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BACKGROUND: We aimed to investigate the association between a diagnosis of untreated unruptured intracranial aneurysms (UIAs) and the development of mental illness. METHODS: This retrospective, propensity-score-matched cohort study was based on the nationwide South Korean database. The UIA diagnosis group included participants newly diagnosed with UIA between 2011 and 2019. For a well-matched control group, patients diagnosed with an acute upper respiratory infection but without UIA during the same period were selected through 1:4 matching based on propensity scores, which were calculated using age, sex, economic status, and comorbidities. The study's outcome measure encompassed the incidence of mental illnesses over a 10-year period, using International Classification of Diseases-Tenth Revision codes for anxiety, stress, depressive, bipolar, and eating disorders, insomnia, and alcohol or drug misuse. RESULTS: After propensity score matching, 85â 438 participants with untreated UIAs (50.75% male; average age, 56.41 [±13.82] years; follow-up, 4.21 [±2.56] years) and 331â 123 controls (49.44% males; average age, 56.69 [±12.92] years; follow-up, 7.48 [±2.12] years) were compared. Incidence rate of mental illness was higher in the UIA group (113.07 versus 90.41 per 1000 person-years; hazard ratio, 1.104 [95% CI, 1.089-1.119]). The risk of mental illness varied slightly by sex (males: hazard ratio, 1.131 [95% CI, 1.108-1.155]; females: hazard ratio, 1.082 [95% CI, 1.063-1.103]). Hazard ratios showed a U-shaped relationship with age, peaking in younger age groups, decreasing in middle-aged groups, and slightly increasing in older age groups, especially in patients with severe mental illness receiving psychotherapy. CONCLUSIONS: Our findings indicate a higher risk of mental illness in patients with UIA diagnosis in specific demographic groups, suggesting a possible psychological burden associated with UIAs. Clinicians treating cerebral aneurysms should be aware that the psychological burden caused by the diagnosis of UIA itself could contribute to mental illness and strive to provide comprehensive care for these patients.
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Aneurisma Intracraneal , Trastornos Mentales , Humanos , Aneurisma Intracraneal/epidemiología , Masculino , Femenino , Persona de Mediana Edad , Trastornos Mentales/epidemiología , Anciano , República de Corea/epidemiología , Adulto , Estudios Retrospectivos , Puntaje de Propensión , Estudios de Cohortes , Incidencia , Factores de RiesgoRESUMEN
Importance: The persistent stigma associated with mental health conditions is a major challenge worldwide. Celebrities may improve this by openly discussing their own mental health issues, potentially influencing public attitudes and encouraging individuals to seek treatment for these conditions. Objective: To evaluate the impact of celebrity mental health disclosures on the incidence and prevalence of panic disorder diagnosis in South Korea. Design, Setting, and Participants: This cohort study included the entire South Korean population from January 2004 to December 2021, as reflected in the National Health Insurance Service data. Analysis was conducted from May 2022 through January 2024. Exposure: Time periods analyzed included the timeframe before (from January 2004 to December 2010) and after the public disclosures of panic disorder by 3 high-profile Korean celebrities between December 2010 and January 2012 (from January 2011 to December 2021). Main Outcomes and Measures: Monthly incidence and prevalence of panic disorder, defined by the presence of a clinical diagnosis of the condition. Trends were assessed using interrupted time series analysis with autoregressive integrated moving average models. To assess public interest in panic disorder, trends in search data were analyzed, examining the association between the timing of increased searches and changes in the incidence and prevalence of panic disorder. Data on obsessive-compulsive disorder (OCD) were included as a control. Results: The study covered the entire population of South Korea, including 48â¯559â¯946 individuals in January 2004 and 52â¯593â¯886 individuals in December 2021. Before 2011, the mean (SD) annual prevalence of panic disorder was stable at 560 (140) persons per 100â¯000 persons per year. The celebrity disclosure in December 2010 was associated with higher monthly incidence rates of panic disorder, as measured by insurance claims data, changes that were observed in both the level (5.8 persons; 95% CI, 2.2-9.5 persons) and slope (0.78 persons per month; 95% CI, 0.19-1.40 persons per month) per 100â¯000 persons. By 2021, the observed annual prevalence per 100â¯000 persons reached 7530 persons, an increase of 775.6% compared with the 860 persons (95% CI, 330-1400 persons) estimated if the disclosures had not occurred. Internet searches anticipated changes in monthly prevalence with a lag of 2 or 3 months (F = 4.26, P = .02 and F = 3.11, P = .03, respectively). The celebrity disclosures had no significant association with the incidence or prevalence of OCD. Conclusions and Relevance: In this observational cohort study, celebrity disclosure of mental health conditions was associated with a sustained reduction in stigma, as reflected in increased help-seeking behavior for the condition over more than a decade. This underscores the influential role celebrities can play in shaping public health perceptions and behaviors, offering valuable insights for the development of future mental health policies and public awareness campaigns.
