Statin administration ameliorates ischemia-induced overactive bladder with improvement of blood flow and anti-inflammatory effects in rats.

AIMS: Statins are widely used to treat dyslipidemia and have been shown to reduce the risk of ischemic heart disease and cerebrovascular disease. The effects of statins on ischemia-induced overactive bladder (OAB) and the associated mechanisms were investigated in a rat model of chronic pelvic ischemia. METHODS: A pelvic ischemia model was created by iliac arterial injury (AI) and a high-fat diet using male Sprague-Dawley rats. Rats were assigned to 3 groups: control group, AI group, and AI + statin group. The control group underwent sham operation and was fed a normal diet. The AI group underwent AI surgery and was fed a high-cholesterol diet. The AI + statin group was administered a statin for 4 weeks. Cystometry was performed for 8 weeks after surgery. Blood flow was evaluated by laser meter. Thickness of the iliac arteries was measured, and microvascular density in the lamina propria was evaluated by immunostaining for CD31. Expressions of inflammatory cytokines in the bladder were measured by real-time PCR. RESULTS: Cystometry showed a significantly shorter voiding interval and lower bladder capacity in the AI group than in the control group. The AI + statin group showed improvement of these findings. The AI group showed decreased bladder blood flow, increased iliac arterial wall thickening, and decreased microvascular density compared to the control group. Statin administration improved blood flow. Iliac arterial wall thickening was suppressed, and microvascular density was increased by statin administration, though not significantly. Real-time PCR showed significantly higher expressions of inflammatory cytokines (IL-6, IL-8, and TNF-α) in the AI group than in the control group, and IL-6 and IL-8 expressions were lower in the AI + statin group than in the AI group. CONCLUSIONS: The present results suggest that statins are effective in OAB caused by arteriosclerosis and ischemia. The mechanism of their effects involves improved bladder blood flow and decreased bladder inflammation.

Prostate-specific antigen follow-up and management for patients undergoing holmium laser enucleation of the prostate.

OBJECTIVES: To investigate who needs a careful postoperative monitoring for prostate cancer (PCa) after holmium laser enucleation of the prostate (HoLEP). We examined characteristics and oncological outcomes of HoLEP-related PCa. METHODS: Patients who underwent HoLEP during 2002-2017 in a Japanese tertiary center were retrospectively analyzed. Patients were divided into non-PCa, PCa with HoLEP specimen (PCa-Ope), and PCa diagnosed during follow-up (PCa-Post). Outcomes of all HoLEP-related PCa were monitored. RESULTS: Of the total 758, 60 (7.9%) were diagnosed with PCa from resected specimen of HoLEP and 9 (1.2%) were diagnosed postoperatively. Preoperative prostate-specific antigen (iPSA), postoperative PSA (pPSA), and PSA density were significantly higher in both PCa groups than those in non-PCa group. While iPSA significantly correlated to prostate volume (PV), pPSA was not associated with PV. A receiver-operating-characteristics curve demonstrated that pPSA 1.2 ng/mL achieved the optimal cut-off (AUC 0.95) for the incidence of PCa-Post. In addition to the incidence of PCa and iPSA, lower enucleation efficiency (enucleated volume /PV) was significantly associated with pPSA >1.2 ng/mL. Among PCa-Ope, 51 were Grade Group (GG) ≤2 and 42 were followed-up with active surveillance, whereas 8 of 9 PCa-Post were GG ≥3 and 2 progressed to death. CONCLUSIONS: Patients undergoing HoLEP are associated with some risk of potential PCa. While oncological outcomes were favorable among PCa-Ope, postoperative PSA should be carefully monitored even if not diagnosed with PCa with HoLEP specimen. Enucleation efficiency should be also considered not to misread pPSA value.

INPP5D modulates TREM2 loss-of-function phenotypes in a ß-amyloidosis mouse model.

