Proteasome Activator Enhances Survival of Huntington's Disease Neuronal Model Cells

In patients with Huntington's disease (HD), the proteolytic activity of the ubiquitin proteasome system (UPS) is reduced in the brain and other tissues. The pathological hallmark of HD is the intraneuronal nuclear protein aggregates of mutant huntingtin. We determined how to enhance UPS function and influence catalytic protein degradation and cell survival in HD. Proteasome activators involved in either the ubiquitinated or the non-ubiquitinated proteolysis were overexpressed in HD patients' skin fibroblasts or mutant huntingtin-expressing striatal neurons. Following compromise of the UPS, overexpression of the proteasome activator subunit PA28γ, but not subunit S5a, recovered proteasome function in the HD cells. PA28γ also improved cell viability in mutant huntingtin-expressing striatal neurons exposed to pathological stressors, such as the excitotoxin quinolinic acid and the reversible proteasome inhibitor MG132. These results demonstrate the specific functional enhancements of the UPS that can provide neuroprotection in HD cells

Impact of COVID-19 Pandemic on Children Visiting Emergency Department for Mental Illness: A Multicenter Database Analysis from Korea

We aimed to identify changes in the proportion of pediatric emergency department (PED) visits due to mental illness during the coronavirus disease 2019 (COVID-19) pandemic. This was a retrospective observational study of visits to the PED at six university hospitals from January 2017 to December 2020. We included children aged 5–17 years who were diagnosed with a mental illness. We used segmented regression analysis to identify the change in the proportion of patients with mental illness. A total of 845 patients were included in the analysis. After the first case of COVID-19 was reported in Korea, the number of PED visits significantly decreased by 560.8 patients per week (95% confidence interval (CI): −665.3 to −456.3, p < 0.001). However, the proportion of patients with mental illness increased significantly, by 0.37% per week (95% CI: 0.04% to 0.70%, p = 0.03), at this time point. Subgroup analyses revealed that emotional disorders significantly increased by 0.06% per month (95% CI: 0.02% to 0.09%, p < 0.001) during the pandemic. Our study revealed that an increased proportion of patients with mental illness visited the PED during the COVID-19 pandemic. Specifically, we identified that the proportion of emotional disorders continues to rise during this pandemic

Association between Stress Hyperglycemia and Adverse Outcomes in Children Visiting the Pediatric Emergency Department

Stress hyperglycemia (SH) is often identified in patients visiting the pediatric emergency department (PED), and SH in adults has been associated with adverse outcomes, including mortality. In this retrospective study, we determined the adverse outcomes according to blood glucose (BG) levels of children visiting the PED of tertiary hospitals. Data were collected from the electronic medical records of children aged p p p < 0.001). Compared to the normoglycemic group of 45 ≤ BG < 150 mg/dL, the odds ratios (95% CI) for mortality were 5.61 (3.35–9.37), 27.96 (14.95–52.26), 44.22 (17.03–114.82), and 39.94 (16.31–97.81) for levels 150 ≤ BG < 200, 200 ≤ BG < 250, 250 ≤ BG < 300 and ≥300 mg/dL, respectively. This suggests that SH is common in children visiting the PED and is associated with higher adverse outcomes. Thus, there is a need to quickly identify its cause and take prompt intervention to resolve it

Distribution of Pediatric Vital Signs in the Emergency Department: A Nationwide Study

To effectively use vital signs as indicators in children, the magnitude of deviation from expected vital sign distribution should be determined. The purpose of this study is to derive age-specific centile charts for the heart rate and respiratory rate of the children who visited the emergency department. This study used the Korea&rsquo;s National Emergency Department Information System dataset. Patients aged &lt;16 years visiting the emergency department between 1 January 2016 and 31 December 2017 were included. Heart rate and respiratory rate centile charts were derived from the population with normal body temperature (36 to &lt;38 &deg;C). Of 1,901,816 data points retrieved from the database, 1,454,372 sets of heart rates and 1,458,791 sets of respiratory rates were used to derive centile charts. Age-specific centile charts and curves of heart rates and respiratory rates showed a decline in heart rate and respiratory rate from birth to early adolescence. There were substantial discrepancies in the reference ranges of Advanced Paediatric Life Support and Pediatric Advanced Life Support guidelines. Age-based heart rate and respiratory rate centile charts at normal body temperature, derived from children visiting emergency departments, serve as new evidence-based data and can be used in follow-up studies to improve clinical care for children

