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Cardiac ischemia, such as angina pectoris or myocardial infarction, is associated with pain in the oral cavity, lower jaw, head, or neck, or spanning from the left upper arm to the shoulder. When presenting to a dentist, however, appropriate treatment for such patients is often delayed, as dental problems are usually the first to be suspected when the chief complaint is orofacial pain. This report describes a case of a 70-year-old woman who was aware of pain and a burning sensation in the oral cavity upon exertion for a year prior to presenting at our clinic. She had been examined by her family physician, an otolaryngologist, and another dentist, none of whom found any abnormalities other than suspected periodontal disease and caries, for which she was treated. An examination at our clinic revealed no abnormal dental findings that would have been consistent with the mandibular pain, however. Although no chest symptoms were reported, pain was elicited on exertion, suggesting cardiogenic toothache. An immediate referral to a cardiologist was therefore made on the same day. The patient visited the cardiology department of the University Hospital of Tokyo Dental College 6 days later. The increased frequency of symptoms on exertion suggested unstable angina, and the patient was admitted to the emergency department on the same day. Emergency coronary angiography showed that right coronary artery #1 was 99% stenosed proximally (highly calcified plaque). The diagnosis was unstable angina pectoris, with the right coronary artery #1 as the responsible lesion, and percutaneous coronary angioplasty was performed on the same day. Subsequently, all the orofacial pain disappeared, confirming unstable angina as the cause. The pain characteristics in this case were consistent with pain associated with cardiac ischemia, which led to the immediate referral to the cardiology department. In cases of toothache associated with cardia ischemia, it is essential to seek cardiological care as soon as possible.

Tietz albinism-deafness syndrome (TADS) is a rare and severe manifestation of Waardenburg syndrome that is primarily linked to mutations in MITF. In this report, we present a case of TADS resulting from a novel c.637G>C mutation in MITF (p.Glu213Gln; GenBank Accession number: NM_000248). A 3-year-old girl presented with congenital generalized hypopigmentation of the hair, skin, and irides along with complete sensorineural hearing loss. Histopathological and electron microscopy investigations indicated that this variant did not alter the number of melanocytes in the skin but significantly impaired melanosome maturation within melanocytes. Comprehensive melanin analysis revealed marked reductions in both eumelanin (EM) and pheomelanin (PM) rather than changes in the EM-to-PM ratio observed in oculocutaneous albinism. We conducted an electrophoretic mobility shift assay to investigate the binding capability of the identified variant to DNA sequences containing the E-box motif along with other known variants (p.Arg217del and p.Glu213Asp). Remarkably, all three variants exhibited dominant-negative effects, thus providing novel insights into the pathogenesis of TADS. This study sheds light on the genetic mechanisms underlying TADS and offers a deeper understanding of this rare condition and its associated mutations in MITF., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Heterogeneity among both primed and naive pluripotent stem cell lines remains a major unresolved problem. Here we show that expressing the maternal-specific linker histone H1FOO fused to a destabilizing domain (H1FOO-DD), together with OCT4, SOX2, KLF4, and LMYC, in human somatic cells improves the quality of reprogramming to both primed and naive pluripotency. H1FOO-DD expression was associated with altered chromatin accessibility around pluripotency genes and with suppression of the innate immune response. Notably, H1FOO-DD generates naive induced pluripotent stem cells with lower variation in transcriptome and methylome among clones and a more uniform and superior differentiation potency. Furthermore, we elucidated that upregulation of FKBP1A, driven by these five factors, plays a key role in H1FOO-DD-mediated reprogramming., Competing Interests: Declaration of interests A.K. and K.F. are co-inventors on a patent describing the method for producing human iPSCs from somatic cells using H1FOO-DD. K.F. is a co-founder and CEO of Heartseed Inc., and S.T., S. Yuasa, and K.F. own equity in Heartseed Inc. S.T. is an advisor of Heartseed Inc. J.K. and H.H. are employees and K.K. is a board member of ID Pharma Co., Ltd., without compensation relating to this study. S. Yamanaka is a scientific advisor to iPS Academia Japan without salary., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Quadricuspid aortic valve (QAV) is a rare congenital disease. The clinical characteristics of this disease remain unclear except for those in relatively young patients reported from tertiary referral hospitals. The aim of this study was to determine the clinical features of QAV in a regional population., Methods and Results: We retrospectively investigated 25 340 consecutive patients over middle age (median age, 73 (IQR 65-80) years; range, 45-102 years) who underwent transthoracic echocardiography (TTE) at our institute during the period from April 2008 to December 2023. Eight (0.032%) of the patients (median age, 65 years; range, 47-91 years) were diagnosed with QAV. Six patients suffered from aortic regurgitation (AR), and one patient had mild aortic stenosis at the time of QAV diagnosis. Two patients who had severe AR at referral underwent aortic valve surgery. The severity of AR in the other patients was moderate or less. During a median follow-up period of 27 months (range, 1-171 months), none of the patients other than above two patients had cardiac events. One patient died from a non-cardiac cause at 94 years of age., Conclusions: Patients diagnosed with QAV after middle age, who do not exhibit severe valve insufficiency at the time of diagnosis, may not experience worse clinical outcomes. However, further research is required for a better understanding of the long-term outcomes., (© 2024 The Authors. Echocardiography published by Wiley Periodicals LLC.)

Background: The classical elephant trunk (ET) technique is a very useful surgical procedure; however, haemolysis in the aorta associated with ET has been previously reported. It normally occurs within several years after the surgery, and it is a rare case of rapidly progressing haemolysis 10 or more years after aortic arch replacement with ET., Case Presentation: A 53-year-old man with a history of Stanford type A aortic dissection (DeBakey type Is), who was treated with total arch aortic replacement and aorto-femoral bypass using a prosthetic graft 17 years ago, developed severe progressive haemolytic anaemia. The ET used for the initial surgery was narrowed, and mechanical haemolysis was suspected. We assumed that progressive mechanical haemolysis occurred because of degeneration of the prosthetic graft. Thoracic endovascular aortic repair was performed, and haemolysis and anaemia were mitigated postoperatively., Conclusions: Haemolysis occurred 17 years after the initial surgery with ET. When haemolysis is suspected in a patient with ET, it must be identified as a cause of haemolysis even if 10 years or more have passed since the ET was inserted. To prevent this complication, attention should be paid to an appropriate ET length and diameter to avoid folding of the ET, particularly when the true cavity diameter is small., (© 2023. The Author(s).)