The genetic associations of TREM2 loss-of-function variants with Alzheimer disease (AD) indicate the protective roles of microglia in AD pathogenesis. Functional deficiencies of TREM2 disrupt microglial clustering around amyloid ß (Aß) plaques, impair their transcriptional response to Aß, and worsen neuritic dystrophy. However, the molecular mechanism underlying these phenotypes remains unclear. In this study, we investigated the pathological role of another AD risk gene, INPP5D, encoding a phosphoinositide PI(3,4,5)P3 phosphatase expressed in microglia. In a Tyrobp-deficient TREM2 loss-of-function mouse model, Inpp5d haplodeficiency restored the association of microglia with Aß plaques, partially restored plaque compaction, and astrogliosis, and reduced phosphorylated tau+ dystrophic neurites. Mechanistic analyses suggest that TREM2/TYROBP and INPP5D exert opposing effects on PI(3,4,5)P3 signaling pathways as well as on phosphoproteins involved in the actin assembly. Our results suggest that INPP5D acts downstream of TREM2/TYROBP to regulate the microglial barrier against Aß toxicity, thereby modulates Aß-dependent pathological conversion of tau.

Research on Omnidirectional Stereo Measurement Using Convex Mirrors and Vertical Disparity.

We propose an omnidirectional measurement method without blind spots by using a convex mirror, which in principle does not cause chromatic aberration, and by using vertical disparity by installing cameras at the top and bottom of the image. In recent years, there has been significant research in the fields of autonomous cars and robots. In these fields, three-dimensional measurements of the surrounding environment have become indispensable. Depth sensing with cameras is one of the most important sensors for recognizing the surrounding environment. Previous studies have attempted to measure a wide range of areas using fisheye and full spherical panoramic cameras. However, these approaches have limitations such as blind spots and the need for multiple cameras to measure all directions. Therefore, this paper describes a stereo camera system that uses a device capable of taking an omnidirectional image with a single shot, enabling omnidirectional measurement with only two cameras. This achievement was challenging to attain with conventional stereo cameras. The results of experiments confirmed an improvement in accuracy of up to 37.4% compared to previous studies. In addition, the system succeeded in generating depth image that can recognize distances in all directions in a single frame, demonstrating the possibility of omnidirectional measurement with two cameras.

Ectopic endometriosis in the pelvic cavity evokes bladder hypersensitivity via transient receptor potential ankyrin 1 hyperexpression in rats.

INTRODUCTION AND HYPOTHESIS: In women with chronic pelvic pain (CPP), interstitial cystitis/bladder pain syndrome (IC/BPS) and endometriosis frequently coexist. The mechanism of these diseases coexisting is explained by cross-sensitization between endometriosis and IC/BPS. The overlapped symptoms may be related to cross-sensitization with transient receptor potential vanilloid 1 (TRPV1) and/or transient receptor potential ankyrin 1 (TRPA1) hyperexpression. This study was aimed at exploring whether bladder hypersensitivity is evoked in the surgically induced ectopic endometriosis rat and whether TRPV1 and/or TRPA1 play a vital role. METHODS: A total of 63 Sprague-Dawley female rats were divided into two groups, 39 for physiological examination and 24 for molecular analysis. Surgical induction of ectopic endometriosis (ENDO, n=27), surgical sham treatment (n=18), and treatment for endometriosis by GnRH analog (ENDO-G) (n=18) were performed. Bladder function was investigated by cystometry (for TRPV1 in the sham [n=6] and ENDO [n=9] groups and for TRPA1 in the sham [n=6], ENDO [n=9], and ENDO+G [n=9] groups), and TRPV1 and TRPA1 mRNA expressions were measured using real-time qPCR in the bladder and dorsal root ganglia (DRGs). RESULTS: On cystometry, the relative intercontraction interval (ICI) after/before resiniferatoxin (RTx; TRPV1 activator) infusion to the bladder showed no significant difference between the two groups, whereas relative ICI after/before allyl isothiocyanate (AITC; TRPA1 activator) infusion was significantly lower in the ENDO group than in the sham group. TRPA1 mRNA expression in the bladder and L5 DRG was considerably higher in the ENDO group than in the sham group on real-time qPCR. TRPA1 mRNA hyperexpression and bladder hypersensitivity after AITC infusion were reduced in the ENDO-G group. CONCLUSIONS: Bladder cross-sensitization in ENDO rats occurs in association with hyperexpression of TRPA1 at both the DRG and the bladder mucosa. This can be understood by the "cross-sensitization of endometriosis to bladder" theory explaining overlapping symptoms among BPS/IC and ectopic endometriosis.

