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Abstract Alzheimer’s disease (AD) and related tauopathies are associated with pathological tau protein aggregation, which plays an important role in neurofibrillary degeneration and dementia. Targeted immunotherapy to eliminate pathological tau aggregates is known to improve cognitive deficits in AD animal models. The tau repeat domain (TauRD) plays a pivotal role in tau-microtubule interactions and is critically involved in the aggregation of hyperphosphorylated tau proteins. Because TauRD forms the structural core of tau aggregates, the development of immunotherapies that selectively target TauRD-induced pathological aggregates holds great promise for the modulation of tauopathies. In this study, we generated recombinant TauRD polypeptide that form neurofibrillary tangle-like structures and evaluated TauRD-specific immune responses following intranasal immunization in combination with the mucosal adjuvant FlaB. In BALB/C mice, repeated immunizations at one-week intervals induced robust TauRD-specific antibody responses in a TLR5-dependent manner. Notably, the resulting antiserum recognized only the aggregated form of TauRD, while ignoring monomeric TauRD. The antiserum effectively inhibited TauRD filament formation and promoted the phagocytic degradation of TauRD aggregate fragments by microglia. The antiserum also specifically recognized pathological tau conformers in the human AD brain. Based on these results, we engineered a built-in flagellin-adjuvanted TauRD (FlaB-TauRD) vaccine and tested its efficacy in a P301S transgenic mouse model. Mucosal immunization with FlaB-TauRD improved quality of life, as indicated by the amelioration of memory deficits, and alleviated tauopathy progression. Notably, the survival of the vaccinated mice was dramatically extended. In conclusion, we developed a mucosal vaccine that exclusively targets pathological tau conformers and prevents disease progression.

Abstract Background Adolescent suicides are more likely to form clusters than those of other age groups. However, the definition of a cluster in the space–time dimension has not been established, neither are the factors contributing to it well known. Therefore, this study aimed to identify space–time clusters in adolescent suicides in Korea and to examine the differences between clustered and non-clustered cases using novel statistical methods. Methods From 2016 to 2020, the dates and locations, including specific addresses from which the latitude and longitude of all student suicides (aged 9–18 years) in Korea were obtained through student suicide reports. Sociodemographic characteristics of the adolescents who died by suicide were collected, and the individual characteristics of each student who died by suicide were reported by teachers using the Strengths and Difficulties Questionnaire (SDQ). Density-Based Spatial Clustering of Applications with Noise (DBSCAN) analysis was used to assess the clustering of suicides. Results We identified 23 clusters through the data analysis of 652 adolescent suicides using DBSCAN. By comparing the size of each cluster, we identified 63 (9.7%) spatiotemporally clustered suicides among adolescents, and the temporal range of these clusters was 7–59 days. The suicide cluster group had a lower economic status than the non-clustered group. There were no significant differences in other characteristics between the two groups. Conclusion This study has defined the space–time cluster of suicides using a novel statistical method. Our findings suggest that when an adolescent suicide occurs, close monitoring and intervention for approximately 2 months are needed to prevent subsequent suicides. Future research using DBSCAN needs to involve a larger sample of adolescents from various countries to further corroborate these findings.

Excessive accumulation of amyloid-β (Aβ) has been associated with the pathogenesis of Alzheimer’s disease (AD). Clinical studies have further proven that elimination of Aβ can be a viable therapeutic option. In the current study, we conceptualized a fusion membrane protein, referred to as synthetic α-secretase (SAS), that can cleave amyloid precursor protein (APP) and Aβ specifically at the α-site. In mammalian cells, SAS indeed cleaved APP and Aβ at the α-site. Overexpression of SAS in the hippocampus was achieved by direct injection of recombinant adeno-associated virus serotype 9 (AAV9) that expresses SAS (AAV9-SAS) into the bilateral ventricles of mouse brains. SAS enhanced the non-amyloidogenic processing of APP, thus reducing the levels of soluble Aβ and plaques in the 5xFAD mice. In addition, SAS significantly attenuated the cognitive deficits in 5xFAD mice, as demonstrated by novel object recognition and Morris water maze tests. Unlike other Aβ-cleaving proteases, SAS has highly strict substrate specificity. We propose that SAS can be an efficient modality to eliminate excessive Aβ from diseased brains.

