Polychlorinated Biphenyls Disrupt Blood–Brain Barrier Integrity and Promote Brain Metastasis Formation

Bac k g r o u n d: Polychlorinated biphenyls (PCBs) comprise a ubiquitous class of toxic substances associated with carcinogenic and tumor-promoting effects as well as neurotoxic properties in the brain. However, the effects of PCBs on the development of tumor metastases are not fully understood. Objective: We evaluated the hypothesis that exposure to individual PCB congeners can facilitate the development of brain metastases in immunocompetent mice via the disruption of the integrity of the blood–brain barrier (BBB). Met h o d s: C57/Bl6 mice were exposed to individual PCBs by oral gavage, and 48 hr later they were injected with luciferase-labeled K1735 M2 melanoma cells into the internal carotid artery. The development of metastatic nodules was monitored by bioluminescent imaging. In addition, we evaluated the functional permeability of the BBB by measuring permeability of sodium fluorescein across the brain microvessels. Expression and colocalization of tight junction (TJ) proteins were studied by Western blotting and immunofluorescence microscopy. Res u l t s: Oral administration of coplanar PCB126, mono-ortho-substituted PCB118, and noncoplanar PCB153 (each at 150 µmol/kg body weight) differentially altered expression of the TJ proteins claudin-5, occludin, and zonula occludens-1 in brain capillaries. These alterations wer

Virtual Reality-Based Psychotherapy in Social Anxiety Disorder: fMRI Study Using a Self-Referential Task

Background: Although it has been well demonstrated that the efficacy of virtual reality therapy for social anxiety disorder is comparable to that of traditional cognitive behavioral therapy, little is known about the effect of virtual reality on pathological self-referential processes in individuals with social anxiety disorder. Objective: We aimed to determine changes in self-referential processing and their neural mechanisms following virtual reality treatment. Methods: We recruited participants with and without a primary diagnosis of social anxiety disorder to undergo clinical assessments (Social Phobia Scale and Post-Event Rumination Scale) and functional magnetic resonance imaging (fMRI) scans. Participants with social anxiety disorder received virtual reality-based exposure treatment for 6 sessions starting immediately after baseline testing. After the sixth session, participants with social anxiety disorder completed follow-up scans during which they were asked to judge whether a series of words (positive, negative, neutral) was relevant to them. Results: Of 25 individuals with social anxiety disorder who participated in the study, 21 completed the sessions and follow-up; 22 control individuals also participated. There were no significant differences in age (P=.36), sex (P=.71), or handedness (P=.51) between the groups. Whole-brain analysis revealed that participants in the social anxiety disorder group had increased neural responses during positive self-referential processing in the medial temporal and frontal cortexes compared with those in the control group. Participants in the social anxiety disorder group also showed increased left insular activation and decreased right middle frontal gyms activation during negative self-referential processing. After undergoing virtual reality based therapy, overall symptoms of the participants with social anxiety disorder were reduced, and these participants exhibited greater activity in a brain regions responsible for self-referential and autobiographical memory processes while viewing positive words during postintervention fMRI scans. Interestingly, the greater the blood oxygen level dependent changes related to positive self-referential processing, the lower the tendency to ruminate on the negative events and the lower the social anxiety following the virtual reality session. Compared with that at baseline, higher activation was also found within broad somatosensory areas in individuals with social anxiety disorder during negative self-referential processing following virtual reality therapy. Conclusions: These fMRI findings might reflect the enhanced physiological and cognitive processing in individuals with social anxiety disorder in response to self-referential information. They also provide neural evidence of the effect of virtual reality exposure therapy on social anxiety and self-derogation

Prediction of Specific Anxiety Symptoms and Virtual Reality Sickness Using In Situ Autonomic Physiological Signals During Virtual Reality Treatment in Patients With Social Anxiety Disorder: Mixed Methods Study

