Search

Abstract Objectives Renal cell carcinoma (RCC) is shown to have a tendency for late recurrence, occurring 5 or more years after curative surgery. Imaging diagnosis is required for follow‐up, and there is no definitive answer as to how long this should continue. Some patients discontinue follow‐up visits at their own discretion. How best to predict late recurrence and loss to follow‐up (LF) remains unclear. Patients and methods This study targeted patients diagnosed with non‐metastatic RCC who underwent either radical or partial nephrectomy at Chiba University Hospital between 1988 and 2021. Follow‐up for patients with RCC is typically lifelong. We used random survival forests (RSFs), a machine learning‐based survival analysis method, to predict late recurrence and LF. For verification of prediction accuracy, we applied the time‐dependent area under the receiver operating characteristic curve (t‐AUC). To analyse the risks of late recurrence and LF, SurvSHAP(t) and partial dependence plots were used. Results We analysed 1051 cases in this study. Median follow‐up was 58.5 (range: 0–376) months. The predictive accuracy of recurrence using RSF was t‐AUC 0.806, 0.761, 0.674 and 0.566 at 60, 120, 180 and 240 months postoperatively, respectively. The recurrence risk impact showed a time‐dependent increase up to approximately 50 months postoperatively. Beyond 50 months, there were no distinct risk factors characteristic of late recurrence. The predictive accuracy of LF using RSF was t‐AUC 0.542, 0.699, 0.685, 0.628 and 0.674 at 60, 120, 180, 240 and 300 months postoperatively, respectively. The risk of LF increased with advancing age beyond 70 years. Conclusion It is difficult to identify factors that predict late recurrence. For long‐term follow‐up observation, it is essential to pay particular attention to patients with RCC aged 70 years and above. Establishing frameworks to facilitate collaboration with local hospitals near patients' residences and providing care within the community is necessary.

Background: The knowledge of the morphology of the human mandible is essential for diverse dental procedures. The potential anatomical variations of the bone, including the presence of accessory foramina, may culminate in significant clinical outcomes and implications, directly impacting dental surgery and anesthesia. Aim of study: This study aimed to evaluate the general morphology of human mandibles in the collection of the State University of Londrina, South Brazil, and to determine the presence of anatomical variations. Materials and methods: A total of 63 mandibles were measured bilaterally with a pachymeter for various dimensions, and a proportional calculation of each parameter was obtained, based on the size of the length of each mandibular base. In addition to the general descriptive morphology of the mandibles, considering that six mandibles presented duplicated foramina, they were divided into two groups, and the mandibles with no anatomical variation (normal group, N = 57) were compared to those with duplicated foramina (N = 6). Data were checked for normal distribution and then tested statistically. Results: Six out of 63 mandibles (9.52 %) presented duplicated foramina, either mental or mandibular. Significant differences between the normal group and the duplicated foramina group were found in the lengths between mandibular angle and condylar process on both sides (right: 65.14 mm vs. 74.91 mm, p = 0.001; left: 65.04 mm vs. 72.34 mm, p = 0.019); between mandibular angle and coronoid process on the right side (59.55 mm vs. 67.67 mm, p = 0.007); and in the diameter of the left mandibular foramen (3.71 mm vs. 4.64 mm, p = 0.04), with the duplicated foramina group presenting a higher average for all parameters. Conclusion: These findings provide a morphological pattern for the Department of Anatomy of the State University of Londrina collection and highlight the presence of anatomical variations of the human mandible, specifically regarding duplicated foramina. The presence of accessory mental and mandibular foramina is clinically significant for dental procedures, potentially impacting the anesthesia. Understanding these variations is crucial for dental surgeons to prevent complications. Future research should further explore the functional implications and clinical significance of these variations.

Previously, we demonstrated unique insertion/deletion polymorphisms of equine histidine-rich glycoprotein (eHRG) with five genotypes composed of 45-bp or 90-bp deletions in the histidine-rich region of eHRG in Thoroughbred horses. Although leukocytes are typically used to collect DNA for genotyping, blood sampling from animals is sometimes difficult and invasive. Moreover, the method for extracting DNA from blood leukocytes involves complicated steps and must be performed soon after blood sampling for sensitive gene analysis. In the present study, we performed eHRG genotyping using DNA, isolated from oral mucosa swabs collected by rubbing the mucosa on the underside of the upper lip of horses and 100 mg of freshly excreted feces obtained by scraping their surface. In the present study, we performed eHRG genotyping using DNA isolated from oral mucosa swabs and feces of horses (18 Thoroughbreds, 17 mixed breeds, 2 warm bloods), and compared the accuracy of this method with that of the method using DNA from leukocytes. The DNA derived from oral mucosa swabs was sufficient in quantity and quality for eHRG genotyping. However, DNA derived from fecal samples requires a more sensitive detection system because of contamination with non-horse DNA, and the test quality is low. Collection of oral mucosa swabs is less invasive than blood sampling; further, oral swabs can be stored for a longer period in a specified high-quality solution. Therefore, collecting DNA samples from oral mucosa swabs is recommended for the genetic analysis of not only horses but also other animals that are not accustomed to humans.