Effect of Different Approaches to Antimicrobial Therapy with Cefmetazole and Meropenem on the Time to Defervescence in Non-Severe Extended-Spectrum ß-Lactamase-Producing Escherichia coli Bacteremia.

Carbapenems are antimicrobial agents commonly used to treat extended-spectrum ß-lactamase (ESBL)-producing bacteria. Although cefmetazole (CMZ) is considered effective for ESBL-producing Escherichia coli (ESBL-EC) bacteremia, previous studies showed its limitations, including the influence of the initial antimicrobial agent. Here, we examined the effects of different approaches to antimicrobial therapy with CMZ and meropenem (MEPM) on the time to defervescence in ESBL-EC bacteremia. Notably, the influence of previous antimicrobial agents was excluded. Inpatients with ESBL-EC detected in blood cultures between April 2018 and March 2023 were included and assigned to CMZ (n = 14), MEPM (n = 8), de-escalation to CMZ (dCMZ; n = 9), or escalation to MEPM (eMEPM; n = 11) groups. The median time to defervescence was 3.5, 1.0, 2.0, and 4.0 days in the CMZ, MEPM, dCMZ, and eMEPM groups, respectively, with no significant differences. Cox proportional hazards analysis showed a significant difference in the hazard ratio (95% confidence interval) of 0.378 (0.145-0.984) for the time to defervescence with CMZ versus MEPM (p = 0.046). The extent of a delayed time to defervescence is greater with early CMZ administration than with MEPM administration in patients with non-severe ESBL-EC bacteremia.

Low-energy shock wave therapy ameliorates ischemic-induced overactive bladder in a rat model.

This study was to evaluate whether Low-energy shock wave therapy (LESW) improves ischemic-induced overactive bladder in rats and investigate its therapeutic mechanisms. Sixteen-week-old male Sprague-Dawley rats were divided into three groups: arterial injury (AI), AI with LESW (AI-SW), and control groups. LESW was irradiated in AI-SW during 20-23 weeks of age. At 24 weeks of age, conscious cystometry was performed (each n = 8). The voiding interval was shortened in AI (mean ± SEM: 5.1 ± 0.8 min) than in control (17.3 ± 3.0 min), whereas significant improvements were observed in AI-SW (14.9 ± 3.3 min). The bladder blood flow was significantly increased in AI-SW than in AI. Microarray analysis revealed higher gene expression of soluble guanylate cyclase (sGC) α1 and ß1 in the bladder of AI-SW compared to AI. Protein expression of sGCα1 and sGCß1 was higher in AI-SW and control groups than in AI. Cyclic guanosine monophosphate (cGMP) was elevated in AI-SW. As an early genetic response, vascular endothelial growth factor and CD31 were highly expressed 24 h after the first LESW. Suburothelial thinning observed in AI was restored in AI-SW. Activation of sGC-cGMP may play a therapeutic role of LESW in the functional recovery of the bladder.

Development of a versatile high-throughput mutagenesis assay with multiplexed short-read NGS using DNA-barcoded supF shuttle vector library amplified in E. coli.

A forward mutagenesis assay using the supF gene has been widely employed for the last several decades in studies addressing mutation frequencies and mutation spectra associated with various intrinsic and environmental mutagens. In this study, by using a supF shuttle vector and non-SOS-induced Escherichia coli with short-read next-generation sequencing (NGS) technology, we present an advanced method for the study of mutations, which is simple, versatile, and cost-effective. We demonstrate the performance of our newly developed assay via pilot experiments with ultraviolet (UV) irradiation, the results from which emerge more relevant than expected. The NGS data obtained from samples of the indicator E. coli grown on titer plates provides mutation frequency and spectrum data, and uncovers obscure mutations that cannot be detected by a conventional supF assay. Furthermore, a very small amount of NGS data from selection plates reveals the almost full spectrum of mutations in each specimen and offers us a novel insight into the mechanisms of mutagenesis, despite them being considered already well known. We believe that the method presented here will contribute to future opportunities for research on mutagenesis, DNA repair, and cancer.

Responses to antibiotics in human iPSC-derived neurons based on the clinical antibiotic-associated encephalopathy classification.

