Differentiation of speech in Parkinson's disease and spinocerebellar degeneration using deep neural networks.

INTRODUCTION: Assessing dysarthria features in patients with neurodegenerative diseases helps diagnose underlying pathologies. Although deep neural network (DNN) techniques have been widely adopted in various audio processing tasks, few studies have tested whether DNNs can help differentiate neurodegenerative diseases using patients' speech data. This study evaluated whether a DNN model using a transformer architecture could differentiate patients with Parkinson's disease (PD) from patients with spinocerebellar degeneration (SCD) using speech data. METHODS: Speech data were obtained from 251 and 101 patients with PD and SCD, respectively, while they read a passage. We fine-tuned a pre-trained DNN model using log-mel spectrograms generated from speech data. The DNN model was trained to predict whether the input spectrogram was generated from patients with PD or SCD. We used fivefold cross-validation to evaluate the predictive performance using the area under the receiver operating characteristic curve (AUC) and accuracy, sensitivity, and specificity. RESULTS: Average ± standard deviation of the AUC, accuracy, sensitivity, and specificity of the trained model for the fivefold cross-validation were 0.93 ± 0.04, 0.87 ± 0.03, 0.83 ± 0.05, and 0.89 ± 0.05, respectively. CONCLUSION: The DNN model can differentiate speech data of patients with PD from that of patients with SCD with relatively high accuracy and AUC. The proposed method can be used as a non-invasive, easy-to-perform screening method to differentiate PD from SCD using patient speech and is expected to be applied to telemedicine.

Association between salivary mature brain-derived neurotrophic factor and psychological distress in healthcare workers.

INTRODUCTION: Previous studies have suggested association between brain-derived neurotrophic factor (BDNF) and the stress level of workers. However, no studies have investigated the potential of salivary mature BDNF (mBDNF) level as a noninvasive biomarker for psychological distress. This study aimed to explore the reliability of salivary mBDNF as a biomarker for psychological distress in healthcare workers. Furthermore, we examined the relationship between salivary and plasma mBDNF levels and their correlation with age, sex, body mass index (BMI), and exercise habits. METHODS: Fifty-one healthy healthcare workers (26 men) from the University of Occupational and Environmental Health, Japan, participated in this study. In this cross-sectional study, participants provided demographic information. Psychological distress was assessed using the Kessler 6 (K6). Saliva and blood samples were collected, and mBDNF was measured by ELISA. Spearman's rank correlation coefficient was performed to analyze the relationship between mBDNF (saliva and plasma) and K6. Statistical analyses were conducted using Stata 17.0, and a significance level of p < .05 was applied. RESULTS: The median K6 score was 1 (interquartile range [IQR]: 0-3). The median (IQR) salivary mBDNF was 1.36 (1.12-1.96) pg/mL, whereas the mean (standard deviation) plasma mBDNF was 1261.11 (242.98) pg/mL. No correlation was observed between salivary and plasma mBDNF concentrations or with the K6 score. Additionally, there were no associations between salivary or plasma mBDNF concentrations and age, sex, or exercise habits. Finally, an association between plasma mBDNF concentration and BMI was found only in univariate analysis. CONCLUSION: Our findings indicate that salivary mBDNF can be accurately measured noninvasively in healthcare workers. Within our study sample, salivary mBDNF did not demonstrate any correlation with K6 and plasma mBDNF. Future studies with a larger study sample and a diverse study population consisting of healthy participants and patients with psychiatric disorders are warranted.

Long-term effects of the gait treatment using a wearable cyborg hybrid assistive limb in a patient with spinal and bulbar muscular atrophy: a case report with 5 years of follow-up.