Objective: This study aimed to determine the maximum safe dose of intranasal insulin administration during cardiac surgery. Methods: This open-label, Phase 1, single-center, dose-escalation clinical trial recruited patients scheduled to undergo elective cardiac surgery or major vascular surgery requiring cardiopulmonary bypass between February and September 2021. They were grouped into 5 dose-escalation cohorts and administered 0, 40, 80, 160, and 240 IU insulin (n = 6 in each group) via a metered nasal dispenser after the induction of general anesthesia. Blood samples were collected at 10-minute intervals for the first 60 minutes and at 30-minute intervals thereafter. Hypoglycemia was defined as a blood glucose level

Abstract Background Postoperative delirium (POD) is a complication after surgery which leads to worse outcomes. The frequency of this syndrome is increasing as more elderly patients undergo major surgery. The frequency is around 10–25% but reaches as high as 50% for cardiac surgery. Although intranasal insulin (INI) administration of up to 160 units in patients with cognitive dysfunction and delirium has been shown to improve memory function and brain metabolism without complications such as hypoglycemia, it remains unknown whether INI prevents POD after cardiac surgery Methods A multicenter, double-blind, randomized, controlled trial will be conducted at University of Tsukuba Hospital and Tsukuba Medical Center Hospital, Japan, from July 1, 2023, to December 31, 2025. A total of 110 elderly patients (65 years old or older) undergoing cardiac surgery requiring cardiopulmonary bypass will be enrolled and randomly allocated to intranasal insulin or intranasal saline groups. The primary outcome is the incidence of POD within 7 days after surgery. Secondary outcomes include days and times of delirium, screening tests of cognitive function, pain scores, duration of postoperative tracheal intubation, and length of ICU stay. Discussion The present objective is to assess whether 80 IU INI administration during surgery prevents POD after cardiac surgery. The results may provide strategic choices to prevent POD in patients with cardiac surgery requiring cardiopulmonary bypass. Trial registration The trial was registered with the Japan Registry for Clinical Trials with identifier jRCTs031230047 on April 21, 2023.

Abstract Immuno-oncology (IO) combination therapy is utilized as a first-line systemic treatment for advanced renal cell carcinoma. However, evidence supporting the use of cabozantinib after IO combination therapy is lacking. We retrospectively analyzed patients who received second-line cabozantinib after IO combination therapy using the Japanese Urological Oncology Group (JUOG) database. In total, 254 patients were enrolled in the JUOG global study, and 118 patients who received second-line cabozantinib comprised the study cohort. The objective response rate, disease control rate, second-line cabozantinib progression-free survival (PFS), and overall survival from second-line for overall were 32%, 75%, 10.5 months, and not reached, respectively, for first-line IO-IO therapy were 37%, 77%, 11.1 months, and not reached, respectively, versus 24%, 71%, 8.3 months, and not reached, respectively, for first-line IO-tyrosine kinase inhibitor therapy. In univariate and multivariate analyses, discontinuation of first-line treatment because of progressive disease and liver metastasis were independent risk factors for PFS. All-grade adverse events occurred in 72% of patients, and grade 3 or higher adverse events occurred in 28% of patients. Second line-cabozantinib after first-line IO combination therapy for advanced renal cell carcinoma was expected to be effective after either IO-IO or IO-TKI treatment and feasible in real-world practice.

Introduction Few reports have presented sporadic multifocal renal cell carcinomas of different histologic types occurring simultaneously in a single kidney. Here, we present a case of three ipsilateral renal cell carcinomas with three histologic types. Case presentation A 44‐year‐old man with end‐stage renal disease due to nephrosclerosis was referred to our hospital for an incidental renal tumor. Following the introduction of hemodialysis, enhanced computed tomography revealed a renal tumor suggestive of clear‐cell renal cell carcinoma with a cystic component. With a preoperative diagnosis of one renal tumor, he underwent laparoscopic radical nephrectomy. However, pathological examination revealed three renal cell carcinomas with three histological diagnoses: clear‐cell, papillary, and clear‐cell papillary renal cell carcinomas. Conclusion Preoperative imaging may not detect all synchronous ipsilateral multifocal renal cell carcinomas. Patients with severe renal function impairment may have synchronous multifocal renal cell carcinomas.

Introduction The incidence of bladder cancer following transplantation is high; however, no previous studies have reported the development of bladder cancer following bone marrow and bilateral lung transplantations. Case presentation A 42‐year‐old man who was followed for bilateral lung transplantation due to chronic graft‐versus‐host disease following bone marrow transplantation complained of gross hematuria. Transurethral resection of the bladder tumor was performed for cT1N0M0 bladder cancer. On the following night, he experienced severe respiratory failure and was intubated. He was discharged on postoperative day 32 with the introduction of home oxygen therapy. The pathological diagnosis was invasive urothelial carcinoma, high‐grade, pT1, with urothelial carcinoma in situ. Further treatment could not be performed because of his poor performance status and immunosuppressive state. Conclusion Vigorous screening for bladder cancer coexisting with other malignancies should be performed for transplant recipients for the early diagnosis and prompt treatment of a relatively aggressive bladder cancer.

We describe a new leafminer, Phyllonorycter quintinipponicella Sato sp. nov. (Lepidoptera: Gracillariidae: Lithocolletinae), of an evergreen oak, Quercus phillyreoides A. Gray (Fagaceae), from Japan. This species is tetravoltine, overwintering as larvae in mines without diapause. It belongs to the P. nipponicella complex associated with oaks. As a result, this complex consists of five species (the others are P. acutissimae (Kumata), P. nipponicella (Issiki), P. similis Kumata, and P. persimilis Fujihara, Sato & Kumata), which are almost indistinguishable from each other in appearance. Nevertheless, the new species can be sharply distinguished from the others by the pupal cremaster as well as male genitalia, but not by the female genitalia. In addition, P. quintinipponicella larvae, unlike those of the other species, do not form the frass into a pile but leave it loose in the mine. Molecular analysis based on sequences of mitochondrial cytochrome c oxidase subunit I showed that the new species is genetically distinct from the others. Their host-plant ranges indicated that evolutionary divergence in the complex should be linked to that of host oaks. Further genetic and ecological studies are needed to clarify the evolutionary history of the P. nipponicella complex in combination with oak divergence.

Entomopathogenic fungi are important component for regulation of pests in ecosystem. Isaria fumosorosea, as one of the entomopathogenic fungi, was reported to successfully controlled the outbreaks of forest defoliators attacked larch (Larix kaempferi) plantation in Furano, Japan and beech (Fagus crenata) forest in Hachimantai, Japan. Instead of semi-cultured method, in this paper, a culture-independent method based on DNA using qPCR was developed for specific detection and quantification of I. fumosorosea directly from soil DNA extract using specific primer. The primer IFU5821F/IFU6061R was designed and found to be the best primer pair for I. fumosorosea. Standard soil DNA was obtained with strong relationship and good fitting with five levels (R2= 0.989, E = 0.58). I. fumosorosea could not be detected from all soil samples which was possibility caused by low density of the fungi. The qPCR was likely a rapid and specific method to detect the fungus from soil.

