The necessity to improve disaster preparedness among patients with amyotrophic lateral sclerosis and their families.

Disaster preparation is an important issue for patients with amyotrophic lateral sclerosis (ALS). However, to the best of our knowledge, no studies have investigated disaster preparedness among patients with ALS. In this study, we aimed to investigate disaster preparation in patients with ALS and their caregivers, including their families, in Japan. We conducted a nationwide webinar in September 2022 titled "ALS Café" and distributed a self-report questionnaire to participants with questions about awareness of disaster preparedness, social countermeasures, stockpiles, and electricity demand. Forty-eight patients with ALS (27 male; average age 60.0 ± 9.3 years) and 23 caregivers (8 male; 55.7 ± 9.9 years) responded. The median revised ALS Functional Rating Scale score was 30.5, and 25% of the patients with ALS were on a ventilator. More than 70% of the respondents answered that they were not prepared for disasters, increasing to 89% in patients not using ventilators. In the event of their phones being down, 86% of the respondents had no plans for alternative means of communication. <30% of the respondents, including ventilator users, had secured human resources for transportation. Twenty-five percent of the respondents did not stockpile food and beverages, and 12% of the ventilator users had no government-recommended ventilator preparation equipment. Thus, although patients with ALS and their families with ventilators have a high awareness of disaster preparedness, their awareness remains insufficient. Furthermore, patients with ALS and their families without ventilators have a low awareness of disaster preparedness. Therefore, better education regarding disaster preparedness is necessary for these groups.

The Burden of Attention-Deficit/Hyperactivity Disorder Traits in Adult Patients with Major Depressive Disorder in Japan.

Purpose: Symptoms of attention-deficit/hyperactivity disorder (ADHD) often overlap with and are hidden by those of mood disorders, including major depressive disorder (MDD), resulting in adult ADHD patients being misdiagnosed as MDD. This study aims to examine if diagnosed MDD patients are more likely to exhibit ADHD traits and if the presence of ADHD traits increases the humanistic burden, including the impairment of health-related quality of life (HRQoL), work productivity and activity impairment (WPAI), and health-care resource utilization (HRU), on MDD patients in Japan. Methods: This study utilized existing National Health and Wellness Survey (NHWS) data. The 2016 Japan NHWS is an internet-based survey comprising a total of 39,000 respondents, including those with MDD and/or ADHD. A randomly selected subset of the respondents responded to the Japanese-version Adult ADHD self-report scale (ASRS-v1.1; ASRS-J) symptom checklist. Respondents were considered ASRS-J-positive if the total score was ≥36. The HRQoL, WPAI, and HRU were assessed. Results: Among MDD patients (n = 267), 19.9% were screened ASRS-J-positive, while 4.0% of non-MDD respondents (n = 8885) were ASRS-J-positive. There was a significant association between MDD status and ASRS-J status (crude odds-ratio [OR]: 5.9) as well as between MDD status and ADHD-diagnosis status (crude OR: 22.6). MDD patients who were ASRS-J positive experienced significantly lower HRQoL and higher WPAI than those who were ASRS-J negative. Limitations of this study include potential recall bias owing to the self-report nature of the survey and lack of objective confirmation of MDD diagnosis through review of medical records. Conclusion: This study demonstrated a significant association between MDD status and exhibiting ADHD traits. Adult MDD patients screened ASRS-J-positive experienced significantly higher humanistic burden than patients screened ASRS-J-negative. Our results emphasize the importance of ensuring appropriate screening of ADHD and looking out for potentially hidden ADHD symptoms when diagnosing and treating MDD in adulthood.

The Assessment of the Diagnostic Delay in Japanese People with Parkinson's Disease Using a Web-based Survey of Patients and Physicians.

