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The mechanism of Pisa syndrome in Parkinson's disease (PD) is unclear. We aimed to analyze the spatial perception of patients with PD with Pisa syndrome using virtual reality.In total, 16 patients with Pisa syndrome, 16 age-matched patients without Pisa syndrome, and 16 age-matched controls were included. They viewed the virtual room gradually tilting to different 8 directions randomized across trials. The 75% discrimination threshold angle and the mean tilting discrimination angle for each direction were evaluated. Participants' lateral trunk deviation was measured using Kinect. Neuropsychological status was evaluated, using the Mini-Mental Status Examination (MMSE), the Japanese version of the Montreal-Cognitive Assessment, Frontal Assessment Battery, and the color-word interference task of the Stroop test. Visuospatial abilities were assessed using Benton Judgement of Line Orientation, and vestibular function was evaluated using Subjective Visual Vertical (SVV).The 75% discrimination threshold in the tilting discrimination angle was larger in all directions for those in the Pisa syndrome group compared to patients in the without Pisa syndrome group and those in the control group. There were significant differences between the three groups for Front-Right, Right, and Back. Patients with Pisa syndrome showed a significantly worse performance in these tests compared with controls and tended to have worse SVV performance compared with patients without Pisa syndrome.The present findings support the hypothesis of visuo-spatial disability and/or attentional impairment in patients with Pisa syndrome.

To determine the incidence and location of lower extremity deep vein thrombosis in patients undergoing radical cystectomy.We performed radical cystectomy in 137 patients with bladder cancer between August 2014 and February 2020. Since 2014, we have had a policy to screen for deep vein thrombosis using lower extremity ultrasonography both before and after radical cystectomy. We determined the incidence and location of deep vein thrombosis and classified it as either proximal or distal type. Furthermore, we explored the incidence of pulmonary embolism within 3 months after radical cystectomy.After excluding six patients with a lack of ultrasonographic data, we evaluated 131 patients. Preoperative deep vein thrombosis (one proximal and 17 distal) was diagnosed in 18 patients (14%) with no symptoms. Postoperative deep vein thrombosis was diagnosed in 41 patients (31%; three proximal and 38 distal), of whom 26 (63%) had new-onset deep vein thrombosis after cystectomy. Three patients, two with proximal and one with distal type deep vein thrombosis, developed nonfatal pulmonary embolism postoperatively. Multivariate analysis showed that preoperative D-dimer levels (odds ratio 5.35, 95% confidence interval 1.74-16.50; P 0.003), type of urinary diversion (ileal neobladder; odds ratio 11.15, 95% confidence interval 2.16-57.55; P = 0.004), and preoperative deep vein thrombosis (odds ratio 15.93, 95% confidence interval 3.82-66.30; P 0.001) were significant risk factors for postoperative deep vein thrombosis.Pre- and post-radical cystectomy whole-leg ultrasonography can lead to an early perioperative diagnosis and immediate treatment of proximal deep vein thrombosis, thereby potentially preventing fatal pulmonary embolism.

(Objectives) We evaluated the association between immune-related adverse events (irAEs) and the efficacy of pembrolizumab therapy in patients with metastatic urothelial carcinoma. (Methods) Data of 42 patients with metastatic urothelial carcinoma treated with pembrolizumab between May 2018 and February 2020 were retrospectively analyzed to determine the association between irAEs and objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). (Results) IrAEs were observed in 19 patients (45.2%). Objective response was observed in 15 patients (35.7%). Thirteen (68.4%) of 19 patients who experienced irAEs showed an objective response, whereas two (8.70%) of 23 patients who did not experience irAEs (odds ratio: 15.0, 95% confidence interval [CI]: 1.70-738, P=0.006). PFS and OS in the irAE group were longer than those in the non-irAE group (PFS: hazard ratio: 0.24, 95% CI: 0.11-0.54, P0.001; OS: hazard ratio: 0.11, 95% CI: 0.03-0.37, P0.001). (Conclusions) During pembrolizumab treatment, the occurrence of irAEs was significantly associated with higher response and survival prolongation in patients with metastatic urothelial carcinoma.