JAV1-associated ubiquitin ligase 1 (JUL1) is a RING-type E3 ubiquitin ligase that catalyzes ubiquitination of JAV1, a jasmonate signaling repressor, in Arabidopsis thaliana in response to herbivore attack. Here we present a new insight into the nature of JUL1 as a multi-targeting enzyme for not only JAV1 but also transcription factors (TFs) screened using in vitro and in vivo protein interaction assays. Reporter assays using protoplasts showed that the JUL1-interacting TFs (JiTFs), including ERF15, bZIP53 and ORA59, were involved in transcriptional activation of jasmonate-responsive PDF1.2 and abscisic acid-responsive GEA6 . Likewise, assays using mutant plants suggested that the 3 JiTFs were indeed responsible for transcriptional regulation of PDF1.2 and/or GEA6 , and ERF15 and ORA59 were substantially responsible for the anti-herbivore trait. In vitro protein ubiqutination assays showed that JUL1 catalyzed ubiqutination of JAV1 but not any of the TFs. This was in accord with the finding that JUL1 abolished JAV1's interference with ERF15 function, according to the reporter assay. Moreover, of great interest is our finding that ERF15 but not bZIP53 or ORA59 serves as a scaffold for the JAV1/JUL1 system, indicating that there is narrow selectivity of the transcriptional reprogramming by the JAV1/JUL1 system.

Naive human induced pluripotent stem cells (iPSCs) can be generated by reprogramming somatic cells with Sendai virus (SeV) vectors. However, only dermal fibroblasts have been successfully reprogrammed this way, and the process requires culture on feeder cells. Moreover, SeV vectors are highly persistent and inhibit subsequent differentiation of iPSCs. Here, we report a modified SeV vector system to generate transgene-free naive human iPSCs with superior differentiation potential. The modified method can be applied not only to fibroblasts but also to other somatic cell types. SeV vectors disappear quickly at early passages, and this approach enables the generation of naive iPSCs in a feeder-free culture. The naive iPSCs generated by this method show better differentiation to trilineage and extra-embryonic trophectoderm than those derived by conventional methods. This method can expand the application of iPSCs to research on early human development and regenerative medicine., Competing Interests: A.K. and J.K. are co-inventors on a patent describing the method for producing naive human iPSCs from somatic cells. J.K. and H.H. are employees and K.K. is a board member of ID Pharma Co., Ltd., without compensation relating to this study. K.T. is on the scientific advisory board of I Peace, Inc., without salary. S.Y. is a scientific advisor to iPS Academia Japan without salary., (© 2022 The Authors.)

The antibiotic alaremycin has a structure that resembles that of 5-aminolevulinic acid (ALA), a universal precursor of porphyrins, and inhibits porphyrin biosynthesis. Genome sequencing of the alaremycin-producing bacterial strain and enzymatic analysis revealed that the first step of alaremcyin biosynthesis is catalysed by the enzyme, AlmA, which exhibits a high degree of similarity to 5-aminolevulinate synthase (ALAS) expressed by animals, protozoa, fungi, and α-proteobacteria. Site-directed mutagenesis of AlmA revealed that the substitution of two amino acids residues around the substrate binding pocket transformed its substrate specificity from that of alaremycin precursor synthesis to ALA synthesis. To estimate the evolutionary trajectory of AlmA and ALAS, we performed an ancestral sequence reconstitution analysis based on a phylogenetic tree of AlmA and ALAS. The reconstructed common ancestral enzyme of AlmA and ALAS exhibited alaremycin precursor synthetic activity, rather than ALA synthetic activity. These results suggest that ALAS evolved from an AlmA-like enzyme. We propose a new evolutionary hypothesis in which a non-essential secondary metabolic enzyme acts as an 'evolutionary seed' to generate an essential primary metabolic enzyme., (© The Author(s) 2022. Published by Oxford University Press on behalf of Society for Molecular Biology and Evolution.)

In this study, we propose a method to reduce noise from speech obtained from a general microphone using the information of a throat microphone. A throat microphone records a sound by detecting the vibration of the skin surface near the throat directly. Therefore, throat microphones are less prone to noise than ordinary microphones. However, as the acoustic characteristics of the throat microphone differ from those of ordinary microphones, its sound quality degrades. To solve this problem, this study aims to improve the speech quality while suppressing the noise of a general microphone by using the information recorded by a throat microphone as reference information to extract the speech signal in general microphones. In this paper, the framework of the proposed method is formulated, and several experiments are conducted to evaluate the noise suppression and speech quality improvement effects of the proposed method.

Background: The natural killer cell cytotoxicity (NKCC) suppressed by nociceptive stimuli, systemic inflammation, and drugs used during cancer surgery may be associated with poor outcomes. We investigated the potential modulation of ketamine on NKCC in vitro and in a clinical setting during cancer surgery. Subjects and Methods. The NK cell line KHYG1 was cultured for the in vitro experiments. The NK cells were treated with 3 and 10  μ M ketamine (the ketamine groups) or without ketamine (the control) for 4, 24, and 48 h. The posttreatment NKCC was measured with a lactate dehydrogenase assay and compared among the treatment groups. For the clinical study, lung cancer patients ( n = 38) and prostate cancer patients ( n = 60) who underwent radical cancer surgeries at a teaching hospital were recruited. The patients received propofol and remifentanil superposed with or without ketamine (ketamine group, n = 47; control group, n = 51). The primary outcome was the difference in NKCC between these groups., Results: In the in vitro experiment, the cytotoxicity of NK cells was similar with or without ketamine at all of the incubation periods. The patients' NKCC was also not significantly different between the patients who received ketamine and those who did not, at the baseline (36.6 ± 16.7% vs. 38.5 ± 15.4%, p = 0.56) and at 24 h (25.6 ± 12.9% vs. 27.7 ± 13.5%, respectively, p = 0.49)., Conclusion: Ketamine does not change NKCC in vitro or in the clinical setting of patients who undergo cancer surgery. This trial is registered with UMIN000021231., Competing Interests: There are no competing interests., (Copyright © 2022 Mirei Kubota et al.)

