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Emotional abuse mediated by negative automatic thoughts impacts functional connectivity during adolescence
No full textBackground: Emotional abuse during childhood and adolescence is thought to be associated with the brain; however, the neural mechanism underlying the cognitive process remains unknown. Therefore, we aimed to investigate the mediating effect of negative automatic thoughts on the relationship between emotional abuse and resting-state functional connectivity (rsFC) during adolescence. Method: Our community sample included 54 adolescents aged 13–17 years in the statistical analysis. Resting-state functional and structural magnetic resonance imaging (MRI) was performed, while emotional abuse and negative automatic thoughts were assessed using self-reported scales. A mediation analysis was used to assess the contributions of early traumatic events and negative automatic thoughts to resting functional connectivity. Result: Higher negative automatic thoughts were associated with lower connectivity in the context of greater emotional abuse (i.e., suppression effect). Thus, the relationships between emotional abuse and connectivity in the precuneus (pCun)-medial prefrontal cortex, parahippocampal cortex-extrastriate cortex, and temporal cortex-temporal pole were decreased by negative automatic thoughts. In contrast, functional connections in the pCun-pCun, pCun-precuneus/posterior cingulate cortex, and nucleus accumbens-somatomotor areas were strongly mediated when emotionally abused adolescents reported a high tendency for negative automatic thoughts. Conclusion: Negative automatic thoughts strengthened the relationship between emotional abuse and rsFC. These findings highlight the underlying cognitive processing of the traumatic event-neural system, supporting the use of cognitive therapy for post-traumatic symptoms
Trajectories of Wok Adjustment and Influencing Factors Among Newly Registered Nurses
Get PDFPurpose: This study explored the work adjustment trajectory and its predictors and characteristics among newly registered nurses. Methods: A total of 245 newly registered nurses working in a university hospital provided general baseline characteristics and completed a work adjustment questionnaire along with self-report measures of clinical competency, psychological capital, preceptor exchange, social support, and role conflict when they started working independently (baseline) and at 7 and 12 months after employment. Data were collected from July 2020 to August 2022. The collected data were subjected to a group-based trajectory model, χ2 test, F test, one-way ANOVA, and multiple logistic regression using SAS 9.4, and SPSS 25.0. Results: Group-based trajectory modeling classified three newly registered nurse groups: nurses with a high work adjustment level in all subscales from the beginning of employment (early adjustment group, 16.1%), nurses with a moderate level of adjustment from beginning to end (standard adjustment group, 60.6%), and nurses with a low level of work adjustment from early to mid-term, rising later (delayed adjustment group, 23.3%). Higher hope, optimism, and emotional support predicted early and standard adjustments. Conclusions: Based on the trajectory characteristics, newly registered nurses need to improve their work adjustment. The early and standard adjustment groups should continuously monitor their levels of work adjustment while monitoring their hopes, optimism, and emotional support. In particular, the delayed adjustment group required customized educational programs and strengthened peer support
Uveitis Risk After the First Dose of COVID-19 Vaccination Based on Uveitis History: Matched Cohort and Crossover Case Series Study
No full textPurpose: To investigate the risk of noninfectious uveitis following the first dose of coronavirus disease 2019 (COVID-19) vaccination based on the uveitis history. Design: Retrospective matched cohort and crossover case series study. Methods: A random sample of 7 917 457 individuals who received COVID-19 vaccine between January 2021 and March 2022 in Korea, and had no recorded history of COVID-19 were categorized into the control and uveitis groups based on their uveitis history. After performing 3:1 propensity score matching, we assessed the cumulative incidence and risk of noninfectious uveitis in the 180 days after COVID-19 vaccination. Additionally, we performed a crossover case series analysis to compare the pre- and postvaccination incidence rate ratios (IRRs) of uveitis in individuals with and without a history of uveitis. Results: In the matched cohort analysis, uveitis