Diacylglycerol kinase gamma (DGKγ) is a subtype of DGK enzyme, which catalyzes ATP-dependent conversion of diacylglycerol to phosphatidic acid. DGKγ, localized in the brain, plays an important role in the central nervous system. However, its function has not been widely investigated. Positron emission tomography (PET) imaging of DGKγ validates target engagement of therapeutic DGKγ inhibitors and investigates DGKγ levels under normal and disease conditions. In this study, we designed and synthesized a series of 3-acetyl indole derivatives as candidates for PET imaging agents for DGKγ. Among the synthesized compounds, 2-((3-acetyl-1-(6-methoxypyridin-3-yl)-2-methyl-1H-indol-5-yl)oxy)-N-methylacetamide (9) exhibited potent inhibitory activity (IC50 = 30 nM) against DGKγ and desirable physicochemical properties allowing efficient blood-brain barrier penetration and low levels of undesirable nonspecific binding. The radiolabeling of 9 followed by PET imaging of wild-type and DGKγ-deficient mice and rats indicated that [11C]9 ([11C]T-278) specifically binds to DGKγ and yields a high signal-to-noise ratio for DGKγ in rodent brains.

Human steady-state locomotion modes are symmetrical, leading to symmetric mechanical function of human feet in general; however, track distance running in a counterclockwise direction exposes the runner’s feet to asymmetrical stress. This may induce asymmetrical adaptation in the runners’ foot arch functions, but this has not been experimentally tested. Here, we show that the plantar fascia (PF), a primary structure of the foot arch elasticity, is stiffer for the left than the right foot as a characteristic of runners, via a cross-sectional study on 10 track distance runners and 10 untrained individuals. Shear wave velocity (index of tissue stiffness: SWV) and thickness of PF and foot dimensions were compared between sides and groups. Runners showed higher PF SWV in their left (9.4 ± 1.0 m/s) than right (8.9 ± 0.9 m/s) feet, whereas untrained individuals showed no bilateral differences (8.5 ± 1.5 m/s and 8.6 ± 1.7 m/s, respectively). Additionally, runners showed higher left to right (L/R) ratio of PF SWV than untrained men (105.1% and 97.7%, respectively). PF thickness and foot dimensions were not significantly different between sides or groups. These results demonstrate stiffer PF in the left feet of runners, which may reflect adaptation to their running-specific training that involves asymmetrical mechanical loading.

Long‐distance running (LDR) can induce transient lowering of the foot arch, which may be associated with mechanical fatigue of the plantar fascia (PF). However, this has not been experimentally tested in vivo. The purpose of this study was to test our hypothesis that LDR induces transient and site‐specific changes in PF stiffness and morphology and that those changes are related to the lowering of the foot arch. Ten male recreational long‐distance runners and 10 untrained men were requested to run overground for 10 km. Before and after running, shear wave velocity (SWV: an index of soft tissue stiffness) and thickness of PF at three different sites from its proximal to distal end were measured using supersonic shear imaging and B‐mode ultrasonography. Foot dimensions including the navicular height were measured using a three‐dimensional foot scanner. SWV at the proximal site of PF and navicular height was significantly decreased in both groups after running, with a higher degree in untrained men (−21.9% and −14.1%, respectively) than in runners (−4.0% and −6.3%, respectively). The relative change (%Δ) in SWV was positively correlated with %Δnavicular height in both groups (r = .69 and r = .65, respectively). Multiple regression analysis revealed that %ΔSWV at the proximal site solely explained 72.7% of the total variance in %Δnavicular height. It is concluded that LDR induces transient and site‐specific decreases in PF stiffness. These results suggest that the majority of running‐induced lowering of the foot arch is attributable to the reduction of PF stiffness at the proximal site.