Background: Spinal and bulbar muscular atrophy (SBMA) is a progressive neuromuscular degenerative disease characterized by the degeneration of lower motor neurons in the spinal cord and brainstem and neurogenic atrophy of the skeletal muscle. Although the short-term effectiveness of gait treatment using a wearable cyborg hybrid assistive limb (HAL) has been demonstrated for the rehabilitation of patients with SBMA, the long-term effects of this treatment are unclear. Thus, this study aimed to investigate the long-term effects of the continued gait treatment with HAL in a patient with SBMA. Results: A 68-year-old man with SBMA had lower limb muscle weakness and atrophy, gait asymmetry, and decreased walking endurance. The patient performed nine courses of HAL gait treatment (as one course three times per week for 3 weeks, totaling nine times) for ~5 years. The patient performed HAL gait treatment to improve gait symmetry and endurance. A physical therapist adjusted HAL based on the gait analysis and physical function of the patient. Outcome measurements, such as 2-min walking distance (2MWD), 10-meter walking test (maximal walking speed, step length, cadence, and gait symmetry), muscle strength, Revised Amyotrophic Lateral Sclerosis Functional Assessment Scale (ALSFRS-R), and patient-reported outcomes, were evaluated immediately before and after gait treatment with HAL for each course. 2MWD improved from 94 m to 101.8 m, and the ALSFRS-R gait items remained unchanged (score 3) for approximately 5 years. The patient could maintain walking ability in terms of gait symmetry, walking endurance, and independence walking despite disease progression during HAL treatment. Conclusion: The long-term gait treatment with HAL in a patient with SBMA may contribute to the maintenance and improvement of the gait endurance and ability to perform activities of daily living. The cybernics treatment using HAL may enable patients to relearn correct gait movements. The gait analysis and physical function assessment by a physical therapist might be important to maximize the benefits of HAL treatment.

Factors associated with thrombocytopenia in patients treated with pegfilgrastim.

OBJECTIVES: Pegfilgrastim is a long-acting, granulocyte colony-stimulating factor approved in Japan for the prevention of neutropenia caused by antineoplastic agents. Severe thrombocytopenia was reported with pegfilgrastim, however, the factors associated with thrombocytopenia are unclear. This study aimed to explore the factors associated with thrombocytopenia in patients with metastatic castration-resistant prostate cancer treated with pegfilgrastim for primary prophylaxis of febrile neutropenia (FN) with cabazitaxel. MATERIALS AND METHODS: This study included metastatic castration-resistant prostate cancer patients who received pegfilgrastim for primary prophylaxis of FN with cabazitaxel. The timing and severity of thrombocytopenia and factors associated with the reduction rate of platelets were examined in patients who received pegfilgrastim for the primary prevention of FN during the first course of cabazitaxel and by multiple regression analysis. RESULTS: Thrombocytopenia was most common within 7 days of pegfilgrastim administration, with 32 cases of grade 1 and 6 cases of grade 2 as per the Common Terminology Criteria for Adverse Events version 5.0. Multiple regression analysis revealed that the reduction rate of platelets after pegfilgrastim administration was significantly positively correlated with monocytes. In contrast, the presence of liver metastases and neutrophils was significantly negatively correlated with the reduction rate of platelets. CONCLUSION: Thrombocytopenia due to pegfilgrastim administered as primary prophylaxis for FN with cabazitaxel was most likely to occur within one week after pegfilgrastim administration, suggesting that monocytes, neutrophils, and liver metastases were associated with a reduction in platelets.

Genetic Creutzfeldt‒Jakob disease with 5-octapeptide repeats presented as frontotemporal dementia.

The N-terminus of the PRNP gene normally contains a 5-octapeptide repeat (R1-R2-R2-R3-R4), and insertions at this locus can cause hereditary prion diseases. In the present study, we found a 5-octapeptide repeat insertion (5-OPRI) in a sibling case of frontotemporal dementia. Consistent with previous literature, 5-OPRI rarely met the diagnostic criteria for Creutzfeldt‒Jakob disease (CJD). We propose 5-OPRI as a suspected causative mutation for early-onset dementia, especially the frontotemporal type.

Comparison between the Effects of Loxoprofen and Acetaminophen on Postoperative Pain Following Radical Prostatectomy: A Propensity Score Matching Analysis.

