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Background: Oral frailty is a concept that encompasses various aspects of impaired oral function in elderly people, leading to reduced food intake and less dietary diversity, which can result in sarcopenia and physical frailty. However, there have been no studies on the relationship between oral frailty and malnutrition, sarcopenia, and physical frailty in patients on hemodialysis (HD). Methods: This prospective observational cohort study assessed the oral status of patients on HD. The patients were divided into an oral frailty group and non-oral frailty group using the Oral Frailty Index-8. Malnutrition was assessed using the Geriatric Nutritional Risk Index (GNRI), the Nutritional Risk Index for Japanese Hemodialysis Patients (NRI-JH), and the Short-Form Mini-Nutritional Assessment (MNA-SF). Sarcopenia was assessed using the Asian Working Group for Sarcopenia 2019's criteria. Physical frailty was assessed using the Japanese version of the Cardiovascular Health Study criteria. One year later, the changes in nutritional status, sarcopenia, and physical frailty risk categories were compared between the oral frailty and non-oral frailty groups. Results: The study enrolled 201 patients (non-oral frailty group, 123; oral frailty group, 78). After 1 year, the oral frailty group had a significantly higher proportion of patients with worsening nutrition status (GNRI, p = 0.0011; NRI-JH, p = 0.0019; MNA-SF, p < 0.001) and sarcopenia (p = 0.0024). There was no significant between-group difference in the proportion of patients in a worse risk category for physical frailty after 1 year. Conclusions: Oral frailty predicts future malnutrition and the progression of sarcopenia in HD patients. In particular, our results strongly suggested that oral frailty was a strong determinant of worsening malnutrition and sarcopenia in HD patients aged ≥65 years. [ABSTRACT FROM AUTHOR]

An equatorial plasma bubble (EPB) is characterized by ionospheric irregularities which disturb radio waves by causing phase and amplitude scintillations or even signal loss. It is becoming increasingly important in space weather to assure the reliability of radio systems in both space and on the ground. This paper presents a newly established GNSS ionospheric observation network (GION) around the north equatorial ionization anomaly (EIA) crest in south China, which has a longitudinal coverage of ∼30° from 94°E to 124°E. The measurement with signals from geostationary earth orbit (GEO) satellites of the BeiDou navigation satellite system (BDS) is capable of separating the temporal and spatial variations of the ionosphere. A temporal fluctuation of TEC (TFT) parameter is proposed to characterize EPBs. The longitude of the EPBs' generation can be located with TFT variations in the time–longitude dimension. It is found that the post-sunset EPBs have a high degree of longitudinal variability. They generally show a quasiperiodic feature, indicating their association with atmospheric gravity wave activities. Wave-like structures with different scale sizes can co-exist in the same night. [ABSTRACT FROM AUTHOR]

Vaccines against coronavirus disease 2019 (COVID-19) have been distributed in most countries for the prevention of onset and aggravation of COVID-19. Recently, there have been increasing numbers of reports on new-onset autoimmune and autoinflammatory diseases following COVID-19 vaccination, however, only little information is available on the long-term safety of these vaccines. Here, we experienced three cases of new-onset rheumatic diseases following COVID-19 vaccination, one case each of rheumatoid arthritis (RA), anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and systemic lupus erythematosus (SLE). The symptom onset ranged from one day to a few days following vaccination. The patients of AAV and SLE were treated successfully with glucocorticoid therapy, and the patient of RA died due to COVID-19. In the literature review of new-onset rheumatic diseases following COVID-19 vaccination, which including seven cases of RA, 37 cases of AAV and 18 cases of SLE, the mean time from vaccination to onset was approximately 11 to 12 days. Most cases improved with glucocorticoid, immunosuppressive drugs and biologic agents. Although such adverse effects are rare, and vaccines are useful in prevent onset and severity of infections, continued accumulation of similar cases is important in terms of examining the long-term safety and understanding pathogenic mechanism of rheumatic diseases. [ABSTRACT FROM AUTHOR]

Background/Objectives: Chronic kidney disease (CKD) and anemia are independent prognostic factors for heart failure. In recent years, hypoxia-inducible factor-prolyl hydroxylase (HIF-PH) inhibitors have become available for the treatment of renal anemia. This prospective randomized controlled study aimed to investigate the effects of switching from a continuous erythropoietin receptor activator (CERA) to one of four HIF-PH inhibitors in patients with chronic heart failure and renal anemia. Methods: Forty patients were randomized by the envelop method to receive treatment with roxadustat, daprodustat, vadadustat, or molidustat. The primary endpoint was the change in the hemoglobin (Hb) level. Secondary endpoints included changes in erythropoietin, changes in free T3, free T4, and thyroid-stimulating hormone (TSH), adverse effects, and drug dose increases and decreases. This study was preregistered in the University Hospital Medical Information Network Clinical Trials Registry (study ID: UMIN000041651). Results: We found no statistically significant difference between Hb levels with HIF-PH inhibitors and CERA, but at month 6, the Hb level was significantly higher with roxadustat than with vadadustat and daprodustat. Erythropoietin decreased significantly after switching to HIF-PH inhibitors. HIF-PH inhibitors had various significant effects on free T3, free T4, and TSH. No adverse events occurred. The doses of some drugs had to be increased or decreased. Conclusions: In patients with heart failure and renal anemia receiving CERA, Hb, NT-ProBNP, and renal function were similar after switching from CERA to HIF-PH inhibitors. The individual HIF-PH inhibitors appear to have different effects on anemia and thyroid function. However, because this was a single-center study with a limited sample size, the efficacy and potential limitations of HIF-PH inhibitors need to be further clarified. [ABSTRACT FROM AUTHOR]

Simple Summary: Predicting the isocitrate dehydrogenase (IDH) mutation status is difficult in preoperative non-enhanced astrocytic tumors. We aimed to differentiate IDH status using preoperative MRI and PET. We found that patients with IDH-mutant (mut) astrocytomas were significantly younger than those with IDH-wildtype (wt) glioblastomas. The tumor location, fractional anisotropy, and mean diffusivity on MRI were significantly related to the IDH mutation status. PET showed significantly higher uptakes for 11C-methionine, 11C-choline, and 18F-fluorodeoxyglucose in IDH-wt than in IDH-mut tumors. Together, these findings reflect the higher malignancy of IDH-wt than of IDH-mut tumors. Composite diagnosis using age, MRI, and PET findings resulted in high accuracy for predicting IDH status. Thus, approaches based on biological tumor behavior in early-stage gliomas are helpful for guiding preoperative treatment decisions. We aimed to differentiate the isocitrate dehydrogenase (IDH) status among non-enhanced astrocytic tumors using preoperative MRI and PET. We analyzed 82 patients with non-contrast-enhanced, diffuse, supratentorial astrocytic tumors (IDH mutant [IDH-mut], 55 patients; IDH-wildtype [IDH-wt], 27 patients) who underwent MRI and PET between May 2012 and December 2022. We calculated the fractional anisotropy (FA) and mean diffusivity (MD) values using diffusion tensor imaging. We evaluated the tumor/normal brain uptake (T/N) ratios using 11C-methionine, 11C-choline, and 18F-fluorodeoxyglucose PET; extracted the parameters with significant differences in distinguishing the IDH status; and verified their diagnostic accuracy. Patients with astrocytomas were significantly younger than those with glioblastomas. The following MRI findings were significant predictors of IDH-wt instead of IDH-mut: thalamus invasion, contralateral cerebral hemisphere invasion, location adjacent to the ventricular walls, higher FA value, and lower MD value. The T/N ratio for all tracers was significantly higher for IDH-wt than for IDH-mut. In a composite diagnosis based on nine parameters, including age, 84.4% of cases with 0–4 points were of IDH-mut; conversely, 100% of cases with 6–9 points were of IDH-wt. Composite diagnosis using all parameters, including MRI and PET findings with significant differences, may help guide treatment decisions for early-stage gliomas. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to evaluate the effectiveness of the Intervention program of Mindfulness and Compassion against COVID-19 (IMACOCO), an online mindfulness-based intervention (MBI), in enhancing mindfulness, mental health, well-being, and productivity among working individuals during the COVID-19 pandemic. Additionally, the study examined the program's efficacy in individuals directly impacted by the pandemic through a randomized controlled trial and pre-post program comparisons. Method: Three hundred working adults, including office workers, educators, and medical welfare workers, were randomly allocated to the intervention or waiting control group. An 8-week online MBI program, with pre-, interim (4 weeks), and post-program (8 weeks) evaluations, was conducted via the Internet; standardized questionnaires were used to assess mindfulness, psychological distress, life satisfaction, and productivity. After the initial 8-week program, the waiting control group participated in the same program and evaluation surveys for pre-post comparisons. Results: There were 99 participants in the intervention group and 111 in the control group. Significant increases in mindfulness (FFMQ) and life satisfaction (SWLS) as well as decrease in psychological distress (GHQ-12) were observed primarily in the intervention group (Cohen's d = 0.18–0.52). Furthermore, the pre-post comparisons with 168 participants demonstrated significant improvements in productivity (Cohen's d = 0.26), and stratified analysis revealed that participants affected by COVID-19 showed more pronounced benefits in mindfulness and life satisfaction than those who were unaffected. Conclusions: Implementing an online MBI program (IMACOCO) can be a potent strategy to reduce mental stress and enhance overall well-being and resilience, in a disaster-prone world. Preregistration: This study is not preregistered. [ABSTRACT FROM AUTHOR]