Transcutaneous immunization (TCI) is an effective vaccination method that is easier and less painful than the conventional injectable vaccination method. We previously developed self-dissolving microneedle patches (sdMN) and demonstrated that this TCI method has a high vaccination efficacy in mice and humans. To elucidate the mechanism of immune response induction, which is the basis for the efficacy and safety of TCI with sdMN, we examined the local reaction of the skin where sdMN was applied and the kinetics and differentiation status of immune cells in the draining lymph nodes (DLNs). We found that gene expression of the proinflammatory cytokine Il1b and the downstream transcription factor Irf7 was markedly upregulated in skin tissues after sdMN application. Moreover, activation of Langerhans cells and CD207

Diacylglycerol kinase gamma (DGKγ) is a subtype of DGK enzyme, which catalyzes ATP-dependent conversion of diacylglycerol to phosphatidic acid. DGKγ, localized in the brain, plays an important role in the central nervous system. However, its function has not been widely investigated. Positron emission tomography (PET) imaging of DGKγ validates target engagement of therapeutic DGKγ inhibitors and investigates DGKγ levels under normal and disease conditions. In this study, we designed and synthesized a series of 3-acetyl indole derivatives as candidates for PET imaging agents for DGKγ. Among the synthesized compounds, 2-((3-acetyl-1-(6-methoxypyridin-3-yl)-2-methyl-1H-indol-5-yl)oxy)-N-methylacetamide (

Background Because of the advanced age of patients with cardiovascular disease (CVD), prevention of sleep disorder and dementia is a priority for cardiac rehabilitation (CR) during their long-term care. This study aimed to investigate the association of physical activity with sleep quality and cognitive function in elderly patients with CVD in the CR maintenance phase. Methods We conducted a multicenter study through the Clinical Exercise Physiology Association Japan network, which included 102 elderly patients (mean age, 74 ± 7.4 years) with CVD undergoing phase III CR at 6 institutions. Physical activity was assessed using a triaxial accelerometer for 7 consecutive days and was classified as locomotive and household activities. Physical fitness was assessed via 6-min walking distance (6MD), hand grip power, 10-m walking speed, one leg standing time with eyes open, and 10 times sit-to-stand tests. Sleep quality and cognitive function were evaluated using the Pittsburgh sleep quality index (PSQI) and mini-mental state examination (MMSE) scores, respectively. Results The patients performed 5506.8 ± 3743.6 steps/day and scored 5.8 ± 3.5 points in the PSQI and 28.4 ± 1.7 points in the MMSE. Sleep latency and MMSE scores correlated with locomotive activity, but not with household activity. Locomotive activity and 6MD were independent predictors of sleep latency and MMSE score, respectively. When patients with heart failure were excluded, the relationship between sleep latency and locomotive activity was preserved, but the relationship between exercise tolerance and cognitive function disappeared. Conclusion Locomotive activity and exercise tolerance are associated with sleep latency and cognitive function in elderly patients with CVD continuing phase III CR. However, in this study, the relationship between exercise tolerance and cognitive function was offset by the presence of heart failure.

Biological or immunological differences in primary lesions between synchronous and metachronous metastatic renal cell carcinoma (mRCC) have been reported. However, the association between the tumor immune microenvironment (TIME) of primary lesions and time to metastasis remains unknown. We investigated the differences in the TIME of primary lesions based on time intervals to metastasis, mainly between the synchronous group (SG; metastasis within 3 months) and metachronous group (MG; metastasis after 3 months), and its association with clinicopathological parameters in patients with mRCC. Overall, 568 patients treated first-line with vascular endothelial growth factor receptor inhibitors comprised the analysis population (SG: N = 307 [54.0%]; MG: N = 261 [46.0%]). SG had a higher proportion of patients with poor prognostic pathological feature tumors: WHO/ISUP grade 4, necrosis, lymphovascular invasion, infiltrative growth pattern, and sarcomatoid differentiation. Regarding the TIME, more immunogenic features were seen in SG than MG, with a higher PD-L1 positivity and a lower proportion of the desert phenotype. This is the first study to examine the differences in the TIME of primary lesions in patients with mRCC based on the time intervals to metastasis. The TIME of primary lesions could affect the time to metastasis.

Pulmonary actinomycosis is a chronic disease characterized by abscess formation, draining sinuses, fistulae, and tissue fibrosis. It can mimic other conditions, particularly malignant and granulomatous diseases, and is perhaps extremely challenging to diagnose.A 64-year-old Japanese man presented with 6-week history of a painful solid lump in the chest wall. Chest computed tomography scan revealed a mass-like consolidation in the left upper lobe, with rib erosion and direct extension into the anterior chest wall.There is no difference in positron emission tomography/computed tomography scan findings between actinomycosis and malignancy. Therefore, pulmonary actinomycosis should be considered in the differential diagnosis of cases involving intensive activity on

Since December 2019, coronavirus disease 2019 (COVID-19) has been an international public health emergency. The possibility of COVID-19 should be considered primarily in patients with new-onset fever or respiratory tract symptoms. However, these symptoms can occur with other viral respiratory illnesses. We reported a case of severe acute respiratory syndrome coronavirus 2 and influenza A virus coinfection. During the epidemic, the possibility of COVID-19 should be considered regardless of positive findings for other pathogens.