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Personajes , Trastorno de Pánico , Humanos , República de Corea/epidemiología , Trastorno de Pánico/epidemiología , Incidencia , Masculino , Femenino , Adulto , Persona de Mediana Edad , Prevalencia , Revelación/estadística & datos numéricos , Estudios de Cohortes , Estigma SocialRESUMEN
BACKGROUND: This study aimed to understand the health-related quality of life (HRQoL) of patients with aneurysmal subarachnoid hemorrhage (aSAH) classified as having "good outcomes" and determine associated sociodemographic, psychological, and clinical factors. METHODS: Participants were 86 patients with aSAH with modified Rankin Scale (mRS) scores of 0-2 in our hospital between February 2003 and April 2014. Participants completed self-report questionnaires examining sociodemographic characteristics and the following self-rating scales: the hospital anxiety and depression scale, Pittsburgh sleep quality index, and EuroQoL-5 Dimension Index (EQ-5D). Further, we retrospectively reviewed clinical data from medical records and radiologic images. Average EQ-5D scores for each variable were compared using Student's t-test and analysis of variance. Correlations between EQ-5D and continuous variables were examined using Pearson correlation analysis. Factors associated with EQ-5D were then examined using univariate and stepwise multivariate analyses through simple and multiple regression. RESULTS: The mean age of the 86 participants was 56.87 ± 10.28 years (range: 29-79 years), while the mean EQ-5D value was 0.738 ± 0.169. There were 54 women (62.8 %) and 33 men (37.2 %). The participants had depressive symptoms (30.2 %), anxiety (10.5 %), and sleep problems (51.2 %). Regarding sociodemographic variables, educational level (p = 0.017) and monthly income (p = 0.037) were positively correlated with HRQoL. Depressive symptoms (r = -0.505, p < 0.001), anxiety (r = -0.498, p < 0.001), sleep problems (r = -0.265, p = 017), and mRS (r = -0.352, p = 0.001) were negatively correlated with HRQoL. Depressive symptoms, diabetes mellitus, and past psychiatric history explained 48.8 % of the variance in HRQoL in good outcome aSAH according to stepwise multiple regression analysis. CONCLUSIONS: Patients with good outcome aSAH had low EQ-5D values, which were negatively correlated with depressive symptoms, anxiety, and sleep problems. In addition, HRQoL in good outcome aSAH is associated with depressive symptoms, diabetes mellitus, and past psychiatric disease history. Depressive symptoms, anxiety, and sleep problems are frequent in patients with good outcome aSAH, and mediation of these factors may help improve HRQoL.
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Diabetes Mellitus , Trastornos del Sueño-Vigilia , Hemorragia Subaracnoidea , Masculino , Humanos , Femenino , Adulto , Persona de Mediana Edad , Anciano , Calidad de Vida/psicología , Hemorragia Subaracnoidea/complicaciones , Hemorragia Subaracnoidea/psicología , Depresión/diagnóstico , Estudios Retrospectivos , Encuestas y Cuestionarios , Trastornos del Sueño-Vigilia/etiología , Estado de SaludRESUMEN
TRIC-A and TRIC-B proteins form homotrimeric cation-permeable channels in the endoplasmic reticulum (ER) and nuclear membranes and are thought to contribute to counterionic flux coupled with store Ca2+ release in various cell types. Serious mutations in the TRIC-B (also referred to as TMEM38B) locus cause autosomal recessive osteogenesis imperfecta (OI), which is characterized by insufficient bone mineralization. We have reported that Tric-b-knockout mice can be used as an OI model; Tric-b deficiency deranges ER Ca2+ handling and thus reduces extracellular matrix (ECM) synthesis in osteoblasts, leading to poor mineralization. Here we report irregular cell death and insufficient ECM in long-bone growth plates from Tric-b-knockout embryos. In the knockout growth plate chondrocytes, excess pro-collagen fibers were occasionally accumulated in severely dilated ER elements. Of the major ER stress pathways, activated PERK/eIF2α (PKR-like ER kinase/ eukaryotic initiation factor 2α) signaling seemed to inordinately alter gene expression to induce apoptosis-related proteins including CHOP (CCAAT/enhancer binding protein homologous protein) and caspase 12 in the knockout chondrocytes. Ca2+ imaging detected aberrant Ca2+ handling in the knockout chondrocytes; ER Ca2+ release was impaired, while cytoplasmic Ca2+ level was elevated. Our observations suggest that Tric-b deficiency directs growth plate chondrocytes to pro-apoptotic states by compromising cellular Ca2+-handling and exacerbating ER stress response, leading to impaired ECM synthesis and accidental cell death.
