Arf GTPase-Activating proteins ADAP1 and ARAP1 regulate incorporation of CD63 in multivesicular bodies.

Arf GTPase-activating proteins (ArfGAPs) mediate the hydrolysis of GTP bound to ADP-ribosylation factors. ArfGAPs are critical for cargo sorting in the Golgi-to-ER traffic. However, the role of ArfGAPs in sorting into intralumenal vesicles (ILVs) in multivesicular bodies (MVBs) in post-Golgi traffic remains unclear. Exosomes are extracellular vesicles (EVs) of endosomal origin. CD63 is an EV marker. CD63 is enriched ILVs in MVBs of cells. However, the secretion of CD63 positive EVs has not been consistent with the data on CD63 localization in MVBs, and how CD63-containing EVs are formed is yet to be understood. To elucidate the mechanism of CD63 transport to ILVs, we focused on CD63 localization in MVBs and searched for the ArfGAPs involved in CD63 localization. We observed that ADAP1 and ARAP1 depletion inhibited CD63 localization to enlarged endosomes after Rab5Q79L overexpression. We tested epidermal growth factor (EGF) and CD9 localization in MVBs. We observed that ADAP1 and ARAP1 depletion inhibited CD9 localization in enlarged endosomes but not EGF. Our results indicate ADAP1 and ARAP1, regulate incorporation of CD63 and CD9, but not EGF, in overlapped and different MVBs. Our work will contribute to distinguish heterogenous ILVs and exosomes by ArfGAPs.

Supervised Exercise Therapy Reduces Presenteeism to Greater Extent Than Unsupervised Self-Care in Workers with Musculoskeletal Pain: a Systematic Review and Meta-Analysis.

PURPOSE: Presenteeism is defined as the loss of work productivity due to health issues in workers, which can be measured subjectively. This study aimed to compare the effectiveness of supervised exercise therapy and unsupervised self-care in reducing presenteeism in workers with musculoskeletal disorders. METHODS: PubMed, Embase, and Cochrane Library were searched for various keywords from their inception to January 2023. Two examiners independently assessed the eligibility of studies: (1) studies involving workers suffering from musculoskeletal pain, (2) those involving supervised exercise therapy intervention with interactive communication, and (3) those in which the comparison group was subjected to interventions other than supervised exercise therapy, and (4) those including patient-reported outcome measures of presenteeism or work productivity or ability. Standardized mean differences (SMD) were calculated using a random effects model, with higher scores indicating reduced presenteeism in the intervention group compared with that in the comparison group. The GRADE assesses the overall certainty of the evidence. RESULTS: Only the short-term effects of interventions on presenteeism could be obtained using four studies. The intervention group showed statistically significant short-term effects on presenteeism compared with the comparison group (p < 0.001; SMD, 0.52; 95% confidence interval, 0.27-0.77). The GRADE score was downgraded by two levels from high to low due to concerns for indirectness. CONCLUSIONS: Although the certainty of the evidence was low, it was assumed that supervised exercise therapy was more effective than unsupervised self-care in reducing presenteeism in workers with musculoskeletal disorders.

Effectiveness and Safety of a Mixture of Nobiletin and Tangeretin in Nocturia Patients: A Randomized, Placebo-Controlled, Double-Blind, Crossover Study.

Nobiletin and tangeretin (NoT) are flavonoids derived from the peel of Citrus depressa, and they have been found to modulate circadian rhythms. Because nocturia can be considered a circadian rhythm disorder, we investigated the efficacy of NoT for treating nocturia. A randomized, placebo-controlled, double-blind, crossover study was conducted. The trial was registered with the Japan Registry of Clinical Trials (jRCTs051180071). Nocturia patients aged ≥50 years who presented nocturia more than 2 times on a frequency-volume chart were recruited. Participants received NoT or a placebo (50 mg once daily for 6 weeks), followed by a washout period of ≥2 weeks. The placebo and NoT conditions were then switched. Changes in nocturnal bladder capacity (NBC) were the primary endpoint, and changes in nighttime frequency and nocturnal polyuria index (NPi) were secondary endpoints. Forty patients (13 women) with an average age of 73.5 years were recruited for the study. Thirty-six completed the study, while four withdrew. No adverse events directly related to NoT were observed. NoT had little effect on NBC compared with the placebo. In contrast, NoT significantly changed nighttime frequency by -0.5 voids compared with the placebo (p = 0.040). The change in NPi from baseline to the end of NoT was significant (-2.8%, p = 0.048). In conclusion, NoT showed little change in NBC but resulted in decreased nighttime frequency with a tendency toward reduced NPi.

