Association between response to enfortumab vedotin and peripheral neuropathy in urothelial carcinoma patients: a multicenter retrospective study.

BACKGROUND: Enfortumab vedotin (EV) was approved for patients with metastatic urothelial carcinoma (mUC) who progressed after anticancer therapy on September 2021 in Japan. The association between the occurrence of EV-related side effects and clinical outcome remains to be elucidated. METHODS: We identified 97 mUC patients treated with EV therapy at our five institutions from the date of approval to March 2023. The median follow-up period was 7.0 months. We retrospectively analyzed the efficacy and safety of EV. RESULTS: The median age of the patients was 71 years old, 39% had PS of 1 or more, and 56.7% had primary tumor in upper urinary tract. Overall response rate (ORR) to EV therapy, median progression-free survival (PFS), and overall survival (OS) were 43.3%, 7.52 months, and 12.78 months, respectively. Any grade of treatment-related skin disorder, dysgeusia, peripheral neuropathy, gastrointestinal disorder, and hyperglycemia occurred in 61 (62.9%), 36 (37.1%), 34 (35.1%), 29 (29.9%), and 18 (18.6%) patients, respectively. The patients with EV-associated peripheral neuropathy had significantly higher ORR (58.8% vs. 34.9%, P = .032) and longer median PFS (8.05 vs. 6.31 months, P = .017) and OS (not reached vs. 11.57 months, P = .008, respectively) than those without. The occurrence of peripheral neuropathy after EV treatment and the presence of peritoneal dissemination were factors independently associated with PFS (hazard ratio = 0.46, P = .008 and hazard raito = 3.83, P = .004, respectively) and OS (hazard ratio = 0.30, P = .005 and hazard raito = 4.53, P = .002, respectively). CONCLUSIONS: The occurrence of EV-related peripheral neuropathy might be associated with the efficacy of EV therapy in mUC patients.

Effectiveness of adjuvant chemotherapy for patients who undergo radical cystectomy without neoadjuvant chemotherapy: A retrospective cohort study of 115 advanced bladder cancer patients with pathological lymph node classification.

OBJECTIVES: We investigated the clinical outcomes of radical cystectomy without cisplatin-based neoadjuvant chemotherapy (NAC) and identified factors affecting the effectiveness of cisplatin-based adjuvant chemotherapy (AC). METHODS: Between September 2002 and February 2020, 288 bladder cancer patients who did not receive NAC underwent radical cystectomy. We retrospectively analyzed the recurrence rates, primary recurrence sites, recurrence-free survival (RFS), and overall survival (OS) of 115 advanced bladder cancer patients (pT3-4 or pN1-3) who were divided into the AC and observation groups. Subgroup analysis was performed, focusing on pathological stage. RESULTS: In total, 51 patients received AC, and 64 patients were observed. The median follow-up duration was 95 months. The recurrence rate was lower in the AC group than in the observation group (35.3% vs. 54.7%, p = 0.041). The rate of recurrences in the lymph node area (dissection site and proximal lymph nodes) was lower in the AC group (9.8% vs. 26.6%; p = 0.031). In the subgroup analysis of patients with pN1, the probability of RFS and OS was higher in the AC group than in the observation group. The hazard ratio for RFS and OS was 0.243 (95% confidence interval [CI]: 0.077-0.768) and 0.259 (95% CI: 0.082-0.816), respectively. The 5-year RFS and OS were significantly higher in the AC group (80.0% and 79.4%) than in the observation group (35.7% and 42.9%; p < 0.008 and p < 0.012, respectively). CONCLUSIONS: AC improved RFS and OS in patients with pN1 disease who did not receive NAC and should be considered for this population.

[Resected Right Upper Lobe Lung Cancer with Displaced Bronchus and Anomalous Pulmonary Vein].