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Retículo Endoplásmico , Placa de Crecimiento , Animales , Ratones , Placa de Crecimiento/metabolismo , Ratones Noqueados , Muerte Celular , Retículo Endoplásmico/metabolismo , Transducción de Señal , Estrés del Retículo Endoplásmico/genética , Canales Iónicos/metabolismoRESUMEN
Preterm birth (PTB), a pregnancy-related disease, is defined as a birth before 37 weeks of gestation. It is a major cause of maternal mortality and morbidity worldwide, and its incidence rate is steadily increasing. Various genetic factors can contribute to the etiology of PTB. Vascular endothelial growth factor A (VEGFA) gene is an important angiogenic gene and its polymorphisms have been reported to be associated with PTB development. Therefore, we conducted a case-control study to evaluate the association between VEGFA rs699947, rs2010963, and rs3025039 polymorphisms and PTB in Korean women. A total of 271 subjects (116 patients with PTB and 155 women at ≥38 weeks of gestation) were analyzed in this study. The genotyping of VEGFA gene polymorphisms was performed using polymerase chain reaction- restriction fragment length polymorphism. No significant association between the patients with PTB and the control groups was confirmed. In the combination analysis, we found a significant association between PTB and VEGFA rs699947 CC-rs2010963 GG-rs3025039 CC combination (odds ratio, 3.77; 95% confidence interval, 1.091 to 13.032; p = 0.031). The VEGFA rs699947, rs2010963, and rs3025039 polymorphisms might have no genetic association with the pathogenesis of PTB in Korean women. However, the combination analysis indicates the possibility that VEGFA acts in PTB pathophysiology. Therefore, larger sample sets and replication studies are required to further elucidate our findings.
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Drought is one of the most stressful environments limiting crop growth and yield throughout the world. Therefore, most efforts have been made to document drought-derived genetic and physiological responses and to find better ways to improve drought tolerance. The interaction among them is unclear and/or less investigated. Therefore, the current study is to find a clue of metabolic connectivity among them in rice root experiencing different levels of drought condition. We selected 19 genes directly involved in abscisic acid (ABA) metabolism (6), suberization (6), and aquaporins (AQPs) activity (7) and analyzed the relatively quantitative gene expression using qRT-PCR from rice roots. In addition, we also analyzed proline, chlorophyll, and fatty acids and observed cross-sectional root structure (aerenchyma) and suberin lamella deposition in the endodermis. All drought conditions resulted in an obvious development of aerenchyma and two- to fourfold greater accumulation of proline. The limited water supply (-1.0 and -1.5 MPa) significantly increased gene expression (ABA metabolism, suberization, and AQPs) and developed greater layer of suberin lamella in root endodermis. In addition, the ratio of the unsaturated to the saturated fatty acids was increased, which could be considered as an adjusted cell permeability. Interestingly, these metabolic adaptations were an exception with a severe drought condition (hygroscopic coefficient, -3.1 MPa). Accordingly, we concluded that the drought-tolerant mechanism in rice roots is sophisticatedly regulated until permanent wilting point (-1.5 MPa), and ABA metabolism, suberization, and AQPs activity might be independent and/or concurrent process as a survival strategy against drought.
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BACKGROUND: With advance of next-generation sequencing (NGS) techniques, the need for mitochondrial DNA analysis is increasing not only in the forensic area, but also in medical fields. METHODS: Two commercial programs, Converge Software (CS) and Torrent Variant Caller for variant calling of NGS data, were compared with a considerable amount of sequence data of 50 samples with a homogeneous ethnicity. RESULTS: About 2,300 variants were identified and the two programs showed about 90% of consistency. CS, a dedicated analysis program for mitochondrial DNA, showed some advantages for forensic use. By additional visual inspection, several causes of discrepancy in variant calling results were identified. Application of different notation rules for mitochondrial sequence and the minor allele frequency close to detection threshold were the two most significant reasons. CONCLUSION: With prospective improvement of each program, researchers and practitioners should be aware of characteristics of the analysis program they use and prepare their own strategies to determine variants.
