Risk of Parkinson's disease-related death in cancer survivors: A population-based study in Japan

Hayano E., Gon Y., Kimura Y., et al. Risk of Parkinson's disease-related death in cancer survivors: A population-based study in Japan. Parkinsonism and Related Disorders 119, 105966 (2024); https://doi.org/10.1016/j.parkreldis.2023.105966.Background: The risk of Parkinson's disease (PD)-related death in patients with cancer largely unexplored. Methods: We analyzed data from the Neoplasms ANd other causes of DEath (NANDE) study, which investigates the causes of death in patients with cancer in Japan. Standardized mortality ratios (SMRs) were calculated to compare the risk of PD-related deaths in patients with cancer to that of the general population. Poisson regression models were employed to estimate the relative risk of PD-related death in the subgroups. Results: The cohort included 548,485 patients with cancer, yielding 2,047,398 person-years at risk from 1995 to 2013. During the study period, 242,250 patients died and 145 deaths were attributable to PD. The SMR for PD-related death was 2.34 (95% confidence interval [CI]: 1.99–2.75). Patients who were diagnosed with cancer before 70 years of age had a high SMR (>5) for PD-related deaths. The SMR of patients with mouth-to-stomach cancers (lip, oral cavity, pharynx, esophagus, and stomach cancers) was 3.72 (95% CI: 2.84–4.86), while that of those with other cancers was 1.93 (95% CI: 1.57–2.37). The multivariate Poisson regression model revealed that patients with mouth-to-stomach cancers were more likely to die of PD than those without (relative risk 2.07, 95 % CI; 1.46–2.93). Conclusions: Patients with cancer are at a high risk of PD-related death; particularly, mouth-to-stomach cancers and potentially obstructing medication for PD are attributable to a high mortality risk. Careful management, including adequate PD treatment, would benefit cancer survivors with PD and reduce the risk of PD-related death

Decreased hepatic enzymes reflect the decreased vitamin B6 levels in Parkinson's disease patients

Ikenaka K., Kajiyama Y., Aguirre C., et al. Decreased hepatic enzymes reflect the decreased vitamin B6 levels in Parkinson's disease patients. Pharmacology Research and Perspectives 12, e1174 (2024); https://doi.org/10.1002/prp2.1174.The study aims to investigate the vitamin B6 levels in Parkinson's disease (PD) patients and their association with liver enzymes and evaluate how much dysregulation is associated with levodopa dose. Furthermore, to evaluate the effect of Opicapone, a catechol-o-methyl-transferase inhibitor, on vitamin B6 levels by monitoring the AST and ALT levels in patients treated with Levodopa–Carbidopa Intestinal Gel Infusion (LCIG). For these aims, serum vitamin B6 levels were measured (PD, n = 72 and controls, n = 31). The vitamin B6 level was compared with the total levodopa dose, clinical parameters, and blood homocysteine, albumin, and hemoglobin levels in PD patients. Correlations between vitamin B6 levels and AST and ALT levels, as well as the ratio ALT/AST, were analyzed. Changes in the AST and ALT levels and ALT/AST were analyzed in the patients treated with LCIG before and after the therapy (n = 24) and in the patients treated with LCIG + Opicapone before and after Opicapone treatment (n = 12). We found vitamin B6 levels were significantly lower in PD patients. Total levodopa dose and albumin levels were independently associated with vitamin B6 levels. Decreased vitamin B6 levels appeared as lower AST and ALT levels and ALT/AS. Treatment with LCIG decreased the AST and ALT levels and ALT/AST. Adjunctive therapy with Opicapone to LCIG ameliorated the decreased ALT and ALT/AST. We conclude that the ALT and ALT/AST can be useful parameters for monitoring vitamin B6 levels and Opicapone can ameliorate the dysregulated vitamin B6 in PD patients

The validation of a Japanese version of the New Freezing of Gait Questionnaire (NFOG-Q)

The version of record of this article, first published in Neurological Sciences, is available online at Publisher’s website: https://doi.org/10.1007/s10072-024-07405-y.Objective: This study aimed to develop a Japanese version of the New Freezing of Gait Questionnaire (NFOG-Q) and investigate its validity and reliability. Methods: After translating the NFOG-Q according to a standardised protocol, 56 patients with Parkinson’s disease (PD) were administered it. Additionally, the MDS-UPDRS parts II and III, Hoehn and Yahr (H&Y) stage, and number of falls over 1 month were evaluated. Spearman’s correlation coefficients (rho) were used to determine construct validity, and Cronbach’s alpha (α) was used to examine reliability. Results: The interquartile range of the NFOG-Q scores was 10.0–25.3 (range 0–29). The NFOG-Q scores were strongly correlated with the MDS-UPDRS part II, items 2.12 (walking and balance), 2.13 (freezing), 3.11 (freezing of gait), and 3.12 (postural stability) and the postural instability and gait difficulty score (rho = 0.515–0.669), but only moderately related to the MDS-UPDRS item 3.10 (gait), number of falls, disease duration, H&Y stage, and time of the Timed Up-and-Go test (rho = 0.319–0.434). No significant correlations were observed between age and the time of the 10-m walk test. The internal consistency was excellent (α = 0.96). Conclusions: The Japanese version of the NFOG-Q is a valid and reliable tool for assessing the severity of freezing in patients with PD

