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Background: Computed tomography-defined low skeletal muscle mass is associated with oncological outcomes in patients with prostate cancer. However, its association with the outcomes of hormone-treated metastatic castration-sensitive prostate cancer remains unclear. We aimed to determine the association between metastatic castration-sensitive prostate cancer and psoas muscle parameters. Methods: We retrospectively reviewed 121 patients with N1 and/or M1 metastatic castration-sensitive prostate cancer who underwent primary androgen deprivation therapy between 2005 and 2021, either by administration of luteinizing hormone-releasing hormone agonist/antagonist or by surgical castration accompanied by bicalutamide, a first-generation antiandrogen. Before treatment administration, the psoas muscle index at the level of the third lumbar vertebra (psoas muscle area [cm2]/height2 [m2]) and the mean Hounsfield units of the psoas muscle were evaluated using non-contrast computed tomography and in relation to oncological outcomes. Results: The median follow-up was 56.9 months. Furthermore, during follow-up, 82 (67.7%) and 53 (43.8%) patients progressed to castration-resistant prostate cancer and died, respectively. Multivariate analysis of castration-resistant prostate cancer-free survival and overall survival showed significant differences in the Gleason score, clinical N-stage, and psoas muscle index (median cutoff: 3.044 cm2/m2). Conclusions: Pretreatment psoas muscle index is an independent predictor of poor castration-resistant prostate cancer-free survival and overall survival in patients with N1 and/or M1 metastatic castration-sensitive prostate cancer. [ABSTRACT FROM AUTHOR]

Purpose: There are no definitive prognostic factors for patients with pathological Grade Group 5 (pGG 5) prostate cancer (PCa) undergoing robot-associated radical prostatectomy (RARP). This study aimed to explore the prognostic factors among patients with pGG 5 PCa in a large Japanese cohort (MSUG94). Methods: This retrospective, multi-institutional cohort study was conducted between 2012 and 2021 at ten centers in Japan and included 3195 patients. Patients with clinically metastatic PCa (cN1 or cM1) and those receiving neoadjuvant and/or adjuvant therapy were excluded. Finally, 217 patients with pGG5 PCa were analyzed. Results: The median follow-up period was 28.0 months. The 3- and 5-year biochemical recurrence-free survival (BCRFS) rates of the overall population were 66.1% and 57.7%, respectively. The optimal threshold value (47.2%) for the percentage of positive cancer cores (PPCC) with any GG by systematic biopsy was chosen based on receiver operating characteristic curve analysis. Univariate analysis revealed that the prostate-specific antigen level at diagnosis, pT, pN, positive surgical margins (PSMs), lymphovascular invasion, and PPCC were independent prognostic factors for BCRFS. A multivariate analysis revealed that PSMs and PPCC were independent prognostic factors for BCRFS. Using these two predictors, we stratified BCRFS, metastasis-free survival (MFS), and castration-resistant PCa-free survival (CRPC-FS) among patients with pGG 5 PCa. Conclusion: The combination of PSMs and PPCC may be an important predictor of BCRFS, MFS, and CRPC-FS in patients with pGG 5 PCa undergoing RARP. [ABSTRACT FROM AUTHOR]

Fenestration closure is considered to remove the persistent right-to-left shunt after the Fontan operation. However, the criteria for effective transcatheter closure of fenestration to avoid both acute and chronic Fontan failure have not been clarified. The objective of this study was to describe the hemodynamic data with test occlusion of the Fontan fenestration for patients who underwent a closure and those who did not, along with subsequent development of Fontan-associated diseases (FAD) at follow-up. This was a retrospective study conducted to assess the outcome of Fontan fenestration closure at Children's Hospital of Michigan over 27 years (1993–2019). The inclusion criteria were patients undergoing cardiac catheterization indicated for Fontan fenestration closure. Data were compared between the two groups: closure and non-closure patients. Baseline characteristics and hemodynamic variables with the fenestration occlusion test were analyzed. The primary outcome was the development of composite events of death/transplant, deteriorated New York Heart Association class symptoms, or FAD. Among the 38 patients who were brought to the catheterization laboratory, 33 received fenestration closure and 5 did not. On a median follow-up of 3.4 years (range, 1 month–12.6 years), the incidence of primary adverse outcomes was 13% (5/38). The incidence of primary outcome was significantly higher in the non-closure group (60% vs. 6%, p < 0.01). The non-closure group had a higher incidence of moderate or severe atrioventricular valve regurgitation, New York Heart Association class III symptoms, use of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, furosemide use, and sildenafil use. The multivariable logistic regression model showed that the hemodynamic variables associated with the non-closure group were mean left atrial pressure (odds ratio 1.74, p < 0.05) and change of mean Fontan pressure at the balloon occlusion (odds ratio 2.2, p < 0.05). The judgment of fenestration closure appeared appropriate in our cohort. Fontan fenestration closure may not be advisable in cases with a high baseline left atrial pressure or a significant increase in Fontan pressure on balloon occlusion testing. [ABSTRACT FROM AUTHOR]

Background: Breast fibroadenoma (FA) and phyllodes tumour (PT) often have variations of gene mediator complex subunit 12 (MED12) and mutations in the telomerase reverse transcriptase promoter region (TERTp). TERTp mutation is usually tested by Sanger sequencing. In this study, we compared Sanger sequencing and droplet-digital PCR (ddPCR) to measure TERTp mutations in FA and PT samples.Methods: FA and PT samples were collected from 82 patients who underwent surgery at our institution from 2005 to 2016. MED12 mutations for all cases and TERTp mutations for 17 tumours were detected by Sanger sequencing. ddPCR was performed to analyse TERTp mutation in all cases.Results: A total of 75 samples were eligible for analysis. Sanger sequencing detected MED12 mutations in 19/44 FA (42%) and 21/31 PT (68%). Among 17 Sanger sequencing-tested samples, 2/17 (12%) were TERTp mutation-positive. In ddPCR analyses, a significantly greater percentage of PT (19/31, 61%) was TERTp mutation-positive than was FA (13/44, 30%; P = 0.0046). The mutation positivity of TERTp and MED12 did not correlate, in either FA or PT.Conclusions: ddPCR was more sensitive for detecting TERTp mutation than Sanger sequencing, being able to elucidate tumorigenesis in FA and PT. [ABSTRACT FROM AUTHOR]