Background: Social anxiety disorder (SAD) is the fear of social situations where a person anticipates being evaluated negatively. Changes in autonomic response patterns are related to the expression of anxiety symptoms. Virtual reality (VR) sickness can inhibit VR experiences. Objective: This study aimed to predict the severity of specific anxiety symptoms and VR sickness in patients with SAD, using machine learning based on in situ autonomic physiological signals (heart rate and galvanic skin response) during VR treatment sessions. Methods: This study included 32 participants with SAD taking part in 6 VR sessions. During each VR session, the heart rate and galvanic skin response of all participants were measured in real time. We assessed specific anxiety symptoms using the Internalized Shame Scale (ISS) and the Post-Event Rumination Scale (PERS), and VR sickness using the Simulator Sickness Questionnaire (SSQ) during 4 VR sessions (#1, #2, #4, and #6). Logistic regression, random forest, and naive Bayes classification classified and predicted the severity groups in the ISS, PERS, and SSQ subdomains based on in situ autonomic physiological signal data. Results: The severity of SAD was predicted with 3 machine learning models. According to the F1 score, the highest prediction performance among each domain for severity was determined. The F1 score of the ISS mistake anxiety subdomain was 0.8421 using the logistic regression model, that of the PERS positive subdomain was 0.7619 using the naive Bayes classifier, and that of total VR sickness was 0.7059 using the random forest model. Conclusions: This study could predict specific anxiety symptoms and VR sickness during VR intervention by autonomic physiological signals alone in real time. Machine learning models can predict the severe and nonsevere psychological states of individuals based on in situ physiological signal data during VR interventions for real-time interactive services. These models can support the diagnosis of specific anxiety symptoms and VR sickness with minimal participant bias

Investigating the Influence of Heavy Metals and Environmental Factors on Metabolic Syndrome Risk Based on Nutrient Intake: Machine Learning Analysis of Data from the Eighth Korea National Health and Nutrition Examination Survey (KNHANES)

This study delves into the complex interrelations among nutrient intake, environmental exposures (particularly to heavy metals), and metabolic syndrome. Utilizing data from the Korea National Health and Nutrition Examination Survey (KNHANES), machine learning techniques were applied to analyze associations in a cohort of 5719 participants, categorized into four distinct nutrient intake phenotypes. Our findings reveal that different nutrient intake patterns are associated with varying levels of heavy metal exposure and metabolic health outcomes. Key findings include significant variations in metal levels (Pb, Hg, Cd, Ni) across the clusters, with certain clusters showing heightened levels of specific metals. These variations were associated with distinct metabolic health profiles, including differences in obesity, diabetes prevalence, hypertension, and cholesterol levels. Notably, Cluster 3, characterized by high-energy and nutrient-rich diets, showed the highest levels of Pb and Hg exposure and had the most concerning metabolic health indicators. Moreover, the study highlights the significant impact of lifestyle habits, such as smoking and eating out, on nutrient intake phenotypes and associated health risks. Physical activity emerged as a critical factor, with its absence linked to imbalanced nutrient intake in certain clusters. In conclusion, our research underscores the intricate connections among diet, environmental factors, and metabolic health. The findings emphasize the need for tailored health interventions and policies that consider these complex interplays, potentially informing future strategies to combat metabolic syndrome and related health issues

Nutritional intake, environmental factors, and their impact on myopia prevalence in Korean children aged 5–12 years

Abstract Background Myopia is a complex condition influenced by numerous factors, including genetic predisposition, environmental factors, and lifestyle choices. Although evidence indicates that certain dietary factors may influence the development of myopia, this relationship is still not completely understood and is a topic of ongoing research. Methods This study analyzed the relationship between dietary habits, environmental factors, and the prevalence of myopia in a sample of 24,345 children aged 5–12 years from the seventh Korea National Health and Nutrition Examination Survey (KNHANES VII). The average daily intake of dietary nutrients associated with the refractive error status of the participants was analyzed using analysis of variance (GLM) and the Scheffe method for post-hoc comparison. Multiple logistic regression analysis was conducted between the participant’s refractive error status and daily dietary nutrient intake, while taking into consideration the age, sex, BMI, parental myopia, and near-work hours. Results The risk of myopia increased with age, especially notable between ages 11 and 12, and was higher in children with both parents having myopia. Dietary factors played a crucial role; children with myopia had significantly lower intake of fat, omega-3 fatty acids, and retinol but higher intake of other nutrients compared to emmetropic and hyperopic counterparts. High consumption of carbohydrates, protein, phosphorus, iron, potassium, and sodium was associated with increased myopia risk. High sodium intake was particularly associated with a 2.05-fold increased myopia risk. Conclusions This study highlights the significant role of diet and lifestyle choices in the development of myopia in children. Our findings suggest the importance of considering these specific factors in the management and prevention strategies for myopia, underscoring the need for targeted interventions in children's health and vision care

