Positional relationship between ball and fingers for accurate baseball pitching.

Accurately throwing an object to a target position repeatedly is one of the specific human motor skills. The final arrival position of a thrown ball can be determined by its physical state at release. In baseball pitching, reducing the variability of the velocity angle of the ball at release (release angle) is important for reducing the variability of the pitch location. Although previous studies have suggested that hand and finger movements are important for accurate throwing, their relationship with the release angle has not yet been investigated in detail. This study focused on the positional relationship between the ball and fingers, which is considered to be closely related to ball movement as an action point of the force, and examined its relationship with the variability of release angle. To obtain accurate finger positions relative to the ball without impeding movement or sensation, an automatic image recognition technology based on deep learning was employed. This approach revealed a noteworthy correlation between the lower middle finger positions prior to acceleration peaks and the reduced variability in release angle, emphasizing the importance of consistent finger positioning during the pre-release phase. This finger positioning of the pitchers with low variability in the release angle is suggested to be robust against the spatial variability of ball movement.

Bilateral Nephrectomy for Resistant Hypertension and Secondary Aldosteronism in a Hemodialysis Patient: A Case Report.

A 42-year-old Japanese woman with end-stage renal failure due to hypertension presented with a systolic blood pressure of 160-200 mmHg despite treatment with 4 different antihypertensive agents. The plasma aldosterone concentration (PAC) and plasma renin activity (PRA) were elevated. Adrenal vein sampling suggested bilateral excessive aldosterone secretion, whereas adrenocortical scintigraphy showed right-dominant accumulation. Open bilateral nephrectomy and right adrenalectomy improved the systolic blood pressure, PAC, and PRA. A pathological examination revealed zona glomerulosa hyperplasia but not microaldosteronoma. This report shows that bilateral nephrectomy, not unilateral adrenalectomy, is a potentially effective treatment option for resistant hypertension with an elevated renin-angiotensin-aldosterone system in hemodialysis patients.

Limited social support is associated with depression, anxiety, and insomnia in a Japanese working population.

Background: Lack of social support is associated with depression, anxiety, and insomnia. This study aimed to determine the source of support related to depression, anxiety, and insomnia among Japanese workers. Methods: As part of a cohort study, we conducted a questionnaire survey among city government employees in Koka City, Shiga Prefecture, Japan, from September 2021 to March 2022. We used the Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), and Insomnia Severity Index (ISI) to assess depressive symptoms, anxiety symptoms, and insomnia, respectively. We used the Brief Job Stress Questionnaire (BJSQ) to assess job stressors and social support (from supervisors, colleagues, and family). Results: A total of 1,852 Japanese employees (38.4% male, 45.9 ± 12.9 years) participated in the survey, with 15.5, 10.8, and 8.2% of the participants having depressive symptoms (PHQ-9 ≥ 10), anxiety symptoms (GAD-7 ≥ 10), and insomnia (ISI ≥ 15), respectively. The logistic regression analysis suggested that job stressors were associated with depressive symptoms (p < 0.001), anxiety symptoms (p < 0.001), and insomnia (p = 0.009). In contrast, support from co-workers (p = 0.016) and family members (p = 0.001) was associated with decreased depressive symptoms. Support from family members was associated with decreased insomnia (p = 0.005). Conclusion: Social support from co-workers and family may be associated with reduced depressive symptoms, and family support may be associated with reduced insomnia in the Japanese working population. Clinical trial registration: https://clinicaltrials.gov/ct2/show/NCT03276585.

Percutaneous Thermal Ablation for Managing Small Renal Metastatic Tumors.