Previous findings on relationships between inhibition that is a core executive function, and trait rumination have been inconsistent. This inconsistency could be overcome by investigating the association between rumination and the two subcomponents of inhibition: response inhibition and attentional inhibition. This study examined whether and how response inhibition and attentional inhibition were related to rumination as well as worry. University students in Japan (N = 213) conducted the Go/No-Go Task and the Modified Stroop Task. They also completed self-report measures of depression, trait rumination, trait worry, stressors, and aggressive behaviors. Results indicated that response inhibition deficits were positively associated with trait rumination, and this association was mediated by increases in aggressive behaviors and interpersonal stressors. The associations between these variables remained significant even after controlling for depression level. There were no significant direct or indirect associations between attentional inhibition deficits and rumination. These results suggest that response inhibition deficits, among the subcomponents of inhibition, have an indirect positive association with rumination through interpersonal processes. Results also showed nonsignificant differences between rumination and worry in the magnitude of correlation coefficients with the two subcomponents of inhibition. Therefore, it remains unclear whether the positive association with response inhibition is unique to rumination., (© 2021. The Author(s).)

Human pluripotent stem cells have the potential to differentiate into various cell types including skeletal muscles (SkM), and they are applied to regenerative medicine or in vitro modelling for intractable diseases. A simple differentiation method is required for SkM cells to accelerate neuromuscular disease studies. Here, we established a simple method to convert human pluripotent stem cells into SkM cells by using temperature-sensitive Sendai virus (SeV) vector encoding myoblast determination protein 1 (SeV-Myod1), a myogenic master transcription factor. SeV-Myod1 treatment converted human embryonic stem cells (ESCs) into SkM cells, which expressed SkM markers including myosin heavy chain (MHC). We then removed the SeV vector by temporal treatment at a high temperature of 38℃, which also accelerated mesodermal differentiation, and found that SkM cells exhibited fibre-like morphology. Finally, after removal of the residual human ESCs by pluripotent stem cell-targeting delivery of cytotoxic compound, we generated SkM cells with 80% MHC positivity and responsiveness to electrical stimulation. This simple method for myogenic differentiation was applicable to human-induced pluripotent stem cells and will be beneficial for investigations of disease mechanisms and drug discovery in the future., (© 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Overgeneral autobiographical memory (OGM) refers to the tendency toward increased general memory and reduced specific memory recall, observed in various psychiatric disorders. Previous studies have suggested that inhibitory processes involved in resolving competition between competing memories may reduce memory specificity via retrieval-induced forgetting (RIF). However, it remains unclear whether the repeated retrieval of general memories can induce forgetting of specific memories. We adapted the RIF paradigm to address this question across three experiments. Participants first generated specific memories in response to positively and negatively valenced cue words. They then generated and repeatedly retrieved general memories for half of the cue words. Recall for all of the original specific memories was later tested. Experiment 1 showed that the retrieval practice of general memories reduced the recall of associated specific memories, regardless of cue valence. Experiment 2 demonstrated that this forgetting effect was cue independent, occurring even when novel retrieval cues were used on the final test. Experiment 3 suggested that this effect was competition dependent, finding a greater RIF effect following practice of general memories (high competition) than following a cue-color association task (low competition). These results suggest that repeated retrieval of general memories suppressed specific memory representations through RIF. These findings are discussed in relation to hierarchical models of autobiographical memory, mechanisms that maintain overgeneral memory tendencies, and the role of retrieval in shaping autobiographical memory. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Human pathogenic RNA viruses are threats to public health because they are prone to escaping the human immune system through mutations of genomic RNA, thereby causing local outbreaks and global pandemics of emerging or re-emerging viral diseases. While specific therapeutics and vaccines are being developed, a broad-spectrum therapeutic agent for RNA viruses would be beneficial for targeting newly emerging and mutated RNA viruses. In this study, we conducted a screen of repurposed drugs using Sendai virus (an RNA virus of the family Paramyxoviridae), with human-induced pluripotent stem cells (iPSCs) to explore existing drugs that may present anti-RNA viral activity. Selected hit compounds were evaluated for their efficacy against two important human pathogens: Ebola virus (EBOV) using Huh7 cells and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using Vero E6 cells. Selective estrogen receptor modulators (SERMs), including raloxifene, exhibited antiviral activities against EBOV and SARS-CoV-2. Pioglitazone, a PPARγ agonist, also exhibited antiviral activities against SARS-CoV-2, and both raloxifene and pioglitazone presented a synergistic antiviral effect. Finally, we demonstrated that SERMs blocked entry steps of SARS-CoV-2 into host cells. These findings suggest that the identified FDA-approved drugs can modulate host cell susceptibility against RNA viruses., (© 2021 The Authors. FEBS Open Bio published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Young, Sutherland, and McCoy indicated that a Go/No-Go Task (GNG) becomes more difficult as the inter-stimulus intervals (ISIs) becomes shorter. However, is the number of commission errors under extremely short ISIs a useful metric for assessing response inhibition? This study challenges the assumption that a shorter ISI in the GNG enables better assessment of response inhibition. University students (N = 213) completed the GNG, the Conners Continuous Performance Test 3rd Edition (CCPT), and the Modified Stroop Task. The GNG comprised four blocks of 400, 600, 800, and 1000 ms ISIs, whereas the stimulus presentation was fixed at 250 ms. Consistent with Young et al., shorter ISIs in the GNG resulted in more commission errors. In the block with the shortest ISI, participants also failed more frequently in responses in go trials than in the other blocks, which appears to increase in error variance of commission errors. Consistent with this interpretation, the association between the number of commission errors in the block with 400 ms ISI and CCPT performance was weaker than those between the number of commission errors in other blocks and CCPT performance. It is concluded that using the number of commission errors in the condition with extremely short ISIs in the GNG might be inappropriate for assessing response inhibition., (© 2020 The Authors. Scandinavian Journal of Psychology published by Scandinavian Psychological Associations and John Wiley & Sons Ltd.)

