB nuclear translocation and Akt phosphorylation. Our results suggest that postconditioning has neuroprotective effects by activating NF-κB and Akt survival pathways via TLR5 after cerebral ischemia. Additionally, the TLR5 agonist flagellin can simulate the neuroprotective mechanism of postconditioning in cerebral ischemia.

Anti-inflammatory Effect of Glucagon Like Peptide-1 Receptor Agonist, Exendin-4, through Modulation of IB1/JIP1 Expression and JNK Signaling in Stroke

Glucagon like peptide-1 (GLP-1) stimulates glucose-dependent insulin secretion. Dipeptidyl peptidase-4 (DPP-4) inhibitors, which block inactivation of GLP-1, are currently in clinical use for type 2 diabetes mellitus. Recently, GLP-1 has also been reported to have neuroprotective effects in cases of cerebral ischemia. We therefore investigated the neuroprotective effects of GLP-1 receptor (GLP-1R) agonist, exendin-4 (ex-4), after cerebral ischemia-reperfusion injury. Transient middle cerebral artery occlusion (tMCAO) was induced in rats by intracerebroventricular (i.c.v.) administration of ex-4 or ex9-39. Oxygen-glucose deprivation was also induced in primary neurons, bEnd.3 cells, and BV-2. Ischemia-reperfusion injury reduced expression of GLP-1R. Additionally, higher oxidative stress in SOD2 KO mice decreased expression of GLP-1R. Downregulation of GLP-1R by ischemic injury was 70% restored by GLP-1R agonist, ex-4, which resulted in significant reduction of infarct volume. Levels of intracellular cyclic AMP, a second messenger of GLP-1R, were also increased by 2.7-fold as a result of high GLP-1R expression. Moreover, our results showed that ex-4 attenuated pro-inflammatory cyclooxygenase-2 (COX-2) and prostaglandin E₂ after MCAO. C-Jun NH₂ terminal kinase (JNK) signaling, which stimulates activation of COX-2, was 36% inhibited by i.c.v. injection of ex-4 at 24 h. Islet-brain 1 (IB1), a scaffold regulator of JNK, was 1.7-fold increased by ex-4. GLP-1R activation by ex-4 resulted in reduction of COX-2 through increasing IB1 expression, resulting in anti-inflammatory neuroprotection during stroke. Our study suggests that the anti-inflammatory action of GLP-1 could be used as a new strategy for the treatment of neuroinflammation after stroke accompanied by hyperglycemia.

Performance of the BacT Alert 3D System Versus Solid Media for Recovery and Drug Susceptibility Testing of Mycobacterium tuberculosis in a Tertiary Hospital in Korea / 결핵및호흡기질환

BACKGROUND: Tuberculosis (TB) is a major health problem, and accurate and rapid diagnosis of multidrug-resistant (MDR) and extended drug-resistant (XDR) TB is important for appropriate treatment. In this study, performances of solid and liquid culture methods were compared with respect to MDR- and XDR-TB isolate recovery and drug susceptibility testing. METHODS: Sputum specimens from 304 patients were stained with Ziehl-Neelsen method. Mycobacterium tuberculosis (Mtb) isolates were tested for recovery on Löwenstein-Jensen (LJ) medium and the BacT Alert 3D system. For drug susceptibility testing of Mtb, isolates were evaluated on M-KIT plates and the BacT Alert 3D system. RESULTS: The recovery rates were 94.9% (206/217) and 98.2% (213/217) for LJ medium and the BacT Alert 3D system, respectively (kappa coefficient, 0.884). The rate of drug resistance was 13.4% for at least one or more drugs, 6.0% for MDR-TB and 2.3% for XDR-TB. M-KIT plate and BacT 3D Alert 3D system were comparable in drug susceptibility testing for isoniazid (97.7%; kappa coefficient, 0.905) and rifampin (98.6%; kappa coefficient, 0.907). Antibiotic resistance was observed using M-KIT plates for 24 of the total 29 Mtb isolates (82.8%). CONCLUSION: The liquid culture system showed greater reduction in the culture period, as compared with LJ medium; however, drug susceptibility testing using M-KIT plates was advantageous for simultaneous testing against multiple drug targets.

The Effects of a Positive Psychology Program on Nursing Students' Positive Thinking, Ego Resilience and Stress Coping / 한국간호교육학회지

PURPOSE: The purpose of this study was to examine effects of a positive psychology program for improving positive thinking, ego resilience and stress coping of in nursing students. METHODS: A non-equivalent control group pretest-posttest design was used. The subjects for the study were 78 students in G city(experimental group=41, control group=37). The positive psychology program was provided for 4 weeks (8 sessions, 16 hours). Positive thinking, ego resilience, and stress coping were measured with using self-report structured questionnaires. This study collected data between November 23, 2014 and January 9, 2015, and which were analyzed using SPSSWIN 20.0. RESULTS: The positive psychology program was effective in increasing positive thinking, ego resilience and stress coping. CONCLUSION: The results of this study should contribute as baseline data for positive intervention strategies and planning ability of potentials and strengths in nursing students.