New Insights into Freezing of Gait in Parkinson's Disease from Spectral Dynamic Causal Modeling

Taniguchi S., Kajiyama Y., Kochiyama T., et al. New Insights into Freezing of Gait in Parkinson's Disease from Spectral Dynamic Causal Modeling. Movement Disorders, (2024); https://doi.org/10.1002/mds.29988.Background: Freezing of gait is one of the most disturbing motor symptoms of Parkinson's disease (PD). However, the effective connectivity between key brain hubs that are associated with the pathophysiological mechanism of freezing of gait remains elusive. Objective: The aim of this study was to identify effective connectivity underlying freezing of gait. Methods: This study applied spectral dynamic causal modeling (DCM) of resting-state functional magnetic resonance imaging in dedicated regions of interest determined using a data-driven approach. Results: Abnormally increased functional connectivity between the bilateral dorsolateral prefrontal cortex (DLPFC) and the bilateral mesencephalic locomotor region (MLR) was identified in freezers compared with nonfreezers. Subsequently, spectral DCM analysis revealed that increased top-down excitatory effective connectivity from the left DLPFC to bilateral MLR and an independent self-inhibitory connectivity within the left DLPFC in freezers versus nonfreezers (>99% posterior probability) were inversely associated with the severity of freezing of gait. The lateralization of these effective connectivity patterns was not attributable to the initial dopaminergic deficit nor to structural changes in these regions. Conclusions: We have identified novel effective connectivity and an independent self-inhibitory connectivity underlying freezing of gait. Our findings imply that modulating the effective connectivity between the left DLPFC and MLR through neurostimulation or other interventions could be a target for reducing freezing of gait in PD

Clinical Usefulness of Multiplex PCR Lateral Flow in MRSA Detection: A Novel, Rapid Genetic Testing Method

Methicillin-resistant Staphylococcus aureus (MRSA) with exogenous cassette DNA containing the methicillin-resistant gene mecA (SCCmec) poses a problem as a drug-resistant bacterium responsible for hospital- and community-acquired infections. The frequency of MRSA detection has recently been increasing rapidly in Japan, and SCCmec has also been classified more diversely into types I–V. A rapid test is essential for early diagnosis and treatment of MRSA infections, but detection by conventional methods requires at least two days. The newly developed multiplex PCR lateral flow method allows specific amplification of femA to detect S. aureus, mecA to detect SCCmec, and kdpC to detect SCCmec type II; moreover, PCR products can be evaluated visually in about 3 h. In the present study, we developed a PCR lateral flow method for MRSA using this method and investigated its clinical usefulness in the detection of MRSA. The results showed a diagnostic concordance rate of 91.7% for MRSA and methicillin-susceptible S. aureus between bacteriological examination and PCR lateral flow, and a high level of specificity in PCR lateral flow. In addition, a higher detection rate for S. aureus using the same sample was observed for PCR lateral flow (70.2%) than for bacteriological tests (48.6%). The above results show that PCR lateral flow for MRSA detection has high sensitivity, specificity, and speed, and its clinical application as a method for early diagnosis of MRSA infections appears to be feasible

Example-based Speech Intention Understanding and Its Application to In-Car Spoken Dialogue System

This paper proposes a method of speech intention understanding based on dialogue examples. The method uses a spoken dialogue corpus with intention tags to regard the intention of each input utterance as that of the sentence to which it is the most similar in the corpus. The degree of similarity is calculated according to the degree of correspondence in morphemes and dependencies between sentences, and it is weighted by the dialogue context information. An experiment on inference of utterance intentions using a large-scale in-car spoken dialogue corpus of CIAIR has shown 68.9 % accuracy. Furthermore, we have developed a prototype system of in-car spoken dialogue processing for a restaurant retrieval task based on our method, and confirmed the feasiblity of the system.

Generation and Utilization of a Monoclonal Antibody against Hepatitis B Virus Core Protein for a Comprehensive Interactome Analysis

Hepatitis B virus (HBV) core antigen (HBc) is a structural protein that forms the viral nucleocapsid and is involved in various steps of the viral replication cycle, but its role in the pathogenesis of HBV infection is still elusive. In this study, we generated a mouse monoclonal antibody (mAb) against HBc and used it in antibody-based in situ biotinylation analysis in order to identify host proteins that interact with HBc. HBc antigen was produced with a wheat germ cell-free protein synthesis system and used to immunize mice. Among the established hybridoma clones, a single clone (mAb #7) was selected and further characterized for its ability in the antibody-based in situ biotinylation analysis to collect host proteins that are in the vicinity of HBc. Using mass spectrometry, we identified 215 HBc-interacting host proteins, three of which bind HBc most significantly under hypoxic conditions. Our results indicate that mAb #7 can be used to systematically identify host proteins that interact with HBc under pathophysiological conditions, and thus may be useful to explore the molecular pathways involved in HBV-induced cytopathogenesis

Mode of Transposition and Expression of 16S rRNA Methyltransferase Gene rmtC Accompanied by ISEcp1

A newly identified 16S rRNA methyltransferase gene, rmtC, was accompanied by an ISEcp1 element at its 5′ end. This ISEcp1 element, which contained a transposase gene, tnpA, provided a promoter activity for expression of the adjacent rmtC; and this structure enabled the rmtC gene to be transposed onto another plasmid in Escherichia coli