Objective Although diagnostic criteria of Parkinson's disease (PD) have been established, the details of the process by which patients notice symptoms, visit a physician, and receive a diagnosis of PD is unclear. We therefore explored factors influencing latency in diagnosing PD. Methods We performed an internet-based survey of patients with PD and their families as well as physicians treating patients with PD to identify any diagnostic latency and its determinants. Evaluated factors included motor and non-motor symptoms, the diagnosis history and symptoms, patients' feelings toward PD prior to the diagnosis, and physician-determined reasons for the diagnostic delay. Results Among the 186 eligible patient respondents (including 87 responses from family members of patients), 24% received a PD diagnosis >1 year after the onset of PD-related symptoms, 58.6% had mid- or late-stage PD at the diagnosis, and 29% of patients had initially thought their symptoms were common age-related phenomena. Tremor (42%) was the most frequent symptom that led patients to visit a medical institution, whereas gait disturbance (14%) was the least frequent. More patients diagnosed with early-stage PD than those diagnosed with mid- or late-stage PD consulted a neurologist at their first visit. Among the 331 eligible physicians, patients' misinterpretation of their symptoms as being age-related was deemed one of or the most common cause (s) of a diagnostic delay by 67% and 36%, respectively. Conclusion Patients' insufficient or misinterpreted information about PD may cause delays in accessing healthcare services, leading to diagnostic delay.

Liver Abscess due to Streptococcus intermedius Bacteremia and Its Association with Colonic Carcinoma: Is Bacteremia with Streptococcus intermedius an Alert for Colonic Carcinoma?

Liver abscess caused by some kinds of Streptococcus group such as Streptococcus bovis group has been recognized to associate with colorectal cancer. Streptococcus milleri group with liver abscess has not been received much attention in this point of view. Here, we report the case of a 63-year-old man who developed liver abscess with S. intermedius, which belongs to the S. milleri group. We confirmed that this case was accompanied by cecal carcinoma by colonoscopy. The tumor was a pathological lead point of intussusception of cecum. On the 26th day, open right hemicolectomy was performed. In this case, bacterial endophthalmitis was a complication due to bacteremia. The patient underwent ophthalmic surgery on the 98th day. Research investigating 16S rRNA of the mucosal colon microbiome reported that the S. intermedius gene was upregulated in patients with colorectal carcinoma. It is recommended that liver abscess with S. intermedius bacteremia should alert the clinician about the risks of carcinoma of the colon and abscess formation in distant organs. We here list the case reports of liver abscess caused by Streptococcus other than S. bovis group, which was associated with colonic carcinoma, and suggest the need for further research about S. milleri group.

Rasagiline as Adjunct to Levodopa for Treatment of Parkinson's Disease: A Systematic Review and Meta-Analysis.

Background: Rasagiline is a selective, irreversible monoamine oxidase type B inhibitor used as monotherapy in early Parkinson's disease and as an adjunct therapy to levodopa in Parkinson's disease with motor fluctuations. Objectives: This meta-analysis aimed to provide updated evidence on the efficacy for motor and nonmotor symptoms and the safety of rasagiline/levodopa versus levodopa in patients with Parkinson's disease experiencing motor fluctuations. Methods: A systematic literature search was conducted (January 18-19, 2021) using PubMed, Cochrane Library, EMBASE, Web of Science, and Google Scholar to identify randomized controlled trials comparing rasagiline/levodopa versus placebo/levodopa in patients with Parkinson's disease experiencing motor fluctuations. Outcomes included change in wearing-off time, Unified Parkinson's Disease Rating Scale (UPDRS)/Movement Disorder Society-UPDRS (MDS-UPDRS) II and III scores, treatment-emergent adverse events (TEAEs), and Parkinson's Disease Questionnaire (PDQ-39) summary index score. A random effect model was used to estimate the treatment effects. Results: Six studies were included (1912 patients). Significant improvements in wearing-off time (standardized mean difference [SMD]: -0.50, 95% confidence interval [CI]: -0.92 to -0.09, p = 0.002), levodopa dosage (SMD: -0.18, 95% CI: -0.35 to -0.01, p = 0.041), UPDRS/MDS-UPDRS II (SMD: -0.39, 95% CI: -0.52 to -0.25, p < 0.0001), UPDRS/MDS-UPDRS III (SMD: -0.30, 95% CI: -0.44 to -0.16, p < 0.0001), and PDQ-39 summary index score (SMD: -0.21, 95% CI: -0.37 to -0.04, p = 0.013) were observed with rasagiline/levodopa versus placebo/levodopa. The incidence of TEAEs did not differ between treatments (risk ratio: 1.13, 95% CI: 0.98-1.30, p = 0.093). Conclusions: This meta-analysis further indicated the superiority of rasagiline/levodopa in improving motor and nonmotor symptoms of Parkinson's disease, with a similar safety profile to that of levodopa in Parkinson's disease with motor fluctuations.