Non-steroidal anti-inflammatory medications are associated with renal impairment. However, there is little information on whether these medications affect postoperative renal function compared with acetaminophen. The objective of this study was to compare the effects of acetaminophen and loxoprofen, used as postoperative analgesic, effect on postoperative analgesia using propensity score matching analysis. We retrospectively enrolled 328 patients treated with loxoprofen or acetaminophen after open radical prostatectomy between October 2017 and February 2020. We analyzed postoperative pain intensity, the incidence rate of acute kidney injury, drug-induced liver injury, and rate of elevation in serum creatinine after open radical prostatectomy. Eighty-one matched pairs of patients treated with loxoprofen or acetaminophen were selected using propensity score matching analysis. The postoperative numerical rating scale was significantly higher in the acetaminophen group than in the loxoprofen group on postoperative day 5. The use of patient-controlled anesthesia and rescue analgesics was significantly higher in the acetaminophen group than in the loxoprofen group. The loxoprofen group had a significantly higher postoperative increase in serum creatinine than the acetaminophen group on postoperative days 5 and 8. The incidence of acute kidney injury was 4.9% in the loxoprofen group and 0% in the acetaminophen group, while the incidence of drug-induced liver injury was 0% in both groups. Acetaminophen appears to be safer than loxoprofen in terms of effects on renal function. Nevertheless, the number of acetaminophen doses and the dose per dose may need to be increased for patients with significant postoperative pain.

Evaluation of renal function using cystatin C-based estimated glomerular filtration rate in patients with urothelial carcinoma treated with gemcitabine and cisplatin chemotherapy.

WHAT IS KNOWN AND OBJECTIVE: Cisplatin-based chemotherapy is a first-line treatment for advanced or metastatic urinary tract urothelial carcinoma (UC). Accurate assessment of renal function is indispensable for determining cisplatin dosing to enhance the safety and effectiveness of cisplatin. The objective of this study was to assess serum cystatin C (sCys C) levels in patients with urothelial carcinoma and to explore its clinical value as a serum marker of glomerular filtration rate (GFR). METHODS: This study retrospectively enrolled 18 UC patients treated with a combination of gemcitabine and cisplatin between April 2018 and November 2020. We calculated the estimated GFR (eGFR) based on serum creatinine (sCr) or sCys C and estimated Cr clearance (eCCr) based on sCr. The correlation, bias, accuracy and creatinine height index between eGFR or eCCr and measured GFR (mGFR) based on Cr clearance were calculated from urinary Cr and sCr. RESULTS AND DISCUSSION: Estimated GFR based on sCys C correlated most strongly with mGFR. Moreover, the bias, mean error, mean absolute error and root mean square error were significantly lower in eGFRs based on sCyc C than in eGFRs based on sCr and eCCr. The correlation between eGFR based on sCys C/mGFR and creatinine height index was weaker than that between eGFR based on sCr/mGFR and creatinine height index, suggesting that sCys C was less affected by muscle mass. WHAT IS NEW AND CONCLUSION: In UC patients, eGFR based on sCys C reflected renal function more accurately than eGFR based on sCr, suggesting that sCys C may be useful for assessing renal function in clinical practice.

Association Between Serum Insulin-Like Growth Factor 1 Levels and the Clinical Symptoms of Chronic Schizophrenia: Preliminary Findings.

Purpose: Insulin-like growth factor 1 (IGF-1) is a trophic mediator that is regulated by growth hormone and associated with the proliferation, development, and growth of neural cells. IGF-1 may be associated with the pathophysiology of schizophrenia, but this association remains controversial. This study aimed to investigate the relationship between serum IGF-1 levels and psychiatric symptoms in patients with chronic schizophrenia. Patients and Methods: A total of 65 patients were recruited from the University of Occupational and Environmental Health, Komine Eto Hospital, Moji Matsugae Hospital, Shin-Moji Hospital, and Tsutsumi Hospital in Kitakyushu between September 2019 and June 2020. Further, 20 healthy age- and sex-matched control participants were recruited from the Komine Eto Hospital and the University of Occupational and Environmental Health. Patients with schizophrenia were assessed using the Positive and Negative Syndrome Scale (PANSS) and the Drug-Induced Extrapyramidal Symptoms Scale. Serum levels of free plus albumin-bound IGF-1 (IGF-1) were measured by immunoradiometric assay. The measurements were performed using antibody beads for bound/free separation. Associations between serum IGF-1 levels and the PANSS scores were determined. We also examined the associations between serum IGF-1 levels and diabetes, antipsychotic drug use, and disease duration. Results: No significant difference was found in the serum IGF-1 level between patients with schizophrenia and healthy controls. Serum IGF-1 levels were significantly negatively correlated with the PANSS total score (R 2 = 0.06, p = 0.015) and PANSS general score (R 2 = 0.088, p = 0.008), but not with the PANSS positive scores and PANSS negative scores. Serum IGF-1 levels were not related to the prevalence of diabetes (p = 0.64). However, a significant correlation was observed between serum IGF-1 levels and age (B = -1.88, p < 0.0001). Serum IGF-1 levels could not distinguish patients with schizophrenia and healthy controls. Conclusion: The association between serum IGF-1 levels and psychiatric symptoms may be complicated in patients with chronic schizophrenia.