Background: Epidemiological studies have shown an association between obesity and prostate cancer (PCa) aggressiveness. However, little is known about periprostatic fat (PPF) and its relationship with overall fat deposition in PCa. PPF is thought to contribute to PCa growth and migration via secreted factors and induction of chronic inflammation. We investigated if pre-treatment PPF thickness correlates with overall survival (OS). Methods: We reviewed 85 hormone-naïve men with advanced PCa who had received androgen deprivation therapy (ADT). PPF thickness was measured by magnetic resonance imaging (MRI) and compared with subcutaneous fat (SCF) thickness as an internal control. Visceral fat (VF) area measured by computed tomography served as an additional control. We evaluated the relationship between laboratory data, pathology results, and obesity parameters and OS. Results: Median follow-up was 50.6 months. Thirty-six patients died during follow-up. Univariate analysis revealed that nadir PSA titer, Gleason score, N stage, M stage, extent of disease by bone scan grade, hemoglobin, lactate dehydrogenase, alkaline phosphatase, and PPF/SCF ratio were associated with OS. Multivariate analysis revealed that nadir PSA titer, N stage, and PPF/SCF ratio were independent prognostic factors for survival. The 5-year OS in the patients with higher PPF/SCF ratio (≥ 1) and lower PPF/SCF ratio (< 1) was 49.5% and 66.5%, respectively (P = 0.039). Conclusions: Pre-treatment ratio of PPF–to-SCF thickness on MRI is an independent predictor of survival in hormone-naïve men with advanced PCa. This could be useful for predicting which patients are more likely to develop castration-resistant PCa. [ABSTRACT FROM AUTHOR]

Background: Few reports have evaluated the long-term outcomes of pathological T1 (pT1) lower rectal cancer (LRC), perhaps because pT1 LRC is classified as TNM stage I if lymph node metastasis (LNM) is absent and stage IIIA if LNM is present. Moreover, it is difficult to diagnose regional LNM preoperatively. This study aimed to clarify the long-term outcomes of radical surgery for pT1 LRC and risk factor(s) for LNM. Additionally, we examined whether preoperative computed tomography (CT) and magnetic resonance imaging (MRI) findings were predictive of LNM in pT1 LRC.Methods: This was a retrospective analysis of the clinical characteristics, short-term operative outcomes, and long-term survival rates of 155 patients who received radical surgery and were diagnosed with pT1 LRC at our hospital between January 1993 and February 2017.Results: Among patients with pT1 LRC, 5-year recurrence-free and overall survival rates were 94.0% and 95.8%, respectively. LNM status was not associated with statistically significant differences in recurrence-free or overall survival. Even in patients with LNM, the recurrence rate was only 9%. Among patients who lacked visible mesorectal lymph nodes on preoperative CT and MRI, LNM rates were 3.5% and 4.3%, respectively.Conclusion: The long-term outcomes after radical surgery for pT1 LRC are satisfactory or good, regardless of the presence or absence of LNM. In patients with pT1 LRC, the absence of visible mesorectal lymph nodes on preoperative CT and MRI is associated with a reduced likelihood of LNM and has a high negative predictive value for LNM. [ABSTRACT FROM AUTHOR]

Purpose: An amino acid-containing elemental diet (ED) does not require digestion for nutritional absorption, making it a good option for patients with gastrointestinal malabsorption. We conducted a randomized trial to confirm that perioperative ED enhanced the recovery of patients undergoing laparoscopic colectomy. Methods: Patients in the intervention arm received commercially available ED from the day prior to surgery until postoperative day (POD) 3, whereas patients in the control group received a conventional perioperative diet program. To verify the endpoints, 'estimated minimum length of stay in hospital after surgery' (emLOS) was defined as the number of days necessary to reach all the five criteria; namely, 'sufficient oral intake', 'sufficient pain control', 'withdrawal of intravenous alimentation', 'no abnormal findings in routine examinations', and 'no rise in fever'. Results: A total of 102 patients were randomized, 94 of whom were analyzed (ED 45, control 49). There was no morbidity or mortality. Shorter emLOS (POD 4 vs. POD 7; p = 0.018), earlier resumption of sufficient oral intake (POD 3 vs. POD 4; p = 0.034) and faster recovery to defecation (2.2 vs. 3.1 days; p = 0.005) were observed in the ED group vs. the control group. Conclusions: The perioperative ingestion of ED by patients undergoing laparoscopic colectomy is safe and can reduce the postoperative hospital stay by supporting the acceleration of oral intake. [ABSTRACT FROM AUTHOR]

It has been demonstrated from free mating experiments using multiple males and females of the medaka, Oryzias latipes species complex, that lower-latitude males exhibit more active courtship behavior than higher-latitude males. In this study, courtship activeness in males from two latitudinal populations of Northern medaka, Oryzias sakaizumii, was measured in the presence of only one male and one female, where male-male interactions were completely eliminated. We found that males from the low-latitude population performed quick circles (i.e., courtship dance) and approached females more frequently than males from the high-latitude population. Moreover, the low-latitude males tended to start courtships sooner after encountering a female than the high-latitude males. Thus, the latitudinal variation in male courtship activeness persisted even in the absence of rival males. These probably reflect that sexual selection pressures are stronger at low latitudes. [ABSTRACT FROM AUTHOR]

We study a 2-dimensional manifold that admits a homogeneous action of a 3-dimensional Lie group G, and has a 2-form invariant under G. We show that such a manifold can be realized as a surface in the affine 3-space, and list such realizations. [ABSTRACT FROM AUTHOR]

The immunoreceptor tyrosine-based activation motif (ITAM) plays an important role in signal transduction through antigen receptors in mammalian lymphocytes. We previously reported that an ITAM-containing receptor, ascidian hemocyte ITAM-containing receptor 1 (AhITAMR1), exists on the hemocyte surfaces of the ascidian Halocynthia roretzi, and is involved in both phagocytosis and hemocyte aggregation. In this study, we carried out differential display screening of upregulated genes during H. roretzi hemocyte aggregation and found that at least three genes are upregulated. One encodes glutathione S-transferase ω (GSTω), while the other two encode novel proteins. The expression of all three genes was induced by treatment with a specific monoclonal antibody against AhITAMR1, while their expression was inhibited by wortmannin, BAPTA-AM, and cyclosporin A. We also found that the expression of GSTω was induced by treatment with anti-T cell receptor antibody in mouse peripheral T cells. We propose that signal transduction pathways mediated by ITAM-containing receptors are conserved from ascidian hemocytes to mammalian T cells. [ABSTRACT FROM AUTHOR]

We describe a case with three focal atrial tachycardias (ATs) and focal atrial fibrillation (AF) originating from the interatrial septum (IAS) near the atrioventricular node (AVN). Contrast-enhanced computed tomography demonstrated the association of fat deposition within the anterior IAS near the AVN with successful ablation sites of these ATs and AF. This is the first report that the intramural fat deposition in the IAS could be associated with the formation of AT and AF re-entry circuits originating near the AVN. [ABSTRACT FROM AUTHOR]

