Improvement of lower urinary tract dysfunction by a monoacylglycerol lipase inhibitor in mice with spinal cord injury.

AIMS: Activation of the endocannabinoid system by monoacylglycerol lipase (MAGL) blockade may affect the lower urinary tract function. We investigated the effect of an MAGL inhibitor, MJN110, on neurogenic lower urinary tract dysfunction (LUTD) in the mouse model of spinal cord injury (SCI). METHODS: Female C57BL/6 mice that underwent spinal cord transection at T8-10 level were divided into three groups consisting of (1) vehicle-treated SCI mice, (2) 5 mg/kg, or (3) 10 mg/kg of MJN110-treated SCI mice. MJN110 and vehicle were administered intraperitoneally for 7 days from 4 weeks after spinal cord transection. We then conducted awake cystometrograms and compared urodynamic parameters between three groups. The expression of cannabinoid (CB) receptors, TRP receptors, and inflammatory cytokines in L6-S1 dorsal root ganglia (DRG) or the bladder mucosa were evaluated and compared among three groups. Changes in the level of serum 2-arachidonoylglycerol (2-AG) and bladder MAGL were also evaluated. RESULTS: In the cystometrogram, detrusor overactivity (DO) parameters, such as the number of nonvoiding contraction (NVC), a ratio of time to the 1st NVC to intercontraction interval (ICI), and NVC integrals were improved by MJN110 treatment, and some effects were dose dependent. Although MJN110 did not improve voiding efficiency, it decreased bladder capacity, ICI, and residual urine volume compared to vehicle injection. MJN110 treatment groups had lower CB2, TRPV1, TRPA1, and inflammatory cytokines mRNA levels in DRG and bladder mucosa. Serum 2-AG was increased, and bladder MAGL was decreased after MAGL inhibitor treatment. CONCLUSIONS: MAGL inhibition improved LUTD including attenuation of DO after SCI. Thus, MAGL can be a therapeutic target for neurogenic LUTD after SCI.

Sex differences in lower urinary tract function in mice with or without spinal cord injury.

OBJECTIVES: We examined sex differences of lower urinary tract function and molecular mechanisms in mice with and without spinal cord injury (SCI). METHODS: SCI was induced by Th8-9 spinal cord transection in male and female mice. We evaluated cystometrograms (CMG) and electromyography (EMG) of external urethral sphincter (EUS) at 6 weeks after SCI in spinal intact (SI) and SCI mice. The mRNA levels of Piezo2 and TRPV1 were measured in L6-S1 dorsal root ganglia (DRG). Protein levels of nerve growth factor (NGF) in the bladder mucosa was evaluated using an enzyme-linked immunosorbent assay. RESULTS: Sex differences were found in the EUS behavior during voiding as voiding events in female mice with or without SCI occurred during EUS relaxation periods without EUS bursting activity whereas male mice with or without SCI urinated during EUS bursting activity in EMG recordings. In both sexes, SCI decreased voiding efficiency along with increased tonic EUS activities evident as reduced EUS relaxation time in females and longer active periods of EUS bursting activity in males. mRNA levels of Piezo2 and TRPV1 of DRG in male and female SCI mice were significantly upregulated compared with SI mice. NGF in the bladder mucosa showed a significant increase in male and female SCI mice compared with SI mice. However, there were no significant differences in Piezo2 or TRPV1 levels in DRG or NGF protein levels in the bladder mucosa between male and female SCI mice. CONCLUSIONS: We demonstrated that female and male mice voided during EUS relaxation and EUS bursting activity, respectively. Also, upregulation of TRPV1 and Piezo2 in L6-S1 DRG and NGF in the bladder could be involved in SCI-induced lower urinary tract dysfunction in both sexes of mice.

Eating problems in people with dementia with Lewy bodies: Associations with various symptoms and the physician's understanding.