Working Conditions, Work Productivity, Quality of Life, and Depressive Symptoms in Undiagnosed Adults with and without Attention-Deficit/Hyperactivity Disorder (ADHD) Symptoms During the COVID-19 Pandemic.

Purpose: This study aims to evaluate the impact of the COVID-19 pandemic on employment status, work productivity, quality of life (QOL), and depressive symptoms in undiagnosed adults with and without attention-deficit/hyperactivity disorder (ADHD) symptoms in Japan. Methods: An observational study used baseline data from a Japanese Medilead Healthcare Panel before the COVID-19 pandemic (October-December 2019). Eligible panel participants were then surveyed during the pandemic (March 2021). ADHD symptoms were screened using the Adult ADHD Self-Report Scale. Changes in QOL (EuroQol 5-Dimensions 5-Levels; EQ-5D-5L) and productivity impairment (Work Productivity and Activity Impairment scale; WPAI) from before to during the pandemic were analyzed in undiagnosed adults with and without ADHD symptoms. Unemployment rate and depressive symptoms (Patient Health Questionnaire; PHQ-9) during the pandemic were compared between groups. Results: Participants with (N=949) and without (N=942) ADHD symptoms completed the survey. The unemployment rate was not significantly different between participants with and without ADHD symptoms. Participants with ADHD symptoms were more likely to change jobs or employers during the pandemic. PHQ-9 scores in participants with ADHD symptoms were significantly higher than in those without ADHD symptoms (8.96 vs 3.57, respectively) during the pandemic. Before the pandemic, WPAI scores were significantly higher and EQ-5D-5L scores lower in participants with ADHD symptoms than in those without. Productivity improved and QOL was not altered during the pandemic in both groups, but productivity and QOL remained poorer among participants with ADHD symptoms than in those without. Conclusion: Productivity was improved among all participants during the COVID-19 pandemic, contrary to expectations. However, adults with ADHD symptoms consistently had lower productivity, poorer QOL, and more depressive symptoms than those without ADHD symptoms.

Second-order moiré method for accurate deformation measurement with a large field of view.

In this study, we propose a second-order moiré method by performing digital sampling at two stages to realize high-accuracy deformation measurement in a wide field of view, where a grid image is recorded at a low magnification. Simulations have verified that this method has high strain measurement accuracy when the grid pitch is close to or even smaller than two pixels for both parallel and oblique grids with random noise. As an application, the two-dimensional microscale strain distributions of a carbon fiber reinforced plastic specimen when the grid pitch was about 2.1 pixels were presented. Shear strain concentration was detected before an interlaminar crack emerged, and tensile strain concentration was found prior to the occurrence of a transverse crack. The proposed method makes the two-step phase-shifting technique achieved indirectly, not only enlarging the field of view, but also maintaining the measurement accuracy.

Plasma Exchange Therapy to Reduce Mortality in Japanese Patients With Diffuse Alveolar Hemorrhage and Microscopic Polyangiitis.

Diffuse alveolar hemorrhage (DAH) is well known as a serious complication of microscopic polyangiitis (MPA). We examined the effectiveness of plasma exchange (PLEX) therapy to reduce mortality in Japanese DAH patients with MPA. This retrospective, double-center, observational cohort study included 20 DAH patients with MPA who were admitted to Juntendo University Hospital or Juntendo Koto Geriatric Medical Center between April 1998 and March 2018. The primary outcome was non-disease-specific mortality. The 1-year survival rate of patients with PLEX therapy (N = 4) was higher than that of patients with conventional therapy (N = 16, 75% and 13%, respectively, P = 0.037). Higher values of the 1996 Five-Factor Score (FFS) and 2009 FFS were associated with increased mortality, with hazard ratios of 2.29 (P = 0.040) and 2.41 (P = 0.043), respectively, by Cox univariate analysis. We investigated PLEX therapy for reducing mortality in DAH patients with MPA, and the 1996 FFS and 2009 FFS were both independent prognostic factors.

Structurally distinct α-synuclein fibrils induce robust parkinsonian pathology.