The gut–brain axis (GBA) plays a significant role in various neurodegenerative disorders, such as Alzheimer’s disease (AD), and the gut microbiome (GM) can bidirectionally communicate with the brain through the GBA. Thus, recent evidence indicates that the GM may affect the pathological features and the progression of AD in humans. The aim of our study was to elucidate the impact of probiotics on the pathological features of AD in a 5xFAD model. Probiotics (Bifidobacterium lactis, Levilactobacillus brevis, and Limosilactobacillus fermentum) were orally administered in 5xFAD mice to modify the GM composition. Additionally, freeze-dried food containing phosphatidylserine was used as the positive control. Behavioral pathogenesis was assessed through the cross maze and Morris water maze tests. Our findings revealed that probiotic administration resulted in significant improvements in spatial and recognition memories. Furthermore, the neuroprotective effects of probiotics were substantiated by a reduction in amyloid-β accumulation in critical brain regions. Microglial activation in 5xFAD mice was also attenuated by probiotics in the hippocampus and cerebral cortex. Moreover, elevated tau phosphorylation in 5xFAD mice was ameliorated in the probiotics-treated group. The results highlight the potential use of probiotics as a neuroprotective intervention in AD.

IntroductionMany adolescents with suicidal ideation receive support through the Internet. However, they also find ways to attempt suicide or strengthen their suicidal ideation through this medium. This study analyzed the association between the search volume of suicide-related terms and the number of suicides among Korean adolescents. We also analyzed the correlations between the search volumes of suicide-related terms.MethodsWe selected seven words (suicide, self-injury, depression, academic score, school violence, outcasts, and family trouble) related to adolescent suicide. A dataset was constructed by combining data from the most commonly used search engine in Korea (Naver Datalab) and the daily number of adolescent suicides in school settings (n = 347) from January 1, 2016 to December 31, 2018, collected from the Ministry of Education. Poisson regression and Pearson correlation analyses were performed.ResultsSignificant associations were found between suicide attempts and search term volumes, which differed according to sex and time interval. Among the search terms, “self-injury” was most strongly associated with suicide, and this association was significant at all time intervals (daily, weekly, and monthly) in female adolescents and in the total population. Further, the association was strongest in the daily suicide data. More search term volumes were related to suicide in the daily and weekly data than in the monthly data. There were positive correlations between “suicide,” “self-injury,” and “depression” search volumes.ConclusionFurther studies with larger sample sizes, more search terms, and analysis of time intervals between suicide-related term search and suicide death are required. These studies can contribute to the establishment of an online suicide prevention system to detect suicide risk in adolescents and provide interventions.

BackgroundPrevious studies have investigated the association between suicide and internet search volumes of terms related to suicide or self-harm. However, the results varied by people’s age, period, and country, and no study has exclusively investigated suicide or self-harm rates among adolescents. ObjectiveThis study aims to determine the association between the internet search volumes of terms related to suicide/self-harm and the number of suicides among South Korean adolescents. We investigated gender differences in this association and the time lag between the internet search volumes of the terms and the connected suicide deaths. MethodsWe selected 26 search terms related to suicide and self-harm among South Korean adolescents, and the search volumes of these terms for adolescents aged 13-18 years were obtained from the leading internet search engine in South Korea (Naver Datalab). A data set was constructed by combining data from Naver Datalab and the number of suicide deaths of adolescents on a daily basis from January 1, 2016, to December 31, 2020. Spearman rank correlation and multivariate Poisson regression analyses were performed to identify the association between the search volumes of the terms and the suicide deaths during that period. The time lag between suicide death and the increasing trend in the search volumes of the related terms was estimated from the cross-correlation coefficients. ResultsSignificant correlations were observed within the search volumes of the 26 terms related to suicide/self-harm. The internet search volumes of several terms were associated with the number of suicide deaths among South Korean adolescents, and this association differed by gender. The search volume for “dropout” showed a statistically significant correlation with the number of suicides in all adolescent population groups. The correlation between the internet search volume for “dropout” and the connected suicide deaths was the strongest for a time lag of 0 days. In females, self-harm and academic score showed significant associations with suicide deaths, but academic score showed a negative correlation, and the time lags with the strongest correlations were 0 and –11 days, respectively. In the total population, self-harm and suicide method were associated with the number of suicides, and the time lags with the strongest correlations were +7 and 0 days, respectively. ConclusionsThis study identifies a correlation between suicides and internet search volumes related to suicide/self-harm among South Korean adolescents, but the relatively weak correlation (incidence rate ratio 0.990-1.068) should be interpreted with caution.