Multiple reports have emphasized the significance of protecting cladding from windborne debris or falling cinders during strong winds or volcanic eruptions. Japan has no available building codes or standards for protecting the cladding against the windborne debris or falling cinders. In contrast, certain specifications for cladding performance when impacted by windborne debris, along with associated testing methods, are outlined in American, ISO, and JIS standards. A series of impact tests was conducted on selected specimens, like cladding used for residential projects, to evaluate their impact resistance performance. This study presents the outcomes of the impact performance tests, including their destruction modes, for representative materials of cladding like float glass, Japanese tiled roof, batten-seam roof, and slate-tiled roof. The tests were conducted using an air cannon as the gravel-propulsion device. The impact-resistant speed corresponding to the mass of gravel was clarified for the specimens. [ABSTRACT FROM AUTHOR]

Tumor metastasis is one of the worst prognostic features of cancer. Although metastasis is a major cause of cancer-related deaths, an effective treatment has not yet been established. Here, we explore the antitumor effects of GO-Y030, a curcumin analog, via various mechanisms using a mouse model. GO-Y030 treatment of B16-F10 melanoma cells inhibited TGF-β expression and glycolysis. The invasion assay results showed almost complete invasion inhibition following GO-Y030 treatment. Mouse experiments demonstrated that GO-Y030 administration inhibited lung tumor metastasis without affecting vascular endothelial cells. Consistent with this result, GO-Y030 treatment led to the downregulation of MMP2 and VEGFα, inhibiting tumor invasion and metastasis. The silencing of eIF4B, a downstream molecule of S6, attenuated MMP2 expression. Our study demonstrates the novel efficacy of GO-Y030 in inhibiting tumor metastasis by regulating metastasis-associated gene expression via inhibiting dual access, glycolytic and TGF-β pathways. [ABSTRACT FROM AUTHOR]

When a tornado lofts debris to the height of the radar beam, a signature known as the tornadic debris signature (TDS) can sometimes be observed on radar. The TDS is a useful signature for operational forecasters because it can confirm the presence of a tornado and provide information about the amount of damage occurring. Since real-time estimates of tornadic intensity do not have a high degree of accuracy, past studies have hypothesized that the TDS could also be an indicator of the strength of a tornado. However, few studies have related the tornadic wind field to TDS characteristics because of the difficulty of obtaining accurate, three-dimensional wind data in tornadoes from radar data. With this in mind, the goals of this study are twofold: 1) to investigate the relationships between polarimetric characteristics of TDSs and the three-dimensional tornadic winds, and 2) to define relationships between polarimetric radar variables and debris characteristics. Simulations are performed using a dual-polarization radar simulator called SimRadar; large-eddy simulations (LESs) of tornadoes; and a single-volume, T -matrix-based emulator. Results show that for all simulated debris types increases in horizontal and vertical wind speeds are related to decreases in correlation coefficient and increases in TDS area and height and that, conversely, decreases in horizontal and vertical wind speeds are related to increases in correlation coefficient and decreases in TDS area and height. However, the range of correlation coefficient values varies with debris type, indicating that TDSs that are composed of similar debris types can appear remarkably different on radar in comparison with a TDS with diverse scatterers. Such findings confirm past observational hypotheses and can aid operational forecasters in tornado detection and potentially the categorization of damage severity using radar data. [ABSTRACT FROM AUTHOR]

This research aimed to objectively evaluate the optimal state of desk work (flow state) through physiological measurements and use the data to support workers' mental health and well-being. We suppose that the flow state evaluation in real-time can contribute to a concentrated work environment, improved work efficiency, and stabilize worker's minds. This study reports on the development of the mental task modeled on daily work for the physiological measurement experiment. In the first phase of the research, a field survey was conducted with 55 desk workers to understand the details of their jobs and develop suitable mental tasks. Further, the relationship between daily work content and subjective stress was clarified. In the second phase, based on the results of the field survey, a task inducing the flow state was developed for practical use. Through empirical experiments with 35 participants (22 adults and 13 students), the developed task was evaluated for its usefulness and possible issues by examining the relationships among subjective assessment, task performance, degree of flow state, and individual characteristics. The study results showed that the proposed mental task developed in this study constitutes practical work that can be used for concentrated and goal-directed efforts. The task also demonstrated the property of inducing a flow state. Further, the results suggest that it is necessary to adjust the task difficulty level and implement effective feedback methods to induce the flow state more effectively. [ABSTRACT FROM AUTHOR]

The mechanisms behind reported decreases in plasma insulin and glucagon during hemodialysis (HD) are not clear. Here, we investigated these mechanisms during HD treatment and the characteristics of insulin and glucagon removal when using two super high-flux membranes. In an experimental study, clearance, adsorption rates, and reduction rates of insulin and glucagon were investigated when using cellulose triacetate (CTA) and polysulfone (PS) membranes in a closed circuit using bovine blood. In a clinical study, 20 diabetes patients with end-stage kidney disease who were stable on HD were randomly selected for two HD sessions with two different membranes. At 1 h after the initiation of HD, insulin and glucagon clearance were measured, and the reduction rates were also investigated. In the experimental study, the PS membrane showed significantly higher clearance, adsorption rates, and reduction rates of insulin and glucagon compared with the CTA membrane. Although glucagon was detected in the ultrafiltration fluids in both membranes, insulin was absent in the PS membrane. In the clinical study, both membranes showed significant reductions in plasma insulin and glucagon at each time point. The PS membrane showed significantly higher insulin clearance and reduction rates compared with the CTA membrane. The two membranes showed no significant difference in glucagon clearance, but the glucagon reduction rate was significantly higher with the PS membrane. Our findings show that HD with the two super high-flux membranes used removes significant amounts of glucoregulatory peptide hormones from plasma in patients with diabetes and end-stage kidney disease, potentially affecting their glucose metabolism. [ABSTRACT FROM AUTHOR]

Proinflammatory cytokines play critical roles in the pathogenesis of joint diseases. Using a mass spectrometry–based cloning approach, we identified Semaphorin 4D (Sema4D) as an inflammatory cytokine that directly promoted cartilage destruction. Sema4d-deficient mice showed less cartilage destruction than wild-type mice in a model of rheumatoid arthritis. Sema4D induced a proinflammatory response in mouse articular chondrocytes characterized by the induction of proteolytic enzymes that degrade cartilage, such as matrix metalloproteinases (MMPs) and aggrecanases. The activation of Mmp13 and Mmp3 expression in articular chondrocytes by Sema4D did not depend on RhoA, a GTPase that mediates Sema4D-induced cytoskeletal rearrangements. Instead, it required NF-κB signaling and Ras-MEK-Erk1/2 signaling downstream of the receptors Plexin-B2 and c-Met and depended on the transcription factors IκBζ and C/EBPδ. Genetic and pharmacological blockade of these Sema4D signaling pathways inhibited MMP induction in chondrocytes and cartilage destruction in femoral head organ culture. Our results reveal a mechanism by which Sema4D signaling promotes cartilage destruction. Sema4D as cartilage destroyer: Various classical proinflammatory cytokines contribute to cartilage destruction in joint diseases. Murakami et al. found that Semaphorin 4D (Sema4D) was released by inflamed macrophages and stimulated cartilage begin{bmatrix} degradation in articular chondrocytes and cartilage explants. In a mouse model of inflammatory arthritis, Sema4D was increased in synovial fluid, and loss of Sema4D protected against cartilage degeneration. Sema4D elicited these effects by stimulating the expression of transcripts encoding begin{bmatrix}-degrading enzymes downstream of the receptors Plexin-B2 and c-Met and intracellular signaling pathways distinct from those by which Sema4D regulates cell morphology and motility. These findings identify Sema4D as a proinflammatory cytokine in joints and contribute to a broader understanding of the factors that drive joint degeneration. [ABSTRACT FROM AUTHOR]