Introduction Combination therapy using immuno‐oncology drugs with tyrosine kinase inhibitors is increasingly important in the therapeutic strategy for metastatic renal cell carcinomas. Here, we report a case of metastatic renal cell carcinoma that was successfully treated with deferred cytoreductive nephrectomy following lenvatinib plus pembrolizumab combination therapy. Case presentation A 49‐year‐old man was referred to our hospital with a diagnosis of advanced right kidney cancer with multiple lung metastases (cT3aN0M1). The size of the primary tumor was so huge that it exceeded 20 cm in diameter, pushing the liver and intestines to the left. After administration of lenvatinib and pembrolizumab combination as first‐line treatment, all the metastatic lung lesions disappeared, and the primary lesion shrank significantly. Robot‐assisted radical nephrectomy was successfully performed, resulting in complete surgical remission. Conclusion Deferred cytoreductive nephrectomy following a lenvatinib plus pembrolizumab combination is a useful therapeutic strategy for achieving complete remission of metastatic renal cell carcinomas.

Background: Acute aortic dissection has a high mortality rate, especially for Stanford type A with a dissected ascending aorta. Cardiac tamponade is one of the most common complications of acute type A aortic dissection (ATAAD) and can cause death. However, the pathogenesis is often unclear. We aimed to examine laboratory findings at the onset of disease and macrophage involvement. Methods: Hematological and biochemical parameters, and D-dimer, brain natriuretic peptide (BNP), and high-sensitivity troponin I (hs-cTnI) levels in 70 patients with ATAAD at our hospital were investigated. Additionally, the myocardium and aorta after autopsy of an ATAAD case with cardiac tamponade were pathologically examined. Results: Forty-four ATAAD cases were complicated by cardiac tamponade. The mean age of patients with cardiac tamponade and proportion of patients over 70 years of age were both significantly higher than for those without cardiac tamponade. Evaluable D-dimer values were higher than 0.5 μg/mL in all patients. Significantly elevated laboratory parameters in patients with cardiac tamponade included: lactate dehydrogenase, aspartate aminotransferase, C-reactive protein, lactate, BNP, and hs-cTnI. However, multivariate analysis showed only hs-cTnI was significantly associated with cardiac tamponade. Histological examination revealed numerous M2-like macrophages infiltrating the myocardium and dissecting aorta, expressing CC chemokine ligand (CCL)2 together with vascular endothelial growth factor-C and matrix metalloproteinase-9. The peripheral monocyte-to-neutrophil ratio (MNR) was also significantly higher in cardiac tamponade. Conclusions: In ATAAD patients with cardiac tamponade, hs-cTnI was significantly elevated and CCL2 expression was observed, which may be involved in the expression of M2-like macrophages via an increased MNR.

Abstract Histidine-rich glycoprotein (HRG) is abundant plasma protein with various effects on angiogenesis, coagulation, and immune responses. Previously, we identified the base and amino acid sequences of equine HRG (eHRG) and revealed that eHRG regulates neutrophil functions. In this study, we first conducted a large-scale gene analysis with DNA samples extracted from 1700 Thoroughbred horses and identified unique insertion/deletion polymorphisms in the histidine-rich region (HRR) of eHRG. Here we report two types of polymorphisms (deletion type 1 [D1] and deletion type 2 [D2]) containing either a 45 bp or 90 bp deletion in the HRR of eHRG, and five genotypes of eHRG (insertion/insertion [II], ID1, ID2, D1D1, and D1D2) in Thoroughbred horses. Allele frequency of I, D1, and D2, was 0.483, 0.480, and 0.037 and the incidence of each genotype was II: 23.4%, ID1: 46.2%, ID2: 3.6%, D1D1: 23.1%, and D1D2: 3.7%, respectively. The molecular weights of each plasma eHRG protein collected from horses with each genotype was detected as bands of different molecular size, which corresponded to the estimated amino acid sequence. The nickel-binding affinity of the D1 or D2 deletion eHRG was reduced, indicating a loss of function at the site. eHRG proteins show a variety of biological and immunological activities in vivo, and HRR is its active center, suggesting that genetic polymorphisms in eHRG may be involved in the performance in athletic ability, productivity, and susceptibility to infectious diseases in Thoroughbred horses.

Abstract Cancer-associated fibroblasts (CAFs) play a significant role in tumor progression within the tumor microenvironment. Previously, we used near-infrared photoimmunotherapy (NIR-PIT), a next-generation cancer cell-targeted phototherapy, to establish CAF-targeted NIR-PIT. In this study, we investigated whether dual-targeted NIR-PIT, targeting cancer cells and CAFs, could be a therapeutic strategy. A total of 132 cases of esophageal cancer were analyzed for epidermal growth factor receptor (EGFR), human epidermal growth factor 2 (HER2), and fibroblast activation protein (FAP) expression using immunohistochemistry. Human esophageal cancer cells and CAFs were co-cultured and treated with single- or dual-targeted NIR-PIT in vitro. These cells were co-inoculated into BALB/c-nu/nu mice and the tumors were treated with single-targeted NIR-PIT or dual-targeted NIR-PIT in vivo. Survival analysis showed FAP- or EGFR-high patients had worse survival than patients with low expression of FAP or EGFR (log-rank, P

