The Effect of Mobile Neurofeedback Training in Children with Attention Deficit Hyperactivity Disorder: A Randomized Controlled Trial.

Objective: : To examine the effect of mobile neurofeedback training on the clinical symptoms, attention abilities, and execution functions of children with attention deficit hyperactivity disorder (ADHD). Methods: : The participants were 74 children with ADHD aged 8-15 years who visited the Department of Child and Adolescent Psychiatry at Seoul National University Children's Hospital. The participants were randomly assigned to the mobile neurofeedback (n = 35) or control (sham; n = 39) group. Neurofeedback training was administered using a mobile app (equipped with a headset with a 2-channel electroencephalogram [EEG] sensor) for 30 min/day, 3 days/week, for 3 months. Children with ADHD were individually administered various neuropsychological tests, including the continuous performance test, Children's Color Trails Test-1 and 2, and Stroop Color and Word Tests. The effects of mobile neurofeedback were evaluated at baseline and at 3 and 6 months after treatment initiation. Results: : Following treatment, both mobile neurofeedback-only and sham-only groups showed significant improvements in attention and response inhibition. In the visual continuous performance test, omission errors decreased to the normal range in the mobile neurofeedback-only group after training, suggesting that mobile neurofeedback effectively reduced inattention in children with ADHD. In the advanced test of attention, auditory response times decreased in the mobile neurofeedback + medication group after training, but increased in the sham+medication group. Overall, there were no significant between-group differences in other performance outcomes. Conclusion: : Mobile neurofeedback may have potential as an additional therapeutic option alongside medication for children with ADHD.

Unveiling the inhibition mechanism of Clostridioides difficile by Bifidobacterium longum via multiomics approach.

Antibiotic-induced gut microbiota disruption constitutes a major risk factor for Clostridioides difficile infection (CDI). Further, antibiotic therapy, which is the standard treatment option for CDI, exacerbates gut microbiota imbalance, thereby causing high recurrent CDI incidence. Consequently, probiotic-based CDI treatment has emerged as a long-term management and preventive option. However, the mechanisms underlying the therapeutic effects of probiotics for CDI remain uninvestigated, thereby creating a knowledge gap that needs to be addressed. To fill this gap, we used a multiomics approach to holistically investigate the mechanisms underlying the therapeutic effects of probiotics for CDI at a molecular level. We first screened Bifidobacterium longum owing to its inhibitory effect on C. difficile growth, then observed the physiological changes associated with the inhibition of C. difficile growth and toxin production via a multiomics approach. Regarding the mechanism underlying C. difficile growth inhibition, we detected a decrease in intracellular adenosine triphosphate (ATP) synthesis due to B. longum-produced lactate and a subsequent decrease in (deoxy)ribonucleoside triphosphate synthesis. Via the differential regulation of proteins involved in translation and protein quality control, we identified B. longum-induced proteinaceous stress. Finally, we found that B. longum suppressed the toxin production of C. difficile by replenishing proline consumed by it. Overall, the findings of the present study expand our understanding of the mechanisms by which probiotics inhibit C. difficile growth and contribute to the development of live biotherapeutic products based on molecular mechanisms for treating CDI.

Multiomics analysis reveals the biological effects of live Roseburia intestinalis as a high-butyrate-producing bacterium in human intestinal epithelial cells.

Butyrate-producing bacteria play a key role in human health, and recent studies have triggered interest in their development as next-generation probiotics. However, there remains limited knowledge not only on the identification of high-butyrate-producing bacteria in the human gut but also in the metabolic capacities for prebiotic carbohydrates and their interaction with the host. Herein, it was discovered that Roseburia intestinalis produces higher levels of butyrate and digests a wider variety of prebiotic polysaccharide structures compared with other human major butyrate-producing bacteria (Eubacterium rectale, Faecalibacterium prausnitzii, and Roseburia hominis). Moreover, R. intestinalis extracts upregulated the mRNA expression of tight junction proteins (TJP1, OCLN, and CLDN3) in human intestinal epithelial cells more than other butyrate-producing bacteria. R. intestinalis was cultured with human intestinal epithelial cells in the mimetic intestinal host-microbe interaction coculture system to explore the health-promoting effects using multiomics approaches. Consequently, it was discovered that live R. intestinalis only enhances purine metabolism and the oxidative pathway, increasing adenosine triphosphate levels in human intestinal epithelial cells, but that heat-killed bacteria had no effect. Therefore, this study proposes that R. intestinalis has potentially high value as a next-generation probiotic to promote host intestinal health.

Investigation of metabolic crosstalk between host and pathogenic Clostridioides difficile via multiomics approaches.

Clostridioides difficile is a gram-positive anaerobic bacterium that causes antibiotic-associated infections in the gut. C. difficile infection develops in the intestine of a host with an imbalance of the intestinal microbiota and, in severe cases, can lead to toxic megacolon, intestinal perforation, and even death. Despite its severity and importance, however, the lack of a model to understand host-pathogen interactions and the lack of research results on host cell effects and response mechanisms under C. difficile infection remain limited. Here, we developed an in vitro anaerobic-aerobic C. difficile infection model that enables direct interaction between human gut epithelial cells and C. difficile through the Mimetic Intestinal Host-Microbe Interaction Coculture System. Additionally, an integrative multiomics approach was applied to investigate the biological changes and response mechanisms of host cells caused by C. difficile in the early stage of infection. The C. difficile infection model was validated through the induction of disaggregation of the actin filaments and disruption of the intestinal epithelial barrier as the toxin-mediated phenotypes following infection progression. In addition, an upregulation of stress-induced chaperones and an increase in the ubiquitin proteasomal pathway were identified in response to protein stress that occurred in the early stage of infection, and downregulation of proteins contained in the electron transfer chain and ATP synthase was observed. It has been demonstrated that host cell energy metabolism is inhibited through the glycolysis of Caco-2 cells and the reduction of metabolites belonging to the TCA cycle. Taken together, our C. difficile infection model suggests a new biological response pathway in the host cell induced by C. difficile during the early stage of infection at the molecular level under anaerobic-aerobic conditions. Therefore, this study has the potential to be applied to the development of future therapeutics through basic metabolic studies of C. difficile infection.

Factors on the Pathway from Trauma to Suicidal Ideation in Adolescents.

OBJECTIVES: Suicide is the most frequent cause of death among Korean adolescents, and adolescents who have experienced trauma have an increased risk of post-traumatic stress disorder (PTSD) symptoms, depression, and suicide attempts. However, resilience and self-esteem are protective factors. We examined the effects of resilience and self-esteem on the relationship among traumatic experiences, PTSD symptoms, depression, and suicidal ideation. METHODS: -school students (n=403) completed questionnaires assessing traumatic experiences, PTSD symptoms, depression, suicidal ideation, resilience, and self-esteem. Path analysis was performed to investigate the mediating effects of PTSD symptoms, resilience, self-esteem, and depression on the relationship between trauma exposure and suicidal ideation. RESULTS: Traumatic experience was positively correlated with PTSD symptoms, depression, and suicidal ideation. PTSD symptoms and depression were positively correlated with suicidal ideation. The relationship between traumatic experiences and suicidal ideation was mediated by PTSD symptoms, which had both direct and indirect effects on suicidal ideation; the indirect effect was mediated by resilience, self-esteem, and depression. CONCLUSION: Korean adolescents who had experienced trauma were more likely to develop PTSD symptoms, increasing their risk of depression and suicidal ideation. However, self-esteem and resilience may help protect against depression and suicidal ideation. Our findings could inform suicide prevention initiatives.