OBJECTIVE: Alpha-synuclein (α-syn) is a major component of Lewy bodies, which are the pathological hallmark in Parkinson's disease, and its genetic mutations cause familial forms of Parkinson's disease. Patients with α-syn G51D mutation exhibit severe clinical symptoms. However, in vitro studies showed low propensity for α-syn with the G51D mutation. We studied the mechanisms associated with severe neurotoxicity of α-syn G51D mutation using a murine model generated by G51D α-syn fibril injection into the brain. METHODS: Structural analysis of wild-type and G51D α-syn-fibrils were performed using Fourier transform infrared spectroscopy. The ability of α-syn fibrils forming aggregates was first assessed in in vitro mammalian cells. An in vivo mouse model with an intranigral injection of α-syn fibrils was then used to evaluate the propagation pattern of α-syn and related cellular changes. RESULTS: We found that G51D α-syn fibrils have higher ß-sheet contents than wild-type α-syn fibrils. The addition of G51D α-syn fibrils to mammalian cells overexpressing α-syn resulted in the formation of phosphorylated α-syn inclusions at a higher rate. Similarly, an injection of G51D α-syn fibrils into the substantia nigra of a mouse brain induced more widespread phosphorylated α-syn pathology. Notably, the mice injected with G51D α-syn fibrils exhibited progressive nigral neuronal loss accompanied with mitochondrial abnormalities and motor impairment. CONCLUSION: Our findings indicate that the structural difference of G51D α-syn fibrils plays an important role in the rapidly developed and more severe neurotoxicity of G51D mutation-linked Parkinson's disease. © 2019 International Parkinson and Movement Disorder Society.

A clinicopathological study of ALS with L126S mutation in the SOD1 gene presenting with isolated inferior olivary hypertrophy.

We report an autopsy case of amyotrophic lateral sclerosis with L126S mutation in the superoxide dismutase 1 (SOD1) gene (SOD1). The patient was a 69-year-old Japanese man without relevant family history, who initially presented with slow progressive muscle weakness of the lower extremities without upper motor neuron signs, and died of respiratory failure 6 years after the onset. Neuropathological examination revealed a loss of lower motor neurons and degeneration of Clarke's column commensurate with that of the posterior spinocerebellar tract and the middle root zone of the posterior column. The primary motor area was minimally affected. Characteristic SOD1-immunopositive neuronal intracytoplasmic inclusions, mixed with neurofilament accumulation, were present in the affected areas. Isolated inferior olivary hypertrophy was observed, but did not involve the contralateral dentate nucleus, or the ipsilateral red nucleus and central tegmental tract, where no neuronal inclusions were found. In combination with data from a previous autopsy case, this study suggests that the L126S mutation may cause focal neuronal degeneration in the brainstem.

Amido-bridged nucleic acid (AmNA)-modified antisense oligonucleotides targeting α-synuclein as a novel therapy for Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disease caused by the loss of dopaminergic neurons in the substantia nigra. A characteristic pathological feature of PD is cytoplasmic accumulation of α-synuclein (SNCA) protein. Multiplication of the SNCA gene in familial PD and pathological accumulation of SNCA protein during progression of sporadic PD suggest that increased SNCA protein levels increase the risk of PD. Thus, reducing SNCA expression levels could delay PD onset or modify the disease course. For efficient knock down, we designed and synthesized an amido-bridged nucleic acids (AmNA)-modified antisense oligonucleotide (ASO) that targeted SNCA with improved stability and cellular uptake in vivo. AmNA-ASO efficiently downregulated SNCA at both the mRNA and protein level in vitro and in vivo. Notably, AmNA-ASO was efficiently delivered into the mouse brain by intracerebroventricular injection without the aid of additional chemicals. Furthermore, administration of AmNA-ASO ameliorated neurological defects in PD model mice expressing human wild type SNCA. Taken together, these findings suggest that AmNA-ASO is a promising therapeutic strategy for SNCA-associated pathology in PD.

Ultrasonication-based rapid amplification of α-synuclein aggregates in cerebrospinal fluid.