Purpose: To retrospectively evaluate the treatment outcomes of thermal ablation for renal metastatic tumors. Materials and Methods: Thirteen consecutive patients with small renal metastatic tumors (≤3 cm), who underwent thermal ablation between 2009 and 2020, were included in this study. Eight patients had extra-renal tumors during renal ablation. The primary tumors were adenoid cystic carcinoma in four patients, lung cancer in three, hemangiopericytoma in three, leiomyosarcoma in two, and thyroid cancer in one. The therapeutic effects, safety, survival rate, prognostic factor, and renal function were evaluated. Results: We performed 18 ablation sessions (cryoablation, n = 13; radiofrequency ablation, n = 5) on 19 renal metastases with a mean diameter of 1.7 cm, which resulted in a primary technique efficacy rate of 100% without procedure-related deaths or major complications. Renal function significantly declined 6 months after ablation (P = 0.0039). During the mean follow-up period of 31.2 ± 22.4 months (range, 2.7-71.4 months), one patient had local tumor progression at 11.9 months following radiofrequency ablation. The overall survival rates at 1 and 3 years after ablation were 76.9% (95% confidence interval [CI], 54.0%-99.8%) and 59.3% (95% CI, 31.3%-87.3%), respectively. Tumor size ≥ 2 cm (P = 0.02) and metastasis from non-small cell lung cancer (P = 0.001) were significant worse prognostic factors in univariate analysis, and metastasis from non-small cell lung cancer (P = 0.01) was significant in multivariate analysis. Conclusions: Percutaneous thermal ablation for small renal metastases is safe and feasible and can control local tumors.

Monitoring of blood immunosuppressant concentrations and lymphocyte activation for predicting viral infections following kidney transplantation: A pilot study.

The current standard pharmacokinetic monitoring of immunosuppressive therapy does not consider inter- and intra-individual differences in the biological response to multidrug immunosuppressive therapy. The authors evaluated the blood levels of the immunosuppressive drugs IL-2 and IFN-γ in circulating lymphocytes as surrogate indicators of the development of viral infections after living kidney transplantation. This single-center prospective study included 20 kidney transplant recipients who underwent living-donor transplantation at the Mie University Hospital. All the study participants received tacrolimus, mycophenolic acid, methylprednisolone, and basiliximab. The area under the concentration curves (AUCs) of blood tacrolimus and serum mycophenolic acid were measured 1 day prior to transplantation and on post-transplantation days (PTD) for up to 5 months. IL-2 and IFN-γ levels in circulating lymphocytes were measured simultaneously. One recipient experienced an acute graft rejection. Although the AUC of tacrolimus at PTD 7 was significantly higher in the virus-infected group than that in the non-infected group, the AUC of mycophenolic acid did not differ significantly between the 2 groups. The expression levels of IFN-γ+ NK, IFN-γ+ CD4+ T, and CD8+ T cells in the infected group also tended to be higher than those in the noninfected group. During the study period, there was a clear difference in the expression of IFN-γ+ CD8+ T cells, which increased significantly during or after infection. Circulating IFN-γ+ CD8+ T cell counts may serve as promising biomarkers for predicting opportunistic viral infections early after kidney transplantation.

Japanese Spotted Fever and Irreversible Renal Dysfunction during Immunosuppressive Therapy after a Living-Donor Kidney Transplant.

Ten years ago, a 56-year-old woman with a history of IgA nephropathy who received a living-donor kidney transplant across ABO barriers was managed with immunosuppressive drugs. The kidney transplant donor was her father who had poor kidney function. The patient's renal function was stable for 10 years. The patient visited our department with a complaint of skin rash, occurring 2 days after an onset of fever. Although a skin rash is atypical for Japanese spotted fever (JSF), we suspected JSF and started treatment with minocycline because we found a scar suggestive of an eschar. Furthermore, the blood test results were similar to those associated with JSF, and the patient lived in a JSF-endemic area. The patient's symptoms improved after 1 week. She was diagnosed with JSF by serological tests against Rickettsia japonica. JSF usually does not cause any complications after recovery. However, the patient's renal function did not completely recover. JSF can cause an atypical rash in patients taking excessive immunosuppressive drugs. Early treatment is required for patients with suspected JSF to prevent complications of renal dysfunction after receiving a living-donor kidney transplant.