Background: Current guidelines recommend that pulmonary vein (PV) velocity should be recorded by using the right upper pulmonary vein (RUPV) during transthoracic echocardiography (TTE) evaluation of left ventricular diastolic function. However, it is uncertain whether the PV displayed during TTE is truly measuring the upper PV. This study aimed to identify the actual site of each PV that is usually detected during TTE., Methods: We retrospectively studied 105 patients who underwent cardiac computed tomography (CT) and TTE, reconstructed images three-dimensionally, and measured the angles between each PV and the left ventricle (LV) that would correspond to the Doppler incident angle of the apical four-chamber view on TTE. We also performed TTE during catheter ablation to confirm the exact site of the PV., Results: Apical four-chamber views on TTE revealed that one certain PV was detectable on the right side of the vertebra. CT scans revealed that the median angle of the axes between the LV and right lower pulmonary vein (RLPV) was smaller than that of RUPV {32.1˚ [interquartile range (IQR): 21.7˚-42.1˚] vs. 62.5˚ (IQR: 51.6˚-70.6˚), P < .001}. During catheter ablation for treatment of atrial fibrillation, in the most well-displayed PV on TTE, we detected the ablation catheter placed in the RLPV., Conclusions: The most well-displayed PV in an apical four-chamber view by TTE was not the RUPV but the RLPV which showed the smallest angle of incidence toward the LV apex. The RLPV is suitable for evaluation of PV velocity to assess LV diastolic function., (© 2021 Wiley Periodicals LLC.)

Human motor neurons are important materials for the research of the pathogenesis and drug discovery of motor neuron diseases. Various methods to generate motor neurons (MNs) from embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs) by the addition of signaling molecules have been reported. However, they require multiple steps and complicated processes. Here we describe an approach for generating human MNs from ESCs/iPSCs using a single Sendai virus vector encoding three transcription factors-Lhx3, Ngn2, and Isl1. This approach enabled us to generate MNs in one step, adding Sendai virus vector in culture medium. This simple method significantly reduces the efforts to generate MNs, and it provides a useful tool for motor neuron disease research., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: It is recommended in current guidelines that the inferior vena cava (IVC) diameter should be measured at 1.0-2.0 cm from the junction with the right atrium. However, right atrial pressure (RAP) is underestimated in some patients who have a small IVC diameter (IVCD) because of a high-echo structure compressing the IVC from the back at that portion. The aim of this study was to identify the structure behind the IVC and to evaluate its influence on RAP., Methods: We retrospectively studied 116 patients who underwent right-heart catheterization. We reviewed computed tomography (CT) scans and analyzed the relation between RAP and IVCD measured by echocardiography not only in the way recommended in the guidelines, but also in a way that avoided the structure., Results: CT scans revealed that the diaphragm, not the vertebra, was located just behind the IVC in most patients. Sixteen patients (13.8%) had RAP ≥ 10 mmHg. In those patients, when IVCs were measured in a way that avoided the diaphragm, IVCDmax diameter was larger and IVC collapsibility index (IVCCI) tended to be smaller than those when IVCDs were measured according to the guideline methods. The sensitivity of IVCD to predict RAP ≥ 10 mmHg (IVCDmax > 21 mm, IVCCI < 50%) increased from 31.3% to 68.8% with our method., Conclusions: The high-echo structure pushing the IVC from the back is the diaphragm in most patients. It might be better to measure IVCD using a method that avoids the diaphragm to accurately estimate RAP.

Background and Objectives: Traumatic or negative stimuli facilitate item memory but impair associated context memory. Vulnerability factors related to the maintenance and onset of posttraumatic stress disorder (PTSD), such as anxiety sensitivity, looming cognitive style, dissociation, and low working memory capacity, have been identified. However, little is known about how these factors influence negative item or associative memory., Methods: Eighty-five undergraduates completed self-report questionnaires, the operation span with words (OSPAN) task, and an item and associative memory task in which incidental encoding of negative and neutral items and context information (Day 1) was followed by an unexpected retrieval test (Day 2)., Results: The results showed greater Hit rates and False Alarms on item memory and lower accuracy on context memory with negative stimuli than with neutral stimuli, replicating previous findings. Low working memory capacity and high dissociation were correlated with low negative item memory. Under low working memory capacity, high levels of anxiety sensitivity and looming cognitive style predicted high dissociation levels and low accuracy for negative item memory. There were no individual differences involving associative memory., Limitations: A nonclinical sample was used, which limits the generalizability of our results to clinical samples., Conclusions: Dissociation could be a coping strategy for reducing negative item memory. Anxiety sensitivity and looming cognitive style facilitate dissociative coping; however, working memory capacity buffers against these vulnerabilities., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Post-surgery immunomodulation, including reduced natural killer cell cytotoxicity (NKCC), is recognized as a predictor of poor outcomes in patients following cancer surgery. The present study investigated direct immunomodulation via ketamine as an anesthetic adjuvant in patients undergoing cancer surgery. The present non-double blinded randomized trial was conducted at Hirosaki University Hospital with 60 patients who underwent minimally invasive robotic radical prostatectomy to minimize the immunomodulation due to surgical stress. Patients received total intravenous anesthesia using propofol and remifentanil, with ketamine as an anesthetic adjuvant (the ketamine group) or without ketamine (the control group). The primary outcome was the difference in NKCC between these groups. The secondary outcomes were the differences in neutrophil-lymphocyte ratio (NLR) and levels of interleukin (IL)-6, IL-1β, IL-10 and tumor necrosis factor-alpha (TNF-α). NKCC and cytokines were measured before anesthesia (baseline) and at 6 and 24 h after baseline measurements were recorded. NLR was determined on the last day before admission and at 48 h post-baseline. NKCC values were similar in each group at 6 h when compared with respective baseline results (baseline control, 36.9±15.6%; 6 h control, 38.3±13.4%; baseline ketamine, 36.1±17.0%; 6 h ketamine, 36.6±16.4%) but significantly decreased at 24 h (control, 26.5±12.2%; ketamine, 24.1±12.7%; P<0.001). There were no significant differences in NKCC between the ketamine and control groups (P=0.64) at any of the assessed time points. NLR, IL-1β, IL-10 and TNF-α levels were also similar between two groups. In contrast, IL-6 at 24 h was significantly lower in the ketamine group compared with the control group (mean difference, -7.3 pg ml -1 ; 95% confidence interval, -14.4 to -0.2; P=0.04). Ketamine as an anesthetic adjuvant did not provide direct immunomodulation in patients who underwent cancer surgery., (Copyright © 2020, Spandidos Publications.)