Antibiotic-associated encephalopathy (AAE) is a central nervous system disorder caused by antibiotics administration and classified into three types based on clinical symptoms. Type 1 AAE causes seizures and myoclonus, type 2 causes psychiatric symptoms, and type 3 is characterized by cerebellar ataxia. In this study, we investigated whether the electrical activity of in vitro human iPSC-derived neurons to antibiotics could be classified based on the 3 types of AAEs classified by clinical symptoms. Glutamatergic, GABAergic neurons and astrocytes differentiated from human iPS cells were seeded on micro-electrode array (MEA). The cumulative administration of 13 different antimicrobials detected changes in neural activity that differed according to AAE type. Next, we classified the antimicrobials by principal component analysis (PCA) and confirmed the AAE type of each agent. We found that Types 1-3 AAE agents were distributed separately. The classification of antibiotics depending on electrophysiological response characteristics was consistent with the clinical practice classification of AAEs. In conclusion, the combination of electrophysiological responses of human iPS cell-derived neural networks measured by MEA plus multivariate analysis methods will effectively detect and classify antibiotics developmental risks.

Natal origin of Pacific bluefin tuna Thunnus orientalis determined by SIMS oxygen isotope analysis of otoliths.

Accurate understanding of changing population dynamics associated with climate change is critical for managing highly migratory fish species. However, long-term data on population dynamics and the resulting recruitment variability is still lacking for many species, making it difficult to predict and integrate the effects of ocean warming into management schemes. In this study, high-resolution stable oxygen isotope (δ18O) analysis was performed on the otoliths of adult Pacific bluefin tuna Thunnus orientalis using secondary ion mass spectrometry (SIMS) to determine the natal origin of an individual fish. The core δ18Ootolith corresponding to the larval stage greatly varied among the individuals, indicating that the larvae experienced a wide range of thermal environments. The non-hierarchical cluster analysis performed on the core δ18Ootolith grouped fish into those with higher δ18Ootolith (lower temperature) and those with lower δ18Ootolith (higher temperature), most likely representing relative temperature difference experienced between fish born in the Sea of Japan and in the Nansei Islands area. The Nansei Islands area cluster showed more variability in the early otolith growth indicating a longer spawning season, which is consistent with the observed longer spawning duration in this area. The absolute temperature estimates based on the SIMS-measured core δ18Ootolith were significantly higher than those expected from sea surface temperature data, suggesting the effects of matrix-related bias on the temperature offsets. The relative temperature difference, however, matched well with the known spawning temperature range of the two spawning grounds. The recruitment contribution from each spawning ground (all year-classes pooled, n = 51) was 45% in the Sea of Japan and 55% in the Nansei Islands area. Overall, this study demonstrated the effectiveness of SIMS δ18Ootolith analysis for investigating the natal origin of fish and its potential application in fish population dynamics studies.

Morphological and gonadal histological characteristics of the silver-phase male Indo-Pacific eel Anguilla marmorata.

Eight silver-phase male Indo-Pacific eels (giant mottled eels) Anguilla marmorata were collected from three small rivers on subtropical Amami-Oshima Island, Japan, and their morphological and gonadal-histological characteristics were examined. The total length, body mass and age of the silver eels were 543.8 ± 49.3 (496-659) mm, 376.0 ± 116.0 (282-660) g and 14.6 ± 2.3 (11-19) years old, respectively. The silvering-related characteristics (eye index, pectoral-fin index, gut-somatic index) and reproductive characteristics (gonadosomatic index, histological stage) of the silver eels were significantly advanced compared to those of yellow eels, which is similar to other anguillid species.

Neurogenic lower urinary tract dysfunction in association with severity of degenerative spinal diseases: Short-term outcomes of decompression surgery.