Prolonged Sleep Latency and Reduced REM Latency Are Associated with Depressive Symptoms in a Japanese Working Population.

BACKGROUND: Examining the relationship between sleep and depression may be important for understanding the aetiology of affective disorders. Most studies that use electroencephalography (EEG) to objectively assess sleep have been conducted using polysomnography in the laboratory. Impaired sleep continuity, including prolonged sleep latency and changes in rapid eye movement (REM) sleep, have been reported to be associated with depression in clinical settings. Here, we aimed to use home EEG to analyse the association between sleep and depressive symptoms. METHODS: We performed a cross-sectional epidemiological study in a large Japanese working population to identify the EEG parameters associated with depressive symptoms based on the results of a questionnaire survey and home EEG measurements using 1-channel (1-Ch) EEG. RESULTS: The study included 650 Japanese patients (41.2% male, 44.7 ± 11.5 years) who underwent home EEG monitoring along with the Patient Health Questionnaire-9 (PHQ-9) to assess depressive symptoms. Logistic regression analysis revealed that depressive symptoms (PHQ-9 ≥ 10) were associated with sleep latency (odds ratio (OR) 1.02; 95% confidence interval (CI): 1.00-1.04) and REM latency (OR, 0.99; 95% CI: 0.99-1.00). CONCLUSIONS: Our results suggest that depressive symptoms are associated with prolonged sleep latency and reduced REM latency in a Japanese working population. The 1-Ch EEG may be a useful tool to monitor sleep and screen depression/depressive symptoms in non-clinical settings.

STAT3 Polymorphism Associates With mTOR Inhibitor-Induced Interstitial Lung Disease in Patients With Renal Cell Carcinoma.

We evaluated the association of signal transducer and activator of transcription 3 (STAT3) polymorphisms with the incidence of mammalian target of rapamycin (mTOR) inhibitor-induced interstitial lung disease (ILD) in patients with renal cell carcinoma (RCC). We also used lung-derived cell lines to investigate the mechanisms of this association. Japanese patients with metastatic RCC who were treated with mTOR inhibitors were genotyped for the STAT3 polymorphism, rs4796793 (1697C/G). We evaluated the association of the STAT3 genotype with the incidence of ILD and therapeutic outcome. In the 57 patients included in the primary analysis, the ILD rate within 140 days was significantly higher in patients with the GG genotype compared with those with other genotypes (77.8% vs. 23.1%, odds ratio=11.67, 95% confidential interval=3.0644.46). There were no significant differences in progression-free survival or time-to-treatment failure between the patients with the GG genotype and those with other genotypes. An in vitro study demonstrated that some lung-derived cell lines carrying the GG genotype exhibited an increase in the expression of mesenchymal markers, such as fibronectin, N-cadherin, and vimentin, and decreases in E-cadherin, which is an epithelial marker associated with exposure to everolimus, although STAT3 expression and activity were not related to the genotype. In conclusion, the GG genotype of the STAT3 rs4796793 polymorphism increases the risk of mTOR inhibitor-induced ILD, supporting its use as a predictive marker for RCC.

CuI-Catalyzed Coupling Reactions of 4-Iodopyrazoles and Alcohols: Application toward Withasomnine and Homologs.

The direct 4-alkoxylation of 4-iodo-1H-pyrazoles with alcohols was achieved by a CuI-catalyzed coupling protocol. The optimal reaction conditions employed excess alcohol and potassium t-butoxide (2 equiv) in the presence of CuI (20 mol%) and 3,4,7,8-tetramethyl-1,10-phenanthroline (20 mol%) at 130 °C for 1 h under microwave irradiation. The present method was efficiently applied to the synthesis of withasomnine and its six- and seven-membered cyclic homologs.

Effects of Cognitive Behavioral Therapy for Insomnia on Subjective-Objective Sleep Discrepancy in Patients with Primary Insomnia: a Small-Scale Cohort Pilot Study.