[A Case of Castration-Resistant Prostate Cancer after Prostatectomy Treated with Resection of A Solitary Metastatic Site].

A 72-year-old man underwent a bilateral nerve-sparing radical retropubic prostatectomy (RRP) with pelvic lymph node dissection 11 years earlier. His prostate specific antigen (PSA) value at diagnosis was 61.024 ng/ml. Bone scans and computed tomographic (CT) scans showed no metastasis. Pathological findings and stage were adenocarcinoma, Gleason score 4+3, positive surgical margin, pT3b, and no lymph node metastasis. The postoperative PSA nadir was 0.218 ng/ml, and salvage radiotherapy (SRT, total 66 Gy) was performed six months after RRP. However, the PSA value continued to rise after SRT. Therefore, androgen deprivation therapy (ADT) was started 11 months after SRT. Nine years postoperatively, the PSA value showed a continuous rise despite ADT, and prostate cancer was considered to be castration-resistant. Although he was taking enzalutamide, his PSA value rose to 18. 271 ng/ml. Repeated bone scans and CT scans were negative. Eleven years after RRP, the fluoro-2-deoxy-D-glucosepositronemissiontomography (FDG-PET) revealed a nodule lesiondorsal to the left pubic bone. The patient underwent a resection of the lesion. Three months after the resection, his PSA level declined to 0.038 ng/ml, thus ADT was discontinued. Thirteen months after the resection, PSA re-elevation was absent, and follow-up without ADT is ongoing.

Peritoneal Tuberculosis After Robot-Assisted Laparoscopic Prostatectomy with Extended Lymph Node Dissection.

Background: Peritoneal tuberculosis (TB) is a relatively uncommon presentation of extrapulmonary TB. Early diagnosis of peritoneal TB is difficult because of its nonspecific clinical manifestation such as abdominal pain, fever, or ascites. Especially early after surgery of abdomen or pelvis, these symptoms can be misdiagnosed as septic peritonitis. There are few reports of peritoneal TB as a postoperative complication of laparoscopic surgery. Here, we describe a first case of peritoneal TB after robot-assisted laparoscopic prostatectomy (RALP) with extended lymph node dissection. Case Presentation: A 78-year-old man presented 25 days after this surgery with fever and abdominal distension. Ultrasonography and computed tomography (CT) revealed massive abdominal ascites. Ascites sample was cloudy, with increased white blood cells and normal creatinine level. No anastomotic leak was found. Bacterial infection of a lymphocele was considered, and cefmetazole 2 g/day for 3 days was prescribed. Despite antibacterial therapy, fever persisted. Polymerase chain reaction testing of ascitic fluid was positive for Mycobacterium tuberculosis. The patient was effectively treated with anti-TB therapy. Conclusion: This is the first report of peritoneal TB as a postoperative complication of RALP with extended lymph node dissection. His preoperative chest CT showed granular shadows in left upper lung, indicating his old asymptomatic TB infection. Flare-up of TB can happen even after robot-assisted laparoscopic surgery, which is minimally invasive. Peritoneal TB must be considered especially when there is unexplained ascites unresponsive to antibiotics.

[Gastric metastasis from renal cell carcinoma: two case reports].