Abstract Background: Lactoferrin, an iron-binding glycoprotein, is known to have protective effects against intestinal and cerebral ischemia-reperfusion (IR) injuries; however, its cardioprotective effects against the stunned myocardium are unknown. This study aimed to test the hypothesis that lactoferrin has cardioprotective effects against stunned myocardium. Methods: Using isolated rat hearts (Langendorff system), we determined the effects of lactoferrin administered enterally and by direct cardiac perfusion. Rat hearts were perfused using the Langendorff system, and two experiments were performed. In experiment 1, the hearts were divided into the enteral lactoferrin (E-LF) 7.5 m, 15 m, 30 m, and 60 m groups, where lactoferrin (1000 mg/kg) was administered enterally 7.5, 15, 30, and 60 min, respectively, before perfusion; and a control group, where saline was administered 30 min before perfusion. In experiment 2, hearts were allocated to the perfusate lactoferrin (P-LF) 15 and 100 groups, where 15 mg/L and 100 mg/L lactoferrin were respectively added to the perfusate, and a control group. Each group was perfused for 20 min prior to 15 min of no-flow ischemia with pacing, followed by 20 min of reperfusion. The primary outcome was the maximum left ventricular derivative of pressure development (LV dP/dt max) 15 min after reperfusion. Myocardial phospho-protein kinase B (p-Akt) was assayed using western blotting. Results: The LV dP/dt max 15 min after reperfusion in the E-LF 15 and 30 m groups was significantly higher than that in the control group. However, the effects disappeared in the E-LF 60 m group. In the second experiment, there were no significant differences in LV dP/dt max. Myocardial p-Akt was not significantly activated in any lactoferrin group. Conclusion: Cardioprotection was observed 15–30 min after enteral lactoferrin but not by direct cardiac perfusion with lactoferrin. Myocardial p-Akt was not associated with the cardioprotective effect. The cardioprotective effect may be induced by enteral lactoferrin-induced substances.

Abstract Insulin exerts positive inotropic effects on cardiac muscle; however, the relationship between cardiac contractility and phosphoinositol-3-kinase/Akt (PI3K/Akt) activation remains unclear. We hypothesized that the positive inotropic effects of insulin are dose-dependent and mediated via the PI3K/Akt pathway in isolated normal rat hearts. The Institutional Animal Investigation Committee approved the use of hearts excised from rats under pentobarbital anesthesia. The hearts were perfused at a constant pressure using the Langendorff technique. After stabilization (baseline), the hearts were randomly divided into the following four insulin (Ins) groups: 1) Ins0 (0 IU/L), 2) Ins0.5 (0.5 IU/L), 3) Ins5 (5 IU/L), and 4) Ins50 (50 IU/L) (n = 8 in each group). To clarify the role of the PI3K/Akt pathway in insulin-dependent inotropic effects, we also treated the insulin groups with the PI3K inhibitor wortmannin (InsW): 5) InsW0 (0 IU/L), 6) InsW0.5 (0.5 IU/L), 7) InsW5 (5 IU/L), and 8) InsW50 (50 IU/L). Hearts were perfused with Krebs–Henseleit buffer solution with or without wortmannin for 10 min, followed by 20 min perfusion with the solution containing each concentration of insulin. The data were recorded as the maximum left ventricular derivative of pressure development (LV dP/dt max). Myocardial p-Akt levels were measured at 3 min, 5 min, and at the end of the perfusion. In the Ins groups, LV dP/dt max in Ins5 and Ins50 increased by 14% and 48%, respectively, 3 min after insulin perfusion compared with the baseline. Tachyphylaxis was observed after 10 min in the Ins5 and Ins50 treatment groups. Wortmannin partially inhibited the positive inotropic effect of insulin; although insulin enhanced p-Akt levels at all time points compared with the control group, this increase was suppressed in the presence of wortmannin. The positive inotropic effect of insulin is dose-dependent and consistent with Akt activation. This effect mediated by high doses of insulin on cardiac tissue was temporary and caused tachyphylaxis, potentially triggered by Akt overactivation, which leads beta 1 deactivation.

Objective:. To examine the association of the quality of preoperative glycemic control and insulin sensitivity during major upper abdominal surgery. Background:. In cardiac surgery, glycated hemoglobin A1c (HbA1c), an indicator of glycemic control during the preceding 3 months, correlated with intraoperative insulin sensitivity. Furthermore, insulin resistance showed a significant association with adverse clinical outcomes. Methods:. This study is a post hoc exploratory analysis of a randomized controlled trial in patients undergoing elective hepatectomy and receiving the hyperinsulinemic-normoglycemic clamp (HNC) as a potential intervention to reduce surgical site infections (ClinicalTrials.gov NCT01528189). Immediately before skin incision, the HNC was initiated by infusing insulin at the rate of 2 mU/kg/min. Dextrose was administered at rates titrated to maintain normoglycemia (4.0–6.0 mmol/L). The average of 3 consecutive dextrose infusion rates during steady state was used as a measure of insulin sensitivity. Primary outcome was the relationship between preoperative HbA1c and insulin sensitivity during surgery. Secondary outcomes were the associations of insulin sensitivity with the patient’s body mass index (BMI) and postoperative morbidity. Results:. Thirty-four patients were studied. HbA1c (Y = −0.52X + 4.8, P < 0.001, R2 = 0.29), BMI (Y = −0.12X + 5.0, P < 0.001, R2 = 0.43) showed negative correlations with insulin sensitivity. The odds ratio of postoperative complications within 30 days of surgery for every increase in insulin sensitivity by 1 mg/kg/min was 0.22 (95% confidential interval, 0.06–0.59; P = 0.009). Conclusions:. We demonstrate significant associations of the quality of preoperative glycemic control and body mass index with insulin sensitivity during hepatectomy. The degree of insulin resistance correlated with postoperative morbidity.

Background: Gestational diabetes mellitus (GDM) with poorly controlled glycemia is associated with poor pregnancy outcomes. However, adequate markers for glycemic control in GDM have not been fully evaluated. Methods: We retrospectively studied 77 patients with GDM and their infants. Mean glycated albumin (GA), glycated hemoglobin (HbA1c), and GA/HbA1c in GDM were compared between two groups stratified by the presence or absence of infant complications (complications or non-complications). We assessed the predictability of infant complications in GA, HbA1c, and GA/HbA1c of women with GDM by receiver operating characteristic analysis (ROC). Results: In complications and non-complications, GA and GA/HbA1c were significantly associated with neonatal hypoglycemia (13.9% vs. 13.0%, p

There are few well-balanced heat storage materials up to date. Here, the authors report that δ-type K0.33MnO2 ∙ nH2O can be an excellently balanced heat storage material exhibiting a “water-intercalation mechanism”.