Background: In the field of palliative care, morphine is known to be effective for alleviating dyspnea in cancer patients. However, little is known regarding the safety and efficacy of morphine therapy for refractory dyspnea as palliative care in advanced heart failure (HF) patients., Methods: We retrospectively reviewed consecutive advanced HF patients who were referred to the Palliative Care Team at our institution and administered morphine for refractory dyspnea during hospitalization between September 2013 and December 2018. We investigated the details of morphine usage, vital signs, an 11-point quantitative symptom scale, and adverse events at baseline, 24 h, and 72 h after the start of treatment., Results: Morphine was administered for refractory dyspnea in 43 advanced HF patients [mean age: 73.5 years, male: 28 (65%), New York Heart Association functional class IV: 43 (100%), median left ventricular ejection fraction: 25%, median B-type natriuretic peptide level: 927 pg/ml, concurrent intravenous inotrope: 33 (77%)]. Median initial dose of morphine was 5 mg/day in both oral and intravenous administration and median duration of administration was 5 days. Significant decreases in an 11-point quantitative symptom scale [7 (5, 9) vs. 2 (1, 6); p <  0.01, (data available in 8 patients)] and respiratory rate (22.2 ± 6.1 vs. 19.7 ± 5.2 breaths per minute; p < 0.01) were observed 24 h after the start of morphine administration. Meanwhile, oxygen saturation, blood pressure, and heart rate were not significantly altered after treatment (NS). Common adverse events were delirium (18%) and constipation (8%); however, no lethal adverse event definitely related to morphine therapy occurred during treatment., Conclusions: This single-center retrospective study revealed the clinical practice of morphine therapy and suggested that morphine therapy might be feasible for refractory dyspnea as palliative care in advanced HF patients., (Copyright © 2020 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Background: Tracheo-innominate artery fistula (TIF) is a life-threatening complication of tracheostomy. We describe perioperative management for innominate artery transection in a case with TIF., Case Presentation: A 4-year-old Japanese female with Marshal-Smith syndrome presented for management of TIF. She underwent tracheostomy at the age of 3 months and an uncuffed tracheostomy tube was inserted. One month before admission to our hospital, intermittent tracheal bleeding, suggesting TIF, occurred. Although we considered to change to a cuffed endotracheal tube, craniofacial abnormality suggested difficult oral intubation, and there was a possibility of rebleeding. Finally, innominate artery transection was performed under total intravenous anesthesia without changing the tracheostomy tube. Surgery completed uneventfully and she received mechanical ventilation under sedation for a day, followed by weaning without complications., Conclusions: A cuffed tracheostomy tube should have been inserted before surgery for effective hemostasis against sudden bleeding from TIF even though conversion to oral intubation was difficult.

We examined the predictability of preoperative cerebral and renal rSO 2 values for outcomes in pediatric patients undergoing cardiac surgery under cardiopulmonary bypass (CPB). Patients who underwent pediatric cardiac surgery under CPB between September 2015 and September 2017 were enrolled in this study. Patients monitored with both cerebral and renal rSO 2 at the beginning of surgery were included. The primary outcome was the prediction of outcomes after pediatric cardiac surgery. Outcome was defined as any of: (1) death within 30 days after surgery, or the need for (2) renal replacement therapy or (3) extracorporeal membrane oxygenation, (4) shorten mechanical ventilator-free day,(5) shorten ICU-free survival day. We included 59 patients: cyanotic n = 31; non-cyanotic n = 28. Among all patients, 15 (25%) had poor outcomes, including three deaths. The cerebral and renal rSO 2 values were significantly lower in the cyanotic patients with poor outcomes compared to those without poor outcomes (cerebral: 59 ± 11 vs. 50 ± 5, p = 0.021; renal: 59 ± 15 vs. 51 ± 14, p = 0.015) but only the renal rSO 2 value was significantly lower in the non-cyanotic patients (77 ± 10 vs. 61 ± 14, p = 0.011). The cut-off value (51%) of cerebral rSO 2 were associated with risk of mechanical ventilator-free day and ICU-free survival day [ORs of 22.8 (95% CI 2.21-235.0, p = 0.0087) and 15.8 (95% CI 1.53-164.0, p = 0.0204), respectively] in the cyanotic patients. The cut-off value (66%) of cerebral rSO 2 value was associated with risk of mechanical ventilator-free day [OR of 11.3 (95% CI 1.05-25.3, p = 0.0456)] and the cut-off value (66%) of renal rSO 2 value was associated with risk of ICU-free survival day [ORs of 33.0 (95% CI 2.25-484.0, p = 0.0107)] in the noncyanotic patients. The preoperative low rSO 2 values were associated with outcomes including 30-day mortality and might be reflective of the severity of cardiopulmonary function. Further studies are needed to confirm our results.