Ionospheric irregularities have been studied since ~ 70 years ago. With the development of Global Navigation Satellite system (GNSS), networks of GNSS receivers have been used to obtain the characteristics of the irregularities, including the drift velocity, the structure, and the evolution. In this paper, keograms based on the Crustal Movement Observation Network of China (CMONOC) were used to characterize the irregularities over the area from longitude 85 to 125 °E and latitude 11 to 35 °N in 2014. Keograms were obtained for the rate of TEC index (ROTI) for every 0.5 degree longitude and 30 min universal time pixel. The results showed that the occurrence rate of irregularities in 2014 was high in the equinox months and December, and lowest in June. In equinox months the irregularities often appeared after sunset. In March the irregularities usually had long lifetime of ~ 5–7 h and ~ 5 degrees apparent longitudinal width. The long lifetime usually was accompanied by obvious eastward drift of ~ 100 m/s and large vertical ROTI (vROTI). In September the irregularities had weaker ROTI and shorter lifetime than those in March. The irregularities in the 2 equinox months should be related to the equatorial plasma bubbles (EPBs). In June, they appeared ~ 2–3 h later than those in equinoxes and drifted westward. The summer irregularities had weakest ROTI and their latitude was ~ 30 °N, much higher than those in equinoxes. In December, the irregularities were discrete patches with a longitudinal width of ~ 2 degrees and short lifetime of ~ 2 h. Unlike the equatorial irregularities in equinox months which are part of equatorial plasma bubbles, the solstice irregularities mainly appear to be a local phenomenon. [ABSTRACT FROM AUTHOR]

Oxytocin (OXT) is produced in the hypothalamic nuclei and secreted into systemic circulation from the posterior pituitary gland. In the central nervous system, OXT regulates behaviours including maternal and feeding behaviours. Our aim is to evaluate whether oestrogen regulates hypothalamic OXT dynamics. Herein, we provide the first evidence that OXT dynamics in the hypothalamus vary with sex and that oestrogen may modulate dynamic changes in OXT levels, using OXT-mRFP1 transgenic rats. The fluorescence intensity of OXT-mRFP1 and expression of the OXT and mRFP1 genes in the hypothalamic nuclei is highest during the oestrus stage in female rats and decreased significantly in ovariectomised rats. Oestrogen replacement caused significant increases in fluorescence intensity and gene expression in a dose-related manner. This is also demonstrated in the rats' feeding behaviour and hypothalamic Fos neurons using cholecystokinin-8 and immunohistochemistry. Hypothalamic OXT expression is oestrogen-dependent and can be enhanced centrally by the administration of oestrogen. Following fluorescently tagged oxytocin in hypothalamic nuclei of rats, its regulation by oestrogen and a variation of oxytocin dynamics between sexes is shown. [ABSTRACT FROM AUTHOR]

Oxytocin is involved in pain transmission, although the detailed mechanism is not fully understood. Here, we generate a transgenic rat line that expresses human muscarinic acetylcholine receptors (hM3Dq) and mCherry in oxytocin neurons. We report that clozapine-N-oxide (CNO) treatment of our oxytocin-hM3Dq-mCherry rats exclusively activates oxytocin neurons within the supraoptic and paraventricular nuclei, leading to activation of neurons in the locus coeruleus (LC) and dorsal raphe nucleus (DR), and differential gene expression in GABA-ergic neurons in the L5 spinal dorsal horn. Hyperalgesia, which is robustly exacerbated in experimental pain models, is significantly attenuated after CNO injection. The analgesic effects of CNO are ablated by co-treatment with oxytocin receptor antagonist. Endogenous oxytocin also exerts anti-inflammatory effects via activation of the hypothalamus-pituitary-adrenal axis. Moreover, inhibition of mast cell degranulation is found to be involved in the response. Taken together, our results suggest that oxytocin may exert anti-nociceptive and anti-inflammatory effects via both neuronal and humoral pathways. The analgesic effect of oxytocin appears to be mediated via an oxytocin receptor and endogenous oxytocin contributes to the anti-nociception and anti-inflammatory response. [ABSTRACT FROM AUTHOR]

Arginine vasopressin (AVP) is a hypothalamic neurosecretory hormone well known as an antidiuretic, and recently reported to be involved in pain modulation. The expression kinetics of AVP and its potential involvement in the descending pain modulation system (DPMS) in neuropathic pain (NP) remains unclear. We investigated AVP expression and its effects on mechanical and thermal nociceptive thresholds using a unilateral spinal nerve ligation (SNL) model. All rats with SNL developed NP. Intensities of enhanced green fluorescent protein (eGFP) in the supraoptic and paraventricular nuclei, median eminence, and posterior pituitary were significantly increased at 7 and 14 days post-SNL in AVP-eGFP rats. In situ hybridisation histochemistry revealed significantly increased AVP mRNA expression at 14 days post-SNL compared with the sham control group. The chemogenetic activation of AVP neurones significantly attenuated mechanical and thermal hyperalgesia with elevated plasma AVP concentration. These analgesic effects were suppressed by pre-administration with V1a receptor antagonist. AVP neurones increased the neuronal activity of serotonergic dorsal raphe, noradrenergic locus coeruleus, and inhibitory interneurones in the spinal dorsal horn. These results suggest that the hypothalamo-neurohypophysial system of AVP is upregulated in NP and activated endogenous AVP exerts analgesic effects via the V1a receptors. AVP neurones may activate the DPMS. [ABSTRACT FROM AUTHOR]

Introduction: The implantation of dedifferentiated fat (DFAT) cells has been shown to exert immunosuppressive effects. To develop DFAT cell therapy for antineutrophil cytoplasmic antibody (ANCA) glomerulonephritis, the effects of the implantation of DFAT cells on ANCA glomerulonephritis were investigated in mice. Methods: PKH26-labeled DFAT cells (105) were infused through the posterior orbital venous plexus to investigate delivery of DFAT cells in ICR mice. DFAT cells (105) were also implanted in SCG mice as a model for ANCA glomerulonephritis. Expression of tumor necrosis factor-stimulated gene-6 (TSG-6) mRNA and protein in kidney was evaluated, and the expression of microRNAs associated with TSG-6 in plasma, lung and kidney was analyzed. Expressions of CD44, prostaglandin (PG) E2, interleukin (IL)-10, IL-1β, tumor necrosis factor (TNF)-α mRNAs, C–C motif chemokine ligand 17 (CCL-17) and monocyte chemoattractant protein (MCP)-1 proteins were measured in kidney from SCG mice implanted with DFAT cells. Results: After their intravenous infusion, almost all DFAT cells were trapped in the lung and not delivered into the kidney. Implantation of DFAT cells in SCG mice suppressed glomerular crescent formation, decreased urinary protein excretions and increased expression of TSG-6 mRNA, protein and immunostaining in kidney from these mice. Increased expression of microRNA 23b-3p in plasma, kidney and lung; decreased expression of CD44 mRNA; and increased expression of PGE2 and IL-10 mRNAs were also observed in kidney from these mice. Implantation of DFAT cells also decreased the expression of TNF-α and MCP-1 proteins and increased that of CCL-17 protein in kidney from the SCG mice. Survival rates were higher in SCG mice implanted with DFAT cells than in SCG mice without implantation. Conclusion: Mechanisms underlying the effects of improvement of ANCA glomerulonephritis are associated with immunosuppressive effects by TSG-6 and the transition of M1–M2 macrophages, suggesting that implantation of DFAT cells may become a cell therapy for ANCA glomerulonephritis. [ABSTRACT FROM AUTHOR]