INTRODUCTION AND OBJECTIVE:No reliable biomarker is available for predicting worse clinical outcome in chemo-resistant urothelial carcinoma (UC) patients treated with pembrolizumab. We focused on a...

Prevalence of antibodies to Toxoplasm gondii was studied using the latex agglutination (LA) method, followed by sucrose density gradient centrifugation (SDGC) method on the small Indian mongoose (Herpestes auropunctatus), which inhabits Amami-Oshima Island. Of the 362 samples, 38 (10.5%) revealed positive. Single or double peaks in the 7-8 and/or 12-14 fraction to LA titer by SDGC indicated the early stage of T. gondii infection. It is suggested that domestic/feral cats play an important role for spreading this zoonotic pathogen to the mongoose as well as other species that are endemic to this island. Future studies are warranted to prevent the transmission of T. gondii among cats and wild animals in order to maintain the ecosystem health.

A 25-year-old man, with a retroperitoneal bulky mass invading the posterior pancreas head, was referred to investigate and treat his rapidly advancing disease. An endoscopic ultrasonography guided-fine needle aspiration biopsy (EUS-FNAB), performed the next day, and followed by immunostaining for human chorionic gonadotropin (hCG), led to a histological diagnosis of choriocarcinoma. An elevated level of serum hCG also supported the diagnosis. Systemic chemotherapy by etoposide and cisplatin was initiated within a week, with precautions taken to avoid tumour lysis syndrome and choriocarcinoma syndrome. EUS-FNAB enabled a prompt diagnosis and suitable treatment for choriocarcinoma and was considered as an effective diagnostic tool for rare tumours with rapid progression.

Background Financial incentives have been used to increase physical activity. However, the benefit of financial incentives is lost when an intervention ends. Thus, for this study, we combined social network incentives that leverage the power of peer pressure with financial incentives. Few reports have examined the impact of physical activity on social capital. Therefore, the main goal of this study was to ascertain whether a combination of two incentives could lead to more significant changes in physical activity and social capital during and after an intervention. Methods The participants were 39 older women over 65 years of age in Kumamoto, Japan. The participants were randomly divided into a financial incentive group (FI group) and a social network incentive plus financial incentive group (SNI + FI group). Both groups underwent a three-month intervention. Measurements of physical activity and social capital were performed before and after the intervention. Additionally, the effects of the incentives on physical activity and social capital maintenance were measured 6 months postintervention. The financial incentive group received a payment ranging from US$4.40 to US$6.20 per month, depending on the number of steps taken during the intervention. For the other group, we provided a social network incentive in addition to the financial incentive. The SNI + FI group walked in groups of three people to use the power of peer pressure. Results A two-way ANOVA revealed that in terms of physical activity, there was a statistically significant interaction between group and time (p = 0.017). The FI group showed no statistically significant improvement in physical activity during the observation period. In terms of the value of social capital, there was no significant interaction between group and time. Conclusion Our results suggest that social network incentives, in combination with financial incentives, are more effective for promoting physical activity than financial incentives alone among older women and that these effects can continue after an intervention. In the meantime, further studies should be conducted on the effect of physical activity on social capital. Trial registration UMIN000038080, registered on 09/22/2019 (Retrospectively registered).

