Circadian Rhythms and Depression in Adolescents: A Comparative Analysis of First Episode and Recurrent-Episode Groups.

Circadian rhythm disruptions are a hallmark feature of mood disorders. Patients experiencing acute depressive episodes report noticeable changes in their sleep-wake cycles. This research explains the association between depression and various circadian rhythm metrics, explicitly focusing on adolescents diagnosed with depressive disorders. Adolescence is a critical period marked by significant physiological and psychological changes, making it imperative to understand how mood disorders manifest during this phase. However, there have been minimal specific studies in pediatric populations to determine whether circadian rhythm changes differ between adolescents with first and multiple-recurrent depressive episodes. Our study involved a group of 61 adolescents aged between 13 and 18. We performed a cross-sectional study of a clinical population of patients presenting to a child and adolescent psychiatry clinic diagnosed with depression. Participants were asked to complete self-report evaluations using several tools: the Korean version of the Biological Rhythms Interview of Assessment in Neuropsychiatry (K-BRIAN), the Korean Translation of Composite Scale to Measure Morningness-Eveningness (KtCS), and the Seasonal Pattern Assessment Questionnaire (SPAQ). Tools such as the Children's Depression Inventory (CDI), State-Trait Anxiety Inventory (STAI), and K-Mood Disorder Questionnaire (K-MDQ) were employed for the assessment of clinical characteristics of depression. Based on the frequency of their depressive episodes, participants were bifurcated into two distinct groups: those experiencing their first episode (n = 22, mean age: 15.09 ± 1.44 years) and those with recurrent episodes (n = 39, mean age: 15.95 ± 1.26 years). At first, the two groups' data revealed no significant differences regarding mood or circadian rhythm metrics (CDI: first episode 26.18 ± 10.54 and recurrent episode 25.90 ± 10.59, STAI-S: first episode 56.91 ± 12.12 and recurrent episode 57.49 ± 11.93, STAI-T: first episode 60.36 ± 11.63 and recurrent episode 59.09 ± 12.10, SPAQ-total: first episode 6.59 ± 4.86 and recurrent episode 6.77 ± 5.23, KtCS: first episode 30.32 ± 5.83 and recurrent episode 28.13 ± 7.36). However, we observed significant correlations between circadian rhythm disruptions and depression scales (CDI with SPAQ-weight (r = 0.26), KtCS (r = -0.48), K-BRIAN-sleep (r = 0.58), K-BRIAN-activity (r = 0.64), K-BRIAN-social (r = 0.71), and K-BRIAN-eating (r = 0.40)). These correlations were especially pronounced in the recurrent episode group, suggesting that with the progression and chronicity of depression, the relationship between circadian rhythms and depression becomes more intertwined and evident. In conclusion, especially in adolescents, as the severity and chronicity of depression increase, the interplay between circadian rhythms and mood disorders becomes more pronounced, warranting further research and clinical attention.

Impact of the Coronavirus Disease Pandemic on Mental Health Among School Students in Korea During the COVID-19 Pandemic.

Objectives: The coronavirus disease (COVID-19) pandemic has had various effects on mankind, especially children and adolescents. Because children and adolescents spend a lot of time at school, COVID-19 has had a great impact on school mental health. In this study, we investigated the effect of prolonged COVID-19 on school mental health. Methods: We prepared self-report questionnaires for depression (Children's Depression Inventory, CDI), anxiety (Korean version of the Penn State Worry Questionnaire for Children; Generalized Anxiety Disorder-7, GAD-7), and post-traumatic stress (Primary Care Post-traumatic Stress Disorder, PC-PTSD) for administering to students aged between 7 and 18 years, recruited by a COVID-19 psychological prevention support group in the Gwangmyeong Mental Health Welfare Center for 2 years, in 2020 and 2021. Results: For children aged 7-12 years, there was no significant difference between the years 2020 and 2021 in the assessment of depression, anxiety, and post-traumatic stress. Conversely, for adolescents aged 13-18 years, there was a significant increase in the scale scores (CDI, PC-PTSD, and GAD-7). Conclusion: Prolonged COVID-19 might have had a significant impact on the mental health of adolescents who spent a lot of time at school. When comparing the years 2020 and 2021, middle and high school students were more affected by COVID-19 than elementary school students.