IκBζ is a transcriptional regulator that augments inflammatory responses from the Toll-like receptor or interleukin signaling. These innate immune responses contribute to the progression of nonalcoholic fatty liver disease (NAFLD); however, the role of IκBζ in the pathogenesis of NAFLD remains elusive. We investigated whether IκBζ was involved in the progression of NAFLD in mice. We generated hepatocyte-specific IκBζ-deficient mice (Alb-Cre; Nfkbizfl/fl) by crossing Nfkbizfl/fl mice with Alb-Cre transgenic mice. NAFLD was induced by feeding the mice a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD). CDAHFD-induced IκBζ expression in the liver was observed in Nfkbizfl/fl mice, but not in Alb-Cre; Nfkbizfl/fl mice. Contrary to our initial expectation, IκBζ deletion in hepatocytes accelerated the progression of NAFLD after CDAHFD treatment. Although the increased expression of inflammatory cytokines and apoptosis-related proteins by CDAHFD remained unchanged between Nfkbizfl/fl and Alb-Cre; Nfkbizfl/fl mice, early-stage steatosis of the liver was significantly augmented in Alb-Cre; Nfkbizfl/fl mice. Overexpression of IκBζ in hepatocytes via the adeno-associated virus vector attenuated liver steatosis caused by the CDAHFD in wild-type C57BL/6 mice. This preventive effect of IκBζ overexpression on steatosis was not observed without transcriptional activity. Microarray analysis revealed a correlation between IκBζ expression and the changes of factors related to triglyceride biosynthesis and lipoprotein uptake. Our data suggest that hepatic IκBζ attenuates the progression of NAFLD possibly through the regulation of the factors related to triglyceride metabolism. [ABSTRACT FROM AUTHOR]

Suppressing the elevation in core body temperature is an important factor in preventing heatstroke. However, there is still no non-invasive method to sense core body temperature. This study proposed an algorithm that estimates core body temperature based on electrocardiogram signals. A total of 12 healthy men (mean age ± SD = 39.6 ± 13.4) performed an ergometric exercise load test under two conditions of exercise load in an environmental chamber adjusted to a temperature of 35°C and humidity of 50%. Vital sensing data such as electrocardiograms, core body temperatures, and body surface temperatures were continuously measured, and physical data such as body weight were obtained from participants pre- and post-experiment. According to basic physiological knowledge, heart rate and body temperature are closely related. We analyzed the relationship between core body temperature and several indexes obtained from electrocardiograms and found that the amount of change in core body temperature had a strong relationship with analyzed data from electrocardiograms. Based on these findings, we developed the amount of change in core body temperature estimation model using multiple regression analysis including the Poincaré plot index of the ECG R-R interval. The estimation model showed an average estimation error of -0.007°C (average error rate = -0.02%) and an error range of 0.457–0.445°C. It is suggested that continuous core body temperature change can be estimated using electrocardiogram signals regardless of individual characteristics such as age and physique. Based on this applicable estimation model, we plan to enhance estimation accuracy and further verify efficacy by considering clothing and environmental conditions. [ABSTRACT FROM AUTHOR]

Background: The Toll-like receptor signaling pathway contributes to the regulation of intestinal homeostasis through interactions with commensal bacteria. Although the transcriptional regulator IκB-ζ can be induced by Toll-like receptor signaling, its role in intestinal homeostasis is still unclear. Aims: To investigate the role of IκB-ζ in gut homeostasis. Methods: DSS-administration induced colitis in control and IκB-ζ-deficient mice. The level of immunoglobulins in feces was detected by ELISA. The immunological population in lamina propria (LP) was analyzed by FACS. Results: IκB-ζ-deficient mice showed severe inflammatory diseases with DSS administration in the gut. The level of IgM in the feces after DSS administration was less in IκB-ζ-deficient mice compared to control mice. Upon administration of DSS, IκB-ζ-deficient mice showed exaggerated intestinal inflammation (more IFN-g-producing CD4+ T cells in LP), and antibiotic treatment canceled this inflammatory phenotype. Conclusion: IκB-ζ plays a crucial role in maintaining homeostasis in the gut. [ABSTRACT FROM AUTHOR]

Purpose: We developed a navigation system that superimposes the fractional anisotropy (FA) color map of pre-operative diffusion tensor imaging (DTI) and intraoperative magnetic resonance imaging (MRI). The current study aimed to investigate the usefulness of this system for neurophysiological monitoring and examination under awake craniotomy during tumor removal. Method: A total of 10 glioma patients (4 patients with right-side tumors; 5 men and 5 women; average age, 34 years) were evaluated. Among them, the tumor was localized to the frontal lobe, insular cortex, and parietal lobe in 8, 1, and 1 patient, respectively. There were 3 patients who underwent surgery on general anesthesia, while 7 patients underwent awake craniotomy. The index of DTI anisotropy taken pre-operatively (magnetic field: 3 tesla, 6 motion probing gradient directions) was analyzed as a color map (FA color map) and concurrently co-registered in the intraoperative MRI within the navigation. In addition to localization of the bipolar coagulator and the cortical stimulator for brain mapping on intraoperative MRI, the pre-operative FA color map was also concurrently integrated and displayed on the navigation monitor. This white matter nerve functional information was confirmed directly by using neurological examination and referring to the electrophysiological monitoring. Results: Intraoperative MRI, integrated pre-operative FA color map, and microscopic surgical view were displayed on one screen in all 10 patients, and white matter fibers including the pyramidal tract were displayed as a reference in blue. Regarding motor function, motor-evoked potential was monitored as appropriate in all cases, and removal was possible while directly confirming motor symptoms under awake craniotomy. Furthermore, the white matter fibers including the superior longitudinal fasciculus were displayed in green. Importantly, it was useful not only to localize the resection site, but to identify language-related, eye movement-related, and motor fibers at the electrical stimulation site. All motor and/or language white matter tracts were identified and visualized with the co-registration and then with an acceptable post-operative neurological outcome. Conclusion: Co-registering an intraoperative MR images and a pre-operative FA color map is a practical and useful method to predict the localization of critical white matter nerve functions intraoperatively in glioma surgery. [ABSTRACT FROM AUTHOR]

Purpose: Intraoperative anxiety is the most common psychological response of the patient during awake craniotomy. Psychological stress can trigger patient decline, resulting in failed awake craniotomy and significantly poor outcomes. This study aimed to identify the risk factors for panic attack (PA) during awake craniotomies. Methods: With the local ethics committee approval, we conducted a manual chart review of the medical record of patients who underwent consecutive awake craniotomies between November 1999 and October 2016 at Tokyo Women's Medical University. A total of 405 patients were identified and assigned to 2 groups based on the Diagnostic and Statistical Manual of Mental Disorders-V criteria: those that met the PA criteria (Group PA) and those that did not (Group non-PA). Patient characteristics and the incidence of the PA specifier were collected. The features of the two groups were statistically compared, and risk factors for PA occurrence were determined by regression analysis. Results: Sixteen of 405 patients met the diagnostic criteria of PA. Patients' characteristics were not statistically different between the groups. Multivariate logistic regression showed that intraoperative anxiety (p = 0.0002) and age younger than 39 years (as opposed to age > = 39 years; p = 0.0328) were significantly associated with the occurrence of PA during awake craniotomy. Conclusions: For patients undergoing awake craniotomy, intraoperative anxiety and age younger than 39 years were considered risk factors of PA. As PA often necessitates conversion to general anesthesia, intensive perioperative psychological support and pain management are required to achieve patient satisfaction and the surgical goal of awake craniotomy. [ABSTRACT FROM AUTHOR]

Glioma patients were frequently associated with mucosal thickening of the maxillary sinus (MTMS), which reflects mucosal inflammation. We suspected that MTMS is associated with impaired mucosal immune response and correlated with dysfunction in the anti-tumor immune response in diffuse glioma patients. Therefore, the aim of this study was to determine whether the occurrence of diffuse glioma is correlated with MTMS compared to meningioma and control groups. Furthermore, we investigated whether MTMS is associated with overall survival (OS) in glioblastoma (GBM) patients. This study included 343 patients with newly diagnosed diffuse gliomas and 218 patients with meningioma treated at our institution between 2015 and 2018. As control, 201 patients with headache who did not have an intracranial organic lesion were included. Using three-axis MR images, we evaluated the incidence of MTMS in all patients. Additionally, we investigated the relationship between MTMS and OS. The incidence of MTMS in patients with diffuse glioma was significantly higher than that in the meningioma (p <.0001) and control groups (p <.0001). In 128 patients with GBM, MTMS status correlated significantly with OS (p =.0064). We revealed that the incidence of MTMS is significantly associated with patients with diffuse glioma. This suggests that MTMS is indirectly involved in the occurrence of diffuse gliomas. Furthermore, the presence of MTMS correlated significantly with shorter OS in GBM patients, indicating that MTMS is involved in suppression of anti-tumor immune response. Preoperative recognition of MTMS might be useful for improving the clinical management of GBM patients. [ABSTRACT FROM AUTHOR]