Background: Although various work-related adverse events affect workers' mental health, the association between long working hours and mental disorders remains unclear. We investigated the characteristics of overtime work and work-related adverse events among all cases of compensated work-related suicide in Japan to empirically reveal the context of the serious consequences. Methods: We analysed all 167 cases of mental disorders resulting in suicide that were compensated in fiscal year 2015–2016. Hierarchical clustering was applied to the overtime working history. Work-related adverse events were also evaluated as the qualitative aspects of their jobs. Results: More than half of the cases committed suicide within a month of developing a mental disorder. The Administrative and professional or engineering workers had a higher suicide rate. The clustering analysis revealed chronic long working hours (19%), gradual increase (27%), or rapid increase (25%) in working hours before the onset of a mental disorder. A group of cases with less overwork experienced more interpersonal conflicts. Conclusion: This is the first study to employ a clustering technique to objectively reveal the actual working patterns behind suicide. The patterns of working overtime before the onset of mental disorders varied considerably among the cases. Taking the transition of working overtime into account may provide clearer insight into the relationship between long working hours and workers' mental health. These results highlight the need for countermeasures especially for causes of chronic overworking, drastic increases in working hours, and interpersonal conflicts to prevent work-related suicide. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to cross-sectionally investigate how work and sleep conditions could be associated with excessive fatigue symptoms as an early sign of Karoshi (overwork-related cerebrovascular and cardiovascular diseases; CCVDs). Methods: We distributed a questionnaire regarding work, sleep, and excessive fatigue symptoms to 5410 truck drivers, as the riskiest occupation for overwork-related CCVDs, and collected 1992 total samples (response rate: 36.8%). The research team collected 1564 investigation reports required for compensation for Karoshi. Of them, 190 reports listed the prodromes of Karoshi, which were used to develop the new excessive fatigue symptoms inventory. Results: One-way analyses of variance showed that the excessive fatigue symptoms differed significantly by monthly overtime hours (p < 0.001), daily working time (p < 0.001), work schedule (p = 0.025), waiting time on-site (p = 0.049), number of night shifts (p = 0.011), and sleep duration on workdays (p < 0.001). Multivariate mixed-model regression analyses revealed shorter sleep duration as the most effective parameter for predicting excessive fatigue symptoms. Multiple logistic regression analysis confirmed that the occurrences of CCVDs were significantly higher in the middle [adjusted ORs = 3.56 (1.28–9.94)] and high-score groups [3.55 (1.24–10.21)] than in the low-score group. Conclusion: The findings suggested that shorter sleep duration was associated more closely with a marked increase in fatigue, as compared with the other work and sleep factors. Hence, ensuring sleep opportunities could be targeted for reducing the potential risks of Karoshi among truck drivers. [ABSTRACT FROM AUTHOR]

Purpose: The topological distribution of dopamine-related proteins is determined by gene transcription and subsequent regulations. Recent research strategies integrating positron emission tomography with a transcriptome atlas have opened new opportunities to understand the influence of regulation after transcription on protein distribution. Previous studies have reported that messenger (m)-RNA expression levels spatially correlate with the density maps of serotonin receptors but not with those of transporters. This discrepancy may be due to differences in regulation after transcription between presynaptic and postsynaptic proteins, which have not been studied in the dopaminergic system. Here, we focused on dopamine D1 and D2/D3 receptors and dopamine transporters and investigated their region-wise relationship between mRNA expression and protein distribution. Methods: We examined the region-wise correlation between regional binding potentials of the target region relative to that of non-displaceable tissue (BPND) values of 11C-SCH-23390 and mRNA expression levels of dopamine D1 receptors (D1R); regional BPND values of 11C-FLB-457 and mRNA expression levels of dopamine D2/D3 receptors (D2/D3R); and regional total distribution volume (VT) values of 18F-FE-PE2I and mRNA expression levels of dopamine transporters (DAT) using Spearman's rank correlation. Results: We found significant positive correlations between regional BPND values of 11C-SCH-23390 and the mRNA expression levels of D1R (r = 0.769, p = 0.0021). Similar to D1R, regional BPND values of 11C-FLB-457 positively correlated with the mRNA expression levels of D2R (r = 0.809, p = 0.0151) but not with those of D3R (r = 0.413, p = 0.3095). In contrast to D1R and D2R, no significant correlation between VT values of 18F-FE-PE2I and mRNA expression levels of DAT was observed (r = -0.5934, p = 0.140). Conclusion: We found a region-wise correlation between the mRNA expression levels of dopamine D1 and D2 receptors and their respective protein distributions. However, we found no region-wise correlation between the mRNA expression levels of dopamine transporters and their protein distributions, indicating different regulatory mechanisms for the localization of pre- and postsynaptic proteins. These results provide a broader understanding of the application of the transcriptome atlas to neuroimaging studies of the dopaminergic nervous system. [ABSTRACT FROM AUTHOR]

Background: Transanal total mesorectal excision is a promising surgical treatment for rectal cancer. However, evidence regarding the differences in outcomes between the transanal and laparoscopic total mesorectal excisions is scarce. We compared the short-term outcomes of transanal and laparoscopic total mesorectal excisions for low and middle rectal cancers. Methods: This retrospective study included patients who underwent low anterior or intersphincteric resection for middle (5–10 cm) or low (< 5 cm) rectal cancer at the National Cancer Center Hospital East, Japan, from May 2013 to March 2020. Primary rectal adenocarcinoma was confirmed histologically. Circumferential resection margins (CRMs) of resected specimens were measured; margins ≤ 1 mm were considered positive. The operative time, blood loss, hospitalization length, postoperative readmission rate, and short-term treatment results were compared. Results: Four hundred twenty-nine patients were divided into two mesorectal excision groups: transanal (n = 295) and laparoscopic (n = 134). Operative times were significantly shorter in the transanal group than in the laparoscopic group (p < 0.001). The pathological T stage and N status were not significantly different. The transanal group had significantly lower positive CRM rates (p = 0.04), and significantly lower incidence of the Clavien–Dindo grade III (p = 0.02) and IV (p = 0.03) complications. Both groups had distal margin positivity rates of 0%. Conclusions: Compared to laparoscopic, transanal total mesorectal excision for low and middle rectal cancers has lower incident postoperative complication and CRM-positivity rates, demonstrating the safety and usefulness of local curability for middle and low rectal cancers. [ABSTRACT FROM AUTHOR]

During voluntary muscle contraction, sensory information induced by electrostimulation of the nerves supplying the contracting muscle is inhibited and the amplitude of the corresponding somatosensory evoked potential (SEP) decreases. This phenomenon is called "gating." The reduction of the SEP amplitude is reportedly significantly larger when task performance is high. However, the relationship between dexterous movement skills and gating remains unclear. In this study, we investigated through a ball rotation (BR) task how dexterous movement skills affect the SEP amplitudes. Thirty healthy subjects performed the BR task comprising the rotation of two wooden balls as quickly as possible. We estimated the median number of ball rotations for each participant and classified the participants into two (fast and slow) groups based on the results. Moreover, we recorded SEPs, while the subjects performed BR tasks or rested. SEP amplitude reduction (P45) was significantly larger in the fast than in the slow group. We also observed that the P45 amplitude during the BR task was attenuated even more so in the case of the participants with better dexterous movement skills. Our results suggest that the participants with better dexterous movement skills might display stronger somatosensory information suppression because of increasing the motor cortex activity and the afferent input during the BR task. [ABSTRACT FROM AUTHOR]