OBJECTIVES: Eating problems frequently occur in people with dementia with Lewy bodies (DLB), but few studies have investigated the clinical background of this phenomenon. This study examined the relationship between eating problems and various symptoms of DLB and the relation between the treatment needs for DLB people with eating problems and the understanding of their eating problems by caregivers and physicians. DESIGN, MEASUREMENTS, AND PARTICIPANTS: This was a subanalysis of a cross-sectional, questionnaire-based survey study. Two hundred sixty-one subjects with DLB were divided into subjects with or without eating problems. Logistic or linear regression analysis was used to investigate the factors influencing eating problems. The treatment needs of DLB people for their eating problems and the understanding of these needs by caregivers and physicians were calculated as participant-caregiver and participant-physician kappa coefficient. RESULTS: Of the 261 participants, 27% suffered from eating problems. The presence of eating problems in participants with DLB was related to depression (p = 0.01, OR : 2.19, 95% CI: 1.23-3.91) and apathy (p = 0.01, OR 2.15, 95% CI: 1.20-3.87), while the worsening of eating problems was related to dysphagia (ß = 0.24, p = 0.03), apathy (ß = 0.23, p = 0.05), and nighttime behavior (ß = 0.24, p = 0.04). The participant-physician kappa coefficient for physician understanding of constipation, weight loss, dysphagia, weight gain, and increase in appetite was significantly lower than the corresponding participant-caregiver kappa coefficient (p-value of five symptoms < 0.01). CONCLUSIONS: Physicians need to pay more attention to eating problems and their neuropsychiatric background in the long-term support and management of DLB subjects.

Validation of the Japanese version of the Social Functioning in Dementia scale and COVID-19 pandemic's impact on social function in mild cognitive impairment and mild dementia.

OBJECTIVES: We aimed to psychometrically evaluate and validate a Japanese version of the Social Functioning in Dementia scale (SF-DEM-J) and investigate changes in social function in people with dementia during the coronavirus disease-19 (COVID-19) pandemic. DESIGN: We interviewed people with mild cognitive impairment (MCI) and mild dementia and their caregivers during June 2020-March 2021 to validate patient- and caregiver-rated SF-DEM-J and compared their scores at baseline (April 2020 to May 2020) and at 6-8 months (January 2021 to March 2021) during a time of tighter COVID-19 restrictions. SETTING: The neuropsychology clinic in the Department of Psychiatry at Osaka University Hospital and outpatient clinic in the Department of Psychiatry and Neurology at Daini Osaka Police Hospital, Japan. PARTICIPANTS: 103 dyads of patients and caregivers. MEASUREMENTS: SF-DEM-J, Mini-Mental State Examination, Neuropsychiatric Inventory, UCLA Loneliness Scale, and Apathy Evaluation Scale. RESULTS: The scale's interrater reliability was excellent and test-retest reliability was substantial. Content validity was confirmed for the caregiver-rated SF-DEM-J, and convergent validity was moderate. Caregiver-rated SF-DEM-J was associated with apathy, irritability, loneliness, and cognitive impairment. The total score of caregiver-rated SF-DEM-J and the score of Section 2, "communication with others," significantly improved at 6-8 months of follow-up. CONCLUSIONS: The SF-DEM-J is acceptable as a measure of social function in MCI and mild dementia. Our results show that the social functioning of people with dementia, especially communicating with others, improved during the COVID-19 pandemic, probably as a result of adaptation to the restrictive life.

Urinary markers for bladder cancer diagnosis: A review of current status and future challenges.

Bladder cancer is a common urological cancer with a high recurrence rate that requires long-term follow-up, and early detection positively affects prognosis. To date, the initial diagnosis and follow-up for bladder cancer rely on cystoscopy, which is an invasive and expensive procedure. Therefore, urinary markers for the detection of bladder cancer have attracted research attention for decades to reduce unnecessary cystoscopies. Urine, which is in continuous contact with bladder cancer, is considered a suitable fluid for providing tumor information. Urinary cytology is the only widely used urinary marker in clinical practice; however, it has poor sensitivity for low-grade tumors; indicating the need for novel urinary markers. Considerable research has been conducted on this topic over the years, resulting in a complex landscape with a wide range of urinary markers, including protein-, exfoliated cell-, RNA-, DNA-, and extracellular vesicle-based markers. Although some of these markers have been approved by the U.S. Food and Drug Administration and are commercially available, their use in clinical practice is limited. To facilitate clinical application, potential urinary markers must withstand prospective clinical trials and be easy for patients and clinicians to understand and utilize in a clinical context. This review provides a comprehensive overview of currently available and recently reported promising urinary markers for bladder cancer. Additionally, the challenges and the prospects of these urinary markers for clinical implementation in bladder cancer treatment were discussed.