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Genoma Mitocondrial , Humanos , Estudios Prospectivos , Secuenciación de Nucleótidos de Alto Rendimiento , Concienciación , ADN Mitocondrial/genéticaRESUMEN
Arachnoid cysts are usually asymptomatic and discovered incidentally. However, cysts may occasionally rupture because of minor head trauma. We describe the radiologic follow-up of 5 patients with ruptured arachnoid cysts featuring spontaneous resolution, subdural hygroma formation, and cystic and subdural hemorrhage. From January 2004 through July 2020, 5 patients (1.3%) with ruptured arachnoid cysts were evaluated out of 388 patients with arachnoid cysts encountered at our institution at that time. The 5 patients were all male, and they ranged in age from 6-17 years (median, 12 years). The median duration of radiologic follow-up was 3.5 years (range, 2.3-10.1 years). All of the ruptured arachnoid cysts were overlying the temporal lobe with Galassi type II. The median cyst diameter was 4.9 cm (range, 4.4-8.9 cm). Four patients had a history of recent minor head trauma. There were no particular neurologic symptoms in their past medical history in all patients. In the follow-up, two patients' cysts resolved spontaneously without hemorrhage. One patient's cyst resolved post-burr-hole drainage for chronic subdural hemorrhage. Another patient, whose cyst led to a hemorrhage and chronic subdural hemorrhage, recovered following a craniotomy, hematoma removal, and cyst fenestration. Another patient, presenting with hygroma, cystic hemorrhage, and chronic subdural hemorrhage, was treated with burr-hole drainage. Three patients recovered postoperatively. Arachnoid cysts rarely rupture, and surgical intervention is required for some cases associated with hemorrhage. Postoperatively, all patients had good outcomes without complications in this series.
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Background: Spirometry is an unrivalled tool for determining asthma and asthma severity. The ratio of forced expiratory volume (FEV) in 1 second (FEV1) to forced vital capacity (FVC) and the forced expiratory flow between 25% and 75% of FVC (FEF25-75) are well-known markers of airway obstruction, but they are limited by low reproducibility, particularly in children. In this study, we defined terminal expiration volume (TEV) as FEV in 3 seconds forced expiratory volume in 3 seconds (FEV3) minus forced expiratory volume in 1 seconds (FEV1) and investigate whether TEV/FEV3 can function as a coherent marker to compensate for existing markers. Methods: This retrospective study comprised 980 children ages ≤ 18 years who underwent spirometry and the bronchial provocation testing. TEV/FEV3 was compared with regard to asthma presence and severity. The findings were verified with an external validation group (n = 105). Results: FEV3 was obtained in 837 children (85.4%). TEV/FEV3 was significantly higher in patients with asthma than in patients who did not have asthma (17.1 ± 5.5 versus 12.0 ± 4.4, p < 0.001). External validation with 73 patients showed similar results (18.0 ± 5.9 in asthma versus 10.2 ± 5.1 in non-asthma, p < 0.001). The discriminatory power of TEV/FEV3 for asthma was comparable with that of FEF25-75 (p = 0.804). TEV/FEV3 significantly increased with asthma severity (mild, 16.1 ± 5.4; moderate, 17.7 ± 5.4; severe, 22.0 ± 5.3; p < 0.001). For patients who could not achieve FEV3, FEF25-75 demonstrated no significant difference between mild and moderate asthma, and could not discriminate asthma or asthma severity. Conclusion: TEV/FEV3 is a new metric that may help diagnose and determine asthma severity by using conventional spirometry by assessing small airway dysfunction. TEV/FEV3 promotes a reassessment of the reliability of other spirometric parameters, particularly in young children. Caution is needed in interpreting the result of spirometry in children who cannot achieve FEV3.