Episodic future simulation is supported by both the retrieval and recombination of episodic details. It remains unclear, however, how individuals retrieve episodic details from memory to construct possible future scenarios; for this people must use details related to the planned future events appropriately. A potentially relevant cognitive process is the spontaneous activation of intention observed in prospective memory (i.e., the intention superiority effect). Previous studies on prospective memory have shown that the approximation of retrieval opportunities for future intentions activate related information, suggesting that the intention superiority effect is context-sensitive. We hypothesized that the same cognitive process underlies future simulation-that is, details related to future events should spontaneously become activated at the appropriate moment of future simulation to make that simulation plausible. In Experiment 1, participants took part in future experiments and formed intentions to perform particular actions for the next experiments. Subsequently, they imagined events that could occur up until they arrived at the experimental room on the day of the next experiment. During this exercise, they did not imagine engaging in the required experimental task. We measured the conceptual activation of intention-related information via a recognition task using intended action words as targets. The results showed the intention superiority effect-concepts related to participants' future intentions became active when envisioning future events approaching the next experiment. In Experiments 2 and 3, we ensured that the intention superiority effect in future simulation was context-sensitive by adding a control condition that required participants to imagine events other than the approaching future experiments. These results indicated that concepts related to the intended actions were spontaneously activated when imagined future events became both temporally and spatially close to the future simulation. Our finding suggests that spontaneous activation of details approaching the context of a future simulation helps in constructing plausible future scenarios.

Background: FOLFIRINOX (FX) has been reported as an effective treatment for unresectable advanced pancreatic cancer. However, FX is associated with a high incidence of adverse events (AEs). A previous phase II study in Japan showed high incidences of hematological AEs, including febrile neutropenia (22.2%). A modified FX regimen (mFX) may decrease the rates of AEs and be more effective than FX by improving the treatment compliance., Aims: To assess the safety and efficacy of first-line mFX for unresectable advanced pancreatic cancer., Patients and Methods: This was as a multicenter prospective phase II study in chemotherapy-naïve Japanese patients with pathologically confirmed unresectable advanced pancreatic adenocarcinoma or adenosquamous carcinoma. Treatment with mFX (85 mg/m2 oxaliplatin, 150 mg/m2 irinotecan, and 200 mg/m2 l-leucovorin, followed by 46-h continuous infusion of 2400 mg/m2 5-fluorouracil) was administered every 2 weeks. The primary endpoint was the response rate. The secondary endpoints were overall survival, progression-free survival, and safety., Results: Thirty-one patients (18 men; median age, 64 years) were enrolled. A median of 13 treatment cycles were administered during a median follow-up period of 14.2 months. The response rate, median overall survival, and median progression-free survival were 38.7%, 14.9 months, and 7.0 months, respectively. Grade 3 or 4 AEs included neutropenia (83.9%), febrile neutropenia (16.1%), peripheral sensory neuropathy (9.7%), thrombocytopenia (6.5%), diarrhea (6.5%), anorexia (6.5%), and vomiting (3.2%)., Conclusion: Compared to FX, mFX may result in fewer Grade 3 or 4 non-hematological AEs, with a comparable response rate. However, further efforts might be required to reduce hematological AEs., Competing Interests: CONFLICTS OF INTEREST Kensaku Yoshida, Takuji Iwashita, Shinya Uemura, Akinori Maruta, Mitsuru Okuno, Nobuhiro Ando, Keisuke Iwata, Jyunji Kawaguchi, Tsuyoshi Mukai, Masahito Shimizu have nothing to declare.

An approach to finger motion capture that places fewer restrictions on the usage environment and actions of the user is an important research topic in biomechanics and human-computer interaction. We proposed a system that electrically detects finger motion from the associated deformation of the wrist and estimates the finger joint angles using multiple regression models. A wrist-mounted sensing device with 16 electrodes detects deformation of the wrist from changes in electrical contact resistance at the skin. In this study, we experimentally investigated the accuracy of finger joint angle estimation, the adequacy of two multiple regression models, and the resolution of the estimation of total finger joint angles. In experiments, both the finger joint angles and the system output voltage were recorded as subjects performed flexion/extension of the fingers. These data were used for calibration using the least-squares method. The system was found to be capable of estimating the total finger joint angle with a root-mean-square error of 29-34 degrees. A multiple regression model with a second-order polynomial basis function was shown to be suitable for the estimation of all total finger joint angles, but not those of the thumb.

Humans can pronounce a nonword (e.g., rint). Some researchers have interpreted this behavior as requiring a sequential mechanism by which a grapheme-phoneme correspondence rule is applied to each grapheme in turn. However, several parallel-distributed processing (PDP) models in English have simulated human nonword reading accuracy without a sequential mechanism. Interestingly, the Japanese psycholinguistic literature went partly in the same direction, but it has since concluded that a sequential parsing mechanism is required to reproduce human nonword reading accuracy. In this study, by manipulating the list composition (i.e., pure word/nonword list vs. mixed list), we demonstrated that past psycholinguistic studies in Japanese have overestimated human nonword reading accuracy. When the more fairly reevaluated human performance was targeted, a newly implemented Japanese PDP model simulated the target accuracy as well as the error patterns. These findings suggest that PDP models are a more parsimonious way of explaining reading across various languages., (Copyright © 2016 Cognitive Science Society, Inc.)