Purpose: Rectal gastrointestinal stromal tumors (GISTs) surgery is often challenging owing to the anatomical constraints of the narrow pelvis and tumor hugeness. Despite the increasing number of patients undergoing trans-anal total mesorectal excision (taTME) globally, the feasibility of trans-anal surgery with the taTME technique for rectal GISTs remains unclear. We aimed to evaluate the feasibility of trans-anal surgery with the taTME technique for rectal GISTs. Methods: Using a prospectively collected database, we retrospectively analyzed the clinical findings, surgical outcomes, pathological outcomes, urinary and anal functions, and prognoses of patients who underwent trans-anal surgery with the taTME technique for primary rectal GISTs at the National Cancer Center Hospital East from September 2014 to March 2020. Results: Twenty-one patients with primary rectal GISTs were included in this study. The median distance from the anal verge to the lower edge of the tumor was 40 mm (range, 15–60 mm), and the median tumor size was 59 mm (range, 11–175 mm). Moreover, seven and 14 patients underwent one-team and two-team surgeries, respectively, with curative intent. Nineteen patients (90.5%) underwent anus-preserving surgery, and the urinary tracts were preserved in all cases. Two-team surgery showed a significantly lower blood loss volume and shorter operation time than one-team surgery (58 vs. 222 mL, P = 0.017; 184 vs 356 min, P = 0.041, respectively). The pathological negative-margin resection rate was 100%. During the follow-up period, no patient developed local GIST recurrence and one (4.8%) developed distant metastasis. Conclusion: Trans-anal surgery with the taTME technique is feasible for rectal GISTs, and two-team surgery may be more advantageous than one-team surgery in terms of operation time and blood loss. [ABSTRACT FROM AUTHOR]

The sigmoid colon simulator was designed to accurately reproduce the anatomical layer structure and the arrangement of characteristic organs in each layer, and to have conductivity so that energy devices can be used. Dry polyester fibers were used to reproduce the layered structures, which included characteristic blood vessels, nerve sheaths, and intestinal tracts. The adhesive strength of the layers was controlled to allow realistic peeling techniques. The features of the Sigmaster are illustrated through a comparison of simulated sigmoidectomy using Sigmaster and actual surgery. We developed a laparoscopic sigmoidectomy simulator called Sigmaster. Sigmaster is a training device that closely reproduces the membrane structures of the human body and allows surgeons to experience the entire laparoscopic sigmoidectomy process. [ABSTRACT FROM AUTHOR]

Breast-conserving surgery has become the preferred treatment method for breast cancer. Surgical margin assessment is performed during surgery, as it can reduce local recurrence in the preserved breast. Development of reliable and lower-cost ex vivo cancer detection methods would offer several benefits for patient care. Here, a practical and quantitative evaluation method for the ex vivo fluorescent diagnosis of breast lesions was developed and confirmed through a three-step clinical study. Gamma-glutamyl-hydroxymethyl rhodamine green (gGlu-HMRG) has been reported to generate fluorescence in breast lesions. Using this probe, we constructed a reliable and reproducible procedure for the quantitative evaluation of fluorescence levels. We evaluated the reliability of the method by considering reproducibility, temperature sensitivity, and the effects of other clinicopathological factors. The results suggest that the fluorescence increase of gGlu-HMRG is a good indicator of the malignancy of breast lesions. However, the distributions overlapped. A 5 min reaction with this probe could be used to distinguish at least part of the normal breast tissue. This method did not affect the final pathological examination. In summary, our results indicate that the methods developed in this study may serve as a feasible intraoperative negative-margin assessment tool during breast-conserving surgery. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to examine the prospective associations of monthly working hours measured in a month, the 6-month averaged hours, and the frequency of long working hours (≥ 205 h/month) during the past 6 months with health indicators. Methods: This study included 6,806 Japanese company workers (response rate = 86.6%). Data on the workers' monthly attendance during the second half of fiscal year 2016 and annual health checkups in fiscal years 2016 and 2017 were collected. We evaluated the association of the above three types of monthly working hours with subsequent health checkup data in fiscal year 2017. We adjusted for the corresponding data in fiscal year 2016. Results: Multivariate logistic regression analyses revealed significant associations between monthly working hours and workers' systolic and diastolic blood pressure as well as aspartate aminotransferase, alanine aminotransferase, low-density lipoprotein cholesterol (LDL), and triglyceride levels. However, the associations were not consistent between months. The average monthly working hours were significantly associated with higher LDL levels for the 220–240 h/mo group (OR: 1.49, 95%CI: 1.07–2.08) and lower triglyceride levels for the < 140 h/mo group (OR: 0.15, 95%CI: 0.03–0.77), compared to the 140–180 h/mo group. The frequency of long working hours was significantly associated with higher LDL levels. Conclusions: Working hours over several months produced various associations with health indicators compared to those measured in a single month. Our present data suggest that the effects of average or frequency of long working hours during the past 6 months are likely to appear in LDL levels. [ABSTRACT FROM AUTHOR]

Centroaffine minimal surfaces are considered as an interesting class of surfaces from the viewpoint of not only variational problems in centroaffine differential geometry but also integrable systems. Typical examples of centroaffine minimal surfaces are proper affine spheres centered at the origin when we regard them as centroaffine surfaces. On the other hand, the study of projective minimal surfaces has a long history in projective differential geometry. Typical examples of projective minimal surfaces are proper affine spheres again, and so-called Demoulin surfaces or Godeaux-Rozet surfaces. In this paper, we shall regard centroaffine surfaces as projective surfaces and study projective minimality of centroaffine minimal surfaces. Using the fact that any centroaffine minimal surfaces have a one-parameter family of deformation known as associated surfaces, we shall give a classification of indefinite centroaffine minimal surfaces whose associated surfaces are all projective minimal, which includes centroaffine surfaces with vanishing Tchebychev operator and those found by the first author before. We shall also show that any indefinite centroaffine minimal surface whose associated surfaces are all Godeaux-Rozet surfaces is a proper affine sphere. [ABSTRACT FROM AUTHOR]

Absent pulmonary valve (APV) syndrome with tricuspid atresia or tricuspid stenosis (TA/TS) is an extremely rare malformation recently reported as a variant of APV with intact ventricular septum (VS). The condition, however, has univentricular physiology and unique structural and clinical features. The purpose of this study was to update the current knowledge about this condition by describing long-term outcomes of three new cases and reviewing the available literatures. A systematic literature search was performed to collect clinical and anatomical data of APV with TA/TS. Institutional medical records were retrospectively reviewed to identify APV with TA/TS patients. In a total of 62 (59 reported and 3 new) cases, patent ductus arteriosus was present in 98% of APV patients with TA/TS. A large ventricular septal defect, dilatation of the pulmonary arteries, which is typically found in APV with tetralogy of Fallot, and respiratory distress at birth were rarely reported. Most of the recent cases were successfully managed by the Glenn or Fontan procedure. Coronary artery anomaly and ventricular arrhythmia were more frequently reported as the cause of death or severe neurological sequelae (9/16 and 3/8, respectively). Additional surgical intervention was required in the mid/long-term period in three cases due to left-ventricular outflow obstruction and in two due to aortic dilatation. The Fontan and Glenn procedures improved the survival in the last two decades. In addition to coronary artery anomaly and ventricular arrhythmia, left-ventricular outflow tract obstruction and aortic dilatation should be carefully monitored. [ABSTRACT FROM AUTHOR]