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Asma , Niño , Humanos , Preescolar , Reproducibilidad de los Resultados , Estudios Retrospectivos , Asma/diagnóstico , Pruebas de Función Respiratoria , EspirometríaRESUMEN
Attention deficit hyperactivity disorder (ADHD) is a common and heritable neurodevelopmental disorder. Particularly, ADHD is known to be related to the dopaminergic system. ADHD symptoms can appear when the dopamine binding affinity diminishes due to dopamine receptor abnormalities, such as the dopamine D2 receptor (D2R). This receptor interacts with the adenosine A2A receptor (A2AR). The A2AR acts as an antagonist of D2R, that is, the increased binding of adenosine with A2AR inhibits the D2R activity. Furthermore, it is found that the single nucleotide polymorphisms of the adenosine A2A receptor gene (ADORA2A) revealed a significant relationship with ADHD in various populations. Therefore, we examined the genetic relationship between ADORA2A polymorphisms (rs2297838, rs5751876, and rs4822492) and Korean ADHD children. A case-control study was performed for 150 cases and 322 controls. Genotyping of ADORA2A polymorphisms was conducted by PCR-RFLP. The results demonstrated that the rs5751876 TC genotype was associated with children with ADHD (p = 0.018). The rs2298383 CC genotype was significantly associated with children with ADHD/HI (p = 0.026). However, when Bonferroni correction was used, the significance vanished (padjusted = 0.054 and padjusted = 0.078, respectively). Haplotype analysis showed that TTC, TCC, and CTG demonstrated a significant difference between ADHD/C children and control groups (padjusted = 0.006, padjusted = 0.011, and padjusted = 0.028, respectively). In conclusion, we propose a possible association between ADORA2A polymorphisms with Korean children having ADHD.
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Trastorno por Déficit de Atención con Hiperactividad , Receptor de Adenosina A2A , Niño , Humanos , Adenosina , Trastorno por Déficit de Atención con Hiperactividad/genética , Estudios de Casos y Controles , Dopamina/metabolismo , Genotipo , Polimorfismo de Nucleótido Simple , Receptor de Adenosina A2A/genética , República de CoreaRESUMEN
BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is a common childhood neurodevelopmental disorder, and the prevalence of ADHD among Korean children has attained about 8.5%. Various genetic factors can contribute to the etiology of the disease. Synaptophysin (SYP) regulates neurotransmitter release and synaptic plasticity. According to previous studies, several genetic polymorphisms on SYP were risk factors for ADHD. OBJECTIVE: We investigated the effect of the SYP gene polymorphisms (rs2293945 and rs3817678) on ADHD in Korean children. METHODS: In this study, we examined the case-control study in 150 ADHD cases and 322 controls. The genotyping of SYP gene polymorphisms was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: Significant associations in the genotype and genetic models of SYP rs2293945 polymorphism between girls with ADHD and control girls were found. The girls with ADHD having the C/T genotype were significantly associated with ADHD. In the dominant model of rs3817678, C/T + T/T genotypes were significantly associated with ADHD. The haplotype analyses showed significant associations from haplotypes of rs2293945 T-rs3817678 G and rs2293945 C-rs3817678 A. CONCLUSION: Our results imply that the SYP rs2293945 C/T polymorphism in female participants may provide a possible effect on the genetic etiology of ADHD.
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Trastorno por Déficit de Atención con Hiperactividad , Niño , Femenino , Humanos , Trastorno por Déficit de Atención con Hiperactividad/genética , Estudios de Casos y Controles , Predisposición Genética a la Enfermedad , Polimorfismo Genético , República de Corea , Sinaptofisina/genéticaRESUMEN
BACKGROUND: Although emerging evidence suggests that PM2.5 is linked to neurological symptoms (NSs) via neuroinflammation, relevant studies are scarce. This study aimed to investigate the risks and excess costs of hospital admission for five NSs-fatigue, headache, dizziness, convulsion, and paralysis-attributable to long-term exposure to PM2.5 in New York State, USA. METHODS: We analyzed the New York Statewide Planning and Research Cooperative System (SPARCS) from 2010 to 2016. A Bayesian hierarchical model with integrated nested Laplace approximations was performed to estimate the risks and excess costs of hospital admission for NSs due to long-term exposure to PM2.5 at the county level. RESULTS: A 1 µg/m3 increase in lag 0-1 years PM2.5 was associated with an increased risk of headache and convulsion by 1.06 (1.01, 1.11) and 1.04 (1.01, 1.06), respectively. The excess hospital admission cost for five NSs attributable to lag 0-1 years PM2.5 above the new World Health Organization guideline (annual standard: 5 µg/m3) was $200.24 (95% CI: 6.00, 376.96) million during 2011-2016, recording the highest for convulsion ($153.73 [95% CI: 63.61, 244.19] million). CONCLUSIONS: This study provides quantitative estimates of risks and excess costs for NSs attributable to long-term PM2.5 and suggests that policies that reduce long-term PM2.5 concentration in accordance with the new WHO air quality guidelines can yield substantial health and economic benefits related to NSs in the New York State population.