OBJECTIVES: Cervical myelopathy (CM) and lumbar canal stenosis (LCS) are common degenerative spinal diseases among the elderly, and the major associated complaints include lower urinary tract symptoms (LUTS). The aim of this study was to investigate subjective and objective urological parameters of patients undergoing decompression surgery for CM and LCS. METHODS: We retrospectively reviewed patients who underwent evaluation by the International Prostate Symptom Score (IPSS) and uroflowmetry before decompression surgery for CM and LCS. Patients with comorbidities that can affect LUTS were excluded. Postoperative changes were evaluated in patients followed up within 1 month. RESULTS: Among referrals to urological consultations for LUTS, 231 patients were evaluated preoperatively. Moderate-severe urinary symptoms (IPSS ≥ 8) were present in 59.8% of 92 CM patients and 64.0% of 139 LCS patients. Poor voiding patterns defined as maximum urinary flow rate <12 mL/s or postvoid residual volume >100 mL were identified in 26.1% of CM and 25.2% of LCS. While IPSS did not associate with disease severity, poor voiders presented with worse Japanese Orthopedic Association scores. Moreover, poor voiders suffered for a longer period of time from orthopedic symptoms due to LCS. In followed-up patients (CM, n = 32; LCS, n = 47), total IPSS, storage subscores, and voiding subscores were significantly improved after surgery, as was voiding time from uroflowmetry. CONCLUSIONS: This study demonstrated high prevalence of lower urinary tract dysfunction of CM and LCS as well as short-term effectiveness of decompression surgery. These results would encourage urologists to consider an orthopedic consultation when lower urinary tract dysfunction is identified in patients with degenerative spinal diseases.

A Randomized Controlled Trial for the Intervention Effect of Early Exercise Therapy on Axial Pain after Cervical Laminoplasty.

Introduction: Cervical isometric muscle strengthening and cervical range of motion (ROM) training are recommended after laminoplasty (LP). However, their preventive effects on axial pain are unclear. We examined whether neck extension muscle strengthening and cervical ROM training from the early postoperative period effectively suppress postoperative axial pain. Methods: Sixty-one patients undergoing a muscle-preserving LP attached to C2 and C7 for cervical spondylotic myelopathy or ossification of the posterior longitudinal ligament were randomly allocated to the cervical exercise (33 patients) or nonexercize (28 patients) groups. Postoperative cervical collars were not worn in any cases. The cervical exercise group underwent neck extension isometric muscle strengthening and cervical ROM exercises for 3 months starting on postoperative day 2. Changes in axial pain (visual analog scale [VAS]) from baseline at 2 weeks and 3 months after surgery were evaluated as the primary outcome. Cervical muscle strength, cervical ROM, and Japanese Orthopedic Association Cervical Myelopathy Evaluation Questionnaire (JOACMEQ) scores were evaluated as secondary outcomes. Results: Axial pain was significantly exacerbated at 2 weeks after LP compared with before surgery, and then, a significant improvement was observed at 3 months after surgery. No significant interaction was observed between the intervention and nonintervention groups. There was no difference in secondary outcomes between groups. The change in the VAS of axial pain from before surgery to 3 months after surgery showed a greater decreased neck extension muscle strength resulting in severer axial pain. Conclusions: Cervical muscle strengthening and cervical ROM exercise from the early postoperative period did not relieve axial pain at 2 weeks and 3 months after a muscle-preserving LP attached to C2 and C7. No significant difference in neck extension muscle and cervical movement was observed between the intervention and nonintervention groups. Therefore, a muscle-preserving LP attached to C2 and C7 is a good strategy to prevent axial pain in the early postoperative period.Clinical Trials Registration Number: UMIN000040692.

Can Hip-Knee Line Angle Distinguish the Size of Pelvic Incidence?-Development of Quick Noninvasive Assessment Tool for Pelvic Incidence Classification.

This study aimed to explore effective measurement angles for pelvic incidence (PI) classification and to develop a quick, noninvasive assessment tool for PI classification. We defined five variation types of hip-knee line (HKL) angles and tested the discrimination ability of the receiver operating characteristic (ROC) analysis using 125 photographs of upright standing posture from the right lateral side. ROC analysis revealed an applicable HKL angle defined by the line connecting the most raised part of the buttock and the central point of the knee and the midthigh line. The acceptable cut-off points for discriminating small or large PIs in terms of HKL angle were 18.5° for small PI (sensitivity, 0.91; specificity, 0.79) and 21.5° for large PI discrimination (sensitivity, 0.74; specificity, 0.72). In addition, we devised a quick noninvasive assessment tool for PI classification using the cut-offs of the HKL angle with a view to practical application. The results of intra- and inter-rater reliability ensured a substantial/moderate level of the tool (Cohen's kappa coefficient, 0.79; Fleiss's kappa coefficient, 0.50-0.54). These results revealed that the HKL angle can distinguish the size of the PI with a high/moderate discrimination ability. Furthermore, the tool indicated acceptable inter-/intra-rater reliability for practical applications.