Regulatory T cells (Tregs) in the tumor microenvironment regulate tumor immunity. Programmed cell death protein 1 (PD‐1) is known to be expressed on Tregs and plays crucial roles in suppressing tumor immunity. However, the immune checkpoint inhibitor, anti‐PD‐1 antibody, is known to promote the proliferation of the Treg population in tumor‐infiltrating lymphocytes, thereby restricting the efficacy of cancer immunotherapy. In this study, we focused on the curcumin analog GO‐Y030, an antitumor chemical. GO‐Y030 inhibited the immune‐suppressive ability of Tregs via metabolic changes in vitro, even in the presence of immune checkpoint inhibitors. Mechanistically, GO‐Y030 inhibited the mTOR‐S6 axis in Tregs, which plays a pivotal role in their immune‐suppressive ability. GO‐Y030 also controlled the metabolism in cultured CD4+ T cells in the presence of TGF‐β + IL‐6; however, it did not prevent Th17 differentiation. Notably, GO‐Y030 significantly inhibited IL‐10 production from Th17 cells. In the tumor microenvironment, L‐lactate produced by tumors is known to support the suppressive ability of Tregs, and GO‐Y030 treatment inhibited L‐lactate production via metabolic changes. In addition, experiments in the B16‐F10 melanoma mouse model revealed that GO‐Y030 helped inhibit the anti‐PD‐1 immune checkpoint and reduce the Treg population in tumor‐infiltrating lymphocytes. Thus, GO‐Y030 controls the metabolism of both Tregs and tumors and could serve as a booster for anti‐immune checkpoint inhibitors. [ABSTRACT FROM AUTHOR]

An ionospheric positive disturbance during a moderate geomagnetic storm on October 13, 2016 was studied with total electron content (TEC) from a chain of GNSS receivers and F2 layer peak parameters from two ionosondes at the Greenwich meridian. During a slow decrease of Dst, a large enhancement of the daytime TEC was observed from high to middle latitudes successively while there was small disturbance observed in low latitudes. The occurrence of TEC peak delayed with decreasing latitude. Similarly, positive disturbance of hmF2 and foF2 was recorded and their onsets were earlier in high latitude than middle latitude. These observations indicated that the ionospheric positive disturbance propagated equatorward which denied the dominant effect of prompt penetration eastward electric field (PPEF). Using the latitudinal and temporal variations of TEC peaks, the propagation velocity of the disturbance was estimated and found to decrease with decreasing latitude. Two available Fabry‐Perot interferometers (FPI) at the meridian 70°W of the Greenwich showed that nighttime equatorward wind in middle latitude increased significantly after the storm sudden commencement (SSC), while no change of that was observed in low latitude. The coincidence of the directional and latitudinal features between the ionospheric disturbance and the wind observation suggested the impact of the positive storm was most likely the equatorward wind surge which raised the ionosphere to higher altitude where lower chemical loss led to increase of electron density in the daytime. Key Points: The ionospheric storm exhibited a large enhancement of TEC in middle and high latitudesThe disturbances of hmF2 and foF2 at 51°N were earlier than that of at 41°NThe positive disturbance was caused most likely by the equatorward wind surge rather than the prompt penetrating eastward electric field [ABSTRACT FROM AUTHOR]

Regulatory T cells (Tregs) play a crucial role in preventing antitumor immune responses in cancer tissues. Cancer tissues produce large amounts of transforming growth factor beta (TGF-β), which promotes the generation of Foxp3+ Tregs from naïve CD4+ T cells in the local tumor microenvironment. TGF-β activates nuclear factor kappa B (NF-κB)/p300 and SMAD signaling, which increases the number of acetylated histones at the Foxp3 locus and induces Foxp3 gene expression. TGF-β also helps stabilize Foxp3 expression. The curcumin analog and antitumor agent, GO-Y030, prevented the TGF-β-induced generation of Tregs by preventing p300 from accelerating NF-κB-induced Foxp3 expression. Moreover, the addition of GO-Y030 resulted in a significant reduction in the number of acetylated histones at the Foxp3 promoter and at the conserved noncoding sequence 1 regions that are generated in response to TGF-β. In vivo tumor models demonstrated that GO-Y030-treatment prevented tumor growth and reduced the Foxp3+ Tregs population in tumor-infiltrating lymphocytes. Therefore, GO-Y030 exerts a potent anticancer effect by controlling Treg generation and stability. [ABSTRACT FROM AUTHOR]

Background: Fatty acid‐binding protein 3 (FABP3) is a cytosolic carrier protein of polyunsaturated fatty acids (PUFAs) and regulates cellular metabolism. However, the physiological functions of FABP3 in immune cells and how FABP3 regulates inflammatory responses remain unclear. Methods: Contact hypersensitivity (CHS) induced by 2,4‐dinitrofluorobenzene (DNFB) and fluorescein isothiocyanate was applied to the skin wild‐type and Fabp3−/− mice. Skin inflammation was assessed using FACS, histological, and qPCR analyses. The development of γ/δ T cells was evaluated by a co‐culture system with OP9/Dll1 cells in the presence or absence of transgene of FABP3. Results: Fabp3‐deficient mice exhibit a more severe phenotype of contact hypersensitivity (CHS) accompanied by infiltration of IL‐17‐producing Vγ4+ γ/δ T cells that critically control skin inflammation. In Fabp3−/− mice, we found a larger proportion of Vγ4+ γ/δ T cells in the skin, even though the percentage of total γ/δ T cells did not change at steady state. Similarly, juvenile Fabp3−/− mice also contained a higher amount of Vγ4+ γ/δ T cells not only in the skin but in the thymus when compared with wild‐type mice. Furthermore, thymic double‐negative (DN) cells expressed FABP3, and FABP3 negatively regulates the development of Vγ4+ γ/δ T cells in the thymus. Conclusions: These findings suggest that FABP3 functions as a negative regulator of skin inflammation through limiting pathogenic Vγ4+ γ/δ T‐cell generation in the thymus. [ABSTRACT FROM AUTHOR]

A new technique was developed to estimate the ionospheric total electron content (TEC) from Global Navigation Satellite System (GNSS) satellite signals. The vertically distributed electron density was parameterized by two thin-shell layers (double-shell approach). The spatiotemporal variation of TEC (strictly speaking, partial electron content) associated with each shell was approximated by the functional fitting of spherical surface harmonics. The major improvements over the conventional single-shell approach were as follows: (1) the precise estimation of TEC was achieved; (2) the estimated TEC was less dependent on the choice of shell heights; and (3) the equatorial anomaly was captured more correctly. Furthermore, higher and lower shells exhibited a different pattern of local time vs latitude variation, providing information on the ionosphere–thermosphere dynamics. [ABSTRACT FROM AUTHOR]

Plasma cells (PCs), which aim to protect host health, produce various subsets of immunoglobulin (Ig) in response to extracellular pathogens. Blimp‐1 (encoded by Prdm1)—a protein that is highly expressed by PCs—is important for PC functions, including the generation of Igs. Fatty acid‐binding protein 3 (FABP3) is a carrier protein of polyunsaturated fatty acids (PUFAs) and participates in multiple cellular functions. Although the functions of FABP3 in neurons and cardiac myocytes are well‐noted, their roles in immune cells remain to be fully elucidated. In this study, we demonstrate that FABP3 is expressed in activated B cells and that FABP3 promotes PC development and IgM secretion. Moreover, we provide the first evidence that FABP3 is necessary for Blimp‐1 expression, by regulating the histone modification of its promoter region. Taken together, our findings reveal that FABP3 acts as a positive regulator of B‐cell activation by controlling histone acetylation of the Blimp‐1 gene, thereby playing a role in host defense against pathogens. [ABSTRACT FROM AUTHOR]