Gesture imitation performance in community-dwelling older people: assessment of a gesture imitation task in the screening and diagnosis of mild cognitive impairment and dementia.

BACKGROUND: Gesture imitation, a simple tool for assessing visuospatial/visuoconstructive functions, is reportedly useful for screening and diagnosing dementia. However, gesture imitation performance in healthy older adults is largely unknown, as are the factors associated with lower performance. To address these unknowns, we examined the gesture imitation performance of a large number of community-dwelling older adults aged ≥65 years in Arao City, Kumamoto Prefecture (southern Japan). METHODS: The examiner presented the participants with eight gesture patterns and considered it a success if they could imitate them within 10 s. The success rate of each gesture imitation was calculated for three diagnostic groups: cognitively normal (CN) (n = 1184), mild cognitive impairment (MCI) (n = 237), and dementia (n = 47). Next, we reorganised the original gesture imitation battery by combining six selected gestures with the following scoring method: if the participants successfully imitated the gestures, immediately or within 5 s, two points were assigned. If they succeeded within 5-10 s, one point was assigned. The sensitivity and specificity of the battery were investigated to detect the dementia and MCI groups. Factors associated with gesture imitation battery scores were examined. RESULTS: Except one complex gesture, the success rate of imitation in the CN group was high, approximately 90%. The sensitivity and specificity of the gesture imitation battery for discriminating between the dementia and CN groups and between the MCI and CN groups were 70%/88%, and 45%/75%, respectively. Ageing, male sex, and a diagnosis of dementia or MCI were associated with lower scores on the gesture imitation battery. CONCLUSION: Gesture imitation tasks alone may not be sufficient to detect MCI. However, by combining gestures with set time limits, gesture imitation tasks can be a low-burden and effective method for detecting dementia, even in community medicine, such as during health check-ups.

Utility of the Japanese version of the Clinical Dementia Rating® plus National Alzheimer's Coordinating Centre Behaviour and Language Domains for sporadic cases of frontotemporal dementia in Japan.

BACKGROUND: We aimed to validate the Clinical Dementia Rating (CDR®) dementia staging instrument plus the National Alzheimer's Coordinating Centre Behaviour and Language Domains (CDR® plus NACC FTLD) for use in clinical settings in Japan and in the Japanese language. METHODS: This prospective observational study enrolled 29 patients with frontotemporal dementia (FTD) and 21 patients with Alzheimer's disease (AD) dementia from the Departments of Psychiatry at Osaka University Hospital and Asakayama General Hospital and the Brain Function Centre at Nippon Life Hospital. CDR® plus NACC FTLD, CDR®, Mini-Mental State Examination (MMSE), Western Aphasia Battery (WAB), Neuropsychiatric Inventory-plus (NPI-plus), Stereotypy Rating Inventory (SRI), and frontal behavioural symptom scores obtained from items of NPI-plus and SRI, were conducted to assess inter- and intra-rater reliability, validity, and responsiveness. We performed receiver operating characteristic (ROC) curve analysis to evaluate the discriminating power of the Behaviour/Comportment/Personality (BEHAV) and Language (LANG) domains of the CDR® plus NACC FTLD and the MEMORY domain of the CDR® in patients AD dementia and FTD. RESULTS: The CDR® plus NACC FTLD showed good inter- and intra-rater reliabilities. In patients with FTD, the BEHAV domain of the CDR® plus NACC FTLD was significantly correlated with all clinical measures except for the SRI total score, while the LANG domain of the CDR® plus NACC FTLD was significantly correlated with the MMSE and the WAB-Aphasia quotient. In addition, the CDR® plus NACC FTLD sum of boxes significantly changed after 6 months and after 1 year. ROC curve analysis showed that the BEHAV and LANG domains of the CDR® plus NACC FTLD distinguished between patients with AD dementia and FTD better than the MEMORY domain of the CDR®. CONCLUSIONS: This study validated the Japanese version of the CDR® plus NACC FTLD with good reliability, validity, and responsiveness.