Recent studies on logical reasoning have suggested that people are intuitively aware of the logical validity of syllogisms or that they intuitively detect conflict between heuristic responses and logical norms via slight changes in their feelings. According to logical intuition studies, logically valid or heuristic logic no-conflict reasoning is fluently processed and induces positive feelings without conscious awareness. One criticism states that such effects of logicality disappear when confounding factors such as the content of syllogisms are controlled. The present study used abstract propositions and tested whether people intuitively detect logical value. Experiment 1 presented four logical propositions (conjunctive, biconditional, conditional, and material implications) regarding a target case and asked the participants to rate the extent to which they liked the statement. Experiment 2 tested the effects of matching bias, as well as intuitive logic, on the reasoners' feelings by manipulating whether the antecedent or consequent (or both) of the conditional was affirmed or negated. The results showed that both logicality and matching bias affected the reasoners' feelings, and people preferred logically true targets over logically false ones for all forms of propositions. These results suggest that people intuitively detect what is true from what is false during abstract reasoning. Additionally, a Bayesian mixed model meta-analysis of conditionals indicated that people's intuitive interpretation of the conditional "if p then q" fits better with the conditional probability, q given p., Competing Interests: The authors have declared that no competing interests exist.

Intrusive thoughts and difficulty in controlling thoughts are common, not only for people with psychological disorders, but also for healthy people. Individual differences in thought control ability may underlie such problems. The Thought Control Ability Questionnaire (TCAQ), which consists of 25 items, was developed by Luciano et al. (2005) in order to measure individual differences in the perceived ability to control unwanted intrusive thoughts. The purpose of the present study was to develop the Japanese version of the TCAQ and evaluate its reliability and validity. We translated the English version of the TCAQ into Japanese. We also conducted confirmatory factor analysis with a one factor solution, similar to the previous study. Based on the analysis, we excluded items whose factor loadings were lower than .30, resulting in 22 items for the Japanese version of the TCAQ. The model exhibited acceptable goodness-of-fit. The Japanese version of the TCAQ also demonstrated good reliability as well as evidence of construct validity. Thus, the development of the Japanese version of the TCAQ was successful.

The standard treatment for advanced pancreatic cancer is chemotherapy, but its clinical outcome remains unsatisfactory. Therefore, the development of novel treatments for this malignancy is urgently required. In the present study, the anticancer effect of arsenite on platelet-derived growth factor (PDGF)-BB-induced migration, cell cycle and apoptosis was investigated in pancreatic cancer cells (AsPC-1 and BxPC-3), and compared with the effect on normal pancreatic epithelial (PE) cells. In the cell migration assay, arsenite clearly inhibited PDGF-BB-induced cell migration in AsPC-1 cells, but not in BxPC-3 or PE cells. Arsenite also caused cell apoptosis in AsPC-1 cells, but not in BxPC-3 or PE cells. In AsPC-1 cells, the levels of cyclin D1 and phosphorylated retinoblastoma protein decreased following treatment with arsenite, but this was not observed in BxPC-3 cells. To further examine the differences between these two cell lines, the effect of arsenite on upstream p44/p42 mitogen-activated protein kinase (MAPK) and Akt was investigated. PDGF-BB caused phosphorylation of p44/p42 MAPK and Akt in both cell lines. Pretreatment with arsenite significantly suppressed PDGF-BB-induced phosphorylation of Akt, but not of p44/p42 MAPK in AsPC-1 cells. By contrast, arsenite did not affect these molecules in BxPC-3 cells. Since the inhibition of the Akt signaling pathway markedly reduced PDGF-BB-induced migration in AsPC-1 cells, the present results strongly suggest that arsenite inhibits PDGF-BB-induced migration by suppressing the Akt signaling pathway in AsPC-1 cells. Therefore, arsenite may be a useful tool for the treatment of patients with certain types of pancreatic cancer, without causing adverse effects on normal pancreatic cells.

Background and Aim: The precise role of phosphorylated heat shock protein (HSP) 27 (p-HSP27) in pancreatic cancer remains to be elucidated. The aim of this study was to investigate whether the expression of p-HSP27 predicts the prognosis of patients with pancreatic cancer., Methods: We retrospectively assessed 49 biopsied pancreatic cancer tissue samples that were obtained prior to the treatment with gemcitabine. The correlations between p-HSP27 and the clinicopathological characteristics were analyzed., Results: p-HSP27 was not correlated with the response to chemotherapy or histological type. However, the median survival time was significantly longer in the patients with high p-HSP27 (275 days, n = 18) than those with low p-HSP27 (205 days, n = 31) (P = 0.0158). A multivariate Cox proportional hazards regression analysis revealed that low p-HSP27 predicted a worse prognosis., Conclusions: Higher p-HSP27 expression before chemotherapy was correlated with better survival, indicating that p-HSP27 expression could be used to predict the prognosis of pancreatic cancer.

A bad reputation can persistently affect judgments of an individual even when it turns out to be invalid and ought to be disregarded. Such indelible distrust may reflect that the negative evaluation elicited by a bad reputation transfers to a person. Consequently, the person him/herself may come to activate this negative evaluation irrespective of the accuracy of the reputation. If this theoretical model is correct, an evaluation-related brain region will be activated when witnessing a person whose bad reputation one has learned about, regardless of whether the reputation is deemed valid or not. Here, we tested this neural hypothesis with functional magnetic resonance imaging (fMRI). Participants memorized faces paired with either a good or a bad reputation. Next, they viewed the faces alone and inferred whether each person was likely to cooperate, first while retrieving the reputations, and then while trying to disregard them as false. A region of the left ventrolateral prefrontal cortex (vlPFC), which may be involved in negative evaluation, was activated by faces previously paired with bad reputations, irrespective of whether participants attempted to retrieve or disregard these reputations. Furthermore, participants showing greater activity of the left ventrolateral prefrontal region in response to the faces with bad reputations were more likely to infer that these individuals would not cooperate. Thus, once associated with a bad reputation, a person may elicit evaluation-related brain responses on their own, thereby evoking distrust independently of their reputation.

