Abstract This study aimed to examine negative life events (NLEs) and depressive tendencies as predictors of homebound status, which poses a risk of long-term frailty in older adults. A population-based cohort study (2018-2020) using self-administered questionnaires was conducted with older adults (65-94 years) in the rural community of Akita Prefecture, Japan. The response rate at the baseline survey in 2018(T1) was 61.5%. About 81.1% (1,048 out of 1,291) of the participants at T1 responded to the follow-up survey in 2020 (T2). Among them, 77.3% (810) were not homebound at T1. After data cleaning, 790 participants’ data were analyzed. A frequency of going out less than once a week was considered a homebound status. In this study, NLEs included 1) loss of a close relative, 2) major illness or injury to oneself, 3) major illness or injury to a family member, 4) financial difficulties, and 5) loss of one’s role (family, workplace, society, others). Depressive tendencies were evaluated using the 6-item Kessler Psychological Distress Scale (0-24 scale). A K6 score ≥ 9 indicates depressive tendencies. Logistic regression analysis was adjusted for potential confounders. The incidence of being homebound at two years was 10.1% for men and 17.1% for women, with a significant gender difference (p< 0.01). The adjusted odds ratio for depressive tendencies was 3.37 (95%CI= 1.62-7.01) among homebound (vs. non-homebound) individuals. However, the five NLEs were not statistically significant. Our results suggest that depressive tendencies, but not NLEs, can cause older adults to remain housebound.
Gamma knife radiosurgery (RS) has been introduced as a modern therapy for brain tumors. However, the effects of RS for neuroepithelial tumors are still obscure. The present study investigates the radiological and histological changes after RS to elucidate the biological effect. There were seven cases (two males and five females), ranging from 4 to 71 years with a mean age of 33 years. Two cases were located in the brainstem, another two in the cerebellum, and one each in the thalamus, the hypothalamus, and the frontal lobe. Histologically, two cases had gangliogliomas, four astrocytomas (1 pilocytic, 1 fibrillary, 2 anaplastic), and one glioblastoma. RS was performed after surgery with a central dose of 30-36 Gy. All cases were evaluated radiologically on MRI before and after RS. Four cases (3 astrocytomas and 1 glioblastoma) which neurologically deteriorated after RS were reoperated. These cases were examined using HE and immunohistochemical studies with antibodies of CD34, alpha-smooth muscle actin (SMA), p53, p21 and MIB-1 on the sections before and after RS. MRI demonstrated perifocal edema and intratumoral hypointensity on T2 weighted imaging (T2WI), suggesting radionecrosis in most of the cases within 6 months after RS. In the central part of the RS, destructive changes were observed in the tumor cells and endothelial cells: decrease in the tumor cell population, coagulation necrosis, and fibrinoid degeneration of vascular walls were revealed. In the peripheral part, however, some tumors contained viable tumor cells intermingled with blood vessels showing endothelial and pericytic proliferations. The increase of MIB-1 staining index was found in only one case. The p21 immunoreactivity was increased in endothelial cells, although the p53 immunoreactivity was unchanged. These results suggested that radionecrosis occurred earlier and more frequently in neuroepithelial tumors after RS than after conventional radiation.
Abstract Background Primary lateral sclerosis (PLS) is an extremely rare condition; therefore, to date no clinical studies have been conducted. The Primary Lateral Sclerosis Functional Rating Scale (PLSFRS) was developed in the United States of America. The PLSFRS is a crucial assessment scale for international collaborative research and future clinical trials for PLS. It is useful for evaluating medical conditions through face-to-face assessments and telephone interviews such as when a face-to-face assessment is not possible due to disasters or the burden of hospital visits. This study assessed the reliability and consistency of in-person and telephone interviews using the Japanese version of the PLSFRS. Methods We enrolled 19 Japanese patients who met the specific criteria for inclusion at the six collaborating institutions. The PLSFRS assessments were performed by two evaluators at defined time points and analyzed for intra-rater and inter-rater reliability and consistency between the in-person and telephone interviews. Results The Japanese version of the PLSFRS was developed by a specialized company and translator, and modified to consider the Japanese lifestyle through a consensus among motor neuron specialists. The quadratic-weighted kappa coefficients for the intra-rater and the inter-rater agreement were substantial (intra-rater: 0.691-1.000, inter-rater: 0.634-1.000). Moreover, the intraclass correlation coefficient for the PLSFRS total score was 0.997 (95% confidence interval, 0.992–0.999). Conclusions This study provides results regarding the Japanese version of the PLSFRS intra-rater and inter-rater reliability and consistency between in-person and telephone interviews.