α-Synuclein aggregates, a key hallmark of the pathogenesis of Parkinson's disease, can be amplified by using their seeding activity, and the evaluation of the seeding activity of cerebrospinal fluid (CSF) is reportedly useful for diagnosis. However, conventional shaking-based assays are time-consuming procedures, and the clinical significance of the diversity of seeding activity among patients remains to be clarified. Previously, we reported a high-throughput ultrasonication-induced amyloid fibrillation assay. Here, we adapted this assay to amplify and detect α-synuclein aggregates from CSF, and investigated the correlation between seeding activity and clinical indicators. We confirmed that this assay could detect α-synuclein aggregates prepared in vitro and also aggregates released from cultured cells. The seeding activity of CSF correlated with the levels of α-synuclein oligomers measured by an enzyme-linked immunosorbent assay. Moreover, the seeding activity of CSF from patients with Parkinson's disease was higher than that of control patients. Notably, the lag time of patients with Parkinson's disease was significantly correlated with the MIBG heart-to-mediastinum ratio. These findings showed that our ultrasonication-based assay can rapidly amplify misfolded α-synuclein and can evaluate the seeding activity of CSF.

MarmoDetector: A novel 3D automated system for the quantitative assessment of marmoset behavior.

BACKGROUND: Callithrix jacchus, generally known as the common marmoset, has recently garnered interest as an experimental primate model for better understanding the basis of human social behavior, architecture and function. Modelling human neurological and psychological diseases in marmosets can enhance the knowledge obtained from rodent research for future pre-clinical studies. Hence, comprehensive and quantitative assessments of marmoset behaviors are crucial. However, systems for monitoring and analyzing marmoset behaviors have yet to be established. NEW METHOD: In this paper, we present a novel multimodal system, MarmoDetector, for the automated 3D analysis of marmoset behavior under freely moving conditions. MarmoDetector allows the quantitative assessment of marmoset behaviors using computerised tracking analysis techniques that are based on a Kinect system equipped with video recordings, infrared images and depth analysis. RESULTS: Using MarmoDetector, we assessed behavioral circadian rhythms continuously over several days in home cages. In addition, MarmoDetector detected acute, transient complex behaviors of alcohol injected marmosets. COMPARISON TO EXISTING METHOD: Compared to 2D recording, MarmoDetector detects activities more precisely and is very sensitive as we could detect behavioral defects specifically induced by alcohol administration. CONCLUSION: MarmoDetector facilitates the rapid and accurate analysis of marmoset behavior and will enhance research on the neural basis of brain disorders.

Note: Optical filter method for high-resolution magnetostriction measurement using fiber Bragg grating under millisecond-pulsed high magnetic fields at cryogenic temperatures.

High-resolution magnetostriction measurement of ΔL/L ∼ 10-6 at a speed of 5 MHz is performed using the optical filter method as the detection scheme for the fiber Bragg grating (FBG) based strain monitor under 35-ms pulsed high magnetic fields up to 45 T at 2.2 K. The resolution of magnetostriction is about the same order as the conventionally reported value from FBG based magnetostriction measurement systems for millisecond pulsed magnetic fields. The measurement speed is ∼100 times the conventional ones. The present system can be a faster alternative for the conventional FBG based magnetostriction measurement system for millisecond pulsed high magnetic fields.

Interlaminar Shear Behavior of Laminated Carbon Fiber Reinforced Plastic from Microscale Strain Distributions Measured by Sampling Moiré Technique.

In this article, the interlaminar shear behavior of a [±45°]4s laminated carbon fiber reinforced plastic (CFRP) specimen is investigated, by utilizing microscale strain mapping in a wide field of view. A three-point bending device is developed under a laser scanning microscope, and the full-field strain distributions, including normal, shear and principal strains on the cross section of CFRP, in a three-point bending test, are measured using a developed sampling Moiré technique. The microscale shear strain concentrations at interfaces between each two adjacent layers were successfully detected and found to be positive-negative alternately distributed before damage occurrence. The 45° layers slipped to the right relative to the -45° layers, visualized from the revised Moiré phases, and shear strain distributions of the angle-ply CFRP under different loads. The absolute values of the shear strain at interfaces gradually rose with the increase of the bending load, and the sudden decrease of the shear strain peak value implied the occurrence of interlaminar damage. The evolution of the shear strain concentrations is useful in the quantitative evaluation of the potential interlaminar shear failure.