BK Virus-Associated Urothelial Carcinoma in a Patient with Peripheral Blood Stem Cell Transplantation for Acute Lymphoblastic Leukemia: A Case Report.

Bladder tamponade due to hemorrhagic cystitis caused by BK virus in immunocompetent patients is familiar to urologists. BK virus is an important cause of nephropathy and graft loss in kidney transplant recipients. Although urothelial carcinoma of the bladder in kidney transplant recipients with persistent BK viruria is known, BK virus-associated urothelial carcinoma (BKVUC) in peripheral blood stem cell transplantation recipients is not as well known. A 54-year-old man with acute lymphoblastic leukemia was treated in the Department of Hematology of our hospital. After recurrence 25 months later, he received chemotherapy for half a year and underwent peripheral blood stem cell transplantation. He achieved temporarily complete remission, but he developed hematuria with BK virus-positive result 1 month after peripheral blood stem cell transplantation. One month later, he developed bladder tamponade-diagnosed hemorrhagic cystitis due to BK virus in our Urological Department. We performed transurethral coagulation to manage hemorrhage and removed a bleeding lesion in the bladder wall. Pathological examination of the removed bladder wall revealed pT1 stage BKVUC. We found that bladder tamponade could have led to reactivation of BK virus in this immunocompetent patient. This could be the first report of BKVUC of the bladder found in a peripheral blood stem cell transplantation recipient with close urological follow-up for 24 months. Adequate removal of bleeding lesions from the bladder mucosa with appropriate timing during hemorrhagic cystitis due to BKVUC could be essential to achieve good outcomes.

Night-Time Urinary Frequency Is Increased after the Great East Japan Earthquake along with Seasonal Variation: A Five-Year Longitudinal Study in Kesennuma City.

Disasters influence various health conditions; however, little has been reported about urinary symptoms. The objective of this study is to evaluate whether night-time urinary frequency was influenced by the Great East Japan Earthquake (GEJE) in March 2011. We also evaluated seasonal variation of night-time frequency, which may affect the primary objective. A retrospective chart review was conducted on 300 evaluable patients who resided in the impacted area: 263 men with benign prostatic hyperplasia and/or overactive bladder and 37 women with overactive bladder. Data concerning night-time frequency were collected repeatedly every three months from March 2009 until March 2014, then compared yearly and seasonally among same patients. In addition, night-time frequency was analyzed for potential relations to sex, age, comorbidities, and whether residences had been destroyed. There was a significant increase of night-time frequency during 2011-2013 when compared yearly with 2009 and 2010. In seasonal comparisons of the entire period, night-time frequency was greater during autumn and winter compared with summer. In quarterly comparisons, a sudden increase was not observed after the GEJE, but night-time frequency was increased significantly in spring, summer and autumn in 2011 when compared with the corresponding seasons in 2010. While hypertension was related to exacerbation of night-time frequency during winter, we did not find any factors associated with increase after the disaster out of sex, age, comorbidities or residential situations. In conclusion, night-time urinary frequency is increased shortly after the GEJE and remains elevated for the following three years along with seasonal variation.

Distribution of anguillid leptocephali and possible spawning areas in the South Pacific Ocean.