EMR1/ADGRE1 Expression in Cancer Cells Upregulated by Tumor-Associated Macrophages Is Related to Poor Prognosis in Colorectal Cancer.

EMR1, a member of the adhesion G protein-coupled receptor family (ADGRE1), is a macrophage marker that is abnormally expressed in cancer cells. However, its clinical significance in colorectal cancer (CRC) is not well-known. In this investigation, EMR1 expression in tumor cells (EMR1-TC) was found in 91 (22.8%) of the 399 CRC samples tested by immunohistochemical staining and showed a significant relationship with lymph node metastasis. Furthermore, EMR1-TC was significantly associated with CD68+ CD163+ tumor-associated macrophages (TAMs), and CRC with a high combined EMR1-TC+CD68+CD163+ score showed worse recurrence-free survival prognosis. In an in vitro co-culture assay of colon cancer cells with myeloid cells, we found that EMR1 expression significantly upregulated in cancer cells was induced by macrophages. In addition, there was increased expression of M2 markers (CD163 and interleukin-6 & 10) in myeloid portion, while that of M1 markers (CD86 and iNOS) remained unchanged. Accordingly, upon treatment with M2 macrophage polarization inhibitors (O-ATP, trametinib, bardoxolone methyl), EMR1 expression reduced significantly, along with M2 markers (CD163 and interleukin-6 & 10). In conclusion, EMR1-TC was a high-risk factor for lymph node metastasis and correlated with poor recurrence free survival, particularly in patients with TAM-rich CRC. Furthermore, EMR1 expression in colon cancer cells may be related to M2 macrophage polarization and vice versa.

Protective Effects of Spirulina maxima against Blue Light-Induced Retinal Damages in A2E-Laden ARPE-19 Cells and Balb/c Mice.

Age-related macular degeneration (AMD) is a significant visual impairment in older people, and there is no treatment for dry AMD. Spirulina maxima (S. maxima), a cyanobacterium, has inhibitory effects against oxidative stress. However, the protective effects of S. maxima and its underlying mechanisms on blue light (BL)-caused macular degeneration are unknown. We aimed to investigate the protective effects of S. maxima on blue light-caused retinal damage and demonstrate its underlying mechanisms in human retinal pigment epithelial (ARPE-19) cells and Balb/c retinas. Additionally, the active component of S. maxima was examined in the RPE cells. In vitro, S. maxima decreased BL-induced RPE cell death by inhibiting reactive oxygen species (ROS) production. S. maxima inhibited BL-induced inflammation via regulating the NF-κB pathway, inflammatory-related gene expression, and the apoptosis pathway in RPE cells. In vivo, administration of S. maxima inhibited BL-induced retinal degeneration by restoring the thicknesses of whole retina, ONL (outer nuclear layer), INL (inner nuclear layer), and PL (photoreceptor layer) by BL exposure. Phycocyanin exerted protective effects in the pre-and post-treatment system. Therefore, S. maxima could be a potential nutraceutical approach to intercept the patho-physiological processes leading to dry AMD and advancement to wet AMD. Moreover, phycocyanin was a major active compound of S. maxima. These findings need to be investigated in human studies, particularly through a clinical trial.

Impact of the Coronavirus Disease Pandemic on Mental Health among Local Residents in Korea: a Cross Sectional Study.

BACKGROUND: This study aimed to evaluate traumatic stress and mental health problems associated with the prolonged coronavirus disease pandemic and to determine the differences across different age groups. METHODS: A total of 1,151 individuals who visited Gwangmyeong City Mental Health Welfare Center, South Korea, or accessed the website from September 1 to December 31, 2020, were included in the study. Mental health problems such as traumatic stress (Primary Care Posttraumatic Stress Disorder Screen for the Diagnostic and Statistical Manual of Mental Disorder-5); depression (Patient Health Questionnaire-9 and Children's Depression Inventory); anxiety (Generalized Anxiety Disorder-7 and Penn State Worry Questionnaire for Children); suicide risk (P4 Screener); and demographic information were evaluated. The participants were divided into three groups based on age group: children and adolescents, adults, and the elderly. RESULTS: The results showed that 24.7%, 20.9%, 16.8%, and 20.5% of the participants were at high-risk for traumatic stress, depression, anxiety, and suicide, respectively. The difference in the proportion of high-risk groups by age of all participants was significant for traumatic stress, depression, anxiety, and suicide risk. In particular, the percentage of high-risk groups in all areas was the highest in the adult group. Also, in most areas, the ratio of the high-risk groups for children and adolescent group was the lowest, but the suicide risk-related ratio was not (adolescent group: 20.9%, adult group: 25%, elderly group 9.3%). CONCLUSION: These results suggest that there is a need for continued interest in the mental health of the general population even after the initial period of coronavirus disease. Additionally, this study may be helpful when considering the resilience or risk factors of mental health in a prolonged disaster situation.