External beam radiotherapy combination is a risk factor for bladder cancer in patients with prostate cancer treated with brachytherapy.

PURPOSE: To investigate the risk of bladder cancer (BCa) in patients treated with brachytherapy for prostate cancer (PCa). METHODS: We retrospectively analyzed 583 patients with PCa who underwent brachytherapy with or without external beam radiotherapy (EBRT). We analyzed the disease-free survival (DFS) of BCa in patients with PCa who underwent brachytherapy with or without EBRT. We performed multivariate Cox regression analyses of DFS using age, EBRT, and Brinkman index (BI) score (number of cigarettes smoked per day × number of years smoking) ≥ 200 as variables for BCa after brachytherapy. RESULTS: Fourteen patients (2.4%) developed BCa after brachytherapy with or without EBRT. The percentage of high-grade urothelial carcinoma (UC) was 63.6%. A total of 85.7% of patients had non-muscle invasive BCa, and 14.3% of patients had muscle invasive BCa. DFS was longer in brachytherapy monotherapy than in combination therapy (brachytherapy + EBRT). Multivariate Cox regression analysis showed that a BI score ≥ 200 (Hazard Ratio (HR 8.61; 95% Confidence Interval (CI) 1.12-65.98) and EBRT combination (HR 3.29; 95% CI 1.03-10.52) were significantly associated with BCa development in patients with PCa treated with brachytherapy. Furthermore, patients with BI score ≥ 200 and EBRT combination had a significantly higher risk of BCa compared with patients with BI score < 200 (HR Log-rank test P = 0.010). CONCLUSION: Most cases of BCa after brachytherapy with or without EBRT are high grade and invasive. We hypothesized that the EBRT combination might be a risk factor for BCa in patients with PCa who underwent brachytherapy.

Cerebrospinal fluid amyloid beta and response of cognition to a tap test in idiopathic normal pressure hydrocephalus: a case-control study.

OBJECTIVES: To examine the relationship between cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) and tap test response to elucidate the effects of comorbidity of AD in idiopathic normal-pressure hydrocephalus (iNPH). DESIGN: Case-control study. SETTING: Osaka University Hospital. PARTICIPANTS: Patients with possible iNPH underwent a CSF tap test. MEASUREMENTS: Concentrations of amyloid beta (Aß) 1-40, 1-42, and total tau in CSF were measured. The response of tap test was judged using Timed Up and Go test (TUG), 10-m reciprocation walking test (10MWT), Mini-Mental State Examination (MMSE), and iNPH grading scale. The ratio of Aß1-42 to Aß1-40 (Aß42/40 ratio) and total tau concentration was compared between tap test-negative (iNPH-nTT) and -positive (iNPH-pTT) patients. RESULTS: We identified 27 patients as iNPH-nTT and 81 as iNPH-pTT. Aß42/40 ratio was significantly lower (mean [SD] = 0.063 [0.026] vs. 0.083 [0.036], p = 0.008), and total tau in CSF was significantly higher (mean [SD] = 385.6 [237.2] vs. 293.6 [165.0], p = 0.028) in iNPH-nTT than in iNPH-pTT. Stepwise logistic regression analysis revealed that low Aß42/40 ratio was significantly associated with the negativity of the tap test. The response of cognition was significantly related to Aß42/40 ratio. The association between Aß42/40 ratio and tap test response, especially in cognition, remained after adjusting for disease duration and severity at baseline. CONCLUSIONS: A low CSF Aß42/40 ratio is associated with a poorer cognitive response, but not gait and urinary response, to a tap test in iNPH. Even if CSF biomarkers suggest AD comorbidity, treatment with iNPH may be effective for gait and urinary dysfunction.

Molecular Mechanisms of Neurogenic Lower Urinary Tract Dysfunction after Spinal Cord Injury.