Repeated or prolonged, but not short-term, general anesthesia during the early postnatal period causes long-lasting impairments in memory formation in various species. The mechanisms underlying long-lasting impairment in cognitive function are poorly understood. Here, we show that repeated general anesthesia in postnatal mice induces preferential apoptosis and subsequent loss of parvalbumin-positive inhibitory interneurons in the hippocampus. Each parvalbumin interneuron controls the activity of multiple pyramidal excitatory neurons, thereby regulating neuronal circuits and memory consolidation. Preventing the loss of parvalbumin neurons by deleting a proapoptotic protein, mitochondrial anchored protein ligase (MAPL), selectively in parvalbumin neurons rescued anesthesia-induced deficits in pyramidal cell inhibition and hippocampus-dependent long-term memory. Conversely, partial depletion of parvalbumin neurons in neonates was sufficient to engender long-lasting memory impairment. Thus, loss of parvalbumin interneurons in postnatal mice following repeated general anesthesia critically contributes to memory deficits in adulthood.

ObjectiveThe study aimed to evaluate the effect of systemic cisplatin administration on off-frequency masking audiometry.MethodsAmong 26 patients receiving systemic cisplatin, 48 ears were included in the analysis. All patients underwent pure-tone audiometry with ipsilateral narrow-band masking noise (off-frequency masking audiometry). In the off-frequency masking audiometry, 70 dBHL band-pass noise (center frequency 1000 Hz, 1/3 octave bandwidth) was administered to the tested ear. The acquired thresholds were compared to those of standard pure-tone audiometry, and threshold elevations greater than 10 dB were regarded as significant. The number of patients showing abnormal threshold elevation was compared between before and after the cisplatin administration.ResultsBefore cisplatin administration, 91.7, 93.8, 97.9, and 93.8% of ears showed normal off-frequency masking audiometry outcomes at 125, 250, 6000, and 8000 Hz, respectively. After cisplatin administration, a higher number of patients showed abnormal off-frequency masking audiometry outcomes. This change was more prominent with increasing doses of cisplatin. After the cisplatin administration of 100∼200 mg/m2, the prevalence of patients with normal off-frequency masking audiometry outcomes was 77.3, 70.5, 90.9, and 88.6% at 125, 250, 6000, and 8000 Hz, respectively. At 250 Hz, the change was statistically significant (p = 0.01, chi-squared test).

Abstract Background The measurement of circulating substrate concentrations does not provide information about substrate kinetics. It, therefore, remains unclear if a decrease in plasma concentration of albumin, as seen during critical illness, is a consequence of suppressed production in the liver or increased peripheral clearance. In this study, using stable isotope tracer infusions, we measured albumin and fibrinogen kinetics in septic patients and in a control group of non-septic subjects. Methods With the approval from the institutional Research Ethics Board and after obtaining written informed consent from patients or their substitute decision maker, mechanically ventilated patients with sepsis and patients scheduled for elective coronary artery bypass grafting were enrolled. Patients in the non-sepsis group were studied on the day before surgery. The stable isotope L-[ring-2H5]phenylalanine was used to measure absolute synthesis rates (ASR) of albumin and fibrinogen. A priming dose of L-[ring-2H5]phenylalanine (4 µmol/kg) was given followed by a six-hour infusion at a rate of 0.15 µmol/kg/min. At baseline and hourly thereafter, blood was drawn to measure isotope enrichments by gas chromatography/mass spectrometry. Very low density lipoprotein apolipoprotein-B 100 isotopic enrichment was used to represent the isotopic enrichment of the phenylalanine precursor pool from which the liver synthesizes proteins. Plasma albumin and fibrinogen concentrations were also measured. Results Mean plasma albumin in septic patients was decreased when compared to non-septic patients, while synthesis rates were comparable. Mean plasma fibrinogen and ASR in septic patients was increased when compared to non-septic patients. In non-septic patients, no statistically significant correlation between plasma albumin and ASR was observed but plasma fibrinogen significantly correlated with ASR. In septic patients, plasma albumin and fibrinogen significantly correlated with ASR. Conclusions While septic patients showed lower plasma albumin levels than non-septic patients, albumin synthesis was similar in the two groups suggesting that hypoalbuminemia during sepsis was not caused by suppressed hepatic production but a result of enhanced clearance from the circulation. Hyperfibrinogenemia in septic patients was a consequence of increased fibrinogen production. Trial registration: ClinicalTrials.gov: NCT02865408 (registered on August 12, 2016) and ClinicalTrials.gov: NCT02549443 (registered on September 15, 2015).

Abstract Long-lasting cognitive impairment in juveniles undergoing repeated general anesthesia has been observed in numerous preclinical and clinical studies, yet, the underlying mechanisms remain unknown and no preventive treatment is available. We found that daily intranasal insulin administration to juvenile mice for 7 days prior to repeated isoflurane anesthesia rescues deficits in hippocampus-dependent memory and synaptic plasticity in adulthood. Moreover, intranasal insulin prevented anesthesia-induced apoptosis of hippocampal cells, which is thought to underlie cognitive impairment. Inhibition of the mechanistic target of rapamycin complex 1 (mTORC1), a major intracellular effector of insulin receptor, blocked the beneficial effects of intranasal insulin on anesthesia-induced apoptosis. Consistent with this finding, mice lacking mTORC1 downstream translational repressor 4E-BP2 showed no induction of repeated anesthesia-induced apoptosis. Our study demonstrates that intranasal insulin prevents general anesthesia-induced apoptosis of hippocampal cells, and deficits in synaptic plasticity and memory, and suggests that the rescue effect is mediated via mTORC1/4E-BP2 signaling.