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Contaminantes Atmosféricos , Contaminación del Aire , Humanos , Material Particulado/análisis , Contaminantes Atmosféricos/análisis , New York/epidemiología , Teorema de Bayes , Contaminación del Aire/análisis , Convulsiones/inducido químicamente , Cefalea/inducido químicamente , Hospitales , Exposición a Riesgos Ambientales/efectos adversos , Exposición a Riesgos Ambientales/análisisRESUMEN
This study aimed to investigate mental illnesses among patients with hemifacial spasms (HFS) based on nationwide claims data from the South Korea Health Insurance Review and Assessment Service. In this retrospective study, we defined the HFS group as subjects aged between 20 and 79 years with newly diagnosed HFS between January 2011 and December 2019 and set the date of diagnosis of HFS as the index date. Mental illnesses were defined through the International Classification of Diseases, the tenth revision from 90 days before to after the index date. Of these patients, we enrolled the participants who had visited a psychiatric outpatient clinic more than twice or had been admitted to a psychiatric department more than once diagnosed with psychiatric diseases. To select the control group, which was four times larger than the HFS group, propensity scores were used among those not diagnosed with HFS. The patients with HFS were more likely to have a mental illness than the control group (8.5% and 6.5%, respectively, p < 0.001) within 90 days before and after diagnosis. Among mental illnesses, insomnia (46.2% vs. 13.0%, p < 0.001) was significantly more prevalent in the HFS group. Other mental illnesses were significantly more prevalent in the control group or were not statistically significant. The results of this study suggest that patients diagnosed with HFS were significantly more likely to develop insomnia within a relatively short period than the controls.
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BACKGROUND: Acute appendicitis often presents with vague abdominal pain, which fosters diagnostic challenges to clinicians regarding early detection and proper intervention. This is even more problematic with individuals with severe psychiatric disorders who have reduced sensitivity to pain due to long-term or excessive medication use or disturbed bodily sensation perceptions. This study aimed to determine whether psychiatric disorder, psychotropic prescription, and treatment compliance increase the risks of complicated acute appendicitis. METHODS: The diagnosis records of acute appendicitis from four university hospitals in Korea were investigated from 2002 to 2020. A total of 47,500 acute appendicitis-affected participants were divided into groups with complicated and uncomplicated appendicitis to determine whether any of the groups had more cases of psychiatric disorder diagnoses. Further, the ratio of complicated compared to uncomplicated appendicitis in the mentally ill group was calculated regarding psychotropic dose, prescription duration, and treatment compliance. RESULTS: After adjusting for age and sex, presence of psychotic disorder (odds ratio [OR]: 1.951; 95% confidence interval [CI]: 1.218-3.125), and bipolar disorder (OR: 2.323; 95% CI: 1.194-4.520) was associated with a higher risk of having complicated appendicitis compared with absence of psychiatric disorders. Patients who are taking high-daily-dose antipsychotics, regardless of prescription duration, show high complicated appendicitis risks; High-dose antipsychotics for < 1 year (OR: 1.896, 95% CI: 1.077-3.338), high-dose antipsychotics for 1-5 years (OR: 1.930, 95% CI: 1.144-3.256). Poor psychiatric outpatient compliance was associated with a high risk of complicated appendicitis (OR: 1.664, 95% CI: 1.014-2.732). CONCLUSIONS: This study revealed a close relationship in the possibility of complicated appendicitis in patients with severe psychiatric disorders, including psychotic and bipolar disorders. The effect on complicated appendicitis was more remarkable by the psychiatric disease entity itself than by psychotropic prescription patterns. Good treatment compliance and regular visit may reduce the morbidity of complicated appendicitis in patients with psychiatric disorders.