This article provides a synopsis of current progress made in fundamental studies of lower urinary tract dysfunction (LUTD) after spinal cord injury (SCI) above the sacral level. Animal models of SCI allowed us to examine the effects of SCI on the micturition control and the underlying neurophysiological processes of SCI-induced LUTD. Urine storage and elimination are the two primary functions of the LUT, which are governed by complicated regulatory mechanisms in the central and peripheral nervous systems. These neural systems control the action of two functional units in the LUT: the urinary bladder and an outlet consisting of the bladder neck, urethral sphincters, and pelvic-floor striated muscles. During the storage phase, the outlet is closed, and the bladder is inactive to maintain a low intravenous pressure and continence. In contrast, during the voiding phase, the outlet relaxes, and the bladder contracts to facilitate adequate urine flow and bladder emptying. SCI disrupts the normal reflex circuits that regulate co-ordinated bladder and urethral sphincter function, leading to involuntary and inefficient voiding. Following SCI, a spinal micturition reflex pathway develops to induce an overactive bladder condition following the initial areflexic phase. In addition, without proper bladder-urethral-sphincter coordination after SCI, the bladder is not emptied as effectively as in the normal condition. Previous studies using animal models of SCI have shown that hyperexcitability of C-fiber bladder afferent pathways is a fundamental pathophysiological mechanism, inducing neurogenic LUTD, especially detrusor overactivity during the storage phase. SCI also induces neurogenic LUTD during the voiding phase, known as detrusor sphincter dyssynergia, likely due to hyperexcitability of Aδ-fiber bladder afferent pathways rather than C-fiber afferents. The molecular mechanisms underlying SCI-induced LUTD are multifactorial; previous studies have identified significant changes in the expression of various molecules in the peripheral organs and afferent nerves projecting to the spinal cord, including growth factors, ion channels, receptors and neurotransmitters. These findings in animal models of SCI and neurogenic LUTD should increase our understanding of pathophysiological mechanisms of LUTD after SCI for the future development of novel therapies for SCI patients with LUTD.

Questionnaire survey of satisfaction with medication for five symptom domains of dementia with Lewy bodies among patients, their caregivers, and their attending physicians.

BACKGROUND: The real-world status of satisfaction with medication for dementia with Lewy bodies (DLB) has not been elucidated. We assessed the satisfaction of patients with DLB, their caregivers, and their attending physicians (trios) with medication according to the clinical symptom domains of DLB. METHODS: This was a subanalysis of a cross-sectional, questionnaire-based, survey study of trios. The subanalysis set comprised analysis populations for cognitive impairment, parkinsonism, psychiatric symptoms, sleep-related disorders, and autonomic dysfunction (orthostatic hypotension, constipation, and dysuria). These analysis populations included trios of patients who had any symptom domain and took medication for each symptom domain, and for which all trio data on satisfaction with medication for the symptom domain were available. The degrees of satisfaction with medication were classified as 'satisfied', 'neutral', or 'dissatisfied'. RESULTS: The analysis set for this study included 110 trios for cognitive impairment, 62 for parkinsonism, 47 for psychiatric symptoms, 29 for sleep-related disorders, none for orthostatic hypotension, 11 for constipation, and seven for dysuria. There were no statistically significant differences in the degree of satisfaction with medication for symptom domains other than parkinsonism and dysuria between patients-caregivers, patients-physicians, and caregivers-physicians. Regarding satisfaction with medication for parkinsonism, significantly more physicians than patients answered 'satisfied' (75.8% vs. 51.6%), and significantly more patients than physicians answered 'neutral' (35.5% vs. 14.5%) (P = 0.013). Regarding satisfaction with medication for dysuria, significantly more caregivers than physicians answered 'satisfied' (100% vs. 28.6%, P = 0.038). CONCLUSIONS: Satisfaction with medication for symptom domains other than parkinsonism and dysuria was similar among trios. Our results suggest that physicians should pay more attention to patients' satisfaction with medication for parkinsonism, and to caregivers' satisfaction with medication for dysuria to help prevent undermedication.

Comparison of caregiver burden between dementia with Lewy bodies and Alzheimer's disease.