Comparison of FFPE histological versus LBP cytological samples for HPV detection and typing in cervical cancer.

Human papillomavirus (HPV) infection is closely associated with cervical cancer. This study analyzed HPV genotype prevalence in 75 cases of formalin-fixed paraffin embedded (FFPE) tissue samples from patients diagnosed with cervical cancer. Genotype prevalence was assessed using Reverse Blot Assay (REBA) and quantitative polymerase chain reaction (qPCR), which target the HPV L1 and HPV E6/E7 genes, respectively. HPV DNA chip tests were also performed using liquid based preparation (LBP) cytological samples from the same patients who provided the FFPE histological samples. We observed a slight difference in HPV genotype distribution as assessed by DNA chip versus REBA. One possible explanation for this difference is that normal regions could be mixed with lesion regions when cytological samples are extracted from each patient with cancer. For the detection of moderate dysplasia, the main target of diagnosis, this difference is anticipated to be greater. We also made several unexpected observations. For example, HPV multi-infection was not detected. Moreover, the rate of HPV positivity varied radically depending on the cancer origin, e.g. squamous cell carcinoma versus adenocarcinoma. Our results imply that it is important to determine whether cytological specimens are suitable for HPV genotyping analysis and cervical cancer diagnosis. Future research on the mechanisms underlying cervical cancer pathogenesis is also necessary.

Diagnostic performance of HPV E6/E7, hTERT, and Ki67 mRNA RT-qPCR assays on formalin-fixed paraffin-embedded cervical tissue specimens from women with cervical cancer.

Human papillomavirus (HPV) is a major cause of cervical cancer, which is the third most common cancer in women. Human telomerase reverse transcriptase (hTERT) and Ki67 are tumor cell markers indicating cancer cell proliferation in cancer patients, and activation of hTERT and Ki67 leads to progressive cervical carcinogenesis. In the present study, we evaluated the CervicGen HPVE6/E7 mRNA RT-qDx assay, which detects 16 HPV high-risk (HR) genotypes (HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68 and 69), and the CervicGen hTERT and Ki67 mRNA RT-qDx assay using 117 formalin-fixed paraffin-embedded (FFPE) cervical cancer tissue samples. The diagnostic validity of the CervicGen HPV RT-qDx assay for detecting histologically proven prevalent squamous cell carcinoma (SCC) was 94% sensitivity, 100% specificity, 77.8% positive predictive value (PPV), and 78.9% negative predictive value (NPV). The most common HPV genotypes detected in FFPE cervical cancer tissue samples were HPV 16 (56%) and HPV 18 (10%). The positivity rate of hTERT and Ki67 mRNA expressions in FFPE cervical cancer tissue samples on RT-qPCR was 65% and 93% respectively. Moreover, the positivity rates were 92% for a combination of HPV E6/E7 and hTERT mRNA expressions, 97% for HPV E6/E7 and Ki67 mRNA expressions, and 99% (99/100) for the combination of HPV E6/E7, hTERT, and Ki67 mRNA expressions. These data showed that SSC FFPE cervical cancer tissue samples correlated more strongly with high Ki67 mRNA expressions than with hTERT mRNA expressions. Notably, hTERT and Ki67 mRNA expression level was increased in high-grade cervical lesions, but was very low in normal samples. Our findings suggest that the combination of HPV E6/E7, hTERT, and Ki67 mRNA expression levels could be used in a complementary manner in diagnosing high-grade cervical lesions. Further studies are required to evaluate these assays as a useful predictive tool for screening low-grade cervical lesions.