To report the rare case of a patient with a perianeurysmal cyst following stent-assisted coil embolization of an unruptured vertebral artery aneurysm. Case Presentation: A 63-year-old woman underwent stent-assisted coil embolization for an unruptured vertebral artery aneurysm embedded in the brainstem (pons). Complete occlusion of the aneurysm was successfully achieved. However, subsequent magnetic resonance imaging (MRI) conducted 8 months after the procedure showed perilesional edematous changes surrounding the aneurysm, and at 20 months, cyst formation was observed in the vicinity of the aneurysm. Progressive enlargement of the cyst eventually led to the development of paralysis and dysphagia, necessitating cyst fenestration surgery. Although postoperative reduction in the cyst size was achieved, the patient experienced complications in the form of aspiration pneumonia and bacterial meningitis, which resulted in a life-threatening condition. Conclusion: Aneurysms embedded in the brain parenchyma should be carefully followed up, recognizing the risk of perianeurysmal cyst formation after coil embolization. [ABSTRACT FROM AUTHOR]

Abstract Aims/Introduction There are few studies to investigate the relationship between macronutrients and longitudinal changes in arterial stiffness in patients with type 2 diabetes mellitus. This exploratory study sought to determine whether macronutrients were correlated with increased arterial stiffness independently of conventional atherosclerotic risk factors. Materials and Methods The study participants comprised 733 type 2 diabetes outpatients who had no apparent history of cardiovascular diseases. The dietary schedule was assessed with a validated, brief, self‐administered diet history questionnaire. At baseline and at years 2 and 5, brachial‐ankle pulse wave velocity was measured. A multivariable linear mixed‐effects model was used to determine the predictive values of macronutrients and atherosclerotic risk factors for longitudinal changes in brachial‐ankle pulse wave velocity. Results There was a significant increase in brachial‐ankle pulse wave velocity values over the 5‐year follow‐up period. In a multivariable linear mixed‐effects model that adjusted for age and sex, lower saturated fatty acid intake was significantly correlated with persistently higher brachial‐ankle pulse wave velocity, independently of other atherosclerotic risk factors. Lower intake of dairy products in particular showed this correlation. Conclusions Our data showed that lower saturated fatty acids intake was correlated with persistently higher brachial‐ankle pulse wave velocity in type 2 diabetes patients. Among food sources of saturated fatty acids, lower dairy products specifically were correlated with elevated brachial‐ankle pulse wave velocity. This might be because the consumption of dairy products in Japan is much lower than in Western countries.

Abstract Cancer-associated fibroblasts (CAFs) have an important role in the tumor microenvironment. CAFs have the multifunctionality which strongly support cancer progression and the acquisition of therapeutic resistance by cancer cells. Near-infrared photoimmunotherapy (NIR-PIT) is a novel cancer treatment that uses a highly selective monoclonal antibody (mAb)-photosensitizer conjugate. We developed fibroblast activation protein (FAP)-targeted NIR-PIT, in which IR700 was conjugated to a FAP-specific antibody to target CAFs (CAFs-targeted NIR-PIT: CAFs-PIT). Thus, we hypothesized that the control of CAFs could overcome the resistance to conventional chemotherapy in esophageal cancer (EC). In this study, we evaluated whether EC cell acquisition of stronger malignant characteristics and refractoriness to chemoradiotherapy are mediated by CAFs. Next, we assessed whether the resistance could be rescued by eliminating CAF stimulation by CAFs-PIT in vitro and in vivo. Cancer cells acquired chemoradiotherapy resistance via CAF stimulation in vitro and 5-fluorouracil (FU) resistance in CAF-coinoculated tumor models in vivo. CAF stimulation promoted the migration/invasion of cancer cells and a stem-like phenotype in vitro, which were rescued by elimination of CAF stimulation. CAFs-PIT had a highly selective effect on CAFs in vitro. Finally, CAF elimination by CAFs-PIT in vivo demonstrated that the combination of 5-FU and NIR-PIT succeeded in producing 70.9% tumor reduction, while 5-FU alone achieved only 13.3% reduction, suggesting the recovery of 5-FU sensitivity in CAF-rich tumors. In conclusion, CAFs-PIT could overcome therapeutic resistance via CAF elimination. The combined use of novel targeted CAFs-PIT with conventional anticancer treatments can be expected to provide a more effective and sensible treatment strategy.

Abstract Elevated 1‐h plasma glucose (1h‐PG; ≥155 mg/dL) during an oral glucose tolerance test is a risk factor for type 2 diabetes. However, the metabolic characteristics of non‐obese Asians with elevated 1h‐PG are unknown. Thus, we studied 59 non‐obese Japanese men with normal glucose tolerance. We divided study participants into the Low 1h‐PG group (

Abstract Individuals with a monophasic glucose response curve (GRC) during a 75‐g oral glucose tolerance test have a higher risk for type 2 diabetes than those with a biphasic GRC. However, no studies have addressed the association between GRC type and insulin clearance. Thus, we studied 49 healthy non‐obese Japanese men. We divided study participants into the monophasic or biphasic group based on the shape of their GRC. We evaluated tissue‐specific insulin sensitivity and insulin clearance using a two‐step hyperinsulinemic‐euglycemic clamp. The monophasic group had more visceral fat, lower insulin clearance and lower muscle insulin sensitivity than the biphasic group, whereas liver and adipose tissue insulin sensitivity, and insulin secretion were comparable. In conclusion, healthy non‐obese men with a monophasic GRC have lower insulin clearance and muscle insulin sensitivity.