BACKGROUND: Caring for patients with dementia with Lewy bodies (DLB) would be more stressful for their caregivers than those with Alzheimer's disease (AD). In this study, we compared levels of caregiver burden and the possible influential factors on the caregiver burden between DLB and AD. METHODS: Ninety-three DLB patients and 500 AD patients were selected from the Kumamoto University Dementia Registry. Caregiver burden, neuropsychiatric symptoms, basic activities of daily living (BADL) and instrumental activities of daily living (IADL) were assessed by the Japanese version of the Zarit Caregiver Burden Interview (J-ZBI), the Neuropsychiatric Inventory (NPI), the Physical Self-Maintenance Scale (PSMS), and the Lawton IADL scale, respectively. RESULTS: Despite the comparable Mini-Mental State Examination score, the J-ZBI score was significantly higher in the DLB group than the AD group (P = 0.012). A stepwise multiple regression analysis revealed that IADL score (ß = -0.23, P = 0.049), PSMS score (ß = -0.31, P = 0.010), disinhibition (ß = 0.22, P = 0.008), and anxiety (ß = 0.19, P = 0.027) were significantly associated with J-ZBI score in DLB. In AD, caregiver's relationship with patient (child) (ß = 0.104, P = 0.005), caregiver's gender (female) (ß = 0.106, P = 0.004), IADL score (ß = -0.237, P < 0.001), irritability (ß = 0.183, P < 0.001), apathy (ß = 0.132, P = 0.001), agitation (ß = 0.118, P = 0.007), and aberrant motor behaviour (ß = 0.107, P = 0.010) were associated with caregiver burden. CONCLUSIONS: Caring for DLB patients caused a higher degree of caregiver burden than AD patients in the same level of cognitive decline. The factors responsible for the caregiver's burden were different between DLB and AD. The caregiver burden for DLB patients was associated with the disability of basic ADL, IADL impairment, anxiety and disinhibition.

EphA2 on urinary extracellular vesicles as a novel biomarker for bladder cancer diagnosis and its effect on the invasiveness of bladder cancer.

BACKGROUND: Urinary extracellular vesicles (uEVs) secreted from bladder cancer contain cancer-specific proteins that are potential diagnostic biomarkers. We identified and evaluated a uEV-based protein biomarker for bladder cancer diagnosis and analysed its functions. METHODS: Biomarker candidates, selected by shotgun proteomics, were validated using targeted proteomics of uEVs obtained from 49 patients with and 48 individuals without bladder cancer, including patients with non-malignant haematuria. We developed an enzyme-linked immunosorbent assay (ELISA) for quantifying the uEV protein biomarker without ultracentrifugation and evaluated urine samples from 36 patients with and 36 patients without bladder cancer. RESULTS: Thirteen membrane proteins were significantly upregulated in the uEVs from patients with bladder cancer in shotgun proteomics. Among them, eight proteins were validated by target proteomics, and Ephrin type-A receptor 2 (EphA2) was the only protein significantly upregulated in the uEVs of patients with bladder cancer, compared with that of patients with non-malignant haematuria. The EV-EphA2-CD9 ELISA demonstrated good diagnostic performance (sensitivity: 61.1%, specificity: 97.2%). We showed that EphA2 promotes proliferation, invasion and migration and EV-EphA2 promotes the invasion and migration of bladder cancer cells. CONCLUSIONS: We established EV-EphA2-CD9 ELISA for uEV-EphA2 detection for the non-invasive early clinical diagnosis of bladder cancer.

Disseminated intravascular coagulation induced by pazopanib following combination therapy of nivolumab plus ipilimumab in a patient with metastatic renal cell carcinoma.

Recently, combination therapy including immune checkpoint inhibition (ICI) has proven to be effective as first-line therapy for patients with metastatic renal cell carcinoma. Although the first-line combination therapies with ICI have shown clinical benefit, a number of patients require second-line treatment. We report a 60-year-old man with metastatic renal cell carcinoma who was treated with pazopanib soon after nivolumab plus ipilimumab combination therapy. He experienced Grade 3 disseminated intravascular coagulation (DIC). We suspect that this was caused by an interaction between pazopanib and nivolumab even though ICI therapy was discontinued. He was treated with thrombomodulin and platelet transfusion and recovered from DIC. Treatment with pazopanib was subsequently restarted. No evidence of DIC was observed thereafter. This severe adverse reaction may have been induced by an interaction between activated proinflammatory immune cells and cytokines from an exacerbated inflammatory state and pazopanib. This report highlights the need to perform careful monitoring of patients who receive molecular targeted therapy after ICI-based immunotherapy.