Gastric metastasis from renal cell carcinoma (RCC) is a very rare event and treatment for such patients has not been established. We report two cases of gastric metastasis from RCC. The first case was in a 67- year-old man with a past history of right radical nephrectomy for RCC (ypT3aN0M0) six years ago. The whole-body computed tomography (CT) revealed multiple lung nodules. We performed gastrointestinal endoscopy to find the primary lesion, and detected multiple submucosal tumors in the gastric body. Needle biopsy of these tumors revealed gastric metastasis from RCC. Oral sorafenib tosylate therapy was started. Twenty months later, gastrointestinal endoscopy showed only gastric erosion without malignant evidence. The second case was in a 70-year-old man complaining of epigastralgia. He had undergone right partial nephrectomy for RCC (pT1aN0M0) six years ago, and thoracoscopic wedge resection of a solitary lung nodule one year ago. Gastrointestinal endoscopy detected a solitary hyperplastic polyp in the anterior wall of the gastric body. Needle biopsy of this polyp revealed gastric metastasis from RCC. We performed laparoscopic partial gastrectomy. Gastrointestinal endoscopy and CT showed no evidence of metastasis or recurrence for 14 months after gastrectomy.

[Efficacy of prophylactic intravesical mitomycin C in patients with non-muscle-invasive bladder cancer].

Intravesical chemotherapy is beneficial for patients with non-muscle-invasive bladder cancer (NMIBC), but optimal drug and regimen selection can be controversial. Mitomycin C (MMC) is commonly used as adjuvant treatment for NMIBC. We retrospectively evaluated the outcomes of 73 patients with NMIBC who were treated with weekly doses of low-dose MMC (20 mg ; n=28 ; 38.4%) or high-dose MMC (40 mg ; n=45 ; 61.6%) for 6 weeks each, at our hospital between 2001 and 2010. Treatment outcomes were examined by Kaplan‒Meier analysis with log-rank tests. Patients in the high-dose group showed greater recurrent-free survival (61.3%) at 2 years than did patients in the low-dose group (32.6%) (P<0.05). We also found that a single early dose of pirarubicin following transurethral resection of bladder tumor improved MMC efficacy in the high-dose group. The high-dose group had a somewhat higher incidence of dysuria, urinary frequency and drug eruption, but the difference was not significant.

[The role of dynamic contrast-enhanced magnetic resonance imaging in diagnosis of torsion of the testicular appendix : a case report].

A 7-year-old male presented to our hospital with pain and swelling in the right scrotum for 9 days. On physical examination a swollen right scrotum was noted and right side cremasteric reflex disappeared. Ultrasound examination showed enlarged right testis and epididymis. Subsequent dynamic contrast enhanced magnetic resonance imaging (MRI) showed a 7 mm area of high signal intensity anterior to the right testis on coronal imaging of T2-weighted. Subtraction MRI revealed testicular perfusion and a nonenhanced mass was also identified anterior to the right testis. These findings indicated a diagnosis of torsion of the testicular appendix. We performed excision of the torsed appendage.

[Usefulness of MRI prior to prostate needle biopsy in PSA gray zone].

To evaluate the diagnostic accuracy of prostate magnetic resonance imaging (MRI), we compared MRI findings with the results of biopsy as well as findings from specimens following total prostatectomy. The subjects consisted of 260 males who showed a prostate specific antigen (PSA) level in the gray zone (4 ng/ml ≤PSA <10 ng/ml) and also underwent digital rectal examination (DRE), transrectal ultrasound (TRUS), and MRI prior to prostate biopsy between April 2005 and December 2009. In Evaluation 1, the results of DRE/TRUS/MRI were compared with those of prostate biopsy. The biopsy-positive rate was higher in males positive in each examination. However, 24.8% of males negative in all examinations were biopsypositive. Thus, these examinations were considered to be inappropriate for secondary screening. In evaluation 2, the prostate was divided into 4 regions, and the findings from specimens following total prostatectomy were compared with MRI findings in each region. For the region containing prostate cancer, MRI showed a sensitivity of 26.0%, specificity of 98.3%, positive predictive value of 96.2%, and negative predictive value of 44. 4%. In patients with a Gleason score ≥7, cancer foci were more frequently detectable using MRI. MRI prior to prostate biopsy in patients in the PSA gray zone is inappropriate for secondary screening due to its low sensitivity. However, by virtue of its high positive predictive value, MRI is useful for determining patients indicated for biopsy, as well as DRE and TRUS. Accurate evaluation of the localization of all cancer lesions is difficult using MRI. However, when MRI findings are present, they frequently indicate the cancer lesion, which may be useful information for treatment.