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Antipsicóticos , Apendicitis , Trastorno Bipolar , Trastornos Mentales , Trastornos Psicóticos , Humanos , Apendicitis/complicaciones , Apendicitis/tratamiento farmacológico , Antipsicóticos/uso terapéutico , Trastornos Mentales/tratamiento farmacológico , Trastorno Bipolar/complicaciones , Trastorno Bipolar/tratamiento farmacológico , Trastornos Psicóticos/tratamiento farmacológico , Psicotrópicos/uso terapéutico , Enfermedad AgudaRESUMEN
Emerging data have suggested that single short peptides have limited success as a cancer vaccine; however, extending the short peptides into longer multi-epitope peptides overcame the immune tolerance and induced an immune response. Moreover, the combination of adjuvants such as lenalidomide and anti-programmed cell death protein 1 (PD1) with a peptide vaccine showed potential vaccine effects in previous studies. Therefore, the effects of a long multi-epitope peptide vaccine in combination with lenalidomide and anti-PD1 were analyzed in this study. Long multi-epitope peptides from two MHCI peptides (BIRC597-104 and EphA2682-689) and the pan-human leukocyte antigen-DR isotype (HLA-DR) binding epitope (PADRE) were synthesized. The therapeutic effects of long multi-epitope peptides in combination with lenalidomide and anti-PD1 were confirmed in the murine GL261 intracranial glioma model. Immune cells' distribution and responses to the long multi-epitope peptides in combination with these adjuvants were also estimated in the spleens, lymph nodes, and tumor tissues. The difference between long multi-epitope peptides and a cocktail of multi-epitope peptides combined with lenalidomide and anti-PD1 was also clarified. As a result, long multi-epitope peptides combined with lenalidomide and anti-PD1 prolonged the survival of mice according to the suppression of tumor growth in an intracranial mouse model. While long multi-epitope peptides combined with these adjuvants enhanced the percentages of activated and memory effector CD8+ T cells, the increase in percentages of regulatory T cells (Tregs) was observed in a cocktail of multi-epitope peptides combined with lenalidomide and anti-PD1 group in the tumors. Long multi-epitope peptides combined with these adjuvants also enhanced the function of immune cells according to the enhanced pro-inflammatory cytokines and cytotoxicity against GL261 cells in ex vivo. In conclusion, long multi-epitope peptides composed of MHCI peptides, BIRC5 and EphA2, and the MHCII peptide, PADRE, in combination with lenalidomide and anti-PD1 has the potential to improve the therapeutic effects of a vaccine against GBM.
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Glioblastoma , Ratones , Animales , Humanos , Epítopos , Glioblastoma/terapia , Linfocitos T CD8-positivos , Lenalidomida , Vacunas de Subunidad , Adyuvantes Inmunológicos/farmacología , Adyuvantes Farmacéuticos/farmacología , PéptidosRESUMEN
Objectives: We aimed to evaluate the clinical and psychological factors influencing depressive symptoms in children and adolescents with epilepsy. Methods: We administered self-reported questionnaires assessing children's depressive symptoms (Children's Depression Inventory, CDI) and anxiety (Revised Children's Manifest Anxiety Scale, RCMAS) to children and adolescents with epilepsy (n=87, age range=6-17 years). We asked their parents to complete questionnaires on epilepsy-related variables, parental stress (Questionnaire on Resources and Stress, QRS), parental anxiety (State-Trait Anxiety Inventory, STAI), family functioning (Family Adaptability and Cohesion Evaluation Scale, FACES), children's attention problems (Abbreviated Conners Parent Rating Scale Revised, CPRS), and children's behavioral problems (Korean Child Behavior Checklist, K-CBCL). Stepwise multiple regression analysis was performed to identify predictive variables affecting depressive symptoms. Results: Family adaptability (r=-0.240, p=0.026), family cohesion (r=-0.381, p<0.001), children's attention problems (r=0.290, p=0.006), children's anxiety (r=0.714, p<0.001), children's behavioral problems (r=0.371, p<0.001), parental anxiety (r=0.320, p=0.003), and parental stress (r=0.335, p=0.002) were significantly correlated with children's depressive symptoms. Children's anxiety (ß=0.655, p<0.001) and parental stress (ß=0.198, p=0.013) were significantly related to their depressive symptoms (adjusted R2=0.539). Conclusion: Clinicians should detect and manage children's anxiety and parental stress, which may affect depressive symptoms in children and adolescents with epilepsy.