Seven South Pacific anguillid eel species live from New Guinea to French Polynesia, but their spawning areas and life histories are mostly unknown despite previous sampling surveys. A July-October 2016 research cruise was conducted to study the spawning areas and times, and larval distributions of South Pacific anguillid eels, which included a short 155°E station-line northeast of New Guinea and five long transects (5-25°S, 160°E-140°W) crossing the South Equatorial (SEC) and other currents. This survey collected nearly 4000 anguilliform leptocephali at 179 stations using an Isaacs-Kidd Midwater Trawl accompanied by 104 CTD casts. Based on mor-phometric observations and DNA sequencing, 74 anguillid leptocephali were collected, which in the southern areas included 29 larvae of six species: Anguilla bicolor pacifica, A. marmorata, A. australis, A. reinhardtii, A. megastoma, and A. obscura (all anguillid species of the region were caught except A. dieffenbachii). Small A. australis (9.0-16.8 mm) and A. reinhardtii (12.4, 12.5 mm) leptocephali were collected south of the Solomon Islands, other A. australis (10.8-12.0 mm) larvae were caught northwest of Fiji along with an A. obscura (20.0 mm) larva, and an A. marmorata (7.8 mm) larva was collected near Samoa. Considering collection sites, larval ages from otolith analysis, and westward SEC drift, multiple spawning locations occurred from south of the Solomon Islands and the Fiji area (16-20 days old larvae) to near Samoa (19 days old larva) during June and July in areas where high-salinity Subtropical Underwater (STUW, ~150 m depth) and the warm, low-salinity surface Fresh Pool were present. Five long hydrographic sections showed the strong Fresh Pool in the west and the STUW formation area in the east.

Increasing Heme Oxygenase-1-Expressing Macrophages Indicates a Tendency of Poor Prognosis in Advanced Colorectal Cancer.

BACKGROUND: Many cancers express heme oxygenase-1 -(HO-1) at a higher frequency than healthy tissues, and this elevated expression is associated with cancer prognosis. Here, we aim to clarify the correlation between HO-1-expressing macrophage numbers and clinicopathological parameters of advanced colorectal cancer. MATERIALS AND METHODS: Formalin-fixed and paraffin-embedded tissues of patients with advanced colorectal cancer were used. To detect HO-1 expression in macrophages, immunohistochemistry was performed. The number of positive cells was measured. Furthermore, HO-1 mRNA in colorectal cancer was examined by reverse transcription polymerase chain reaction. RESULTS: Among the HO-1-negative and HO-1-positive groups, 58.02 and 85.00% of cases, respectively, were positive for lymph node metastasis. The disease-free survival (DFS) time was significantly shorter (p < 0.05) in the -HO-1-positive group (2.44 years) than in the HO-1-negative group (4.09 years). However, according to the Cox proportional-hazards regression model, the HO-1-positive group could not be a risk factor of poor prognosis. HO-1 mRNA expression was confirmed in colorectal normal and cancer tissues. CONCLUSION: In this study, the correlation between HO-1-expressing macrophages and clinicopathological parameters in the tumor microenvironment of colorectal cancer was studied for the first time, and the expression was associated with lymph node metastasis and shortening of DFS.

Synchronicity of genetic variants between primary sites and metastatic lymph nodes, and prognostic impact in nodal metastatic lung adenocarcinoma.

PURPOSE: Nodal positive lung adenocarcinoma includes wide range of survival. Several methods for the classification of nodal-positive lung cancer have been proposed. However, classification considering the impact of targetable genetic variants are lacking. The possibility of genetic variants for the better stratification of nodal positive lung adenocarcinoma was estimated. METHODS: Mutations of 36 genes between primary sites and metastatic lymph nodes (LNs) were compared using next-generation sequencing. Subsequently, mutations in EGFR and BRAF, rearrangements in ALK and ROS1 were evaluated in 69 resected pN1-2M0 adenocarcinoma cases. Recurrence-free survival (RFS), post-recurrence survival (PRS), and overall survival (OS) were evaluated with respect to targetable variants and tyrosine kinase inhibitor (TKI) therapy after recurrence. RESULTS: About 90% of variants were shared and allele frequencies were similar between primary and metastatic sites. In 69 pN1-2M0 cases, EGFR/ALK were positive in primary sites of 39 cases and same EGFR/ALK variants were confirmed in metastatic LNs of 96.7% tissue-available cases. Multivariate analyses indicated positive EGFR/ALK status was associated with worse RFS (HR 2.366; 95% CI 1.244-4.500; P = 0.009), and PRS was prolonged in cases receiving TKI therapy (no post-recurrence TKI therapies, HR 3.740; 95% CI 1.449-9.650; P = 0.006). OS did not differ with respect to targetable variants or TKI therapy. CONCLUSIONS: Cases harbouring targetable genetic variants had a higher risk of recurrence, but PRS was prolonged by TKI therapy. Classification according to the targetable genetic status provides a basis for predicting recurrence and determining treatment strategies after recurrence.