This article evaluates the overall current disease burden of North Korea through the recent databases of international organizations. It is notable that North Korea as a nation is exhibiting a relatively low burden from deaths and that there is greater burden from deaths caused by non-communicable diseases than from those caused by communicable diseases and malnutrition. However, the absolute magnitude of problems from communicable diseases like TB and from child malnutrition, which will increase the disease burden in the future, remains great. North Korea, which needs to handle both communicable and nutritional conditions, and non-communicable diseases, whose burden is ever more increasing in the nation, can now be understood as a country with the 'double-burden' of disease.

Background Mood disorders require consistent management of symptoms to prevent recurrences of mood episodes. Circadian rhythm (CR) disruption is a key symptom of mood disorders to be proactively managed to prevent mood episode recurrences. This study aims to predict impending mood episodes recurrences using digital phenotypes related to CR obtained from wearable devices and smartphones. Methods The study is a multicenter, nationwide, prospective, observational study with major depressive disorder, bipolar disorder I, and bipolar II disorder. A total of 495 patients were recruited from eight hospitals in South Korea. Patients were followed up for an average of 279.7 days (a total sample of 75 506 days) with wearable devices and smartphones and with clinical interviews conducted every 3 months. Algorithms predicting impending mood episodes were developed with machine learning. Algorithm-predicted mood episodes were then compared to those identified through face-to-face clinical interviews incorporating ecological momentary assessments of daily mood and energy. Results Two hundred seventy mood episodes recurred in 135 subjects during the follow-up period. The prediction accuracies for impending major depressive episodes, manic episodes, and hypomanic episodes for the next 3 days were 90.1, 92.6, and 93.0%, with the area under the curve values of 0.937, 0.957, and 0.963, respectively. Conclusions We predicted the onset of mood episode recurrences exclusively using digital phenotypes. Specifically, phenotypes indicating CR misalignment contributed the most to the prediction of episodes recurrences. Our findings suggest that monitoring of CR using digital devices can be useful in preventing and treating mood disorders.

BackgroundHypertonic saline is often used to resuscitate patients experiencing shock. In such conditions, polymorphonuclear cells and Toll-like receptors (TLRs) form an essential part of early induced innate immunity.ObjectiveTo investigate the immunomodulatory effect of hypertonic saline on polymorphonuclear cells by evaluating the changes in TLR-4 receptors and proinflammatory cytokines.MethodsPolymorphonuclear cells were isolated from whole blood using Polymorphprep (Axis-Shield, Oslo, Norway). The isolated polymorphonuclear cells were plated at a density of 1 × 106 cells/mL in 6-well flat-bottomed culture plates and were stimulated with 1 μg/mL lipopolysaccharide or N-formyl-methionyl-leucyl-phenylalanine. The stimulated polymorphonuclear cells were cultured in hypertonic saline at 10, 20, or 40 mmol/L above isotonicity. After that, the changes in TLR-4 and cytokines were measured by quantitative real-time polymerase chain reaction and flow cytometry.ResultsThe level of TLR-4 mRNA expression decreased after stimulation with N-formyl-methionyl-leucyl-phenylalanine, but hypertonic saline did not affect the TLR-4 mRNA expression. TLR-4 mRNA expression was clearly induced upon stimulation with lipopolysaccharide, and the addition of hypertonic saline restored TLR-4 mRNA expression in polymorphonuclear cells. The interleukin-1β mRNA expression was decreased in the hypertonic environment. On the other hand, the tumor necrosis factor-α value was not influenced by the addition of hypertonic saline.ConclusionsHypertonic saline has an immunomodulatory effect on polymorphonuclear cells through the TLR-4 pathway, and the interleukin–1β-associated pathway is influenced more by hypertonic saline than is the tumor necrosis factor–α-associated pathway.

The objective of this study was to determine whether the circadian rhythm of heart rate or step count using wearable devices was related to that of the salivary cortisol levels and to test the possibility that the data from wearable devices could be used as an indicator of circadian rhythm misalignment, which is emerging as a cause of insomnia and mood disorders. Methods: The heart rate and step count were continuously measured in 12 healthy young adults using wearable wrist devices for 5 days, and saliva was sampled every 4 hours, excluding sleeping time, for a total of 48 hours to measure the circadian rhythm of salivary cortisol concentration. Cortisol concentrations were assessed using the enzyme-linked immunosorbent assay. The cosinor analysis for the three measurements, salivary cortisol concentrations, heart rate, and step count, was used to estimate the circadian rhythm. Results: The mean values of the acrophase of the cosine-fitted curve of cortisol, heart rate, and step count were 9.06, 15.84, and 19.09, respectively, while those of the amplitude were 7.70, 12.60, and 10.68, respectively. In addition, the mean values of the mesor of the cosine-fitted curve for cortisol, heart rate, and step count were 17.19, 73.55, and 45.45, respectively, and those of robustness were 0.82, 0.56, and 0.18, respectively. There was a possible positive correlation between the acrophase of the cosine-fitted curve of salivary cortisol and that of heart rate (r=0.55, p=0.064). However, there was no correlation between the acrophase of the cosine-fitted curve of salivary cortisol and that of step count (r=-0.2, p=0.533). Conclusion: The findings suggest that the heart rate measured using the wearable activity tracker was a relatively reliable biomarker of circadian rhythm.