Purpose: To clarify the subjective and objective impacts of a change in a 12-h shift schedule, involving a reduction in the number of crews, on workers at an electronic parts production company. Methods: Forty-two workers participated in this study. Subjective indicators (e.g. questionnaires) and objective indicators [e.g., psychomotor vigilance task (PVT)], as well as an activity monitor-based sleep assessment, were measured during a > 1-year period that encompassed the shift schedule change. The study outcome was a comparison of work-related injury rates measured 1 year before and after the change in shift schedule. Results: After the shift schedule change, questionnaire scores regarding work-related burdens and PVT performance parameters, including mean response time and number of lapses, increased significantly. However, we also observed divergences in the trends of the subjective and objective measures 1 year after the change. Despite these variations in both types of measures, we observed no significant differences in work-related injury rates measured before and after the shift schedule change. Conclusion: This study revealed that a reduction in the number of crews in a 12-h shift schedule has a negative impact on the subjective and objective indicator after the change in shift schedule; only indicators of alertness did not recover at 1 year after the change. Assessments of the workers' performances and the regular implementation of health and safety programs for more than 1 year are needed to maintain workers' health after the change in shift schedule. [ABSTRACT FROM AUTHOR]

We examined whether the chemogenetic activation of endogenous arginine vasopressin (AVP) affects central nesfatin-1/NucB2 neurons, using a transgenic rat line that was previously generated. Saline (1 mL/kg) or clozapine-N-oxide (CNO, 1 mg/mL/kg), an agonist for hM3Dq, was subcutaneously administered in adult male AVP-hM3Dq-mCherry transgenic rats (300–370 g). Food and water intake were significantly suppressed after subcutaneous (s.c.) injection of CNO, with aberrant circadian rhythmicity. The percentages of Fos expression in nesfatin-1/NucB2-immunoreactive neurons were significantly increased in the hypothalamus and brainstem at 120 min after s.c. injection of CNO. Suppressed food intake that was induced by chemogenetic activation of endogenous AVP was ablated after intracerebroventricularly administered nesfatin-1/NucB2-neutralizing antibody in comparison with vehicle, without any alteration of water intake nor circadian rhythmicity. These results suggest that chemogenetic activation of endogenous AVP affects, at least in part, central nesfatin-1/NucB2 neurons and may exert anorexigenic effects in the transgenic rats. [ABSTRACT FROM AUTHOR]

The prognosis for glioblastoma (GBM) varies among patients. Ventricular opening during surgery has been reported as a prognostic factor for GBM patients, but the influence of ventricular opening itself on patient prognosis remains controversial. We presumed that the degree of ventricular opening would correlate with the degree of subventricular zone (SVZ) resection and with prognosis in GBM patients. This study therefore investigated whether the degree of ventricular opening correlates with prognosis in GBM patients treated with the standard protocol of chemo-radiotherapy. Participants comprised 111 patients with newly diagnosed GBM who underwent surgery and received postoperative radiotherapy and temozolomide-based chemotherapy from 2005 to 2018. We classified 111 patients into "No ventricular opening (NVO)", "Ventricular opening, small (VOS; distance < 23.2 mm)", and "Ventricular opening, wide (VOW; distance ≥ 23.2 mm)" groups. We evaluated the relationship between degree of ventricular opening and prognosis using survival analyses that included other clinicopathological factors. Log-rank testing revealed age, Karnofsky performance status (KPS), extent of resection, O6-methylguanine-DNA methyltransferase (MGMT) status, isocitrate dehydrogenase (IDH)1 mutation, and degree of ventricular opening correlated significantly with overall survival. Multivariate analysis identified the degree of ventricular opening (small vs. wide) as the most significant prognostic factor (hazard ratio = 3.674; p < 0.0001). We demonstrated that wide opening of the lateral ventricle (LV) contributes to longer survival compared with small opening among GBM patients. Our results indicate that wide opening of the LV may correlate with the removal of a larger proportion of tumor stem cells from the SVZ. [ABSTRACT FROM AUTHOR]

We generated a transgenic rat line that expresses oxytocin (OXT)‐monomeric red fluorescent protein 1 (mRFP1) fusion gene to visualize the dynamics of OXT. In this transgenic rat line, hypothalamic OXT can be assessed under diverse physiological and pathophysiological conditions by semiquantitative fluorometry of mRFP1 fluorescence intensity as a surrogate marker for endogenous OXT. Using this transgenic rat line, we identified the changes in hypothalamic OXT synthesis under various physiological conditions. However, few reports have directly examined hypothalamic OXT synthesis under hyperosmolality or hypovolemia. In this study, hypothalamic OXT synthesis was investigated using the transgenic rat line after acute osmotic challenge and acute hypovolemia induced by intraperitoneal (i.p.) administration of 3% hypertonic saline (HTN) and polyethylene glycol (PEG), respectively. The mRFP1 fluorescence intensity in the paraventricular (PVN) and supraoptic nuclei (SON) was significantly increased after i.p. administration of HTN and PEG, along with robust Fos‐like immunoreactivity (co‐expression). Fos expression showed neuronal activation in the brain regions that are associated with the hypothalamus and/or are involved in maintaining water and electrolyte homeostasis in HTN‐ and PEG‐treated rats. OXT and mRFP1 gene expressions were dramatically increased after HTN and PEG administration. The plasma OXT level was extremely increased after HTN and PEG administration. Acute osmotic challenge and acute hypovolemia induced upregulation of hypothalamic OXT in the PVN and SON. These results suggest that not only endogenous arginine vasopressin (AVP) but also endogenous OXT has a key role in maintaining body fluid homeostasis to cope with hyperosmolality and hypovolemia. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) causes chronic joint pain and significantly impacts daily activities. Hence, developing novel treatment options for OA has become an increasingly important area of research. Recently, studies have reported that exogenous, as well as endogenous, hypothalamic‐neurohypophysial hormones, oxytocin (OXT) and arginine‐vasopressin (AVP), significantly contribute to nociception modulation. Moreover, the parvocellular OXT neurone (parvOXT) extends its projection to the superficial spinal dorsal horn, where it controls the transmission of nociceptive signals. Meanwhile, AVP produced in the magnocellular AVP neurone (magnAVP) is released into the systemic circulation where it contributes to pain management at peripheral sites. The parvocellular AVP neurone (parvAVP), as well as corticotrophin‐releasing hormone (CRH), suppresses inflammation via activation of the hypothalamic‐pituitary adrenal (HPA) axis. Previously, we confirmed that the OXT/AVP system is activated in rat models of pain. However, the roles of endogenous hypothalamic‐neurohypophysial hormones in OA have not yet been characterised. In the present study, we investigated whether the OXT/AVP system is activated in a knee OA rat model. Our results show that putative parvOXT is activated and the amount of OXT‐monomeric red fluorescent protein 1 positive granules in the ipsilateral superficial spinal dorsal horn increases in the knee OA rat. Furthermore, both magnAVP and parvAVP are activated, concurrent with HPA axis activation, predominantly modulated by AVP, and not CRH. The OXT/AVP system in OA rats was similar to that in systemic inflammation models, including adjuvant arthritis; however, magnocellular OXT neurones (magnOXT) were not activated in OA. Hence, localised chronic pain conditions, such as knee OA, activate the OXT/AVP system without impacting magnOXT. [ABSTRACT FROM AUTHOR]

We recently demonstrated that sleeping on high rebound [HR] mattress toppers induced a continuous and more rapid decline in core body temperature compared to low rebound [LR] mattress toppers during the initial phase of nocturnal sleep in young healthy volunteers. HR toppers are characterized by their supportive feel and high breathability whereas LR toppers are pressure-absorbing. In the current study, we evaluated effects of HR mattress toppers on objectively-(actigraphy) and subjectively-(questionnaires) evaluated sleep, vigilance (psychomotor vigilance test), and athletic performance (40-m sprint time, long jump distance, and star drill time) in youth male athletes age 10–19, in two sessions: fifty-one subjects in 2013 (study I) and 23 subjects in 2014 (study II). Sleeping on HR mattress toppers for four to six weeks improved some athletic performance measures compared to sleeping on LR or sleeping directly on spring mattresses without a topper. Statistically significant improvements in 40-m sprint time in study I (compared to LR) and in star drill time in study II (no topper) were observed. No changes in sleep and psychomotor vigilance were observed. These results suggest selecting optimal sleep surfaces may contribute to the maximization of athletic performances, and further studies are warranted. [ABSTRACT FROM AUTHOR]