Abstract Mitochondrial dysfunction is a key element in the progression of Parkinson’s disease (PD). The inefficient operation of the electron transport chain (ETC) impairs energy production and enhances the generation of oxidative stress contributing to the loss of dopaminergic cells in the brain. ATPase inhibitory factor 1 (IF1) is a regulator of mitochondrial energy metabolism. IF1 binds directly to the F1Fo ATP synthase and prevents ATP wasting during compromised energy metabolism. In this study, we found treatment with IF1 protects mitochondria against PD-like insult in vitro. SH-SY5Y cells treated with IF1 were resistant to loss of ATP and mitochondrial inner membrane potential during challenge with rotenone, an inhibitor of complex I in the ETC. We further demonstrated that treatment with IF1 reversed rotenone-induced superoxide production in mitochondria and peroxide accumulation in whole cells. Ultimately, IF1 decreased protein levels of pro-apoptotic Bax, cleaved caspase-3, and cleaved PARP, rescuing SH-SY5Y cells from rotenone-mediated apoptotic death. Administration of IF1 significantly improved the results of pole and hanging tests performed by PD mice expressing human α-synuclein. This indicates that IF1 mitigates PD-associated motor deficit. Together, these findings suggest that IF1 exhibits a neuroprotective effect preventing mitochondrial dysfunction in PD pathology.

This study aimed to determine whether and how three demographic factors—age group, gender, and consumption frequency—affect texture perception and liking of two staple foods—cooked rice and wheat bread. In total, 346 adults evaluated three cooked rice and four wheat bread samples in terms of three (hardness, stickiness, and chewiness) and four textural attributes (hardness, moistness, chewiness, and softness), respectively, on both 9-point intensity and 5-point Just-About-Right (JAR) scales. Liking of test samples was also rated on 9-point hedonic scales. Age group and gender differed in mean ratings, standard deviations, and JAR responses regarding textural attribute intensity and overall liking of test samples, while the effect of consumption frequency was minimal in this regard. Significant contributors of textural attributes to overall liking of cooked rice and wheat bread differed with age group, gender, and consumption frequency. Effects of age group, gender, and consumption frequency on texture perception and overall liking also varied with test samples. This study provides agricultural and food systems professionals with systematic evidence of how textural attribute perception and liking of foods can change based on demographics and test samples.

Comorbid psychiatric disorders in adults with ADHD are important because these comorbidities might complicate the diagnosis of ADHD and also worsen the prognosis. However, the prevalence of comorbid psychiatric disorders in adult ADHD varies according to the diagnostic tools used and the characteristics of target populations. The purpose of this review was to describe the prevalence of comorbid psychiatric disorders in adults with ADHD compared with adults without ADHD. Thirty-two studies published before August 2022 were identified and classified according to diagnosis of other psychiatric disorder in those with ADHD. The most frequent comorbid psychiatric disorder in the ADHD group was substance use disorder (SUD), followed by mood disorders, anxiety disorders, and personality disorders. The prevalence of these four disorders was higher in the ADHD group, whether or not subjects were diagnosed with other psychiatric disorders. In addition, the diversity of ADHD diagnostic tools was observed. This also might have affected the variability in prevalence of comorbidities. Standardization of ADHD diagnostic tools is necessary in the future.

Alzheimer’s disease is one of the most critical brain diseases. The prevalence of the disease keeps rising due to increasing life spans. This study aims to examine the use of hemodynamic signals during hypoxic respiratory challenge for the differentiation of Alzheimer’s disease (AD) and wild-type (WT) mice. Diffuse optical spectroscopy, an optical system that can non-invasively monitor transient changes in deoxygenated (ΔRHb) and oxygenated (ΔOHb) hemoglobin concentrations, was used to monitor hemodynamic reactivity during hypoxic respiratory challenges in an animal model. From the acquired signals, 13 hemodynamic features were extracted from each of ΔRHb and −ΔOHb (26 features total) for more in-depth analyses of the differences between AD and WT. The hemodynamic features were statistically analyzed and tested to explore the possibility of using machine learning (ML) to differentiate AD and WT. Among the twenty-six features, two features of ΔRHb and one feature of −ΔOHb showed statistically significant differences between AD and WT. Among ML techniques, a naive Bayes algorithm achieved the best accuracy of 84.3% when whole hemodynamic features were used for differentiation. While further works are required to improve the approach, the suggested approach has the potential to be an alternative method for the differentiation of AD and WT.