Asexual vertebrates are rare and at risk of extinction due to their restricted adaptability through the loss of genetic recombination. We explore the mechanisms behind the generation and maintenance of genetic diversity in triploid asexual (gynogenetic) Carassius auratus fish, which is widespread in East Asian fresh waters and exhibits one of the most extensive distribution among asexual vertebrates despite its dependence on host sperm. Our analyses of genetic composition using dozens of genetic markers and genome-wide transcriptome sequencing uncover admixed genetic composition of Japanese asexual triploid Carassius consisting of both the diverged Japanese and Eurasian alleles, suggesting the involvement of Eurasian lineages in its origin. However, coexisting sexual diploid relatives and asexual triploids in Japan show regional genetic similarity in both mitochondrial and nuclear markers. These results are attributed to a unique unidirectional gene flow from diploids to sympatric triploids, with the involvement of occasional sexual reproduction. Additionally, the asexual triploid shows a weaker population structure than the sexual diploid, and multiple triploid lineages coexist in most Japanese rivers. The generated diversity via repeated interploidy gene flow as well as an increased establishment of immigrants is assumed to offset the cost of asexual reproduction and might contribute to the successful broad distribution of this asexual vertebrate. [ABSTRACT FROM AUTHOR]

Purpose: Severe defecation disorder occurs frequently in coloanal anastomosis for low rectal cancer, and may affect quality of life. Sacral neuromodulation (SNM) has been reported to be successful after rectal resection, but there are no results for patients treated with intersphincteric resection (ISR). Methods: A retrospective single-center study of SNM was performed for patient with defecation disorder following ISR. Pre- and post-treatment bowel frequencies, fecal incontinence episodes, and Wexner, LARS and FIQL scores were assessed to evaluate the efficacy. A good response was defined as ≥ 50% reduction of bowel frequency per day or fecal incontinence episodes per week. Results: 10 patients (7 males, mean age 67.5 years) underwent SNM. All patients had severe fecal incontinence with a median Wexner score of 15 (13–20) and a median LARS score of 41 (36–41). The Wexner score improved after SNM, but not significantly (p = 0.06). LARS and FIQL scores significantly improved after SNM (p = 0.02, p = 0.01). At the end of follow-up, the good response rate was 40%. Three cases without a good response required creation of a permanent stoma. Conclusion: Seven out of 10 patients did not require a permanent colostomy after SNM. SNM should be considered before performing a permanent colostomy. [ABSTRACT FROM AUTHOR]

Describes a patient with myotonia dystrophica undergoing general anesthesia who was unexpectedly resistant to clinical doses of pancuronium. Definition of myotonic dystrophy; Responses to train-of-four stimulation in patients with myotonia dystrophica; Important consideration for anesthesia in the myotonic patient.

Purpose: Mucosal prolapse at the site of anastomosis is a long-term complication unique to ISR. It reduces the QOL of patients due to a worsened anal function and local symptoms around the anus. We herein sought to assess the surgical outcomes after Delorme surgery for these patients. Methods: ISR was performed in 720 patients with low rectal cancer between January 2001 and March 2019 at the National Cancer Center Hospital East. Among these patients, the 33 (4.5%) who underwent initial Delorme surgery for postoperative colonic mucosal prolapse were identified from the medical records and then were analyzed retrospectively. We estimated the anal function using Wexner's incontinence score and assessed whether local anal symptoms due to the prolapse improved postoperatively. Results: Stoma closure was performed before Delorme surgery in 15 (45.5%) patients, and we compared the preoperative and postoperative anal function in these patients. The average Wexner's incontinence score changed from 15.1 before to 12.9 after Delorme surgery. Local symptoms around the anus improved in all 33 (100%) patients. Recurrence of colonic mucosal prolapse occurred in 5 patients (15%), and Delorme surgery was reperformed in these cases. Conclusion: Delorme surgery for colonic mucosal prolapse following ISR has clinical benefits for both improving anal local symptoms and slightly improving the anal function. [ABSTRACT FROM AUTHOR]

Cholesteryl pullulan (CHP) is a novel antigen delivery system. CHP and New York esophageal squamous cell carcinoma 1 (NY-ESO-1) antigen complexes (CHP-NY-ESO-1) present multiple epitope peptides to the MHC class I and II pathways. Adjuvants are essential for cancer vaccines. MIS416 is a non-toxic microparticle that activates immunity via the nucleotide-binding oligomerization domain 2 (NOD2) and TLR9 pathways. However, no reports have explored MIS416 as a cancer vaccine adjuvant. We conducted a first-in-human clinical trial of CHP-NY-ESO-1 with MIS416 in patients with NY-ESO-1-expressing refractory solid tumors. CHP-NY-ESO-1/MIS416 (μg/μg) was administered at 100/200, 200/200, 200/400 or 200/600 (cohorts 1, 2, 3 and 4, respectively) every 2 weeks for a total of 6 doses (treatment phase) followed by one vaccination every 4 weeks until disease progression or unacceptable toxicity (maintenance phase). The primary endpoints were safety and tolerability, and the secondary endpoint was the immune response. In total, 26 patients were enrolled. Seven patients (38%) continued vaccination in the maintenance phase. Grade 3 drug-related adverse events (AEs) were observed in six patients (23%): anorexia and hypertension were observed in one and five patients, respectively. No grade 4–5 drug-related AEs were observed. Eight patients (31%) had stable disease (SD). Neither augmentation of the NY-ESO-1-specific IFN-γ-secreting CD8+ T cell response nor an increase in the level of anti-NY-ESO-1 IgG1 was observed as the dose of MIS416 was increased. In a preclinical study, adding anti-PD-1 monoclonal antibody to CHP-NY-ESO-1 and MIS416 induced significant tumor suppression. This combination therapy is a promising next step. [ABSTRACT FROM AUTHOR]

Purpose: Peristomal skin disorders (PSDs) are common stoma-related complications. However, there is no standard method for the evaluation of PSDs, and the true incidence is unclear. There are also no reports on risk factors for severe PSDs. Therefore, this study was performed to analyze the incidence of PSD in temporary loop stoma based on the DET score and ABCD-stoma score and to determine the risk factors for all and severe PSDs. Methods: A retrospective analysis of patient and surgical characteristics was carried out in 333 consecutive cases of stoma creation with loop ileostomy or colostomy performed at our hospital from January 2014 to December 2016. Results: PSDs were diagnosed in 262 patients (78.7%), including 79 (23.7%) and 71 (21.3%) that were defined as severe based on DET and ABCD-stoma scores, respectively. Multivariate analyses showed that parastomal hernia was an independent risk factor for severe PSD defined by DET score and that adjuvant chemotherapy was an independent risk factor for severe PSD defined by the ABCD-stoma score. Conclusions: Severe PSDs are associated with parastomal hernia when diagnosed by the DET score and with adjuvant chemotherapy when diagnosed by the ABCD-stoma score. [ABSTRACT FROM AUTHOR]