A case of ischemic duodenitis associated with superior mesenteric artery syndrome caused by an abdominal aortic aneurysm.

A 74-year-old woman was admitted to our hospital with upper abdominal pain and bloody vomiting. An abdominal aneurysm compressed the third portion of the duodenum and the second portion of duodenum was distended with thickened walls as in superior mesenteric artery syndrome. Endoscopic examination showed an edematous mucosa with hemorrhagic erosions, shallow longitudinal ulcers, and star-shaped ulcers in the duodenum. We diagnosed this case as ischemic duodenitis associated with superior mesenteric artery syndrome caused by compression by an abdominal aortic aneurysm. The symptoms improved on treatment with bowel rest, total parenteral nutrition and administration of a proton pump inhibitor. We present here a rare case of ischemic duodenitis and summarize the previous medical literature on the disease.

[Risk factors for falls and fractures at night in relation to lower urinary tract symptoms: a survey of outpatients and inpatients at a general hospital].

We investigated potential risk factors, including factors related to lower urinary tract symptoms (LUTS), for falls and fractures at night among outpatients and inpatients in a general hospital, via a questionnaire. The questionnaire included items to record the age, sex, number of consulting doctors, history of 11 particular medical diseases, LUTS, sleep, and falls and fractures at night. We distributed the questionnaire to 1,334 patients 51 years old or older in our hospital. Of the questionnaires completed, 96.9% were valid for analysis. Multivariate analyses revealed that "drinking water before bedtime or while in bed" was the strongest risk factor (odds ratio＝7.499) for bone fractures while "postural syncope" was the strongest risk factor (odds ratio＝5.041, except past medical history) for falls. In terms of LUTS, urge incontinence was a significant risk factor for falls.

Intraperitoneal rupture of the ureter as a cause of generalized peritonitis: report of a case.

We report a rare case of generalized peritonitis caused by nontraumatic, intraperitoneal rupture of the ureter. An 80-year-old woman with a history of bilateral vesicoureteral reflux and long-term urethral indwelling catheter drainage presented with a very distended abdomen. Computed tomography showed massive ascites and intraperitoneal free gas. We performed an emergency laparotomy, assuming a gastrointestinal perforation; but could not find a cause of generalized peritonitis. Postoperatively, she presented with anuria and massive peritoneal drainage. The findings of a cystogram confirmed intraperitoneal ureteral rupture. She was managed successfully with ureteral stenting. The diagnosis of this condition requires a high degree of clinical suspicion, along with radiographic evidence and peritoneal fluid analysis. Image-guided interventions play a crucial role in the management of ureteral urine leaks after a correct diagnosis has been made.

Nitric oxide exhalation correlates with ventilatory response to exercise in patients with heart disease.

AIMS: It is controversial whether or not pulmonary nitric oxide (NO) production, reflected in the end-tidal alveolar NO concentration, is diminished in patients with heart failure. Since pulmonary perfusion is regulated by NO production, decreased NO production in the pulmonary vasculature is assumed to result in diminished lung perfusion and further increases in ventilation-perfusion mismatch. The aim of this study is to investigate whether exhaled NO correlates with both exercise-induced hyperpnea and exercise tolerance in patients with heart disease. METHODS AND RESULTS: Forty-two patients with heart disease were enrolled (history of prior myocardial infarction (n=19), dilated cardiomyopathy (n=2), hypertensive heart disease (n=5) and prior open-heart surgery (n=16)). During cardiopulmonary exercise testing, exhaled air was collected and end-tidal NO (ETNO) was measured using a chemiluminescent method. Peak ETNO was found to correlate positively with both ventilatory anaerobic threshold (r=0.468) and peak VO(2) (r=0.562). The VE-CO(2) slope, which reflects the ventilatory response to exercise, correlated negatively with peak ETNO (r=-0.588). CONCLUSION: These data indicate that NO exhalation correlates, inversely, with the ventilatory response to exercise and directly with exercise intolerance, although the weakness of the correlation coefficient suggests there may be other possible mechanisms.