group had a significantly higher cumulative incidence of uveitis (15.4%) than control group (0.10%). The uveitis group exhibited increased risks of all uveitis types, anterior, and nonanterior uveitis in the first 60 days (hazard ratio [HR]: 169, 158, and 253, respectively) and in days 61 to 180 (HR: 166, 164, and 143, respectively) after vaccination. In the crossover case series analysis, uveitis occurred with relatively equal frequency in 20-day intervals during the 180 days before and after vaccination, regardless of uveitis history. For uveitis group, the adjusted IRRs for early and late postvaccination events were 0.92 (95% CI, 0.88-0.96) and 0.83 (95% CI, 0.80-0.85), respectively. Conclusions: COVID-19 vaccination did not increase the risk of uveitis, regardless of uveitis history
Affective dysfunction mediates the link between neuroimmune markers and the default mode network functional connectivity, and the somatic symptoms in somatic symptom disorder
No full textObjective: Somatic symptom disorder (SSD) is characterized by physical symptoms and associated functional impairments that are often comorbid with depression and anxiety disorders. In this study, we explored relationships between affective symptoms and the functional connectivity of the default mode network (DMN) in SSD patients, as well as the impact of peripheral inflammation. We employed mediation analyses to investigate the potential pathways between these factors. Methods: We recruited a total of 119 individuals (74 unmedicated SSD patients and 45 healthy controls), who were subjected to comprehensive psychiatric and clinical evaluations, blood tests, and resting-state functional magnetic resonance imaging scanning. We assessed neuroimmune markers (interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), tryptophan, serotonin, and 5-hydroxyindoleacetic acid (5-HIAA)), clinical indicators of somatic symptoms, depression, anxiety, anger, alexithymia, and functional connectivity (FC) within the DMN regions. Data were analyzed using correlation and mediation analysis, with a focus on exploring potential relations between clinical symptoms, blood indices, and DMN FCs. Results: Patients with SSD had higher clinical scores as well as IL-6 and TNF-α levels compared with those in the control group (P < 0.05). The SSD group exhibited lower FC strength between the left inferior parietal lobule and left prefrontal cortex (Pfalse discovery rate (FDR) < 0.05). Exploratory correlation analysis revealed that somatic symptom scores were positively correlated with affective symptom scores, negatively correlated with the FC strength between the intra prefrontal cortex regions, and correlated with levels of IL-6, TNF- α, and tryptophan (uncorrected P < 0.01). Mediation analysis showed that levels of anxiety and trait anger significantly mediated the relations between DMN FC strength and somatic symptoms. In addition, the DMN FC mediated the level of trait anger with respect to somatic symptoms (all PFDR < 0.05). The levels of depression and trait anger exhibited significant mediating effects as suppressors of the relations between the level of 5-HIAA and somatic symptom score (all PFDR < 0.05). Further, the level of 5-HIAA had a mediating effect as a suppressor on the relation between DMN FC and state anger. Meanwhile, the levels of hs-CRP and IL-6 had full mediating effects as suppressors when explaining the relations of DMN FC strengths with the level of depression (all PFDR < 0.05). The patterns of valid mediation pathways were different in the control group. Conclusions: Affective symptoms may indirectly mediate the associations between DMN connectivity, somatic symptoms, and neuroimmune markers. Inflammatory markers may also mediate the impact of DMN connectivity on affective symptoms. These results emphasize the importance of affective dysregulation in understanding the mechanisms of SSD and have potential implications for the development of tailored therapeutic approaches for SSD patients with affective symptoms. Furthermore, in SSD research using DMN FC or neuroimmune markers, considering and incorporating such mediating effects of affective symptoms suggests the possibility of more accurate prediction and explanation
Survival pattern of metastatic renal cell carcinoma patients according to WHO/ISUP grade: a long-term multi-institutional study