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Hypoxemia and multiple organ dysfunction are significant contributors to mortality in patients with pediatric acute respiratory distress syndrome (PARDS). P50, the oxygen tension at which hemoglobin is 50% saturated, is a measure of hemoglobin-oxygen affinity, and its alteration might have implications for tissue hypoxia and organ dysfunction. The purpose of this single-center, retrospective study was to evaluate P50 levels in PARDS and to determine the association between P50 and clinical outcomes. The study included 212 children diagnosed with PARDS according to the Pediatric Acute Lung Injury Consensus Conference definition who required invasive mechanical ventilation and had arterial blood gas results of hemoglobin oxygen saturation < 97% at the time of diagnosis. P50 levels were calculated using Doyle's method, and organ dysfunction was assessed using the Pediatric Logistic Organ Dysfunction-2 score. Most patients exhibited more than one dysfunctional extrapulmonary organ at PARDS onset. P50 increased with increasing PARDS severity (mild (26.6 [24.9-29.6]), moderate (26.8 [25.0-29.5]), and severe PARDS (29.1 [26.1-32.4] mmHg; P = 0.025). Moreover, P50 demonstrated a significant positive association with extrapulmonary organ dysfunction score (ß = 0.158, P = 0.007) and risk of mortality (adjusted hazard ratio, 1.056; 95% confidence interval, 1.015-1.098; P = 0.007), irrespective of initial PARDS severity. The relationship between P50 and mortality was largely mediated by extrapulmonary organ dysfunction. A high P50 value at the time of PARDS diagnosis may be associated with mortality via dysfunctional extrapulmonary organs. Future studies should consider P50 as a potential candidate index for risk stratification of PARDS patients.
Asunto(s)
Insuficiencia Multiorgánica , Síndrome de Dificultad Respiratoria , Niño , Humanos , Hipoxia , Insuficiencia Multiorgánica/etiología , Oxígeno , Respiración Artificial/métodos , Síndrome de Dificultad Respiratoria/terapia , Estudios RetrospectivosRESUMEN
Global warming accelerates the destruction of the ozone layer, increasing the amount of UVB reaching the Earth's surface, which in turn alters plant growth and development. The effects of UVB-induced alterations of plant secondary and cell wall metabolism were previously documented; however, there is little knowledge of its effects on rice seedlings during the developmental phase of leaves. In this study, we examined secondary metabolic responses to UVB stress using a transcriptomic approach, focusing on the biosynthetic pathways for lignin, flavonoid, and indole/tryptophan-auxin responses. As new leaves emerged, they were irradiated with UVB for 5 days (for 3 h/day-1). The genes encoding the enzymes related to lignin (4CL, CAD, and POD) and flavonoid biosynthesis (CHS, CHI, and FLS) were highly expressed on day 1 (younger leaves) and day 5 (older leaves) after UVB irradiation. The expression of the genes encoding the enzymes related to tryptophan biosynthesis (AS, PRT, PRAI, IGPS, and TS) increased on day 3 of UVB irradiation, and the level of tryptophan increased and showed the same temporal pattern of occurrence as the expression of the cognate gene. Interestingly, the genes encoding BBX4 and BBX11, negative regulators of UVB signaling, and SAUR27 and SAUR55, auxin response enzymes, were downregulated on day 3 of UVB irradiation. When these results are taken together, they suggest that secondary metabolic pathways in rice seedlings are influenced by the interaction between UVB irradiation and the leaf developmental stage. Thus, the strategies of protection against, adaptation to, and mitigation of UVB might be delicately regulated, and, in this context, our data provide valuable information to understand UVB-induced secondary metabolism in rice seedlings.
RESUMEN
The risk of chronic disease and mortality may differ by metabolic health and obesity status and its transition. We investigated the risk of cardiovascular disease (CVD) and cancer incidence and mortality according to metabolic health and obesity status and their transition using the nationally representative Korea National Health and Nutrition Examination Survey (KNHANES) and the Ansan-Ansung (ASAS) cohort of the Korean Genome and Epidemiology Study. Participants that agreed to mortality linkage (n = 28,468 in KNHANES and n = 7530 adults in ASAS) were analyzed (mean follow-up: 8.2 and 17.4 years, respectively). Adults with no metabolic risk factors and BMI <25 or ≥25 kg/m2 were categorized as metabolically healthy non-obese (MHN) or metabolically healthy obese (MHO), respectively. Metabolically unhealthy non-obese (MUN) and metabolically unhealthy obese (MUO) adults had ≥1 metabolic risk factor and a BMI < or ≥25 kg/m2, respectively. In KNHANES participants, MUN, and MUO had higher risks for cardiovascular mortality, but not cancer mortality, compared with MHN adults. MHO had 47% and 35% lower risks of cancer mortality and all-cause mortality, respectively, compared to MHN. Similar results were observed in the ASAS participants. Compared to those persistently MHN, the risk of CVD was greater when continuously MUN or MUO. Transitioning from a metabolically healthy state to MUO also increased the risk of CVD. Few associations were found for cancer incidence. Using a nationally representative cohort and an 18-year follow-up cohort, we observed that the risk of CVD incidence and mortality and all-cause mortality, but not cancer incidence or mortality, increases with a continuous or a transition to an unhealthy metabolic status in Koreans.