Relationship between preoperative anxiety and onset of delirium after cardiovascular surgery in elderly patients: focus on personality and coping process.

BACKGROUND: Postoperative delirium is associated with increased mortality. Therefore, it is important to manage delirium during the entire perioperative period. Preoperative anxiety is associated with poor prognosis in postoperative patients who have undergone cardiovascular surgery. This study aims to investigate the relationship between preoperative anxiety and onset of delirium after cardiovascular surgery in elderly patients (aged 65 years or older), considering the individual psychological characteristics, such as personality and stress coping skills in response to anxiety, as confounding factors. METHODS: This prospective study included patients aged >65 years in a preoperative state before undergoing cardiovascular surgery. Subjects were divided into two groups based on whether they experienced postoperative delirium, or not. We compared clinical and demographic factors, preoperative psychiatric and psychological factors, and intraoperative and perioperative physical factors between the control and delirium groups. Multiple imputations were used to account for missing data. RESULTS: Out of 168 subjects enrolled in this study, 26 (15.5%) developed postoperative delirium. Univariate analysis showed significant differences in age (P = 0.027), cognitive function (P = 0.007), agreeableness (P = 0.029), and the Acute Physiology and Chronic Health Evaluation-II (APACHE-II) score (P = 0.023) between the delirium and control groups. Multiple logistic regression analysis did not identify a significant association between preoperative anxiety and the onset of postoperative delirium. However, age (odds ratio (OR) = 1.114, P = 0.018), agreeableness (OR = 0.555, P = 0.008), and the APACHE-II score (OR = 1.227, P = 0.008) were identified as risk factors for postoperative delirium. CONCLUSION: Agreeableness, one of the personality traits associated with preoperative anxiety, appears to be involved in the development of postoperative delirium as an independent psychological factor, regardless of age or physical factors.

Avoidance of four-wave mixing in optical fiber bundle for coherent anti-Stokes Raman scattering endomicroscopy.

We propose and demonstrate a method of suppressing four-wave mixing (FWM) in an optical fiber bundle to realize coherent anti-Stokes Raman scattering (CARS) endomicroscopy, which is the leading candidate for a definitive diagnosis of gastrointestinal cancer. Two excitation laser beams with different wavelengths are delivered via different cores to suppress FWM and are then combined with a polarization prism and a dual-wavelength wave plate and are focused to a spot. The background emission from the optical fiber bundle was suppressed to 1/3289, and we demonstrated CARS imaging of a polystyrene bead using the proposed method.

Ultrahigh-speed multiplex coherent anti-Stokes Raman scattering microspectroscopy using scanning elliptical focal spot.

We present a beam-scanning multiplex coherent anti-Stokes Raman scattering (CARS) microspectroscopy system using parallel excitation and parallel detection schemes based on an elliptical focal spot, which enables highly efficient signal acquisition even for short exposures. The elliptical focal spot was used to simultaneously observe the CARS signals of an enlarged region and reduce the peak irradiance. The developed system realized an acquisition rate of 34 139 spectra/s and enabled ultrahigh-speed acquisition of a vibrational spectroscopic image, covering the fingerprint region of 930-1 830 cm-1 with 256(x) × 256(y) × 512(spectrum) pixels in 1.92 s or with 128(x) × 128(y) × 256(spectrum) pixels in 0.54 s. We demonstrated ultrahigh-speed hyperspectral imaging of a mixture of polymer beads in liquid linoleic acid and living adipocytes using the developed system. All of the present demonstrations were performed with a low-peak irradiance excitation of ∼19 GW/cm2, which has been reported in previous studies to cause less photodamage to living cells. The label-free and ultrahigh-speed identification and visualization of various molecules made possible by the present system will accelerate the development of practical live-cell investigation.