Get PDFThe World Health Organization/International Society of Urological Pathology (WHO/ISUP) grading of renal cell carcinoma (RCC) is classified from grade 1–4, regardless of subtype. The National Comprehensive Cancer Network (NCCN) guidelines (2022) state that if there is an adverse pathological feature, such as grade 3 or higher RCC in stage 1 patients, more rigorous follow-up imaging is recommended. However, the RCC guidelines do not provide specific treatment or follow-up policies by tumor grade. Therefore, this study attempted to find out whether tumor grade affects survival rates in patients with metastatic RCC. The Korean Renal Cancer Study Group (KRoCS) database includes 3108 patients diagnosed with metastatic RCC between September 1992 and February 2017, with treatment methods, progression, and survival data collected from 11 tertiary hospitals. To obtain information on survival rates or causes of death, we utilized the Korea National Statistical Office database and institutional medical records. Data were accessed for research purpose on June, 2023. We then reviewed these sources to gather comprehensive and reliable data on the outcomes of our study cohort. This database was retrospectively analyzed, and out of 3108 metastatic RCC patients, 911 had been identified as WHO/ISUP grade. Grades were classified into either a low-grade (WHO/ISUP grade 1–2) or a high-grade group (WHO/ISUP grade 3–4). The patients were then analyzed related to progression and overall survival (OS). In metastatic clear cell RCC patients, the 1-year OS rate was 69.4% and the median OS was 17.0 months (15.5–18.5) followed up to 203.6 months. When comparing the patient groups, 119 low-grade and 873 high-grade cases were identified. No baseline difference was observed between the two groups, except that the high-grade group had a higher ECOG 1 ratio of 50.4% compared with 34.5% for the low-grade group (p = 0.009). There was a significant difference in OS between high-grade and low-grade groups. OS was 16.0 months (14.6–17.4) in the high-grade group and 28.0 months (21.1–34.9) in the low-grade group (p < 0.001). However, there was no difference in progression-free survival (PFS) rates with 9.0 months (8.0–10.0) for the high-grade group and 10.0 months (6.8–13.2) for the low-grade group (p = 0.377) in first-line treatment. In multivariable analysis, WHO/ISUP grade was a risk factor (HR = 1.511[1.135–2.013], p = 0.005) that influenced the OS. In conclusion, WHO/ISUP grade is a major data source that can be used as a ubiquitous marker of metastatic RCC in pre-IO era. Depending on whether the RCC is high or low grade, the follow-up schedule will need to be tailored according to grade, with higher-grade patients needing more active treatment as it can not only affect the OS in the previously known localized/locoregional recurrence but also the metastatic RCC patient
Real-time Histological Evaluation of Gastric Cancer Tissue by Using a Confocal Laser Endomicroscopic System
Get PDFBackground/Aim: The need for instant histological evaluation of fresh tissue, especially in cancer treatment, remains paramount. The conventional frozen section technique has inherent limitations, prompting the exploration of alternative methods. A recently developed confocal laser endomicroscopic system provides real-time imaging of the tissue without the need for glass slide preparation. Herein, we evaluated its applicability in the histologic evaluation of gastric cancer tissues. Materials and Methods: A confocal laser endomicroscopic system (CLES) with a Lissajous pattern laser scanning, was developed. Fourteen fresh gastric cancer tissues and the same number of normal gastric tissues were obtained from advanced gastric cancer patients. Fluorescein sodium was used for staining. Five pathologists interpreted 100 endomicroscopic images and decided their histologic location and the presence of cancer. Following the review of matched hematoxylin and eosin (H&E) slides, their performance was evaluated with another 100 images. Results: CLES images mirrored gastric tissue histology. Pathologists were able to detect the histologic location of the images with 65.7% accuracy and differentiate cancer tissue from normal with 74.7% accuracy. The sensitivity and specificity of cancer detection were 71.9% and 76.1%. Following the review of matched H&E images, the accuracy of identifying the histologic location was increased to 92.8% (p<0.0001), and that of detecting cancer tissue was also increased to 90.9% (p<0.001). The sensitivity and specificity of cancer detection were enhanced to 89.1% and 93.2% (p<0.0001). Conclusion: High-quality histological images were immediately acquired by the CLES. The operator training enabled the accurate detection of cancer and histologic location raising its potential applicability as a real-time tissue imaging modality
Impact of PIK3CA and cell cycle pathway genetic alterations on durvalumab efficacy in patients with head and neck squamous cell carcinoma: Post hoc analysis of TRIUMPH study