The patient is a 77-year-old man. He was referred to our hospital after a chest computed tomography (CT) scan revealed a 6.5 cm-sized mass in the right lung apex. Bronchoscopy revealed adenocarcinoma, clinical stageⅡB, and the patient was referred for surgery. Preoperative 3D-CT revealed the presence of a displaced bronchus, probably B1a, branching from the right main bronchus centrally from the upper lobe bronchus, and an abnormal vessel (V2) running dorsal to the upper lobe bronchus and the right main bronchus, and returning directly to the left atrium. Surgery was performed by resectioning the right upper lobe through a posterolateral incision, combined resection of the wall pleura, and lymph node dissection (ND2a-2). Because lung cancer surgery is sometimes accompanied by abnormal bronchial and pulmonary vascular branches, it is essential to thoroughly examine the patient before surgery for checking abnormal branches by bronchoscopy and 3D-CT.

Effects of small community walking intervention on physical activity, well-being, and social capital among older patients with cardiovascular disease in the maintenance phase: a randomized controlled trial.

[Purpose] Older patients with cardiovascular disease should increase their physical activity and prioritize positive psychological and social approaches in the maintenance phase of their cardiac rehabilitation. This study aimed to clarify the effect of small community walking on physical activity, well-being, and social capital in older patients with cardiovascular disease in the maintenance phase. [Participants and Methods] We conducted a multicenter study in Kumamoto, Japan. We randomly divided 55 patients with cardiovascular disease into two groups: small community walking and walking alone. For three months, a registered cardiac rehabilitation instructor provided walking guidance to both groups using a wearable device. We measured physical activity, social capital, and subjective happiness before and after the intervention. [Results] Results revealed a statistically significant main effect of time on physical activity and social participation. In the subjective happiness scale, there was an association between group and time. [Conclusion] Our results suggest that walking guidance using a wearable device was beneficial in improving overall physical activity, regardless of whether the individual did small community walking or walking alone. Furthermore, small community walking intervention may effectively enhance well-being. The relationship between physical activity and social participation needs to be further investigated.

Utility of urinary presepsin in the diagnosis of pyelonephritis: a cross-sectional study.

BACKGROUND: Presepsin is produced during the phagocytosis of bacteria by granulocytes. Presepsin increases at the site of infection; however, the significance of urinary presepsin in pyelonephritis is unknown. This study aimed to evaluate whether measuring urinary presepsin can distinguish between pyelonephritis and nonpyelonephritis. METHODS: A cross-sectional study of patients with suspected pyelonephritis was conducted. Urinary presepsin at admission was compared between the pyelonephritis and nonpyelonephritis groups using the Mann-Whitney test. The predictive accuracy of urinary presepsin for diagnosing pyelonephritis was evaluated by the area under the receiver operating characteristics (ROC) analysis curve. RESULTS: A total of 35 eligible participants were included in the pyelonephritis group and 25 in the nonpyelonephritis group. The median urinary presepsin level was 2232.0 (interquartile range [IQR], 1029.0-3907.0) pg/mL in the pyelonephritis group and 1348.0 (IQR, 614.5-2304.8) pg/mL in the nonpyelonephritis group. Urinary presepsin concentrations were significantly higher in the pyelonephritis group than in the nonpyelonephritis group (P = 0.023). ROC analysis of urinary presepsin revealed a cutoff value of 3650 pg/mL to distinguish between the pyelonephritis and nonpyelonephritis groups. Sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio for the diagnosis of pyelonephritis were 0.40 (95% confidence interval [CI], 0.24-0.58), 0.96 (95% CI, 0.79-1.00), 0.93 (95% CI, 0.68-1.00), 0.52 (95% CI, 0.37-0.68), 9.60 (95% CI, 1.35-68.23), and 0.62 (95% CI, 0.47-0.83), respectively. CONCLUSIONS: The measurement of urinary presepsin is useful in differentiating pyelonephritis from other diseases.

Influence of Body Mass on Running-Induced Changes in Mechanical Properties of Plantar Fascia.