Catatonia associated with late-life psychosis successfully treated with lithium: a case report.

BACKGROUND: Catatonia is a psychomotor syndrome that presents various symptoms ranging from stupor to agitation, with prominent disturbances of volition. Its pathogenesis is poorly understood. Benzodiazepines and electroconvulsive therapy (ECT) are safe and effective standard treatments for catatonia; however, alternative treatment strategies have not been established in cases where these treatments are either ineffective or unavailable. Here, we report a case of catatonia associated with late-life psychosis, which was successfully treated with lithium. CASE PRESENTATION: A 66-year-old single man with hearing impairment developed hallucination and delusions and presented with catatonic stupor after a fall. He initially responded to benzodiazepine therapy; however, his psychotic symptoms became clinically evident and benzodiazepine provided limited efficacy. Blonanserin was ineffective, and ECT was unavailable. His catatonic and psychotic symptoms were finally relieved by lithium monotherapy. CONCLUSIONS: Catatonic symptoms are common in patients with mood disorders, suggesting that lithium may be effective in these cases. Moreover, lithium may be effective for both catatonic and psychotic symptoms, as it normalizes imbalances of excitatory and inhibitory systems in the brain, which underlies major psychosis. Cumulative evidence from further cases is needed to validate our findings.

Efficacy of vibegron, a novel ß3-adrenoreceptor agonist, for lower urinary tract dysfunction in mice with spinal cord injury.

OBJECTIVES: To investigate the effect of vibegron, a new clinically approved ß3-adrenoceptor agonist in lower urinary tract dysfunction in mice with spinal cord injury. METHODS: Investigators performed cystometry under awake conditions in 4-week spinal cord injury female mice. Two weeks after spinal cord injury, saline or vibegron (30 mg/kg) was orally administered for 2 weeks prior to the urodynamic study. Investigators removed L6-S1 dorsal root ganglia from the saline- or vibegron-treated spinal cord injury mice as well as from saline-treated normal (spinal intact) mice to evaluate the levels of transient receptor potential cation channel subfamily V member 1, transient receptor potential cation channel subfamily A member 1, activating transcription factor 3, and inducible nitric oxide synthase transcripts using real-time polymerase chain reaction. RESULTS: In vibegron-treated spinal cord injury mice, nonvoiding contractions during bladder filling, which were increased in spinal cord injury compared to spinal intact mice, were significantly decreased. Micturition pressure or voiding efficiency was not significantly increased in comparison to measurements in saline-treated spinal cord injury mice. The expression of transient receptor potential cation channel subfamily V member 1, transient receptor potential cation channel subfamily A member 1, activating transcription factor 3, and inducible nitric oxide synthase messenger RNA was increased in spinal cord injury mice compared to spinal intact mice, but significantly decreased after vibegron treatment. CONCLUSIONS: Vibegron improves spinal cord injury-induced detrusor overactivity in addition to significantly reducing C-fiber afferent receptors such as transient receptor potential cation channel subfamily V member 1, transient receptor potential cation channel subfamily A member 1, and inflammatory cytokines/markers, such as activating transcription factor 3 and inducible nitric oxide synthase, in spinal cord injury mice. Thus, vibegron might be effective in the treatment of storage lower urinary tract dysfunction induced by C-fiber afferent activation after spinal cord injury.

Fucosylation in Urological Cancers.

Fucosylation is an oligosaccharide modification that plays an important role in immune response and malignancy, and specific fucosyltransferases (FUTs) catalyze the three types of fucosylations: core-type, Lewis type, and H type. FUTs regulate cancer proliferation, invasiveness, and resistance to chemotherapy by modifying the glycosylation of signaling receptors. Oligosaccharides on PD-1/PD-L1 proteins are specifically fucosylated, leading to functional modifications. Expression of FUTs is upregulated in renal cell carcinoma, bladder cancer, and prostate cancer. Aberrant fucosylation in prostate-specific antigen (PSA) could be used as a novel biomarker for prostate cancer. Furthermore, elucidation of the biological function of fucosylation could result in the development of novel therapeutic targets. Further studies are needed in the field of fucosylation glycobiology in urological malignancies.