The cognitive function to project oneself into the specific past or future is labeled mental time travel (MTT). MTT to the past is considered "episodic memory" and the future is termed "episodic future thinking". Remembering the past and imaging the future during MTT both draw on information stored in episodic memory: a process that enables integration of episodic information into a coherent event representation. Recent studies suggested that episodic information in past/future event representations varies with temporal distance from the present to the event. However, it is unclear whether the influence on temporal distance is actually caused by the function of episodic memory retrieval. The present study investigated the relationship between episodic memory and temporal concepts with a lexical decision task. The results indicate that remembering the past activated temporal concepts of the near future more than that of the far future. This finding suggests that the rich information derived from episodic memory modulates the subjective sense of time in episodic future thinking.

Verbal overshadowing refers to a phenomenon whereby verbalization of non-verbal stimuli (e.g., facial features) during the maintenance phase (after the target information is no longer available from the sensory inputs) impairs subsequent non-verbal recognition accuracy. Two primary mechanisms have been proposed for verbal overshadowing, namely the recoding interference hypothesis, and the transfer-inappropriate processing shift. The former assumes that verbalization renders non-verbal representations less accurate. In contrast, the latter assumes that verbalization shifts processing operations to a verbal mode and increases the chance of failing to return to non-verbal, face-specific processing operations (i.e., intact, yet inaccessible non-verbal representations). To date, certain psychological phenomena have been advocated as inconsistent with the recoding-interference hypothesis. These include a decline in non-verbal memory performance following verbalization of non-target faces, and occasional failures to detect a significant correlation between the accuracy of verbal descriptions and the non-verbal memory performance. Contrary to these arguments against the recoding interference hypothesis, however, the present computational model instantiated core processing principles of the recoding interference hypothesis to simulate face recognition, and nonetheless successfully reproduced these behavioral phenomena, as well as the standard verbal overshadowing. These results demonstrate the plausibility of the recoding interference hypothesis to account for verbal overshadowing, and suggest there is no need to implement separable mechanisms (e.g., operation-specific representations, different processing principles, etc.). In addition, detailed inspections of the internal processing of the model clarified how verbalization rendered internal representations less accurate and how such representations led to reduced recognition accuracy, thereby offering a computationally grounded explanation. Finally, the model also provided an explanation as to why some studies have failed to report verbal overshadowing. Thus, the present study suggests it is not constructive to discuss whether verbal overshadowing exists or not in an all-or-none manner, and instead suggests a better experimental paradigm to further explore this phenomenon.

Purpose: The purpose of this study was to investigate the latency and amplitude of trigeminal somatosensory evoked potentials to clarify how nerve function on the contralateral side is affected after cervical sympathetic block (CSB)., Methods: Subjects comprised 16 volunteers. For CSB, the tip of a needle was contacted with the transverse process of the sixth cervical vertebra on the right side, and lidocaine was injected. Trigeminal somatosensory evoked potentials were recorded bilaterally from C5/C6 scalp positions. Pupil diameters were also measured. Electrical stimulations were applied to the left-side lower lip, and trigeminal somatosensory evoked potentials waveforms derived from both sides of the scalp were recorded. Then, electrical stimulations were applied to the right-side of the lower lip, and recording was again performed. Recordings were performed at 5, 15, and 30 minutes after CSB., Results: On the CSB side, pupil diameter decreased at 5 and 15 minutes after CSB. Trigeminal somatosensory evoked potentials at contralateral stimulation showed a prolongation of the latency in both P20 and N25 components on bilateral recording sites 5 and 15 minutes after CSB. Trigeminal somatosensory evoked potentials' amplitude at contralateral stimulation was smaller than at ipsilateral stimulation 5 minutes after CSB., Conclusions: Cervical sympathetic block prolongs the latency and reduces the amplitude of trigeminal somatosensory evoked potentials on the contralateral side.

Hand motion capture is an important yet challenging topic for biomechanics and human computer interaction. We proposed a novel electrical sensing technology for capturing the finger angles from the variation of the wrist shape. The proposed device detects the signal related to the wrist-electrode contact resistances, which change according to the variation of the wrist shape accompanying finger movements. The developed sensing device consists of a wrist band, sixteen electrodes and a sensing circuit of contact resistances. We investigated the relationships between the finger angles and the system outputs by using a glove-type joint angle sensor. As a result, we confirmed high correlations of the system outputs with the finger angles for several electrodes. Therefore, we conclude that the proposed system can be used for the estimation of the finger joint angles.

To clarify the relationship between visual long-term memory (VLTM) and online visual processing, we investigated whether and how VLTM involuntarily affects the performance of a one-shot change detection task using images consisting of six meaningless geometric objects. In the study phase, participants observed pre-change (Experiment 1), post-change (Experiment 2), or both pre- and post-change (Experiment 3) images appearing in the subsequent change detection phase. In the change detection phase, one object always changed between pre- and post-change images and participants reported which object was changed. Results showed that VLTM of pre-change images enhanced the performance of change detection, while that of post-change images decreased accuracy. Prior exposure to both pre- and post-change images did not influence performance. These results indicate that pre-change information plays an important role in change detection, and that information in VLTM related to the current task does not always have a positive effect on performance., (Copyright © 2014 Elsevier Inc. All rights reserved.)

In the current study, we examine the effect of physical coldness on personal moral dilemma judgment. Previous studies have indicated that utilitarian moral judgment-sacrificing a few people to achieve the greater good for others-was facilitated when: (1) participants suppressed an initial emotional response and deliberately thought about the utility of outcomes; (2) participants had a high-level construal mindset and focused on abstract goals (e.g., save many); or (3) there was a decreasing emotional response to sacrificing a few. In two experiments, we exposed participants to extreme cold or typical room temperature and then asked them to make personal moral dilemma judgments. The results of Experiment 1 indicated that coldness prompted utilitarian judgment, but the effect of coldness was independent from deliberate thought or abstract high-level construal mindset. As Experiment 2 revealed, coldness facilitated utilitarian judgment via reduced empathic feelings. Therefore, physical coldness did not affect the "cool-headed" deliberate process or the abstract high-level construal mindset. Rather, coldness biased people toward being "cold-hearted," reduced empathetic concern, and facilitated utilitarian moral judgments.