The contribution of inflammation to the chronic joint disease osteoarthritis (OA) is unclear, and this lack of clarity is detrimental to efforts to identify therapeutic targets. Here we show that chondrocytes under inflammatory conditions undergo a metabolic shift that is regulated by NF-κB activation, leading to reprogramming of cell metabolism towards glycolysis and lactate dehydrogenase A (LDHA). Inflammation and metabolism can reciprocally modulate each other to regulate cartilage degradation. LDHA binds to NADH and promotes reactive oxygen species (ROS) to induce catabolic changes through stabilization of IκB-ζ, a critical pro-inflammatory mediator in chondrocytes. IκB-ζ is regulated bi-modally at the stages of transcription and protein degradation. Overall, this work highlights the function of NF-κB activity in the OA joint as well as a ROS promoting function for LDHA and identifies LDHA as a potential therapeutic target for OA treatment. Chondrocytes have altered cellular metabolism in the context of osteoarthritis, but whether and how these changes are associated with inflammation is a controversial area. Here the authors show that inflammatory NF-κB signalling drives a glycolytic shift in chondrocytes and the production of ROS, which drives cartilage catabolism. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to explore the genetic alterations and to identify good responders in the experimental arm in the tumor samples from newly diagnosed glioblastoma (GBM) patients enrolled in JCOG0911; a randomized phase II trial was conducted to compare the efficacy of interferonβ (IFNβ) plus temozolomide (TMZ) with that of TMZ alone. Experimental: design: Of 122 tumors, we performed deep targeted sequencing to determine the somatic mutations, copy number variations, and tumor mutation burden; pyrosequencing for O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation; Sanger sequencing for the telomerase reverse transcriptase (TERT) promoter; and microsatellite instability (MSI) testing in 95, 91, 91 and 72 tumors, respectively. We performed a multivariable Cox regression analysis using backward stepwise selection of variables including clinical factors (sex, age, performance status, residual tumor after resection, tumor location) and genetic alterations. Results: Deep sequencing detected an IDH1 mutation in 13 tumors (14%). The MGMT promoter methylation by quantitative pyrosequencing was observed in 41% of the tumors. A mutation in the TERT promoter was observed in 69% of the tumors. While high tumor mutation burden (> 10 mutations per megabase) was seen in four tumors, none of the tumors displayed MSI-high. The clinical and genetic factors considered as independent favorable prognostic factors were gross total resection (hazard ratio [HR]: 0.49, 95% confidence interval, 0.30–0.81, P = 0.0049) and MGMT promoter methylation (HR: 0.43, 0.21–0.88, P = 0.023). However, tumor location at the temporal lobe (HR: 1.90, 1.22–2.95, P = 0.0046) was an independent unfavorable prognostic factor. No predictive factors specific to the TMZ + IFNβ + Radiotherapy (RT) group were found. Conclusion: This additional sub-analytical study of JCOG0911 among patients with newly diagnosed GBM showed that tumor location at the temporal lobe, gross total resection, and MGMT promoter methylation were significant prognostic factors, although no factors specific to IFNβ addition were identified. [ABSTRACT FROM AUTHOR]

X-ray Talbot-Lau interferometry is one of the x-ray phase imaging methods that has high sensitivity in depicting soft tissues. Unlike earlier x-ray phase imaging methods that required particular types of x-ray sources, such as a synchrotron or a micro-focus x-ray tube, x-ray Talbot-Lau interferometry enables to perform clinical x-ray phase imaging using a conventional x-ray source with a relatively compact configuration. We developed an apparatus to depict cartilage in the metacarpophalangeal joints of the hands. In addition, we examined the apparatus performance by applying it to healthy volunteers and patients with rheumatoid arthritis (RA). Cartilage deformation, which is thought to be a precursor of destruction of the joints, was successfully depicted by the apparatus, suggesting a potential early diagnosis of RA. [ABSTRACT FROM AUTHOR]

We have previously revealed that identification of the frontal language area (FLA) can be difficult in patients with dominant frontal glioma involving the pars triangularis (PT). The present study added new cases and performed additional analyses. We noticed a new finding that the presence of extension to the pars orbitalis (POr) was associated with negative response to the FLA. The aim of the present study was to evaluate the impact of PT involvement with extension to the POr on the failure to identify the FLA. From 2000 to 2017, awake craniotomy was performed on 470 patients. Of these patients, the present study included 148 consecutive patients with frontal glioma on the dominant side. We evaluated whether tumors involved the PT or extended to the POr. Thirty one of 148 patients showed involvement of the PT, and we examined the detailed characteristics of these 31 patients. The rate of negative response for the FLA was 61% in patients with involvement of the PT. In 31 patients with frontal glioma involving the PT, univariate analyses showed significant correlation between extension to the POr and failure to identify the FLA (P = 0.0070). Similarly, multivariate analysis showed only extension to the POr correlated significantly with failure to identify the FLA (P = 0.0129). We found new evidence that extension to the POr which impacts connectivity between the PT and POr correlated significantly with negative response to the FLA of patients with dominant frontal glioma. [ABSTRACT FROM AUTHOR]

Previous studies have shown that cognitive impairments in patients with brain tumors are not severe. However, to preserve the postsurgical QOL of patients with brain tumors, it is important to identify "primary" cognitive functions and associated brain regions that are more vulnerable to cognitive impairments following surgery. The objective of this study was to investigate primary cognitive factors affecting not only simple cognitive tasks but also several other cognitive tasks and associated brain regions. Patients with glioma in the left (n = 33) and the right (n = 21) hemisphere participated in the study. Seven neuropsychological tasks from five cognitive domains were conducted pre- and 6 months postoperation. Factor analyses were conducted to identify "primary" common cognitive functions affecting the task performance in left and right glioma groups. Next, lesion analyses were performed using voxel-based lesion-symptom mapping (VLSM) to identify critical brain regions related to impairments of the primary cognitive functions. Factor analysis revealed two primary cognitive components in each glioma group. The first cognitive component in the left glioma group affected the digit span forward and backward tasks and concept shifting and the letter-digit substitution tasks. VLSM analysis revealed significant regions from the posterior middle temporal gyri to the supramarginal gyrus. The second cognitive component affected verbal memory, and verbal fluency tasks and VLSM analysis indicated two different significant regions, the medial temporal regions and the middle temporal gyrus to the posterior parietal lobes. The first cognitive component in the right glioma group affected positive and negative factor loadings on the task, such that the positive cognitive component affected only the Stroop color-word task. VLSM related to deficits of the Stroop task revealed significant regions in the anterior medial frontal cortex. On the other hand, the negative component affected concept shifting, word fluency, and digit span forward tasks, and VLSM revealed significant regions in the right inferior frontal cortex. It is suggested that primary cognitive functions related to specific brain regions were possibly affected by glioma resection. [ABSTRACT FROM AUTHOR]

Various types of acute/chronic nociceptive stimuli cause neuroendocrine responses such as activation of the hypothalamo-neurohypophysial [oxytocin (OXT) and arginine vasopressin (AVP)] system and hypothalamo-pituitary adrenal (HPA) axis. Chronic multiple-arthritis activates the OXT/AVP system, but the effects of acute mono-arthritis on the OXT/AVP system in the same animals has not been simultaneously evaluated. Further, AVP, not corticotropin-releasing hormone (CRH), predominantly activates the HPA axis in chronic multiple-arthritis, but the participation of AVP in HPA axis activation in acute mono-arthritis remains unknown. Therefore, we aimed to simultaneously evaluate the effects of acute mono-arthritis on the activity of the OXT/AVP system and the HPA axis. In the present study, we used an acute mono-arthritic model induced by intra-articular injection of carrageenan in a single knee joint of adult male Wistar rats. Acute mono-arthritis was confirmed by a significant increase in knee diameter in the carrageenan-injected knee and a significant decrease in the mechanical nociceptive threshold in the ipsilateral hind paw. Immunohistochemical analysis revealed that the number of Fos-immunoreactive (ir) cells in the ipsilateral lamina I–II of the dorsal horn was significantly increased, and the percentage of OXT-ir and AVP-ir neurons expressing Fos-ir in both sides of the supraoptic (SON) and paraventricular nuclei (PVN) was increased in acute mono-arthritic rats. in situ hybridization histochemistry revealed that levels of OXT mRNA and AVP hnRNA in the SON and PVN, CRH mRNA in the PVN, and proopiomelanocortin mRNA in the anterior pituitary were also significantly increased in acute mono-arthritic rats. Further, plasma OXT, AVP, and corticosterone levels were significantly increased in acute mono-arthritic rats. These results suggest that acute mono-arthritis activates ipsilateral nociceptive afferent pathways at the spinal level and causes simultaneous and integrative activation of the OXT/AVP system. In addition, the HPA axis is activated by both AVP and CRH in acute mono-arthritis with a distinct pattern compared to that in chronic multiple-arthritis. [ABSTRACT FROM AUTHOR]