Alzheimer's disease (AD) is the most prevalent neurodegenerative disease characterized by cognitive dysfunction and memory loss as the main symptoms. The deposition of amyloid beta (Aβ) and tau hyperphosphorylation are hallmarks of AD and are major therapeutic targets. However, the exact etiology has not yet been fully elucidated; thus, no drug that cures the disease has been approved. JBPOS0101 is a phenyl carbamate compound that has been tested as a drug for epileptic diseases. In our previous study, we showed that JBPOS0101 attenuated the accumulation of Aβ as well as the deficits in learning and memory in the 5xFAD mouse model. Here, we tested the dose effect (70 or 35 mg/kg) of JBPOS0101 on the memory defect and pathological markers and further investigated the underlying mechanisms in 5xFAD mice. In the behavior tests, JBPOS0101 treatment ameliorated deficits in learning and memory. Moreover, JBPOS0101 attenuated Aβ accumulation and tau phosphorylation. The elevated phosphorylation levels of the active GSK3β form (GSK3β-y216) in 5xFAD, which are responsible for tau phosphorylation, decreased in the JBPOS0101-treated groups. Furthermore, the elevation of reactive astrocytes and microglia in 5xFAD mice was attenuated in JBPOS0101-treated groups. These data suggest that JBPOS0101 may be a new drug candidate to lessen amyloid- and tau-related pathology by regulating glial cells.

During 2015-2017, we surveyed the incidence of viral infections of tomato and paprika growing in greenhouses in Cherwon province, Korea. In 2015 and 2016, we collected leaves and fruits from tomato and paprika plants growing in greenhouses. We detected viruses in the samples collected using specific primer sets for Broad bean wilt virus 2 (BBWV2), Cucumber mosaic virus (CMV), Pepper mild mottle virus (PMMoV), Pepper mottle mosaic virus (PepMoV), and Tomato spotted wilt virus (TSWV). We detected PMMoV, CMV, and TSWV in the samples, and CMV and TSWV were the most prevalent. For the prevention of future viral diseases, we then surveyed the routes of infection by these viruses in tomato and paprika plants growing in greenhouses in Cherwon province in 2017. Leaf and fruit samples were collected from seedlings and crops two and four months after transplanting into greenhouses. As a result, we found that TSWV was transferred from seedlings to plants, and outbreaks of the virus occurred at the early stage of cultivation. On the other hand, we found that CMV was a virus indigenous to the soil of some towns in Cherwon province, and thus outbreaks of this virus occurred at the middle stage of cultivation.

Abstract Background This study aimed to investigate the degree of occupational stress and the clinical mental state of dentists. In addition, we investigated the correlation of occupational stress with depression, anxiety, and sleep among dentists in Korea. Methods A cross-sectional survey on 231 dentists was conducted using the Doctor Job Stress Scale, Center for Epidemiologic Studies Depression Scale (CES-D), State-Trait Anxiety Index (STAI), and Pittsburgh Sleep Quality Index (PSQI). Correlation of occupational stress with mental health was investigated by adjusted multiple regression analysis. Results The scores of CES-D, STAI, and PSQI revealed a significant correlation with the Doctor Job Stress Scale (t = 3.93, P

To secure technological competitiveness in shipbuilding and offshore industries, the continuous application and development of various technologies is essential. Efficient scheduling in shipyards is an important management task, whereby materials and manpower are allocated at the appropriate time and to the correct workspace. Although some large shipyards ensure effective scheduling and production management through simulations employing advanced technologies, most shipbuilding industries, including small- and medium-sized shipyards, continue to use an index based on past experiences. However, this legacy index, termed the basic unit, involves poor engineering logic; therefore, it does not appropriately reflect a shipyard’s working environment, which changes rapidly in response to technological developments. Although this has led to a demand for improvements in the basic unit, a clear solution has not been presented thus far. In this study, a method for calculating the man-hours required for assembly, which is the basis for preparing the basic unit, is proposed. First, the assembly process is analyzed, and individual activities involved in the assembly process are quantified and formulated into working hours, which is defined as a production metric. Based on a ship’s computerized block model, the geometric properties and production information required for calculating the metric are generated automatically as far as possible; this is to establish a convenient production metric calculation system. The proposed method features complete applicability in new shipyards through a customization. It also serves as a tool for predicting the metric of new ships or comparisons with those of existing ships.