ABSTRACT: Shiotani, H, Mizokuchi, T, Yamashita, R, Naito, M, and Kawakami, Y. Influence of body mass on running-induced changes in mechanical properties of plantar fascia. J Strength Cond Res 37(11): e588-e592, 2023-Body mass is a major risk factor for plantar fasciopathy; however, evidence explaining the process between risk factors and injury development is limited. Long-distance running induces transient and site-specific reduction in plantar fascia (PF) stiffness, reflecting mechanical fatigue and microscopic damage within the tissue. As greater mechanical loads can induce greater reduction in tissue stiffness, we hypothesized that the degree of running-induced change in PF stiffness is associated with body mass. Ten long-distance male runners (age: 21 - 23 years, body mass: 55.5 ± 4.2 kg; mean ± SD ) and 10 untrained men (age: 20 - 24 years, body mass: 58.4 ± 5.6 kg) ran for 10 km. Before and immediately after running, the shear wave velocity (SWV) of PF at the proximal site, which is an index of tissue stiffness, was measured using ultrasound shear wave elastography. Although the PF SWV significantly decreased after running in runners (-4.0%, p = 0.010) and untrained men (-21.9%, p < 0.001), runners exhibited smaller changes ( p < 0.001). The relative changes in SWV significantly correlated with body mass in both runners ( r = -0.691, p = 0.027) and untrained individuals ( r = -0.723, p = 0.018). These results indicate that a larger body mass is associated with a greater reduction in PF stiffness. Our findings provide in vivo evidence of the biomechanical basis for body mass as a risk factor for plantar fasciopathy. Furthermore, group differences suggest possible factors that reduce the fatigue responses, such as adaptation enhancing the resilience of PF and running mechanics.

Incidence and location of perioperative deep vein thrombosis in patients with bladder cancer undergoing radical cystectomy.

OBJECTIVES: To determine the incidence and location of lower extremity deep vein thrombosis in patients undergoing radical cystectomy. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Effects of social network incentives and financial incentives on physical activity and social capital among older women: a randomized controlled trial.

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).

Acute effects of long-distance running on mechanical and morphological properties of the human plantar fascia.

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.

A Phase III trial of a single early intravesical instillation of pirarubicin to prevent bladder recurrence after radical nephroureterectomy for upper tract urothelial carcinoma (JCOG1403, UTUC THP Phase III).

Observation is the current standard for managing cases of Stage 0a-III upper tract urothelial carcinoma after radical nephroureterectomy. A randomized Phase III trial commenced in Japan during October 2016. The trial is designed to investigate the superiority of a single early intravesical instillation of pirarubicin, compared with observation, in terms of relapse-free survival after radical nephroureterectomy for Stage 0a-III upper tract urothelial carcinoma. During a 5-year period, 310 patients will be recruited from 43 Japanese institutions. The primary endpoint is defined as relapse-free survival, and the secondary endpoints are overall survival, intravesical relapse-free survival, adverse events, and serious adverse events. This trial has been registered in the UMIN Clinical Trials Registry (UMIN000024267, http://www.umin.ac.jp/ctr/index.htm).

Bacillus Calmette-Guérin treatment of urothelial carcinoma arising in the ileal neobladder after radical cystectomy.

In January 2005, a 66-year-old man underwent radical cystectomy and ileal neobladder reconstruction for invasive bladder cancer. A total of 3 years after the cystectomy, left-side ureteral cancer was diagnosed, and a nephroureterectomy was carried out in May 2008. In October 2011, he complained of asymptomatic macroscopic hematuria. We detected multiple papillary pedunculated and broad-based tumors in the left side and the dome of the neobladder. The patient underwent transurethral resection of the bladder tumor, and a pathological diagnosis of high-grade pTa urothelial carcinoma was made. A total of 4 months later, tumors recurred in the right side and anterior wall of the neobladder. We carried out transurethral resection of the bladder tumor again; the pathological diagnosis was high-grade pTa urothelial carcinoma with carcinoma in situ. Bacillus Calmette-Guérin instillation was carried out seven times into the neobladder, without any severe side-effects. Tumor recurrence was not observed up to 8 months after bacillus Calmette-Guérin treatment.