Abstract Primary dystonia is thought to emerge through abnormal functional relationships between basal ganglia and cerebellar motor circuits. These interactions may differ across disease subtypes and provide a novel biomarker for diagnosis and treatment. Using a network mapping algorithm based on resting-state functional MRI (rs-fMRI), a method that is readily implemented on conventional MRI scanners, we identified similar disease topographies in hereditary dystonia associated with the DYT1 or DYT6 mutations and in sporadic patients lacking these mutations. Both networks were characterized by contributions from the basal ganglia, cerebellum, thalamus, sensorimotor areas, as well as cortical association regions. Expression levels for the two networks were elevated in hereditary and sporadic dystonia, and in non-manifesting carriers of dystonia mutations. Nonetheless, the distribution of abnormal functional connections differed across groups, as did metrics of network organization and efficiency in key modules. Despite these differences, network expression correlated with dystonia motor ratings, significantly improving the accuracy of predictions based on thalamocortical tract integrity obtained with diffusion tensor MRI (DTI). Thus, in addition to providing unique information regarding the anatomy of abnormal brain circuits, rs-fMRI functional networks may provide a widely accessible method to help in the objective evaluation of new treatments for this disorder.
Adenoid cystic carcinoma is a malignant epithelial tumor derived from salivary glands and tends to invade the surrounding structures including nervous system. We present a case of adenoid cystic carcinoma with intracranial extension and propose a novel molecular mechanism of adenoid cystic carcinoma metastasis. A 29-year-old Japanese male presented with left trigeminal nerve disturbance. Neuroimaging revealed a tumor located at the right middle cranial and infratemporal fossa. The tumor was removed via a subtemporal extradural and infratemporal fossa approach and histologically diagnosed as adenoid cystic carcinoma. Radiological and operative findings confirmed a perineural spread of the tumor along the mandibular nerve. Immunohistochemical analyses of molecular consequences in this case were performed for better understanding of the biological processes associated with adenoid cystic carcinoma metastasis. First, the neoplastic cells were not immunoreactive for E-cadherin, an epithelial marker, but for vimentin, a mesenchymal marker, suggesting changes in cell phenotype from epithelial to mesenchymal states. Correspondingly, immunoreactivity of transcriptional factors, such as Slug, Twist, matrix metalloproteinase-2 and -9, which are involved in epithelial–mesenchymal transition, were observed. Second, elevated expression of EphA2 receptor, not ephrin-A1, was notable in the neoplastic cells, suggesting morphological changes reminiscent of epithelial–mesenchymal transition and ligand-independent promotion of tumor cell migration and invasion. We report a case of adenoid cystic carcinoma with perineural spread and provide the first published evidence that EphA2 expression without ephrin-A1 and epithelial–mesenchymal transition might play important roles in adenoid cystic carcinoma progression.