BACKGROUND: Cognitive behavioral therapy for insomnia (CBT-I) is a first-line therapy for insomnia disorders. We assessed changes in discrepancies between subjective and objective sleep measures and correlations between discrepancy changes and clinical insomnia severity for CBT-I in patients with primary insomnia METHODS: Fifty-two outpatients (mean age, 60.3 years; 26 women) with primary insomnia were treated by individual CBT-I (50 min, maximum six sessions, once every 1-2 weeks). One week before and after CBT-I, patients recorded a sleep log and wore an actigraphy device. Subjective and objective time in bed (TIB), total sleep time (TST), sleep-onset latency (SOL), wake time after sleep onset (WASO), and sleep efficiency (SE) were evaluated by averaging 1-week records. Relative values of sleep discrepancy in TIB, TST, SOL, WASO, and SE were calculated for estimating effects of CBT-I. The therapeutic effects were also evaluated using psychological scales before and after CBT-I. RESULTS: Subjective and objective discrepancies in sleep measures decreased by 36, 25, and 37 min in TST, SOL, and WASO, respectively, and 7% in SE (all P < 0.001) after CBT-I. Seven patients transitioned from underestimating SE before CBT-I to overestimating SE after CBT-I. Although CBT-I improved relative values of discrepancy in WASO and SE, alongside ISI, the improvement in insomnia severity only correlated with SOL discrepancy. CONCLUSIONS: CBT-I may reduce the discrepancy between subjective and objective sleep measures in patients with primary insomnia. However, a greater therapeutic effect of CBT-I was observed in reducing the ISI, which was slightly influenced by improvements in sleep discrepancies.

Temporary decrease in tacrolimus clearance in cytochrome P450 3A5 non-expressors early after living donor kidney transplantation: Effect of interleukin 6-induced suppression of the cytochrome P450 3A gene.

Tacrolimus is important for immunosuppression in kidney transplantation. In this historical cohort and in vitro study, we evaluated the changes in tacrolimus pharmacokinetics early after living donor kidney transplantation and the effects of interleukin (IL)-6 on cytochrome P450 3A4 (CYP3A4) and cytochrome P450 3A5 (CYP3A5) expression. In the historical cohort study, 22 patients who met the inclusion criteria were classified into CYP3A5 expressors and non-expressors (n = 16 and 6, respectively). The blood tacrolimus concentration per dose ratio (C/D) temporarily increased post-kidney transplantation on days 3-4 only in CYP3A5 non-expressors. The effects of IL-6 on CYP3A4 and CYP3A5 expression were also investigated in vitro using HepG2 and Caco-2 cells. IL-6 induced a significant concentration- and time-dependent decrease in CYP3A4 and CYP3A5 expression in both cells. The mean CYP3A4 expression level at 12 hours after IL-6 exposure (% of 0 hour) was 44.0 and 62.6 in HepG2 and Caco-2 cells, respectively, whereas the CYP3A5 expression level was 30.7 and 52.4, respectively. We hypothesize that CYP3A5 non-expressors might exhibit a temporary decrease in the oral clearance of tacrolimus via an increase in serum IL-6 concentrations early after kidney transplantation. These results may help develop strategies to improve kidney transplant outcome.

[Neoajuvant Chemotherapy with Gemcitabine and Cisplatin Plus S-1 for Primary Female Urethral Adenocarcinoma].

A 67-year-old female presented for evaluation of a left inguinal mass. Contrast-enhanced computed tomography revealed a tumor surrounding the urethra. Magnetic resonance imaging showed that the tumor had invaded the bladder neck on the anterior aspect of the urethra. The serum carbohydrate antigen 19-9 level was elevated. The clinical diagnosis was a primary adenocarcinoma of the female urethra (cT4N2M0). The initial treatment consisted of gemcitabine plus cisplatin (GC) and oral fluoropyrimidine (S-1). A total cysto-urethrectomy with anterior vaginal wall resection, pelvic and inguinal lymphadenectomy, and urinary diversion with ileal conduit formation were performed. The final diagnosis was urethral adenocarcinoma (ypT4ypN2, stage IV). Twelve months post-operatively, there was no evidence of recurrence or distant metastases.