Epidermoid cyst of the testis: A report of three cases.

Testicular epidermoid cysts have characteristic findings. Testicular tumor markers are negative in patients with epidermoid cysts. Clear margins and sole and small testicular tumors (20 mm or less) suggest the possibility of epidermoid cyst. Testicular-sparing surgery with intraoperative frozen section examination should be performed when suspecting epidermoid cysts. Testicular epidermoid cysts are rare tumors that account for 1% of all testicular tumors and are often clinically misdiagnosed as malignant lesions. We report three cases of epidermoid cysts. The chief manifestations were scrotal induration in two patients and pruritus scrotum in one. The median age of the patients was 23 years (18-30). All tumors were determined to be sole lesions (<20 mm in diameter). Testing for tumor markers in all patients revealed negative results. We could not rule out malignancy; hence, we performed high inguinal orchiectomy in all cases. Histologically, the inner walls of the cysts were lined with stratified squamous epithelium; their contents were keratinized. All patients were diagnosed with epidermoid cysts.

Cumulative incidence and risk factors for recurrence of upper tract urothelial carcinoma in patients undergoing radical cystectomy.

Objectives: This study aimed to evaluate the cumulative incidence of upper tract urothelial carcinoma (UTUC) recurrence and identify its risk factors in patients who underwent radical cystectomy (RC). Patients and methods: We performed RC on 385 patients between September 2002 and February 2020. After excluding 20 patients-13 with simultaneous nephroureterectomy, 6 with distal ureteral stump positivity and 1 with urachal cancer-365 patients were included in the analysis. To predict UTUC recurrence, we examined the cancer extension pattern in cystectomy specimens and categorized them into three types: cancer located only in the bladder (bladder-only type), cancer extending to the urethra or distal ureter (one-extension type) and cancer extending to both the urethra and distal ureter (both-extension type). We determined hazard ratios for UTUC recurrence for each covariate, including this cancer extension pattern. Results: Of the 365 patients, 60% had the bladder-only type, 30% had the one-extension type and 10% had the both-extension type. During a median follow-up period of 72 months for survivors, UTUC recurred in 25 of the 365 patients, with cumulative incidences of 3.7% at 5 years and 8.3% at 10 years. The median interval from cystectomy to recurrence was 65 months (interquartile range: 36-92 months). In the multivariate analysis, the extension pattern was a significant predictor of UTUC recurrence. The hazard ratios for UTUC recurrence were 3.12 (95% confidence interval [CI] = 1.15-8.43, p = 0.025) for the one-extension type and 5.96 (95% CI = 1.98-17.91, p = 0.001) for the both-extension type compared with the bladder-only type. Conclusions: The cancer extension pattern in cystectomy specimens is predictive of UTUC recurrence. A more extensive cancer extension in cystectomy specimens elevates the risk of subsequent UTUC recurrence. Intensive long-term monitoring is essential, particularly for patients with the both-extension type.

TIMELESS is overexpressed in lung cancer and its expression correlates with poor patient survival.