Purpose: Whether indocyanine green fluorescence angiography (ICG-FA) during rectal surgery is effective in reducing anastomotic leakage remains unclear. This study aimed to investigate the effect of intraoperative ICG-FA on anastomotic leakage after sphincter-sparing surgery for malignant rectal tumors. Methods: This was a retrospective, single-center cohort study conducted on 852 consecutive patients who underwent laparoscopic sphincter-sparing surgery from January 2007 to June 2017 at our institution. The incidence of anastomotic leakage was compared between patients who underwent ICG-FA to determine the proximal resection margin and those in whom this technique was not performed, using logistic regression analysis, including propensity score. Results: A total of eight patients were excluded (one patient with previous low anterior resection and seven patients who underwent simultaneous resection for other primary cancers), resulting in 844 patients being analyzed. Before propensity score matching, 141 patients (16.7%) who underwent ICG-FA were compared with 703 patients (83.3%) in whom ICG-FA was not performed. The incidence of anastomotic leakage was 2.8% (4/141) in the ICG-FA group and 12.4% (87/703) in the control group (p = 0.001). After propensity score matching (n = 420), the patient characteristics between the two groups were well balanced, and the incidence of anastomotic leakage was 2.8% (4/141) in the ICG-FA group and 13.6% (38/279) in the control group (p = 0.001). Logistic regression analyses using propensity score showed that patients who underwent ICG-FA had significantly lower odds of anastomotic leakage. Conclusion: Intraoperative ICG-FA is a promising method to reduce anastomotic leakage after laparoscopic rectal surgery. [ABSTRACT FROM AUTHOR]

Computed tomography (CT) attenuation value of ureteral stones is one of the predictors of shockwave lithotripsy (SWL) outcome. It is common to use the mean Hounsfield units (HU) to describe the CT attenuation value. However, an observer bias can occur when measuring the mean HU in the conventional method. On the other hand, our way to obtain only the maximum HU is simpler and less biased. We retrospectively evaluated 464 patients with ureteral stones who underwent SWL and compared predictive accuracy of various factors including maximum and mean HU. Results were determined after a single SWL. Predictors of SWL success were examined by the statistical analysis of successful and failed groups. 324 of the 464 patients who underwent SWL were stone-free after a single SWL. Significant differences were found in factors related to CT attenuation value and stone size. As a result of receiver operating characteristic analysis, it was found that maximum HU and mean HU, major diameter and volume have equivalent prediction accuracy, respectively. Multivariate analysis revealed that maximum HU and major diameter were included in independent predictors. We also examined the new original indicators using maximum HU and major diameter. Stone-resistant probability obtained from the logistic model and Maximum HU and Major diameter Index obtained by multiplying maximum HU by major diameter were useful for predicting SWL success, respectively. In conclusion, maximum HU and mean HU have equivalent predictive accuracy, and maximum HU is easier to measure and less biased than mean HU. [ABSTRACT FROM AUTHOR]

Purpose: We developed the "Foot-Site Monitor" (FSM) to permit easy identification of multiple foot pedals of energy devices in endoscopic surgery. The purpose of this study was to evaluate the effectiveness of the use of the FSM. Methods: Using a training box, 20 surgeons performed a task consisting of pressing foot pedals with and without the FSM. The time from showing a color on a PC monitor to pressing the foot pedal that corresponded to this color (defined as the completion time), and the distance of the movement of the tip of the surgeon's forceps from the beginning to the end of the task (defined as shaking of the forceps) were measured. Results: The use of the FSM was associated with significantly reduced shaking of the forceps (1.95 vs. 2.47 mm; p = 0.014), and a tendency toward a shorter completion time (1.39 vs. 1.51 s; p = 0.053). Conclusions: The use of the FSM in endoscopic surgery contributes to reduced shaking of the forceps and may shorten the operative time. [ABSTRACT FROM AUTHOR]

Purpose: Postoperative urinary retention is a common adverse effect after rectal surgery. Current methods for assessing postoperative urinary retention (residual urine volume) are inaccurate and unable to predict long-term retention. Voiding efficiency is an effective indicator of postoperative urinary retention in urological and gynaecological fields, but not in colorectal surgery. We aimed to determine whether voiding efficiency in the initial 24 h after urinary catheter removal was more effective in predicting the incidence of postoperative urinary retention than residual urine volume. Methods: In this retrospective, observational study using prospectively collected data from patients who visited the colorectal department of a single institution, 549 patients who underwent rectal cancer surgery between April 2012 and May 2016 were initially enrolled, of which 46 were excluded and 503 finally included. Results: The incidence of postoperative urinary retention was 18.5% (93/503). Multivariable logistic regression analyses revealed that the association of postoperative urinary retention with voiding efficiency < 50% was stronger than that with residual urine volume > 100 mL (odds ratio, 38.30 (residual urine volume) and 138.0 (voiding efficiency)). Voiding efficiency was significantly lower in patients with long-term than in those with short-term postoperative urinary retention (adjusted p value = 0.02), whereas residual urine volume was not different between the two groups. Multivariable logistic regression analysis for long-term postoperative urinary retention showed the strongest association with voiding efficiency < 20% (odds ratio, 25.70). Conclusions: Voiding efficiency is a more effective predictor of postoperative urinary retention than residual urine volume in rectal cancer patients. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to clarify the frequency of distal spread and the optimal distal margin after preoperative chemotherapy for advanced low rectal cancer.Methods: The study included patients with advanced lower rectal cancer who received preoperative chemotherapy and underwent surgery during 2012-2015. We investigated the distal spread of tumor cells, defined as the distal distance from the intramucosal distal tumor edge to the farthest tumor cells located under the submucosal layer. Clinical characteristics were compared for distal spreads ≥ 10 and < 10 mm, and risk factors for distal spread ≥ 10 mm were investigated.Results: Of the 71 patients, 42 (59%) showed distal spread. Distal spreads of 1-9, 10-19, and ≥ 20 mm were observed in 27 (38%), 11 (15%), and 4 (6%) patients, respectively. Multivariate analysis revealed two independent risk factors for distal spread ≥ 10 mm after preoperative chemotherapy. The first risk factor is the presence of different therapeutic effects between the mucosal and deeper layers (meaning that superficial tumor shrinkage was evident on colonoscopy, but little tumor shrinkage was evident on magnetic resonance imaging) (odds ratio, 11.6; 95% CI, 2.22-61.3). The second risk factor is poorly differentiated or mucinous adenocarcinoma (odds ratio, 8.86; 95% CI, 1.58-49.9).Conclusion: A distal margin of 20 mm is required (10 mm is insufficient) for advanced lower rectal cancer patients who receive preoperative chemotherapy followed by surgery. Independent risk factors for distal spread ≥ 10 mm include (1) the presence of different therapeutic effects between mucosal and deeper layers and (2) poorly differentiated or mucinous adenocarcinomas. [ABSTRACT FROM AUTHOR]