Castration-induced stromal remodeling disrupts the reconstituted prostate epithelial structure.

The normal prostate epithelial structure is maintained by homeostatic interactions with smooth muscle cells. However, structural alterations of the stroma are commonly observed in prostatic proliferative diseases, leading to the abnormalities of prostate epithelial structure. A decrease in the androgen level experimentally induces stromal remodeling, i.e., replacement of smooth muscle cells with fibroblasts or myofibroblasts. In this study, we investigated the effects of castration-induced stromal remodeling and subsequent aberrant activation of epithelial-stromal interactions on the reconstituted human prostate-like epithelial structure. We performed in vivo experiments using the human prostate epithelial cell line BPH-1 and fetal rat urogenital sinus mesenchyme to generate heterotypic tissue recombinants that form human prostate-like epithelial structure (i.e., solid- and canalized-epithelial cords). Host mice were castrated at 12 weeks post transplantation (castration) and implanted with a dihydrotestosterone pellet at 14 days post castration (androgen replacement treatment; ART). In the castration group, the percentages of fibrotic area and disrupted prostate epithelial structure without the basement membrane (BM) increased proportionally in a time-dependent manner, but were suppressed by ART. In the castration group, tenascin-C (TNC)-positive fibroblasts were abundant in the stroma surrounding disrupted prostate epithelial structure without the BM. TGF-ß1 secretion from BPH-1 cells was increased by co-culturing with human primary cultured prostate fibroblasts. TNC mRNA expression was increased in fibroblasts co-culturing with BPH-1 cells and was suppressed by treatment with a TGF-ß RI kinase inhibitor. Moreover, in the castration group, the percentage of p-Smad2-positive cells was significantly higher in the stroma surrounding disrupted prostate epithelial structure without the BM. Our results demonstrate that castration-induced stromal remodeling disrupted the reconstituted human prostate-like epithelial structure and induced the appearance of TNC-positive fibroblasts accompanied by activation of TGF-ß signaling. The alteration of prostate stromal structure may be responsible for loss of the BM and epithelial cell polarity.

Loss of Fibroblast-Dependent Androgen Receptor Activation in Prostate Cancer Cells is Involved in the Mechanism of Acquired Resistance to Castration.

Loss of androgen receptor (AR) dependency in prostate cancer (PCa) cells is associated with progression to castration-resistant prostate cancer (CRPC). The tumor stroma is enriched in fibroblasts that secrete AR-activating factors. To investigate the roles of fibroblasts in AR activation under androgen deprivation, we used three sublines of androgen-sensitive LNCaP cells (E9 and F10 cells: low androgen sensitivity; and AIDL cells: androgen insensitivity) and original fibroblasts derived from patients with PCa. We performed in vivo experiments using three sublines of LNCaP cells and original fibroblasts to form homotypic tumors. The volume of tumors derived from E9 cells plus fibroblasts was reduced following androgen deprivation therapy (ADT), whereas that of F10 or AIDL cells plus fibroblasts was increased even after ADT. In tumors derived from E9 cells plus fibroblasts, serum prostate-specific antigen (PSA) decreased rapidly after ADT, but was still detectable. In contrast, serum PSA was increased even in F10 cells inoculated alone. In indirect cocultures with fibroblasts, PSA production was increased in E9 cells. Epidermal growth factor treatment stimulated Akt and p44/42 mitogen-activated protein kinase phosphorylation in E9 cells. Notably, AR splice variant 7 was detected in F10 cells. Overall, we found that fibroblast-secreted AR-activating factors modulated AR signaling in E9 cells after ADT and loss of fibroblast-dependent AR activation in F10 cells may be responsible for CRPC progression.