Image_1_Association between household income levels and nutritional intake of allergic children under 6 years of age in Korea: 2019 Korea National Health and Nutrition Examination Survey and application of machine learning.png

IntroductionThis study investigated the prevalence of allergic diseases in Korean children aged 6 and below, focusing on the interplay between nutritional status, household income levels, and allergic disease occurrence.MethodsThis study used data from the 2019 Korea National Health and Nutrition Examination Survey, a nationwide comprehensive survey, and included a representative sample of 30,382 children under the age of 6 to investigate in detail the relationship between allergic diseases, nutritional intake, and socioeconomic factors. Logistic regression analysis was performed to identify factors associated with allergic diseases, including gender, BMI, eating habits, dietary supplement intake, and nutrient consumption. To predict childhood asthma, 14 machine learning models were compared using the ‘pycaret’ package in Python.ResultsWe discerned that 24.7% were diagnosed with allergic conditions like atopic dermatitis, asthma, and allergic rhinitis. Notably, household income exhibited a significant influence, with the lowest income quartile exhibiting higher prevalence rates of asthma, allergic rhinitis, and multiple allergic diseases. In contrast, the highest income quartile displayed lower rates of allergic rhinitis. Children diagnosed with allergic diseases demonstrated compromised intake of essential nutrients such as energy, dietary fiber, vitamin B1, sodium, potassium, and iron. Particularly noteworthy were the deficits in dietary fiber, vitamin A, niacin, and potassium intake among children aged 3–5 with allergies. Logistic regression analysis further elucidated that within low-income families, female children with higher BMIs, frequent dining out, dietary supplement usage, and altered consumption of vitamin B1 and iron faced an elevated risk of allergic disease diagnosis. Additionally, machine learning analysis pinpointed influential predictors for childhood asthma, encompassing BMI, household income, subjective health perception, height, and dietary habits.DiscussionOur findings underscore the pronounced impact of income levels on the intricate nexus between allergic diseases and nutritional status. Furthermore, our machine learning insights illuminate the multifaceted determinants of childhood asthma, where physiological traits, socioeconomic circumstances, environmental factors, and dietary choices intertwine to shape disease prevalence. This study emphasizes the urgency of tailored nutritional interventions, particularly in socioeconomically disadvantaged populations, while also underscoring the necessity for comprehensive longitudinal investigations to unravel the intricate relationship between allergic diseases, nutritional factors, and socioeconomic strata.</p

HIV-1 Tat-induced cerebrovascular toxicity is enhanced in mice with amyloid deposits

HIV-1-infected brains are characterized by elevated depositions of amyloid beta (Aβ); however, the interactions between Aβ and HIV-1 are poorly understood. In the present study, we administered specific HIV-1 protein Tat into the cerebral vasculature of 50–52-week-old double transgenic (B6C3-Tg) mice that express a chimeric mouse/human amyloid precursor protein (Mo/HuAPP695swe) and a mutant human presenilin 1 (PS1-dE9) and are characterized by increased Aβ depositions in the brain. Exposure to Tat increased permeability across cerebral capillaries, enhanced disruption of zonula occludens (ZO)-1 tight junction protein, and elevated brain expression of matrix metalloproteinase-9 (MMP-9) in B6C3-Tg mice as compared with age-matched littermate controls. These changes were associated with increased leukocyte attachment and their transcapillary migration. The majority of Tat-induced effects were attenuated by treatment with a specific Rho inhibitor, hydroxyfasudil. The results of animal experiments were reproduced in cultured brain endothelial cells exposed to Aβ and/or Tat. The present data indicate that increased brain levels of Aβ can enhance vascular toxicity and proinflammatory responses induced by HIV-1 protein Tat