Purpose: Perineal wound infection (PWI) rates are high after abdominoperineal resection (APR) and total pelvic exenteration (TPE). This study identified risk factors for PWI after surgery for anorectal tumors and examined the relationship between the surgical excision volume with the PWI degree.Methods: A retrospective review involving 135 patients who underwent surgical excision of anorectal tumors was performed. Superficial PWI included cellulitis and superficial dehiscence; deep PWI included major dehiscence, perineal abscess, and presacral abscess. The adjacent organ resection type was classified according to the dead space size formed by surgical excision.Results: Of the 135 patients, 119 underwent APR, and 16 underwent TPE. PWI occurred in 75 patients (superficial PWI, 44; deep PWI, 31). Adjacent organ resection was an independent risk factor for PWI. The cases with adjacent organ resection were classified into small-defect APR, large-defect APR, and TPE. Large-defect APR and TPE cases had significantly higher rates of deep PWI than APR cases without adjacent organ resection.Conclusions: Adjacent organ resection involving the removal of one or more organs and that involving wide-range muscle resection are strong risk factors for deep PWI. [ABSTRACT FROM AUTHOR]

Purpose: Docetaxel (DTX) is a standard chemotherapeutic drug for castration-resistant prostate cancer (CRPC), although adverse events are common. To overcome this problem, researchers have evaluated the efficacy of DTX treatment in combination with other drugs. Naftopidil is a tubulin-binding drug with fewer adverse events, implying the usefulness of this drug in clinical applications when combined with DTX. Here, we investigated the efficacy of additive naftopidil treatment in combination with DTX on prostate cancer (PCa) cells. Methods: The effects of combination treatment with DTX plus naftopidil were analyzed using two animal models of LNCaP cells plus PrSC xenografts (sub-renal capsule grafting) and PC-3 xenografts (intratibial injection). Results: Combination treatment with DTX plus naftopidil significantly inhibited cell growth in LNCaP cells compared with DTX alone. Analysis of the cooperativity index (CI) showed that combination treatment exhibited additive effects on DTX-induced growth inhibition in LNCaP cells. In contrast, combination treatment showed more than an additive (synergistic) effect on DTX-induced apoptosis in LNCaP and PC-3 cells. In LNCaP cells plus PrSC xenografts, combination treatment showed synergistic effects on DTX-induced apoptosis. The synergistic effects of naftopidil on DTX-induced apoptosis were also observed in PC-3 xenografts. Conclusions: Our results demonstrated that additive naftopidil treatment in combination with DTX increased the efficacy of DTX for the treatment of LNCaP and PC-3 tumors in vivo. Thus, additive naftopidil treatment showed a synergistic effect on DTX-induced apoptosis in PCa cells in vitro and in vivo, suggesting that this treatment approach may yield improved clinical benefits compared with DTX alone. [ABSTRACT FROM AUTHOR]

Rapid growth in infancy considerably increases the risk of obesity and metabolic disorders in adulthood especially among neonates born small. To investigate the mechanism involved, we developed an animal model of undernourishment in utero by maternal caloric restriction, in which the Z scores of body weight at weaning (19.5 days) positively correlated with parameters of obesity, metabolic disorders, and remodeling of subcutaneous adipose tissue, such as numbers of macrophages in adipose tissue, the ratio of inflammatory M1 to anti-inflammatory M2 macrophages, estimated by gene expression of specific antigens, and the relative ratio of small adipocytes less than 30 μm in diameter, on a high-fat diet at 17 weeks of age. To our knowledge, this is the first report of a possible connection between infantile body weight and adipose tissue remodeling in obesity after undernourishment in utero. [ABSTRACT FROM AUTHOR]

Purpose: Dopamine D receptors (DRs) have two affinity states for endogenous dopamine, referred to as high-affinity state (D), which has a high affinity for endogenous dopamine, and low-affinity state (D). The density of D can be measured with ( R)-2-CHO- N-n-propylnorapomorphine ([C]MNPA), while total density of D and D (DRs) can be measured with [C]raclopride using positron emission tomography (PET). Thus, the ratio of the binding potential ( BP) of [C]MNPA to that of [C]raclopride ([C]MNPA/[C]raclopride) may reflect the proportion of the density of D to that of DRs. In the caudate and putamen, [C]MNPA/[C]raclopride reflects the proportion of the density of D to that of DRs. To evaluate the reliability of the PET paradigm with [C]MNPA and [C]raclopride, we investigated the test-retest reproducibility of non-displaceable BP ( BP) measured with [C]MNPA and of [C]MNPA/[C]raclopride in healthy humans. Methods: Eleven healthy male volunteers underwent two sets of PET studies on separate days that each included [C]MNPA and [C]raclopride scans. BP values in the caudate and putamen were calculated. Test-retest reproducibility of BP of [C]MNPA and [C]MNPA/[C]raclopride was assessed by intra-subject variability (absolute variability) and test-retest reliability (intraclass correlation coefficient: ICC). Results: The absolute variability of [C]MNPA BP was 5.30 ± 3.96 % and 12.3 ± 7.95 % and the ICC values of [C]MNPA BP were 0.72 and 0.82 in the caudate and putamen, respectively. The absolute variability of [C]MNPA/[C]raclopride was 6.11 ± 3.68 % and 11.60 ± 5.70 % and the ICC values of [C]MNPA/[C]raclopride were 0.79 and 0.80 in the caudate and putamen, respectively. Conclusion: In the present preliminary study, the test-retest reproducibility of BP of [C]MNPA and of [C]MNPA/[C]raclopride was reliable in the caudate and putamen. [ABSTRACT FROM AUTHOR]

Rationale: Second-generation antipsychotics demonstrate clinical efficacy with fewer extrapyramidal side effects compared with first-generation antipsychotics. One of the proposed explanations is the hypothesis of preferential extrastriatal dopamine D receptor occupancy (limbic selectivity) by antipsychotics. In the present study, we focused on aripiprazole, which has a unique pharmacological profile with partial agonism at dopamine D receptors and the minimal risk of extrapyramidal side effects. Previous positron emission tomography (PET) studies using high-affinity radioligands for dopamine D receptors have reported inconsistent results regarding regional differences of dopamine D receptor occupancy by aripiprazole. Objective: To test the hypothesis of preferential binding to extrastriatal dopamine D receptors by aripiprazole, we investigated its regional dopamine D receptor occupancies in healthy young subjects. Materials and methods: Using PET and two radioligands with different affinities for dopamine D receptors, [C]raclopride and [C]FLB457, striatal and extrastriatal dopamine D receptor bindings at baseline and after oral administration of 6 mg aripiprazole were measured in 11 male healthy subjects. Results: Our data showed that dopamine D receptor occupancies in the striatum measured with [C]raclopride were 70.1% and 74.1%, with the corresponding values for the extrastriatal regions measured with [C]FLB457 ranging from 46.6% to 58.4%. Conclusions: In the present study, preferential extrastriatal dopamine D receptor occupancy by aripiprazole was not observed. Our data suggest partial agonism at dopamine D receptors is the most likely explanation for the minimal risk of extrapyramidal side effects in the treatment by aripiprazole. [ABSTRACT FROM AUTHOR]