Association of CACNA1C Variants with Bipolar Disorder in the Korean Population

OBJECTIVE: Previous studies have suggested an association between CACNA1C and susceptibility of bipolar disorder. In this study, we examined the association of CACNA1C variants with bipolar disorder in the Korean population. METHODS: We selected 2 CACNA1C single nucleotide polymorphisms (SNPs), namely, rs723672 and rs1051375, based on their functions and minor allele frequencies described in previous studies. Genotypes of these 2 SNPs were analyzed by extracting DNA from blood samples collected from 287 patients with bipolar disorder and 340 healthy controls. RESULTS: Genotype frequencies of both rs723672 and rs1051375 SNPs were significantly different in patients and controls (p=0.0462 and 1.732E-14, respectively). Dominant, recessive, and allele models showed significant differences between patients and controls with respect to the rs1051375 SNP (p=1.72E-11, 4.17E-10, 4.95E-16, respectively). CONCLUSION: Our results suggested that CACNA1C SNPs rs723672 and rs1051375 were associated with bipolar disorder in the Korean population. In addition, our results highlighted the importance of CACNA1C in determining susceptibility to bipolar disorder.

The Effectiveness of Silver In Situ Hybridization in Patients with Breast Cancer: A Systematic Review / 한국유방암학회지

PURPOSE: The purpose of this study was to evaluate silver in situ hybridization (SISH) as an effective test to identify HER2 gene amplification in patients with breast cancer. METHODS: A systematic literature review was used to evaluate the effectiveness of SISH. The literature review covered from October 27, 2009 to December 1, 2009, and eight domestic databases including KoreaMed and foreign databases including Ovid-MEDLINE, EMBASE, and Cochrane Library were used. Keywords, such as 'silver in situ hybridization' and 'SISH', were used to search 63 documents. Ten studies regarding the evaluation of diagnostics were included in the final evaluation. The Scottish Intercollegiate Guidelines Network (SIGN) tool was used by two evaluators to independently evaluate the quality of the ten studies. RESULTS: A total of ten studies (nine diagnostic evaluation studies and one correlation study) were identified to evaluate SISH. The effectiveness of this test was evaluated based on diagnostic accuracy, concordance rate, and correlation with fluorescence in situ hybridization (FISH) results. The sensitivity of SISH was 0.81-1.00, and the specificity was 0.82-1.00. The positive predictive value was 0.95-1.00, negative predictive value was 0.81-1.00, and the test accuracy was 0.90-1.00. The concordance rate of SISH was 87.0-100% and two studies reported a correlation with FISH results. The body of evidence as a whole suggests a Grade D for SISH. CONCLUSION: SISH is a safe and useful procedure in patients with breast cancer and at least grade D evidence based on existing positive studies.

The Effects of Intradialytic Exercise on Dialysis Efficacy and Autonomic Function in Hemodialysis Patients: Preliminary Study / 대한스포츠의학회지

The study investigated the effects of an intradialytic exercise program on autonomic function and dialysis efficacy in maintenance hemodialysis in 18 patients. The patients undertook a 6-month intradialysis exercise program. Each session consisted of a 5-minute warm-up, 40-minute main exercise program, and 5-minute cool-down period. Autonomic symptom questionnaire and autonomic function test by heart rate variability on supine and standing position, and dialysis efficacy were assessed at the beginning and end of the study by comparison using the Wilcoxson signed rank test. Heart rate variability in the supine position was not improved. In the standing position the ratio between the low frequency and high frequency (LF/HF) increased significantly after 6 months of exercise (p<0.05), with the LF component being normally dominant. Statistical differences were evident at 6 months in autonomic symptoms questionnaire and autonomic function (p<0.05), but not in dialysis efficacy. The results suggest that intradialytic exercise is an effective therapy to improve autonomic symptoms and a heart rate variability parameter.

A Case of Asymptomatic Giant Right Atrial Aneurysm

A healthy 8 year old boy was referred to our hospital because of cardiomegaly on the chest X ray. No cardiac murmur was detected on chest examination and normal sinus rhythm was checked by electrocardiogram. The 2-D echocardiogram showed a huge dilated right atrium and a normal tricuspid valve and right ventricle. The findings of cardiac angiogram and MRI was compatible with the isolated giant right atrial aneurysm. For the prevention of atrial arrhythmia and thromboembolism, he underwent successful surgical reduction of the right atrium and cryoablation and the follow-up X ray showed no cardiomegaly.