Examining Mechanisms Underlying the Ability to Form Paradigmatic Associations

Paradigmatic associations are second-order associations where the items share a common context rather than being directly associated. Despite the importance of the structure in knowledge representation, the underlying mechanisms to form paradigmatic associations are not well studied. In the current study, we examined whether explicit attentional control is critical for forming paradigmatic associations. We used an implicit learning task, which limits the use of explicit attentional control, to see whether the associations can be formed without attentional control. Results showed evidence for learning, which implies that explicit attentional control may not be necessary for forming paradigmatic associations. We also used the n-back task to examine whether the ability to maintain information is critical for forming paradigmatic associations. Results did not provide evidence for the relationship between the two. We discuss the results in terms of the core mechanisms that may enable the formation of higher-order associations

Impact of Covid-19 on the Visit of Pediatric Patients with Injuries to the Emergency Department in Korea

The total number of pediatric emergency department (PED) visitors has decreased worldwide since the coronavirus disease (COVID-19) outbreak. We hypothesized that this might also affect the number of PED visits due to injuries. Therefore, we investigated these changes in PED visits after the COVID-19 outbreak through a long-term multicenter observational study. We assessed the changes in the proportion of injured pediatric patients’ weekly visits and the trend in the rate changes since the COVID-19 epidemic began by segmented regression analysis. We also evaluated the weekly change in the distribution of detailed diagnostic codes among pediatric patients with injuries before and after the COVID-19 pandemic. The proportion of injury-related PED visits increased when COVID-19 was first confirmed in Korea. After the COVID-19 epidemic, the proportion of foreign body ingestions and fracture patients among all pediatric patients with injuries increased significantly every week. The changes in the proportion of injured pediatric patients after the COVID-19 outbreak may have been the result of social distancing to prevent the spread of the virus. The risk of pediatric infections decreased but the risk of injury remained. Therefore, parents should take precautions to prevent infectious diseases and be careful to prevent children’s injuries at home

Anticancer Activity of Marine Sponge Hyrtios sp. Extract in Human Colorectal Carcinoma RKO Cells with Different p53 Status

Drug development using marine bioresources is limited even though the ocean occupies about 70% of the earth and contains a large number of biological materials. From the screening test of the marine sponge extracts, we found Hyrtios sp. sponge collected from Chuuk island, Micronesia. In this study, the Hyrtios sp. extract was examined for anticancer activity against human colorectal carcinoma RKO cells that are wildtype for p53 and RKO-E6 that are p53 defective. The Hyrtios sp. extract dose-dependently inhibited viability in both cell lines. Multinucleation as an indication of mitotic catastrophe was also observed. Cytotoxicity tests gave significantly different results for RKO and RKO-E6 cells after 48 h exposure to Hyrtios sp. extract. In RKO cells treated with Hyrtios sp. extract, cell death occurred by induction of p53 and p21 proteins. In p53-defective RKO-E6 cells, Hyrtios sp. extract decreased expression of JNK protein and increased p21 protein. These results indicate that Hyrtios sp. extract induced apoptosis via different pathways depending on p53 status and could be a good natural product for developing new anticancer drugs

Impact of COVID-19 Pandemic on Children Visiting Emergency Department for Mental Illness: A Multicenter Database Analysis from Korea

We aimed to identify changes in the proportion of pediatric emergency department (PED) visits due to mental illness during the coronavirus disease 2019 (COVID-19) pandemic. This was a retrospective observational study of visits to the PED at six university hospitals from January 2017 to December 2020. We included children aged 5-17 years who were diagnosed with a mental illness. We used segmented regression analysis to identify the change in the proportion of patients with mental illness. A total of 845 patients were included in the analysis. After the first case of COVID-19 was reported in Korea, the number of PED visits significantly decreased by 560.8 patients per week (95% confidence interval (CI): -665.3 to -456.3, p &lt; 0.001). However, the proportion of patients with mental illness increased significantly, by 0.37% per week (95% CI: 0.04% to 0.70%, p = 0.03), at this time point. Subgroup analyses revealed that emotional disorders significantly increased by 0.06% per month (95% CI: 0.02% to 0.09%, p &lt; 0.001) during the pandemic. Our study revealed that an increased proportion of patients with mental illness visited the PED during the COVID-19 pandemic. Specifically, we identified that the proportion of emotional disorders continues to rise during this pandemic.N