This paper proposes a new technique, namely Phase bias-based Small Grid Model (PSGM), to derive absolute ionospheric vertical total electron content (VTEC) with observations of Global Navigation Satellite System Earth Observation Network of Japan (GEONET). The proposed technique deals with the phase observations alone without handling the pseudoranges, which reduces the noise in VTEC estimation. A new parameter, the arc bias (Barc), is introduced to combine the phase ambiguities and differential phase biases. To solve Barc, equations are constructed under the assumption that the VTEC is identical in the same 0.1° × 0.1° grid. The performance of PSGM is evaluated with the observations in solar maximum year 2014. The root mean square error (RMSE) of PSGM is 0.40 TECU in average, the maximum RMSE is 0.73 TECU and the minimum RMSE is 0.26 TECU. The fitting accuracy of the VTEC results is improved compared with most of the existing methods. [ABSTRACT FROM AUTHOR]

Introduction: It is useful to know the molecular subtype of lower-grade gliomas (LGG) when deciding on a treatment strategy. This study aims to diagnose this preoperatively. Methods: A deep learning model was developed to predict the 3-group molecular subtype using multimodal data including magnetic resonance imaging (MRI), positron emission tomography (PET), and computed tomography (CT). The performance was evaluated using leave-one-out cross validation with a dataset containing information from 217 LGG patients. Results: The model performed best when the dataset contained MRI, PET, and CT data. The model could predict the molecular subtype with an accuracy of 96.6% for the training dataset and 68.7% for the test dataset. The model achieved test accuracies of 58.5%, 60.4%, and 59.4% when the dataset contained only MRI, MRI and PET, and MRI and CT data, respectively. The conventional method used to predict mutations in the isocitrate dehydrogenase (IDH) gene and the codeletion of chromosome arms 1p and 19q (1p/19q) sequentially had an overall accuracy of 65.9%. This is 2.8 percent point lower than the proposed method, which predicts the 3-group molecular subtype directly. Conclusions: A deep learning model was developed to diagnose the molecular subtype preoperatively based on multi-modality data in order to predict the 3-group classification directly. Cross-validation showed that the proposed model had an overall accuracy of 68.7% for the test dataset. This is the first model to double the expected value for a 3-group classification problem, when predicting the LGG molecular subtype. [ABSTRACT FROM AUTHOR]

Cisplatin is one of the most potent anti-cancer drugs, though several side effects can induce stress responses such as activation of the hypothalamic–pituitary adrenal (HPA) axis. Arginine vasopressin (AVP) and corticotrophin-releasing hormone (CRH) expressed in the parvocellular division of the paraventricular nucleus (pPVN) play an important role in the stress-induced activation of the HPA axis. We aimed to evaluate whether intraperitoneal (i.p.) administration of cisplatin could activate parvocellular neurons in the pPVN, using a transgenic rat model that expresses the fusion gene of AVP and enhanced green fluorescent protein (eGFP). Along with the induction of FosB, a marker of neuronal activation, i.p. administration of cisplatin significantly increased eGFP fluorescent intensities in the pPVN. In situ hybridization histochemistry revealed that AVP-eGFP and CRH mRNAs in the pPVN were increased significantly in cisplatin-treated rats. These results suggest that cisplatin administration increases neuronal activation and upregulates AVP and CRH expression in the pPVN. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to transform brain mapping data into a digitized intra-operative MRI and integrated brain function dataset for predictive glioma surgery considering tumor resection volume, as well as the intra-operative and postoperative complication rates. Methods: Brain function data were transformed into digitized localizations on a normalized brain using a modified electric stimulus probe after brain mapping. This normalized brain image with functional information was then projected onto individual patient's brain images including predictive brain function data. Results: Log data were successfully acquired using a medical device integrated into intra-operative MR images, and digitized brain function was converted to a normalized brain data format in 13 cases. For the electrical stimulation positions in which patients showed speech arrest (SA), speech impairment (SI), motor and sensory responses during cortical mapping processes in awake craniotomy, the data were tagged, and the testing task and electric current for the stimulus were recorded. There were 13 SA, 7 SI, 8 motor and 4 sensory responses (32 responses) in total. After evaluation of transformation accuracy in 3 subjects, the first transformation from intra- to pre-operative MRI using non-rigid registration was calculated as 2.6 ± 1.5 and 2.1 ± 0.9 mm, examining neighboring sulci on the electro-stimulator position and the cortex surface near each tumor, respectively; the second transformation from pre-operative to normalized brain was 1.7 ± 0.8 and 1.4 ± 0.5 mm, respectively, representing acceptable accuracy. Conclusion: This image integration and transformation method for brain normalization should facilitate practical intra-operative brain mapping. In the future, this method may be helpful for pre-operatively or intra-operatively predicting brain function. [ABSTRACT FROM AUTHOR]

Introduction: Tumor recurrence patterns after resection of intracranial low-grade gliomas (LGG) generally remain obscured. The objective of the present retrospective study was their multifaceted analysis, evaluation of associated factors, and assessment of impact on prognosis. Methods: Study group comprised 81 consecutive adult patients (46 men and 35 women; median age, 37 years) with recurrent diffuse astrocytomas (DA; 51 cases) and oligodendrogliomas (OD; 30 cases). The median length of follow-up after primary surgery was 6.7 years. Results: Early (within 2 years after primary surgery) and non-early (> 2 years after primary surgery) recurrence was noted in 23 (28%) and 58 (72%) cases, respectively. Fast (≤ 6 months) and slow (> 6 months) radiological progression of relapse was noted in 31 (38%) and 48 (59%) cases, respectively. Tumor recurrence was local and non-local in 71 (88%) and 10 (12%) cases, respectively. Recurrence patterns have differed in OD, IDH1-mutant DA, and IDH wild-type DA. Early onset, fast radiological progression, and non-local site of relapse had statistically significant negative impact on overall survival of patients and were often associated with malignant transformation of the tumor (38 cases). However, in subgroup with extent of resection ≥ 90% (56 cases) no differences in recurrence characteristics were found between 3 molecularly defined groups of LGG. Conclusions: Recurrence patterns after resection of LGG show significant variability, differ in distinct molecularly defined types of tumors, and demonstrate definitive impact on prognosis. Aggressive resection at the time of primary surgery may result in more favorable characteristics of recurrence at the time of its development. [ABSTRACT FROM AUTHOR]

Acute loss of kidney function is a critical internal stressor. Arginine vasopressin (AVP) present in the parvocellular division of the paraventricular nucleus (PVN) plays a key role in the regulation of stress responses. However, hypothalamic AVP dynamics during acute kidney dysfunction remain unclear. In this study, we investigated the effects of bilateral nephrectomy on AVP, using a transgenic rat line that expressed the AVP-enhanced green fluorescent protein (eGFP). The eGFP fluorescent intensities in the PVN were dramatically increased after bilateral nephrectomy. The mRNA levels of eGFP, AVP, and corticotrophin-releasing hormone in the PVN were dramatically increased after bilateral nephrectomy. Bilateral nephrectomy also increased the levels of Fos-like immunoreactive cells in brainstem neurons. These results indicate that bilateral nephrectomy upregulates the AVP-eGFP synthesis. Further studies are needed to identify the neural and/or humoral factors that activate AVP synthesis and regulate neuronal circuits during acute kidney dysfunction. [ABSTRACT FROM AUTHOR]