TIMELESS (TIM) is a mammalian homolog of a Drosophila circadian rhythm gene, but its circadian properties in mammals have yet to be determined. TIM appears to be essential for replication protection and genomic stability. Recently, the involvement of TIM in human malignancies has been reported; therefore, we investigated the role of TIM in lung cancer. Microarray expression analysis of lung cancer cell lines showed that TIM expression was elevated 3.7-fold (P < 0.001) in non-small cell lung cancer cell lines (n = 116) compared to normal lung controls (n = 59). In addition, small cell lung cancer cell lines (n = 29) expressed TIM at levels 2.2-fold (P < 0.001) higher than non-small cell lung cancer. Western blot analysis of 22 lung cancer cell lines revealed that all of them expressed TIM protein and that 20 cell lines (91%) expressed TIM protein at higher levels than a normal control line. Remarkably, immunohistochemistry of 30 surgically resected lung cancer specimens showed that all lung cancer specimens but no matched normal lung tissues were positive for TIM expression. Moreover, immunohistochemistry of surgically resected specimens from 88 consecutive patients showed that high TIM protein levels correlated with poor overall survival (P = 0.013). Mutation analysis for TIM in 23 lung cancer cell lines revealed no mutation. TIM knockdown suppressed proliferation and clonogenic growth, and induced apoptosis in H157 and H460 cells. Taken together, our findings suggest that TIM could be useful as a diagnostic and prognostic marker for lung cancer and targeting it would be of high therapeutic value for this disease.

Droplet duos on water display pairing, autonomous motion, and periodic eruption.

Under non-equilibrium conditions, liquid droplets dynamically couple with their milieu through the continuous flux of matter and energy, forming active systems capable of self-organizing functions reminiscent of those of living organisms. Among the various dynamic behaviors demonstrated by cells, the pairing of heterogeneous cell units is necessary to enable collective activity and cell fusion (to reprogram somatic cells). Furthermore, the cyclic occurrence of eruptive events such as necroptosis or explosive cell lysis is necessary to maintain cell functions. However, unlike the self-propulsion behavior of cells, cyclic cellular behavior involving pairing and eruption has not been successfully modeled using artificial systems. Here, we show that a simple droplet system based on quasi-immiscible hydrophobic oils (perfluorodecalin and decane) deposited on water, mimics such complex cellular dynamics. Perfluorodecalin and decane droplet duos form autonomously moving Janus or coaxial structures, depending on their volumes. Notably, the system with a coaxial structure demonstrates cyclic behavior, alternating between autonomous motion and eruption. Despite their complexity, the dynamic behaviors of the system are consistently explained in terms of the spreading properties of perfluorodecalin/decane duplex interfacial films.

The circadian clock gene BMAL1 is a novel therapeutic target for malignant pleural mesothelioma.

Malignant pleural mesothelioma (MPM) is a highly aggressive neoplasm arising from the mesothelial cells lining the parietal pleura and it exhibits poor prognosis. Although there has been significant progress in MPM treatment, development of more efficient therapeutic approaches is needed. BMAL1 is a core component of the circadian clock machinery and its constitutive overexpression in MPM has been reported. Here, we demonstrate that BMAL1 may serve as a molecular target for MPM. The majority of MPM cell lines and a subset of MPM clinical specimens expressed higher levels of BMAL1 compared to a nontumorigenic mesothelial cell line (MeT-5A) and normal parietal pleural specimens, respectively. A serum shock induced a rhythmical BMAL1 expression change in MeT-5A but not in ACC-MESO-1, suggesting that the circadian rhythm pathway is deregulated in MPM cells. BMAL1 knockdown suppressed proliferation and anchorage-dependent and independent clonal growth in two MPM cell lines (ACC-MESO-1 and H290) but not in MeT-5A. Notably, BMAL1 depletion resulted in cell cycle disruption with a substantial increase in apoptotic and polyploidy cell population in association with downregulation of Wee1, cyclin B and p21(WAF1/CIP1) and upregulation of cyclin E expression. BMAL1 knockdown induced mitotic catastrophe as denoted by disruption of cell cycle regulators and induction of drastic morphological changes including micronucleation and multiple nuclei in ACC-MESO-1 cells that expressed the highest level of BMAL1. Taken together, these findings indicate that BMAL1 has a critical role in MPM and could serve as an attractive therapeutic target for MPM.

Transient but not stable ZEB1 knockdown dramatically inhibits growth of malignant pleural mesothelioma cells.