Reports frequently describe the worsening of oncologic outcome in patients who developed high-grade complications after curative surgery for esophageal, gastric, and breast cancers. We investigated the extent of this correlation in patients with bladder cancer after radical cystectomy (RC). During 2002–2017, we performed 326 RC and urinary diversion procedures and collected data regarding complications in these patients within 90 days postoperatively. We evaluated the severity of complications based on the modified Clavien–Dindo classification (grades 0–5). Grade ≥ 3 complications were considered high grade. After adjusting for confounding factors using a Cox regression model, we calculated the hazard ratios (HRs) for high-grade complications associated with recurrence-free survival (RFS) and cancer-specific survival (CSS). During a median follow-up period of 61 months, 38 patients (12%) developed high-grade complications (grade ≥ 3). The main causes (76%) of high-grade complications were gastrointestinal and infection problems. The RFS and CSS differed significantly between patients with high-grade complications and those without complications. After adjusting for confounding factors in the multivariate analysis, high-grade complications remained a significant risk factor for both RFS [HR 2.11; 95% confidence interval (CI) 1.07–4.15, p = 0.030] and CSS (HR 2.74; 95% CI 1.05–7.14, p = 0.039). High-grade complications after RC led to worse RFS and CSS outcomes, similar to those observed in patients with other cancers. A large-scale study is needed to further verify these findings, and discussions of knowledge and experiences are required to reduce the incidence of postoperative high-grade complications.

INTRODUCTION AND OBJECTIVES:No reliable biomarker is available for predicting worse clinical outcome in chemo-resistant urothelial carcinoma (UC) patients treated with pembrolizumab. We focused on ...

Ammonia (NH3) gas is one of the toxic gases causing a serious health damage, while NH3 is a useful chemical in industrial field. Therefore, for preventing unexpected accidents caused by inhalation, rapid, continuous, and reliable NH3 detection is greatly required by applying smart gas sensor which can put every NH3 emitting site. Among the various kinds of NH3 gas detection tool, the solid electrolyte type sensor is regarded to be a promising candidate for on time monitoring tool due to its selective and quantitative gas detection, thermal stability, and compactness in size, if both the low-temperature sensor operation and satisfactory water durability are realized. In 2011, we have reported a solid electrolyte type NH3 gas sensor showing high water durability at 230°C by using Al3+ ion conducting (Al0.2Zr0.8)20/19Nb(PO4)3 solid electrolyte and water durable NH4 +-β-gallate auxiliary sensing electrode. However, the operation temperature of this sensor (230°C) at which the high sensitivity without electrical noise was obtained are still high for expecting a long-term sensor operation, and it is required to lower the operation temperature. Because a main reason for preventing the low-temperature operation is high electrical resistance of NH4 +-β-gallate, we can expect to lower the operation temperature by newly designing an auxiliary sensing electrode. In this study, we focused on NH4LaNb2O7 in which NH4 + ions existed stably in the layered structure, similar to the NH4 +-β-gallate solid, and fabricated the highly water durable NH3 gas sensor which can operate even at 180°C, by combining with (Al0.2Zr0.8)20/19Nb(PO4)3 solid electrolyte. The NH4LaNb2O7 solid was obtained by the ion-exchange of RbLaNb2O7, which was synthesized by conventional solid-state reaction, in NH4NO3 eutectic solution. Similar to our previous sensor, the sensor element was devised by the combination of (Al0.2Zr0.8)20/19Nb(PO4)3 solid electrolyte, NH4LaNb2O7 auxiliary sensing electrode, and Al metal reference electrode. The NH3 gas sensing performances were investigated at 180°C in atmospheres whose water content was varied from 0 to 4.2 vol.%. From the thermal analysis of the synthesized NH4LaNb2O7 solid, it was found that NH4 + ions stably existed in (NH4)LaNb2O7 solid up to 200°C. Therefore, we decided the sensor operation temperature at 180°C which is slightly lower than the upper temperature limit of NH4LaNb2O7 solid for holding NH4 + ions in its structure. The present sensor exhibited a stable and continuous sensor response to NH3 gas concentration change with a 90% response time of 6 minutes (Response time includes substitution time of test gas in the gas flow line) at 180°C even under humid atmosphere containing 4.2 vol% H2O. Furthermore, the sensor EMF outputs for each NH3 gas concentration were almost same even for varying humidity from 0 to 4.2 vol%, and the EMF changes by changing NH3 gas concentration obeyed a theoretical Nernst relationship over three months, indicating that the present sensor with NH4LaNb2O7 solid as an auxiliary sensing electrode showed the theoretical response for NH3 gas at 180°C with long term stability even in humid atmosphere.