Epstein-Barr virus (EBV) infection is occasionally accompanied by central nervous system (CNS) complications, particularly in immunosuppressed patients. However, the symptoms and clinical features of EBV infection in the CNS are rather heterogeneous and remain unknown. We herein describe the first reported adult case manifesting nonconvulsive status epilepticus (NCSE), possibly associated with reactivation of EBV in an immunosuppressive state. A 63-year-old man with a history of acute myeloid leukemia and taking immunosuppressants was admitted due to progressively impaired consciousness without any focal neurological signs, including paralysis or convulsions. Arterial spin labeling magnetic resonance imaging (ASL-MRI) and brain perfusion single-photon emission computed tomography showed hyperperfusion in the right temporal region, despite no morphological abnormalities in other MRI sequences. White blood cell counts, EBV viral load, and virus-capsid antigen IgG in cerebrospinal fluid were elevated. We diagnosed him with EBV-associated encephalopathy presenting with NCSE. Administration of levetiracetam, an antiepileptic, improved the consciousness and the abnormal hyperperfusion. This case suggests a new concept of EBV-associated encephalopathy leading to epilepsy, particularly in immunosuppressed patients.

Diabetes is known to delay wound healing, and this delay is attributed to prolonged inflammation. We found that microRNAs (miRNAs) might be involved in the dysfunction of diabetic-derived neutrophils, and dynamics of neutrophil and chronic inflammation might be initiated by miRNA-regulated genes. Moreover, studies of miRNA function in nephropathy have suggested that circular RNAs (circRNAs), which function as sponges of miRNA to regulate their expression, are potential biomarkers and new therapeutic targets for the diagnosis of diabetic nephropathy. Accordingly, to investigate the molecular mechanism of the regulation of inflammation in diabetic-derived neutrophils, we identified circRNAs in diabetic-derived neutrophils obtained from BKS.Cg-Dock7m +/+ Leprdb/J (Leprdb/db and Leprdb/+) mice using microarrays. Neutrophils from pooled bone marrow of three diabetic and three non-diabetic mice were isolated and total RNA was extracted. Microarray analysis was performed using the Arraystar Mouse Circular RNA Array. The results showed that three circRNAs were significantly increased and six circRNAs were significantly decreased in diabetic-derived neutrophils compared with non-diabetic-derived neutrophils. The expressions of some circRNAs in diabetic-derived neutrophils were more than double those in non-diabetic-derived neutrophils. The circRNAs contain binding sites of miRNAs, which were differentially expressed in diabetic-derived neutrophils. Our results suggest that circRNAs may be involved in the regulation of inflammation in diabetic-derived neutrophils.

Background: Use of coil embolization for internal carotid artery-posterior communicating artery aneurysms (IC-PC ANs) has been increasing. However, the recurrence rate after embolization is rather high compared to that after surgery. The aim of this study was to evaluate the factors related to recurrence after coil embolization for IC-PC ANs. Methods: A total of 69 patients with IC-PC ANs treated with coil embolization between 2013 and 2019 were retrospectively enrolled, and we evaluated whether the aneurysms recurred after embolization. The patients were divided into two groups (no-recurrence group and recurrence group), and the relationships of several patient or aneurysm characteristics and treatment-related information with aneurysm recurrence were examined. Results: Twenty patients (29%) developed aneurysm recurrence. There were significant differences in dome size (5.19 mm/6.48 mm, p = 0.01), neck width (3.25 mm/4.23 mm p = 0.009), aneurysm volume (47.5 mm3/120 mm3, p = 0.003), and Pcom diameter (1.11 mm/1.96 mm p = 0.005) between the two groups. Pcom diameter was the independent risk factor for recurrence (odds ratio: 3.52, 95%CI 1.43–8.69, p = 0.006). The cutoff for Pcom diameter as the factor related to recurrence was 1.79 mm, with sensitivity of 60% and specificity of 83.7%. Conclusion: In this study, dome size, neck width, aneurysm volume, and Pcom diameter were associated with recurrence after coil embolization for IC-PC ANs. In particular, Pcom diameter could be an independent risk factor for recurrence.

Objectives: We have been performing preoperative coronary artery assessments and implementing coronary revascularization or intraoperative adjunctive therapies as needed in patients scheduled for carotid artery stenting (CAS) to prevent ischemic heart disease. In this study, we report the results of a retrospective observation of patients who underwent CAS under our treatment strategy to prevent perioperative coronary ischemic complications. Methods: A total of 224 cases from January 2014 to December 2021 were included. Following preoperative coronary artery CTA, preoperative coronary artery treatment or intraoperative adjunctive therapy (temporary transcutaneous cardiac pacemaker [TTCP] or intra-aortic balloon pumping [IABP]) was performed based on the degree of stenosis. We analyzed the outcomes of patients treated with CAS under this strategy at our institution. Results: Coronary artery disease was detected preoperatively in 143 cases (64%), with 91 cases (41%) indicated for coronary revascularization. Preoperative coronary artery treatment was performed in 76 cases (34%) prior to CAS, and adjunctive therapy with TTCP or IABP was provided in 28 cases (13%) during the procedure. No case developed perioperative coronary ischemic complication. Conclusion: In patients who have undergone CAS, perioperative coronary ischemic complications might be reduced by evaluating the risk of ischemic heart disease preoperatively, performing pre-CAS coronary artery intervention based on the severity of the lesions, and administering intraoperative adjunctive therapy. [ABSTRACT FROM AUTHOR]

Some moth larvae feed not on plants but on keratin and/or chitin produced by animals. These substances are polymers and are commonly found in bird nests as feathers and raptor pellets. Many qualitative studies have examined the association of keratin/chitin feeding moths with bird nests. However, few studies have quantified the species composition with respect to type of nest and habitat. Hence, we have studied the degree to which the niches of these moths differ in terms of type of nest and habitat. We set-up open-top nest boxes for the Ural owl Strix uralensis (damp exposed nests from which owl chicks were fledged successfully) and artificial bird nests (mesh bags filled with duck down to imitate dry exposed nests) in a deciduous forest and artificial bird nests in an urban setting in Aichi Prefecture, central Japan, and collected the contents of the nests every two months from June to December 2014. We recorded 592 individuals of five keratin/chitin feeding moth species (Tineidae, Tineinae) from the contents. Using non-metric multidimensional scaling and cluster analysis of the relative abundances of individual species in each type of nest in forest and urban settings, these species were classified into three groups: (1) Monopis longella and M. congestella inhabiting forest, (2) M. flavidorsalis and Niditinea tugurialis mainly in damp exposed nests in forest and (3) N. piercella mainly in dry exposed nests in urban areas. This classification was compared with findings of other studies. As a result, these moths probably have different niches with respect to nest type (damp or dry), keratin/chitin as a source of food (raptor pellets or feathers), and habitat (forest or urban area). Furthermore, we suggest that the evolution of larviparity in M. congestella might be related to its preference for feathers as a source of food for the development of its larvae.