Metastatic Small Cell Carcinoma of the Urinary Bladder That Recurred in the Vagina 6 Years after Radical Cystectomy: A Case Report.

Small cell carcinoma (SCC) of the urinary bladder is highly aggressive and portends a poor outcome. Herein, we report a patient with recurrent SCC of the urinary bladder who experienced an unusually long-term disease-free duration after radical cystectomy. The patient was a 60-year-old woman who had undergone transurethral resection followed by radical cystectomy for muscle-invasive bladder cancer (high-grade urothelial carcinoma with adenocarcinomatous differentiation) 6 years prior; the surgical specimen had a negative surgical margin. She was referred to our hospital because of continuous bleeding from her vagina. Magnetic resonance imaging showed a mass located at the anterior wall of her residual vagina, a biopsy of which confirmed a pathological diagnosis of adenocarcinoma. The vaginal tumor and a section of the sigmoid colon were resected en bloc and were pathologically diagnosed as adenocarcinoma and SCC. We reevaluated the initial transurethral resection specimen and found SCC with foci of adenocarcinoma concomitant with high-grade urothelial carcinoma. Local recurrence and metastasis at the pelvic bone occurred 4 months later; although radiation therapy was performed, she died of the progressive disease.

Executive dysfunction in patients with spinocerebellar ataxia type 3.

The aim of this study was to assess the cognitive functions of patients with spinocerebellar ataxia type 3(SCA3). We examined 15 patients with genetically confirmed SCA3 and 15 healthy control subjects matched for age, years of education, and intellectual ability. We administered verbal memory (word recall and word recognition) and executive function tasks (word fluency test, forward and backward digit and visual span tests, Kana Pick-out Test, Trail Making Test, and conflicting instructions and a Go/NoGo task from the Frontal Assessment Battery). We found that patients with SCA3 had significantly lower scores than the healthy control subjects on the word recall, semantic, and letter fluency, and backward digit span tests, while word recognition was well preserved. The other executive function tests showed preserved functions in the SCA3 group, indicating that visual working memory, and attention and inhibition control were not affected. The patients with SCA3 showed impaired word recall and intact word recognition, and accordingly, episodic memory encoding and storage processes in short-term memory were preserved. In category and letter-fluency tests, impairment was attributable to word-retrieval from semantic memory. Impaired verbal working memory may be involved in the retrieval of verbal information from phonological storage by means of continuous subvocal rehearsal, rather than a deficit in initial phonological encoding. Essential executive dysfunction in patients with SCA3 may be due to damage in the cerebellar cortex-ventral dentate nucleus-thalamus-prefrontal cortex circuits, which are involved in strategic retrieval of verbal information from different modes of memory storage.

[CLINICAL STUDY OF SEQUENTIAL THERAPY WITH ABIRATERONE AND ENZALUTAMIDE FOLLOWING DOCETAXEL THERAPY FOR CASTRATION-RESISTANT PROSTATE CANCER].

(Purpose) This study is to evaluate the efficacy and safety of sequential therapy with two novel drugs, abiraterone and enzalutamide after docetaxel (DOC) therapy for castration-resistant prostate cancer (CRPC). (Material and methods) Twenty-one patients were identified received sequential therapy with abiraterone and enzalutamide after DOC therapy at our institution. We investigated PSA response (decrease of 50% or more) to prior administered drug as primary endpoint, and overall survival rate and occurrence of adverse events as secondary endpoint. (Results) There were 12 patients in the group preliminarily administered enzalutamide (Group E) and 9 patients in the group preliminarily administered abiraterone (Group A). The novel drugs were administered immediately following DOC therapy in nearly all cases. Of the 9 patients in Group A, only one patient (11%) and of the 12 patients in Group E, only one patient (9%) achieved PSA decrease of 50% or more, thus resulting in a poor response rate. There was not significantly difference in both groups. The overall survival rates of Group A and E were not significantly difference. There were three adverse events which required change drug. Those were two cases (appetite loss and general fatigue) on enzalutamide and one case (edema) on abiraterone. (Conclusion) This study suggested that sequential therapy with abiraterone and enzalutamide after DOC therapy had poor clinical benefit regardless of the order of administration of both drugs.