This prospective multicenter study was performed to clarify the efficacy and safety of micafungin (MCFG) as an empirical antifungal therapy for suspected fungal infection in patients with hematological disorders and neutropenia. Three hundred and eighty-eight patients were enrolled; 151 patients with possible fungal infection diagnosed by radiological imaging or serological testing and 237 patients with refractory fever were included in this study. The mean dose and duration of treatment with MCFG were 154.6 mg/day and 14.0 days, respectively. The clinical response rate for patients with possible fungal infection and refractory fever was 60.1% and 65.3%, respectively. Even in persistent neutropenic patients with a neutrophil count of <500/μL throughout the MCFG treatment, the clinical response rate was 46.9%. Ninety-one drug-related adverse events (DAEs) were observed in 56 patients (14.4%) and 9 serious DAEs were observed in 6 patients (1.5%). Neither daily dose nor duration of MCFG treatment affected the incidence of DAEs. It was confirmed that MCFG has adequate clinical efficacy and is safe for the treatment of suspected fungal infections in patients with hematological disorders and neutropenia. [ABSTRACT FROM AUTHOR]

Central norepinephrine transporter (NET) is one of the main targets of antidepressants. Although the measurement of NET occupancy has been attempted in humans, the outcomes have been inconclusive. In this study, the occupancy of NET by different doses of an antidepressant, nortriptyline, was measured using positron emission tomography (PET) with (S,S)-[18F]FMeNER-D2. PET scans using (S,S)-[18F]FMeNER-D2 were performed on six healthy men before and after oral administration of a single oral dose of nortriptyline (10–75 mg). After a bolus i.v. injection of (S,S)-[18F]FMeNER-D2, dynamic scanning was performed for 0–90 min, followed by scanning for 120–180 min. The ratio of the thalamus-to-caudate areas under the curve (120–180 min) minus 1 was used as the binding potential (BPND) for NET. NET occupancy was calculated as the percentage reduction of BPND. Venous blood samples were taken to measure the concentrations of nortriptyline just before injection of the tracer and at 180 min after the injection. Mean NET occupancies by nortriptyline were 16.4% at 10 mg, 33.2% at 25 mg, and 41.1% at 75 mg. The mean plasma concentration of nortriptyline was less than the lower limit of detection at 10 mg, 23.7 ng/mL at 25 mg, and 50.5 ng/mL at 75 mg. Estimated ED50 was 76.8 mg of administration dose and 59.8 ng/mL of plasma concentration. NET occupancy by nortriptyline corresponding to the administration dose of 10–75 mg or plasma concentration was observed from 16% to 41%. [ABSTRACT FROM AUTHOR]

Pulsed laser ablation (PLA) in liquid medium was successfully employed to synthesize hydroxyapatite (HAp) colloidal nanoparticles. The crystalline phase, particle morphology, size distribution and microstructure of the HAp nanoparticles were investigated in detail. The obtained HAp nanoparticles had spherical shape with sizes ranging from 5 to 20 nm. The laser ablation and the nanoparticle forming process were studied in terms of the explosive ejection mechanism by investigating the change of the surface morphology on target. The stoichiometry and bonding properties were studied by using XPS, FT-IR and Raman spectroscopy. A molar ratio of Ca/P of the prepared HAp nanoparticles was more stoichiometric than the value reported in the case of ablation in vacuum. [ABSTRACT FROM AUTHOR]

Sarcoidosis is a systemic disease of unknown etiology that is characterized by chronic non-caseating granulomatous inflammation with tissue destruction. It is an uncommon disease in children, and renal sarcoidosis in particular is very rare in adults and children. A 17-year-old boy with renal sarcoidosis was referred to our hospital with an initial diagnosis of pyelonephritis. Prior treatment with various antibiotics had not been effective, but tentative oral daily prednisolone (PSL) had partially ameliorated his symptoms, although the symptoms recurred during steroid tapering. We detected non-caseating granulomatous interstitial nephritis and numerous sclerotic glomeruli in a second biopsy specimen, compatible with the diagnosis of renal sarcoidosis. The patient was treated with pulsed methyl-prednisolone and oral daily doses of PSL and mizoribine (MZR). During the treatment with MZR, the PSL was successfully tapered, and the patient has since presented no signs of recurrence. Our treatment of this patient shows that treatment with MZR can allow steroid sparing and prevent recurrence in a patient with sarcoidosis. [ABSTRACT FROM AUTHOR]

Purpose: Prostate cancer is difficult to visualise in its early stages using current imaging technology. The present study aimed to clarify the utility of 11C-choline PET for localising and evaluating cancer lesions in patients with prostate cancer by conducting a prospective comparison with magnetic resonance (MR) imaging combined with proton MR spectroscopy. Methods: PET and MR imaging combined with proton MR spectroscopy were performed in 20 patients with prostate cancer. Correlations among the metabolite ratio of choline + creatine to citrate (Cho+Crk/Ci) on MR spectroscopy, serum PSA and maximum standardised uptake value (SUVmax) of 11C-choline were assessed. The location of the primary lesion was assessed by the site of SUVmax and the laterality of the highest Cho+Crk/Ci ratio and confirmed by examination of surgical pathology specimens (n=16). Results: PET exhibited a diagnostic sensitivity of 100% (20/20) for primary lesions, while the sensitivities of MR imaging and MR spectroscopy were 60% (12/20) and 65% (13/20), respectively. Weak linear correlations were observed between SUVmax and serum PSA (r=0.52, p<0.05), and between SUVmax and Cho+Crk/Ci ratio (r=0.49, p<0.05). Regarding the localisation of main primary lesions, PET results agreed with pathological findings in 13 patients (81%) (?=0.59), while MR spectroscopy results were in accordance with pathological findings in eight patients (50%) (?=0.11). Conclusion: This preliminary study suggests that 11C-choline PET may provide more accurate information regarding the localisation of main primary prostate cancer lesions than MR imaging/MR spectroscopy. A further clinical study of 11C-choline PET in a large number of patients suspected of prostate cancer will be necessary to determine the clinical utility of 11C-choline PET in patients who clinically require biopsy. [ABSTRACT FROM AUTHOR]

Colon cancer is one of the carcinomas that is resistant to a variety of therapies. To develop a new therapy by regulating the activated K-ras gene in colon cancers, we prepared synthetic DNA encoding the ribozyme (catalytic RNA), and inserted it into an expression vector (LNCX) originated from a retrovirus. Transfection of the vector into SW620 human colon cancer cells brought about significant suppression of K-ras mRNA synthesis and inhibition of the cell growth. Studies in athymic mice, in which K-ras ribozyme-introduced SW620 cells were transplanted, also revealed a marked reduction of tumor growth in vivo. Furthermore, the ribozyme-introduced tumors became more sensitive to treatment with anti-cancer drugs such as cisplatin, adriamycin, 5-fluorouracil, vincristine, and etoposide. These data suggest that the possible efficacy of anti-K-ras ribozyme increases the chemosensitivity of human colon cancers as well as the inhibitory effect on the growth of human colon cancers. [ABSTRACT FROM AUTHOR]