Primary prostate cancer (PC) progresses to castration-resistant PC (CRPC) under androgen deprivation therapy, by mechanisms e.g. expression of androgen receptor (AR) splice variant-7 (AR-V7). Here we conducted comprehensive epigenome and transcriptome analyses comparing LNCaP, primary PC cells, and LNCaP95, AR-V7-expressing CRPC cells derived from LNCaP. Of 399 AR-V7 target regions identified through ChIP-seq analysis, 377 could be commonly targeted by hormone-stimulated AR, and 22 were specifically targeted by AR-V7. Among genes neighboring to these AR-V7 target regions, 78 genes were highly expressed in LNCaP95, while AR-V7 knockdown led to significant repression of these genes and suppression of growth of LNCaP95. Of the 78 AR-V7 target genes, 74 were common AR/AR-V7 target genes and 4 were specific AR-V7 target genes; their most suppressed genes by AR-V7 knockdown were NUP210 and SLC3A2, respectively, and underwent subsequent analyses. NUP210 and SLC3A2 were significantly upregulated in clinical CRPC tissues, and their knockdown resulted in significant suppression of cellular growth of LNCaP95 through apoptosis and growth arrest. Collectively, AR-V7 contributes to CRPC proliferation by activating both common AR/AR-V7 target and specific AR-V7 target, e.g. NUP210 and SLC3A2.

ObjectiveThe purpose of this study was to evaluate the effect of hearing aids on body balance function in a strictly controlled auditory environment.MethodsWe recorded the findings of 10 experienced hearing aid users and 10 normal-hearing participants. All the participants were assessed using posturography under eight conditions in an acoustically shielded non-reverberant room: (1) eyes open with sound stimuli, with and without foam rubber, (2) eyes closed with sound stimuli, with and without foam rubber, (3) eyes open without sound stimuli, with and without foam rubber, and (4) eyes closed without sound stimuli, with and without foam rubber.ResultsThe auditory cue improved the total path area and sway velocity in both the hearing aid users and normal-hearing participants. The analysis of variance showed that the interaction among eye condition, sound condition, and between-group factor was significant in the maximum displacement of the center-of-pressure in the mediolateral axis (F [1, 18] = 6.19, p = 0.02). The maximum displacement of the center-of-pressure in the mediolateral axis improved with the auditory cues in the normal-hearing participants in the eyes closed condition (5.4 cm and 4.7 cm, p < 0.01). In the hearing aid users, this difference was not significant (5.9 cm and 5.7 cm, p = 0.45). The maximum displacement of the center-of-pressure in the anteroposterior axis improved in both the hearing aid users and the normal-hearing participants.

This data article provides the free amino acid contents of Japanese basket clams from different areas of Lake Abashiri and Abashirigawa River, which belong to the same water system. Abashirigawa River flows into the south side of Lake Abashiri and then runs out from the northeast side of the lake. Clams were caught in three different areas in Lake Abashiri (Memanbetsu, Yobito, and Katayama) and from one site at Abashirigawa River (Sancho). Free amino acids in the edible portion of the clams were analyzed using an automated amino acid analyzer. The clams showed high contents in β-alanine, alanine, glutamic acid, and glycine. The clams caught in the river contains relatively higher amino acid contents. The analyzed data are provided in table format. Keywords: Free amino acid, Japanese basket clams, Habitat

This data article reports the chemical properties (moisture, pH, salinity, and soluble solid content) and colors of fermenting materials in salmon fish sauce products. The fish sauce was produced by mixing salt with differing proportions of raw salmon materials and fermenting for three months; the salmon materials comprised flesh, viscera, an inedible portion, and soft roe. Chemical properties and colors of the unrefined fish sauce (moromi), and the refined fish sauce, were analyzed at one, two, and three months following the start of fermentation. Data determined for all products are provided in table format. Keywords: Fish sauce, Chum salmon, Fermentation, Chemical properties, Color

Fish sauce is a brownish liquid seasoning with a characteristic flavor that is produced in Asian countries and limited areas of Europe. The types of fish and shellfish and fermentation process used in its production depend on the region from which it derives. Variations in ingredients and fermentation procedures yield end products with different smells, tastes, and colors. For this data article, we employed an electronic panel (e-panel) technique including an electronic nose (e-nose), electronic tongue (e-tongue), and electronic eye (e-eye), in which smell, taste, and color are evaluated by sensors instead of the human nose, tongue, and eye to avoid subjective error. The presented data comprise clustering of 46 commercially available fish sauce products based separate e-nose, e-tongue, and e-eye test results. Sensory intensity data from the e-nose, e-tongue, and e-eye were separately classified by cluster analysis and are shown in dendrograms. The hierarchical cluster analysis indicates major three groups on e-nose and e-tongue data, and major four groups on e-eye data.

Dried scallop is used in Chinese, Japanese, and French cuisines for its unique flavor and taste. The quality of dried scallop is rated according to its clear, shiny brown color, developed by the Maillard reaction between sugars and amino acids. This article reports the colors, represented by L* and a* values, and chemical composition (water, salinity, Brix, proteins, and amino acids) of dried scallop products. The dried scallops were produced in Tokoro, Sarufutsu, and Saroma in Hokkaido, Japan. The color of the dried scallops had values of 45.7–52.0 for L* and 2.31–5.08 for a*. The salinity of the products was 15.1–17.7%. The amino acid contents were 1350.8–1668.6 mg/100 g. The data collected here are provided in table format. The data can serve as a reference for commercial dried scallop products to determine product quality. Keywords: Quality of products, Dried scallop, Seasoning ingredient, Browning