[A CASE OF METASTATIC BLADDER UROTHELIAL CARCINOMA WHOSE DISEASE WAS CONTROLLED FOR A RELATIVE LONG PERIOD BY MULTIDISCIPLINARY TREATMENT INCLUDING RADIATION TO A LUNG METASTASIS AND MULTIPLE COURSES OF CHEMOTHERAPY].

A 67-year-old woman complained of urinary frequency and gross hematuria. She was referred to our hospital with the diagnosis of bladder tumor. Transurethral resection of the bladder tumor (TURBT) was performed and pathological diagnosis was urothelial carcinoma (G2>G3) with muscular invasion. Because she hoped bladder preservation therapy, she received two courses of M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin) therapy, one course of arterial infusion chemotherapy, and chemoradiotherapy with cisplatin. After those therapies she underwent 4 times of TURBT and two courses intravesical BCG therapy. However, solitary lung metastasis appeared 19 months after the initial TURBT. Multidisciplinary treatments including 25 courses of various multiagent chemotherapies, radiation therapy to the lung metastasis and surgical resection of a urethral recurrence were performed. Although a localized radiation pneumonitis was developed, the lung metastasis appeared to be controlled for 26 months after the radiation therapy to the lung. Bilateral ureteral and renal pelvic tumors appeared after the radiation therapy. Severe bleeding was occurred from renal pelvic tumors several times and she needed the hospital stay 2 times. Active bleeding stopped after the administration of chemotherapy each time. Although she died of occlusive jaundice due to the liver metastasis, she had been alive due to the multidisciplinary treatment for 67 months after lung metastasis appearance with relatively good performance status.

Anhedonia and its correlation with clinical aspects in Parkinson's disease.

Anhedonia is one of the non-motor symptoms observed in the Parkinson's disease (PD). However, there is no clear relationship between anhedonia and its correlation with other symptoms of PD. The aim of this study is to evaluate the characteristics of anhedonia and its correlation with clinical aspects of PD in a relatively large cohort. We enrolled 318 patients with PD and 62 control subjects for this study. Patients and subjects were tested using the Snaith-Hamilton Pleasure Scale Japanese version and the Beck Depression Inventory 2nd edition for the assessment of anhedonia and depression. We also investigated the correlation among clinical aspects of PD, anhedonia, and depression in patients with PD. The Snaith-Hamilton Pleasure Scale Japanese version and the Beck Depression Inventory 2nd edition scores were significantly higher in patients with PD than in control subjects (p=0.03 and p=0.0006, respectively). All PD patients with anhedonia had a significantly higher score on the unified Parkinson's disease rating scale (UPDRS) parts I and II compared to PD patients without anhedonia. Additionally, all PD patients with depression scored significantly higher on UPDRS part I-IV than PD patients without depression. The patients with anhedonia and without depression had mild motor severity and their treatment was relatively low dosage. These results suggest that anhedonia and depression are slightly linked, but not the same. PD patients with only anhedonia may be closely linked apathy found in untreated early stages of PD.

Cognitive dysfunction in patients with spinocerebellar ataxia type 6.