Table S1. Dataset of patients with glioblastoma from Kansai Molecular Diagnosis Network for CNS tumors (n = 234). Table S2. Dataset of patients with glioblastoma from The Cancer Genome Atlas (n = 577). Table S3. Log odds ratio in pair association analysis for genetic aberrations. Table S4. P-value from two-tailed Fisher’s exact test in pair association analysis for genetic aberrations. Table S5. Univariate analysis for each molecular variable using Cox proportional hazards models in Step2. Table S6. Sequences of primers used for amplification and Sanger sequencing. Table S7. Sequences of primers used for quantitative methylation specific PCR. (ZIP 256 kb)
We aimed to compare the cytokine and chemokine profiles of patients with multifocal motor neuropathy (MMN) with those of patients with progressive muscular atrophy (PMA) and amyotrophic lateral sclerosis (ALS) to investigate immunologic differences in the CNS.CSF from 12 patients with MMN, 8 with PMA, 26 with sporadic ALS, and 10 with other noninflammatory neurologic disorders was analyzed for 27 cytokines and chemokines using the multiplex bead array assay. Cytokine titers of the 4 groups were compared, and correlations between the titers of relevant cytokines and clinical parameters were evaluated.There were no obvious intrathecal changes except for interleukin (IL)-1 receptor antagonist in patients with MMN. In contrast, IL-4, IL-7, IL-17, eotaxin/CCL11, fibroblast growth factor-2 (FGF-2), granulocyte colony-stimulating factor (G-CSF), and platelet-derived growth factor BB titers were significantly elevated in patients with PMA and ALS; of these, FGF-2 and G-CSF titers were elevated compared with those in patients with MMN. IL-4 and IL-10 titers were high in patients with ALS, particularly patients with possible ALS presenting with a slowly progressive course or mild symptoms.The CSF cytokine profile of patients with MMN is distinct from that of patients with PMA and ALS. The similarity of the cytokine profiles between patients with PMA and ALS suggests that PMA shares common immunologic features with ALS in the CNS, even without clinical evidence of upper motor neuron involvement.
Background: Globally, adolescent sexual behavior is a major health concern and the focus of many researches. However, negative attitude towards premarital sex and sense of community belonging have not been examined in relation to adolescent sexual behavior. The purpose of this study was to examine whether these two factors are associated with adolescent sexual behavior. Methods: We conducted a cross-sectional survey of 1672 eleventh grade students from three public high schools in Hanoi, Vietnam. Participants’ sense of community belonging and negative attitude towards premarital sex were assessed through a self-administered questionnaire. We performed multiple logistic regression analyses to examine associations between the cognitive social capital concepts, such as a sense of community belonging. Results: 92.3% of students agreed with a sense of community belonging, but only 14.1% of students accepted premarital sex. A high sense of community belonging was significantly associated with negative attitude towards premarital sex OR (95% CI), male 3.16 (2.3-4.34), female 8.77 (5.38-14.29). After adjusting for a sense of community belonging, the association disappeared between acceptance of premarital sex and sexual experience of peers, proper time to wear a condom, and Rosenberg Self-Esteem Scale score. Conclusion: Cognitive social capital, such as sense of community belonging, was associated with negative attitude towards premarital sex. Therefore, cognitive social capital concepts should be included in sexual behavior and health promotions, especially with adolescents.
OBJECTIVE: To detect CNS inflammatory responses which can be associated with the pathogenesis of sporadic Creutzfeldt-Jakob disease (sCJD). BACKGROUND: Inflammatory responses in the cerebrospinal fluid (CSF) of patients with sCJD remain elusive. DESIGN/METHODS: We conducted a case-control study. Fourteen patients with sCJD, 14 with non-inflammatory neurological disorders and 14 with autoimmune encephalitis were enrolled. We used the suspension array system to measure the concentrations of 27 cytokines in CSF. The cytokine titers of the 3 groups were compared, and the correlation between the relevant cytokine titers and clinical parameters were investigated in the patients with sCJD. RESULTS: The 2 cytokines interleukin (IL)-1 receptor antagonist and IL-17 were significantly elevated in the patients with sCJD compared with those in the patients with non-inflammatory neurological disorders: IL-17 in sCJD was approximately 10 times higher compared with that in the non-inflammatory neurological disorders (mean, 35.46 vs. 3.45 pg/ml; p < 0.001) but comparable to that in encephalitis (mean, 32.16 pg/ml). In contrast, classical pro-inflammatory cytokines such as IL-12(p70) and tumor necrosis factor-α were increased only in encephalitis. Although not significant, IL-17 titers tended to be higher in the patients with shorter disease duration before CSF sampling (r = −0.452; p = 0.104) and in those with lower CSF total protein concentrations (r = −0.473; p = 0.086). CONCLUSIONS: IL-17 is significantly increased in CSF in sCJD, which can be an early event in the pathogenesis of sCJD. Study Supported by: JSPS KAKENHI Grant Number 25860715.