BACKGROUND: The role of ZEB1, a master epithelial-to-mesenchymal transition gene, in malignant pleural mesothelioma (MPM) is unclear. METHODS: The expression of ZEB1, E-cadherin, vimentin, and epithelial cell adhesion molecule (EpCAM) in 18 MPM cell lines and a normal pleural mesothelial cell line MeT-5A was determined by quantitative real-time polymerase chain reaction and Western blot testing. RNA interference-mediated transient and/or stable knockdown of ZEB1 and EpCAM was performed. Microarray expression analysis was performed with a TORAY-3D gene chip. Growth was evaluated by colorimetric proliferation and colony formation assays. Luciferase reporter assay was performed to access the effects of ZEB1 knockdown on EpCAM promoter activity. RESULTS: Most MPM cell lines exhibited mesenchymal phenotype and expressed ZEB1. Transient ZEB1 knockdown suppressed growth in all four cell lines studied (ACC-MESO-1, H2052, Y-MESO-8A, Y-MESO-29) while stable ZEB1 knockdown suppressed growth only in Y-MESO-29. Genome-wide gene expression analysis revealed that EpCAM was the most prominently up-regulated gene by both transient and stable ZEB1 knockdown in ACC-MESO-1, with more marked up-regulation in stable knockdown. We hypothesized that EpCAM up-regulation counteracts the stable ZEB1 knockdown-induced growth inhibition in ACC-MESO-1. Transient EpCAM knockdown suppressed growth dramatically in ACC-MESO-1 cells expressing shZEB1 but only modestly in those expressing shGFP, supporting our hypothesis. Luciferase reporter assay showed that ZEB1 knockdown resulted in increased EpCAM promoter activity. EpCAM was also up-regulated in Y-MESO-29 expressing shZEB1, but this EpCAM up-regulation did not counteract ZEB1knockdown-induced growth suppression, suggesting that the counteracting effects of EpCAM may be cellular context dependent. CONCLUSIONS: RNA interference-mediated ZEB1 knockdown may be a promising therapeutic strategy for MPM, but one has to consider the possibility of diminished growth inhibitory effects of long-term ZEB1 knockdown, possibly as a result of EpCAM up-regulation and/or other gene expression changes resulting from ZEB1 knockdown.

Impaired virtual space-tilting perception in Parkinson's disease with Pisa syndrome.

INTRODUCTION: 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. METHODS: 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). RESULTS: 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. CONCLUSION: The present findings support the hypothesis of visuo-spatial disability and/or attentional impairment in patients with Pisa syndrome.

Pulmonary actinomycosis mimicking lung cancer on 18F-fluorodeoxyglucose positron emission tomography: a case report.

BACKGROUND: 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. CASE PRESENTATION: 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. 18F-fluorodeoxyglucose positron emission tomography scan showed increased metabolic activity in the mass, which is indicative of primary lung cancer. The bronchoscopy and computed tomography scan-guided transthoracic biopsy results were considered nondiagnostic. Finally, the patient was diagnosed with pulmonary actinomycosis via surgical resection. He completed an 8-week course of antibiotic therapy and experienced no recurrence. CONCLUSIONS: 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 18F-fluorodeoxyglucose positron emission tomography scan.

Analysis of immune response induction mechanisms implicating the dose-sparing effect of transcutaneous immunization using a self-dissolving microneedle patch.

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- dermal dendritic cells, which are subsets of antigen-presenting cells (APCs) in the skin, and their migration to the DLNs were promoted. Furthermore, the activated APC subsets promoted CD4+ T cell and B cell differentiation and the formation of germinal centers, which are the sites of high-affinity antibody production. These phenomena associated with sdMN application may contribute to the efficient production of antigen-specific antibodies after TCI using sdMN. These findings provide essential information regarding immune response induction mechanisms for the development and improvement of TCI preparations.