Nanometer-order thermal deformation measurement by a calibrated phase-shifting digital holography system.

A thermal deformation measurement system based on calibrated phase-shifting digital holography is proposed. Two synchronized ordinary CMOS cameras are used in the calibrated phase-shifting digital holography system. One is to record the holograms including the object information, and the other is to record the interference fringes to evaluate phase-shifting errors. The calibrated phase-shifting digital holography can provide the high quality reconstructed images which are applied to calculate the thermal deformation of the object. Meanwhile, the thermal images of the object at different temperatures are recorded by a thermal camera. Nanometer-order thermal deformation measurement of an electronic device is achieved in a real experiment. Our measurement system could be useful for electric packaging materials development or the system design.

Computerized Hammer Sounding Interpretation for Concrete Assessment with Online Machine Learning.

Developing efficient Artificial Intelligence (AI)-enabled systems to substitute the human role in non-destructive testing is an emerging topic of considerable interest. In this study, we propose a novel hammering response analysis system using online machine learning, which aims at achieving near-human performance in assessment of concrete structures. Current computerized hammer sounding systems commonly employ lab-scale data to validate the models. In practice, however, the response signal patterns can be far more complicated due to varying geometric shapes and materials of structures. To deal with a large variety of unseen data, we propose a sequential treatment for response characterization. More specifically, the proposed system can adaptively update itself to approach human performance in hammering sounding data interpretation. To this end, a two-stage framework has been introduced, including feature extraction and the model updating scheme. Various state-of-the-art online learning algorithms have been reviewed and evaluated for the task. To conduct experimental validation, we collected 10,940 response instances from multiple inspection sites; each sample was annotated by human experts with healthy/defective condition labels. The results demonstrated that the proposed scheme achieved favorable assessment accuracy with high efficiency and low computation load.

Measurement of endometrial thickness in premenopausal women in office gynecology.

Purpose: To define the median endometrial thickness (ET) in office gynecology is thought to be important for clinical practice. However, there are few reports about ET that have included the general female population on a large scale. The median ET was determined prospectively in premenopausal women who attended office gynecology for cervical cancer screening. Methods: In total, 849 women were enrolled. The median ET was determined by using transvaginal ultrasound and the relationships between the ET and various clinical factors were analyzed. Results: The participants' median age was 38.5 years. The median ET was 8.6 mm (90% and 95% quantiles: 13.8 and 15.8 mm). The ET was not related to their age, symptoms, obstetric history, geographical location, or risk factors for endometrial cancer. In the women with a menstrual cycle length of 28-30 days, the ET was 7 mm on days 1-6, but it increased from 5.4 mm immediately after menstruation (day 7 or 8) to 9.2 mm on days 13-14. Subsequently, the ET increased further to 11.1 mm on day 18. Conclusion: In all the women, the upper limit of the ET was 13.8 mm and 15.8 mm in the 90% and 95% quantile, respectively, in office gynecology.

Calibrated phase-shifting digital holography based on a dual-camera system.

A calibrated phase-shifting digital holography system based on the sampling Moiré technique is proposed. Two synchronized cameras are used in this system. One is to record the conventional holograms that include the object information, and the other is to record the interference fringes to analyze phase-shifting errors. An algorithm for improving the quality of the reconstructed images is proposed. In this Letter, the effectiveness of the proposed system and algorithm is demonstrated in four-step phase-shifting digital holography. The quality of the reconstructed images is greatly improved from both the numerical simulation and experiment.

Two-dimensional Moiré phase analysis for accurate strain distribution measurement and application in crack prediction.

Aimed at the low accuracy problem of shear strain measurement in Moiré methods, a two-dimensional (2D) Moiré phase analysis method is proposed for full-field deformation measurement with high accuracy. A grid image is first processed by the spatial phase-shifting sampling Moiré technique to get the Moiré phases in two directions, which are then conjointly analyzed for measuring 2D displacement and strain distributions. The strain especially the shear strain measurement accuracy is remarkably improved, and dynamic deformation is measurable from automatic batch processing of single-shot grid images. As an application, the 2D microscale strain distributions of a titanium alloy were measured, and the crack occurrence location was successfully predicted from strain concentration.