Endometriosis, defined as the presence of endometrial cells outside of the uterine cavity, is a major cause of infertility and pelvic pain, afflicting more than 10% of reproductive age women. Endometriosis is a chronic inflammatory disease and lipopolysaccharide promotes the proliferation and invasion of endometriotic stromal cells. Cysteine-rich secretory protein LCCL domain-containing 2 (CRISPLD2) has high affinity for lipopolysaccharide and plays a critical role in defense against endotoxin shock. However, the function of CRISPLD2 has not been studied in endometriosis and uterine biology. Herein, we examined the expression of CRISPLD2 in endometrium from patients with and without endometriosis using immunohistochemistry. The expression of CRISPLD2 was higher in the secretory phase in human menstrual cycle compared to proliferative phase. The expression of CRISPLD2 was significantly decreased in the endometrium of women with endometriosis in the early secretory phase compared to women without endometriosis. The increase of CRISPLD2 expression at the early secretory and dysregulation of its expression in endometriosis suggest progesterone (P4) regulation of CRISPLD2. To investigate whether CRISPLD2 is regulated by P4, we examined the expression of the CRISPLD2 in the uteri of wild-type and progesterone receptor knock out (PRKO) mice. The expression of CRISPLD2 was significantly increased after P4 treatment in the wild-type mice. However, CRISPLD2 expression was significantly decreased in the (PRKO) mice treated with P4. During early pregnancy, the expression of CRISPLD2 was increased in decidua of implantation and post-implantation stages. CRISPLD2 levels were also increased in cultured human endometrial stromal cells during in vitro decidualization. These results suggest that the CRISPLD2 is a target of the progesterone receptor and may play an important role in pathogenesis of endometriosis.

Previous studies suggested effectiveness of psilocybin in the field of mental health. FDA designated psilocybin as a "breakthrough therapy" for the treatment of treatment-resistant depression (TRD) in 2018. This paper provided a review of psilocybin's potential role in treatment of depression by focusing on published clinical trials. Studies showed that psilocybin, an agonist on 5-HT2A receptors, manifests antidepressant and anxiolytic effects by increasing glutamate transmission, reducing brain inflammation, decreasing default mode network activity. In terms of clinical trials, eleven studies (six open-label and five double blinded randomized clinical trials, DB-RCTs) trials exploring psilocybin's impact on depression were found. Among open-label studies, a pilot study on TRD patients demonstrated significant reductions in depressive symptoms after two psilocybin sessions. Psilocybin also improved cognitive bias associated with depression. Extension studies confirmed sustained improvements and high remission rates. Among five DB-RCTs, two showed that psilocybin led to significant reductions in anxiety and depression in cancer patients, and the improvements sustained for over 6 months. In MDD, psilocybin showed rapid reductions in depression, with higher remission rates compared to escitalopram in a DB-RCT. Another DB-RCT showed that psilocybin induced higher decrease in depression around 6 hours after their administrations than placebo. The last DB-RCT showed that in patients with TRD, a single dose of psilocybin 25 mg, but not psilocybin 10 mg, resulted in superior antidepressant effect than psilocybin 1 mg. Overall, psilocybin showed promise in treating depression and anxiety, with notable safety profiles. Further research should explore optimal dosages and long-term effects. [ABSTRACT FROM AUTHOR]

The most common aging-related neurodegenerative disorder is Alzheimer's disease (AD), of which the main symptom is memory disturbance. Though the mechanism of AD pathogenesis is not fully defined, abnormal aggregation of amyloid beta (Aβ) plaques and tau have been considered as key factors and main histological hallmarks of the disease. Astrocyte is responsible for the control of cells and the environment around brain and spinal cord cells. Astrocytes have been implicated with AD. However, the exact function of astrocytes in AD has not been established. In this study, we investigated the regulation of astrocytes in the AD model using primary cultures. We have demonstrated that oligomerized Aβ is toxic to neurons and can induce cell death in primary cultures. In the primary cultures containing neurons and astrocytes, amyloid beta uptake was observed in both neurons and astrocytes. To verify if the uptake of amyloid beta in astrocytes is dependent on neurons, we separated and cultured primary astrocytes with no neurons. Amyloid uptake was still observed in this pure astrocyte culture, suggesting that the uptake of amyloid beta is a neuron-independent function of astrocytes. Astrocyte activation was observed in both pure and mixed cultures. Taken together, our data suggest that astrocyte is activated by oligomerized Aβ and uptakes it, which is independent of neurons. [ABSTRACT FROM AUTHOR]