No full textObjectives: This study aimed to investigate whether genetic alterations in PI3KCA and the cell cycle pathways influence the efficacy of durvalumab, an immune checkpoint inhibitor, in patients with head and neck squamous cell carcinoma (HNSCC) who had previously failed platinum-based treatment. Materials and methods: We obtained data from a phase II umbrella trial of patients with HNSCC who failed platinum-based treatment (TRIUMPH, NCT03292250). Patients receiving durvalumab treatment comprised those with PIK3CA alterations (Group A), those with cell cycle pathway alterations such as CDKN2A (Group B), and those with no druggable genetic alterations (Group C). We analyzed the overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) in each group and evaluated the potential predictive factors for durvalumab. Results: We analyzed the data of 87 patients: 18, 12, and 57 in groups A, B, and C, respectively. The ORRs were 27.8 %, 8.3 %, and 15.8 % in Groups A, B, and C, respectively (P = 0.329), and the median PFS for each group was 2.3, 1.6, and 1.7 months, respectively, with no significant differences between the groups (P = 0.24). Notably, patients with lower neutrophil–lymphocyte ratio (NLR) (≤5.8) had longer PFS (median, 2.8 vs 1.6 months, P < 0.001), while those with lower platelet-lymphocyte ratio (PLR) (≤491.2) exhibited longer PFS (median, 1.8 vs 1.2 months, P < 0.001). Conclusion: Durvalumab's efficacy was similar, irrespective of the presence of PIK3CA or cell cycle pathway genetic alterations in patients with platinum-resistant HNSCC. The NLR and PLR may be promising predictive biomarkers
SIAH1 modulates antiviral immune responses by targeting deubiquitinase USP19
Get PDFTight control of the type I interferon (IFN) signaling pathway is critical for maintaining host innate immune responses, and the ubiquitination and deubiquitination of signaling molecules are essential for signal transduction. Deubiquitinase ubiquitin-specific protein 19 (USP19) is known to be involved in deubiquitinating Beclin1, TRAF3, and TRIF for downregulation of the type I IFN signaling. Here, we show that SIAH1, a cellular E3 ubiquitin ligase that is involved in multicellular pathway, is a potent positive regulator of virus-mediated type I IFN signaling that maintains homeostasis within the antiviral immune response by targeting USP19. In the early stages of virus infection, stabilized SIAH1 directly interacts with the USP19 and simultaneously mediates K27-linked ubiquitination of 489, 490, and 610 residues of USP19 for proteasomal degradation. Additionally, we found that USP19 specifically interacts with MAVS and deubiquitinates K63-linked ubiquitinated MAVS for negative regulation of type I IFN signaling. Ultimately, we identified that SIAH1-mediated degradation of USP19 reversed USP19-mediated deubiquitination of MAVS, Beclin1, TRAF3, and TRIF, resulting in the activation of antiviral immune responses. Taken together, these findings provide new insights into the molecular mechanism of USP19 and SIAH1, and suggest a critical role of SIAH1 in antiviral immune response and homeostasis
Risk Factors for Infertility in Korean Women
Get PDFBACKGROUND: Female infertility is a crucial problem with significant implications for individuals and society. In this study, we explore risk factors for infertility in Korean women. METHODS: A total of 986 female patients who visited six major infertility clinics in Korea were recruited from April to December 2014. Fertile age-matched controls were selected from two nationwide survey study participants. Conditional logistic regression after age-matching was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of each risk factor for infertility. RESULTS: Women with a body mass index (BMI) < 18.5 kg/m² had 1.35 times higher odds of infertility (OR, 1.35; 95% CI, 1.03-1.77), while those with a BMI ≥ 25.0 kg/m² had even higher odds (OR, 2.06; 95% CI, 1.61-2.64) compared to women with a normal BMI (18.5 kg/m² ≤ BMI < 25 kg/m²). Ever-smokers exhibited 4.94 times higher odds of infertility compared to never-smokers (95% CI, 3.45-8.85). Concerning alcohol consumption, women who consumed ≥ 7 glasses at a time showed 3.13 times significantly higher odds of infertility than those who consumed ≤ 4 glasses at a time (95% CI, 1.79-5.48). Lastly, women with thyroid disease demonstrated 1.44 times higher odds of infertility compared to women without thyroid disease (95% CI, 1.00-2.08). CONCLUSION: Female infertility in Korea was associated with underweight, obesity, smoking, alcohol consumption, and thyroid disease