Background: Many mood disorder patients experience seasonal changes in varying degrees. Studies on seasonality have shown that bipolar disorder has a higher prevalence rate in such patients; however, there is limited research on seasonality in early-onset mood disorder patients. This study estimated the prevalence of seasonality in early-onset mood disorder patients, and examined the association between seasonality and mood disorders. Methods: Early-onset mood disorder patients (n = 378; 138 major depressive disorder; 101 bipolar I disorder; 139 bipolar II disorder) of the Mood Disorder Cohort Research Consortium and healthy control subjects (n = 235) were assessed for seasonality with Seasonality Pattern Assessment Questionnaire (SPAQ).Results: A higher global seasonality score, an overall seasonal impairment score, and the prevalence of seasonal affective disorder (SAD) and subsyndromal SAD showed that mood disorder subjects had higher seasonality than the healthy subjects. The former subject group had a significantly higher mean overall seasonal impairment score than the healthy subjects (p < .001); in particular, bipolar II disorder subjects had the highest prevalence of SAD, and the diagnosis of bipolar II disorder had significantly higher odds ratios for SAD when compared to major depression and bipolar I disorder (p < .05).Conclusions: Early-onset mood disorders, especially bipolar II disorder, were associated with high seasonality. A thorough assessment of seasonality in early-onset mood disorders may be warranted for more personalized treatment and proactive prevention of mood episodes.

Objective: Benzodiazepines are a widely used class of medications for anxiety, depression, and insomnia. Despite their common use, concerns remain about memory problems with benzodiazepines. Despite the growing financial and social burden of dementia, inconsistent results persist regarding the association between benzodiazepines and dementia. Therefore, we aimed to evaluate the association between benzodiazepines and dementia in Korea. Methods: Diagnostic and prescription information from the Health Insurance Review and Assessment (HIRA) database in South Korea between 2009 and 2014 was utilized. The dementia group included people who were diagnosed with a dementia code and received one or more prescriptions for dementia. A total of 68,241 participants with dementia and 341,205 control participants were matched. Possible confounders, such as major medical and psychiatric disorders, were adjusted, and multivariate logistic regression was conducted to assess the association between benzodiazepines and dementia. Results: The highest odds ratio (OR) for dementia was noted for clonazepam (OR=2.86, 95% confidence interval [CI]=2.77–2.95) followed by those for diazepam (OR=2.60, 95% CI=2.53–2.66), lorazepam (OR=1.34, 95% CI=1.30–1.37), and triazolam (OR=1.26, 95% CI=1.21–1.32). Conclusion: Overall, relatively long-acting benzodiazepines, such as clonazepam, diazepam, and lorazepam, were associated with the incidence of dementia. Triazolam, which is approved for insomnia, was also significantly associated with dementia. Individuals who are prescribed with benzodiazepines should be cautious regarding memory loss and dementia. Further studies are needed to confirm the temporal and biological causality between benzodiazepines and dementia.

Objective Evidence for the association between circadian rhythm delay and depression is accumulating. Genetic studies have shown that certain polymorphisms in circadian genes are potential genetic markers of diurnal preference. Along with circadian genes, there is a growing interest in other genetic effects on circadian rhythms. This study evaluated whether the <i>HTR2A</i> rs6311 (-1438C/T) polymorphism is associated with diurnal preference in a Korean population.Methods A total of 510 healthy subjects were included in this study. All subjects were genotyped for the <i>HTR2A</i> rs6311 polymorphism and they completed the Korean version of the composite scale of morningness (CSM).Results The C allele carriers (C/C+C/T) showed significantly higher CSM scores compared to C allele non-carriers (T/T) (t=2.22, p= 0.03), suggesting the existence of a morning chronotype tendency in C allele carriers. In other words, the T/T genotype may be associated with the evening chronotype.Conclusion These results suggest that the <i>HTR2A</i> rs6311 polymorphism may be associated with diurnal preference in a healthy Korean population. The absence of the C allele may be responsible for the increasing susceptibility to eveningness in the Korean population. Further studies on <i>HTR2A</i> polymorphisms that evaluate their interactions with various candidate genes and differences in phenotypic expression of polymorphisms according to ethnic groups are warranted to fully understand their association with diurnal preference.

In a place such as the department of emergency medicine, it is critical and important for emergency physicians to make a proper judgment and to prepare for the worst scenario. Therefore, the utilization of MIF level in trauma patients has a possibility for assisting emergency physicians.