The aim of this study was to assess the cognitive functions of patients with spinocerebellar ataxia type 6 (SCA6). We examined 13 patients with genetically confirmed SCA6 and 13 healthy control subjects matched for age, years of education, global cognitive status, and intellectual ability. We administered verbal memory (word recall and word recognition), executive function (digit span, category and letter fluency, Frontal Assessment Battery, and Trail Making Test-A and B), and visuospatial construction (figure copying) tests. We found that the patients with SCA6 had significantly lower scores on the demanding word recall and letter fluency tests compared to the control subjects, while word recognition was well preserved in the patients with SCA6. The other executive functions tested, as well as visuospatial construction, were preserved in the SCA6 group. However, although memory encoding and storage processes were preserved, the retrieval of memorized information concerning frontal function might be selectively affected in patients with SCA6 compared to in control subjects. The impaired word recall and letter fluency noted in patients with SCA6 were interpreted as being related to a word-retrieval disability. Such dysfunctions may be attributed to damage in the frontal-cerebellum circuit owing to SCA6.

A case of pure autotopagnosia following Creutzfeldt-Jakob disease.

A 69-year-old male (N.A.) with Creutzfeldt-Jakob disease showed pure autotopagnosia. We administered tests evaluating his ability to name his own body parts, to point to body parts (his own and examiner's), and to recognize positional relationships between his body parts by verbal questions and responses. We found impaired localization of the patient's own body parts by pointing and impaired recognition of positional relationships between his body parts. However, there was no impairment in naming his own body parts or in localizing the examiner's body parts. The results suggest a pure autotopagnosia in N.A. leading to an impairment of recognition of the spatial position of his body parts in a three-dimensional body representation within the egocentric reference frame. We were able to rule out the possibility that his pattern of performance could have been due to a disability in programming reaching movements of the arm.

A Japanese multicenter survey characterizing pain in Parkinson's disease.

BACKGROUND: Pain is a frequent, troublesome symptom of PD but is under-recognized and poorly understood. AIM: We characterized pain prevalence, severity, and location in PD, to better understand its pathophysiology and improve diagnosis and treatment. SUBJECTS AND METHODS: A cross-sectional controlled study was conducted at 19 centers across Japan. A total of 632 subjects with Mini-Mental State Examination scores ≥24 were enrolled, including 324 PD patients and 308 controls. Sex and mean age did not differ between the two groups. Demographic and clinical data were collected. Pain was assessed using questionnaires, the SF-36v2 bodily pain scale, and a body illustration for patients to indicate the location of pain in 45 anatomical areas. RESULTS: Pain prevalence in the PD group was 78.6%, significantly higher than in controls (49.0%), as was its severity. There was no correlation between SF-36v2 score and motor scores, such as Unified Parkinson's Disease Rating Scale III or Hoehn & Yahr scores. Pain distribution was similar between groups, predominantly in the lower back, followed by the gluteal region, lower legs, thighs, posterior neck, and shoulders. CONCLUSION: Pain is a significant problem in the Japanese PD population and we discuss its pathophysiology.

Sialylated IgG-Fc: a novel biomarker of chronic inflammatory demyelinating polyneuropathy.

OBJECTIVE: Sialylation in Fc portion of IgG plays a crucial role in the pathogenesis of autoimmune diseases and the working mechanism of intravenous immunoglobulin (IVIG). We aim to test whether IgG-Fc sialylation is a biomarker of disease activity for chronic inflammatory demyelinating polyneuropathy (CIDP). METHODS: By using specific lectins for sialylation, galactosylation and agalactosylation, lectin-enzyme assay and lectin blotting with pretreatment of IgG degradating enzyme of Streptococcus pyogenes were performed to compare the glycosylation levels of serum IgG-Fc (1) between patients of untreated CIDP (n=107) and normal control subjects (n=27), (2) among patients with untreated CIDP of different clinical severities and (3) before and after IVIG treatment of patients with CIDP (n=12). RESULTS: Sialylation and galactosylation of IgG-Fc were significantly reduced in patients with CIDP than normal control subjects (p=0.003 and 0.033, respectively), whereas agalactosylation was increased in CIDP (p=0.21). Ratios of sialylated/agalactosylated IgG-Fc levels were significantly reduced in CIDP (p<0.001) and inversely related to disease severity (p=0.044). After IVIG treatment, levels of sialylated IgG-Fc significantly increased (p=0.003). CONCLUSIONS: Sialylation of IgG-Fc is reduced in CIDP. Its level correlated with clinical severity and increased after IVIG treatment. Sialylated as well as ratio of sialylated/agalactosylated IgG-Fc could be new measures to monitor the disease severity and treatment status in CIDP.