[LEIOMYOSARCOMA ARISING FROM THE RENAL VEIN].

A 47-year-old female presented to a clinic complaining of right back pain. A CT scan revealed a right retroperitoneal mass and she was referred to our department for further evaluation. Contrast-enhanced CT and MRI revealed a right retroperitoneal mass (6 cm) in the hilum of the right kidney that invaded the right renal vein and inferior vena cava (IVC). Suspecting a tumor arising from retroperitoneal tissues involving the right renal vein and IVC, the decision was made to excise the tumor with the right kidney, renal vein, and a portion of the IVC. The histologic findings indicated that the tumor was a leiomyosarcoma originating from the renal vein wall. The tumor cells were spindle-shaped and stained positive for desmin, caldesmon and HHF35. The post-operative course was uneventful and she was recurrence-free 20 months after surgery. In addition to presenting a case of a leiomyosarcoma of the renal vein, a short review of the literature is provided.

[First 25 cases of photo-selective vaporization of the prostate (PVP) with 120-watt high performance system for benign prostatic hyperplasia].

PURPOSE: We examined the safety and efficacy of photo-selective vaporization of the prostate (PVP) using a 120-W high-performance system (HPS) for benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: We prospectively reviewed the records of 25 patients who had undergone PVP using a 120-W HPS in our institution. Patients were evaluated pre-operatively, and at 2 weeks and 1, 3, and 6 months postoperatively. RESULT: The mean age was 73.6 years, and the mean estimated preoperative prostate volume was 51.5 ml. Laser vaporization was performed successfully in all 25 patients. The operating time was 104 +/- 29 minutes. The mean decrease in hemoglobin was 0.6 g/dl on post-operative day 1. The International Prostate Symptom Score (IPSS), QOL score, maximum flow rate, and residual urine volume were significantly improved 2 weeks after the procedure. There were no serious complications during the peri-operative period, and no patients were transfused. CONCLUSION: PVP using a 120-W HPS was shown to be an effective, safe procedure for patients with BPH and lower urinary tract symptoms.

Naftopidil, a selective {alpha}1-adrenoceptor antagonist, suppresses human prostate tumor growth by altering interactions between tumor cells and stroma.

In prostate cancer, tumor-stroma interactions play a critical role in the promotion of tumorigenesis, and thus the prevention of those interactions is a promising target to suppress tumor growth. Several studies demonstrated that alpha(1)-adrenoceptor (α(1)-AR) antagonists, therapeutic drugs for benign prostatic hyperplasia, have growth inhibitory effects on human prostate cancer (PCa) cells through induction of apoptosis or G(1) cell-cycle arrest. However, their direct actions on stromal cells surrounding cancer cells have not yet been elucidated. In this study, we investigated the effects of subtype-selective α(1)-AR antagonists (naftopidil, tamsulosin, and silodosin) on prostate tumor growth with a focus on the role of stroma, using commercially available fibroblast cells (PrSC). Tumorigenic studies in vivo showed significant reductions in tumor growth when E9 cells (an androgen low-sensitive LNCaP subline) grafted with PrSC were treated with naftopidil. In in vitro analyses, naftopidil and silodosin showed antiproliferative effects on PCa cells regardless of androgen sensitivity and α(1)-AR subtype expression. In PrSC, a strong growth inhibitory effect was observed with naftopidil but not silodosin. Flow cytometric analysis revealed that naftopidil, but not silodosin, induced G(1) cell-cycle arrest in both PCa cells and PrSC. In naftopidil-treated PrSC, total interleukin-6 protein was significantly reduced with increased suppression of cell proliferation. Silodosin induced weak early apoptosis only in PCa cells. These findings demonstrated that naftopidil strongly suppressed cell proliferation of stromal cells, resulting in decreased tumorigenic soluble factor, suggesting that naftopidil might be effective in preventing stromal support of tumor cells.