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Background/purpose: Perioperative oral care is widely provided to prevent postoperative pneumonia and surgical site infections in patients undergoing surgery under general anesthesia. However, there is a lack of clarity regarding the kind of oral care that should be provided for different patients. The purpose of this study was to clarify the factors that influence the increase in salivary bacterial counts before and after gastrointestinal surgery to identify patients with a particular need for oral care. Materials and methods: Twenty patients undergoing gastrointestinal surgery were examined before surgery for denture use, number of remaining teeth, regular dental care, Oral Hygiene Index-Simplfied tongue coating, tongue pressure, bite pressure, masticatory efficiency, and dry mouth. Saliva samples were collected before surgery, in the fasting period after surgery, and in the oral feeding period. Total bacterial counts were determined by real-time PCR, and factors associated with bacterial counts were investigated. Results: Patients with decreased oral functions, such as tongue pressure, bite pressure, and masticatory efficiency, tended to have higher salivary bacterial counts in the preoperative, fasting, and oral feeding periods. Regarding the pre- and postoperative changes, salivary bacterial counts increased in the fasting period compared to the pre-operative period and returned to preoperative values in the oral feeding period. Conclusion: Perioperative oral care is important for patients with reduced oral function because the number of bacteria in saliva tends to be higher in such patients. As the number of bacteria in saliva increases during the fasting period, oral care is important, and oral feeding should be restarted as soon as possible.

Abstract As the current state of the Metaverse is largely driven by corporate interests, which may not align with scientific goals and values, academia should play a more active role in its development. Here, we present the challenges and solutions for building a Metaverse that supports systems biology research and collaboration. Our solution consists of two components: Kosmogora, a server ensuring biological data access, traceability, and integrity in the context of a highly collaborative environment such as a metaverse; and ECellDive, a virtual reality application to explore, interact, and build upon the data managed by Kosmogora. We illustrate the synergy between the two components by visualizing a metabolic network and its flux balance analysis. We also argue that the Metaverse of systems biology will foster closer communication and cooperation between experimentalists and modelers in the field.

Abstract Background Total body water (TBW) fraction, which accounts for 60% of body weight, is an important indicator of body composition, and the extracellular water to TBW ratio (ECW/TBW) is reportedly useful in predicting clinical outcomes of patients with organ disorders. We aimed to clarify the clinical impact of preoperative ECW/TBW status on survival outcomes in cancer patients. Methods We used a database of 320 colorectal cancer (CRC) patients who underwent potentially curative resections. Preoperative ECW/TBW was measured using a bioelectrical impedance analysis (BIA), and its correlation with patient survival outcomes, clinicopathological factors, laboratory data, and comorbidities were analyzed. Results A high preoperative ECW/TBW was significantly associated with poorer relapse‐free survival (RFS; p = 0.001) and overall survival (OS; p = 0.003). A high ECW/TBW ratio was significantly associated with older age (p

Background This review aimed to quantify the impact of socioeconomic status on functional outcomes from stroke and identify the socioeconomic status indicators that exhibit the highest magnitude of association. Methods and Results We performed a systematic literature search across Medline and Embase from inception to May 2022, to identify observational studies (n≥100, and in English). Risk of bias was assessed using the modified Newcastle Ottawa Scale. Random effects meta‐analysis was used to pool data. We included 19 studies (157 715 patients, 47.7% women) reporting functional outcomes measured with modified Rankin Scale or Barthel index, with 10 assessed as low risk of bias. Measures of socioeconomic status reported were education (11 studies), income (8), occupation (4), health insurance status (3), and neighborhood socioeconomic deprivation (3). Pooled data suggested that low socioeconomic status was significantly associated with poor functional outcomes, including incomplete education or below high school level versus high school attainment and above (odds ratio [OR], 1.66 [95% CI, 1.40–1.95]), lowest income versus highest income (OR, 1.36 [95% CI, 1.02–1.83]), a manual job/being unemployed versus a nonmanual job/working (OR, 1.62 [95% CI, 1.29–2.02]), and living in the most disadvantaged socioeconomic neighborhood versus the least disadvantaged (OR, 1.55 [95% CI, 1.25–1.92]). Low health insurance status was also associated with an increased risk of poor functional outcomes (OR, 1.32 [95% CI, 0.95–1.84]), although this was association was not statistically significant. Conclusions Despite great strides in stroke treatment in the past decades, social disadvantage remains a risk factor for poor functional outcome after an acute stroke. Further research is needed to better understand causal mechanisms and disparities.

Background/purpose: Denosumab is used to treat bone metastases from malignant tumors. Unlike bisphosphonates, denosumab is not deposited in the bone; thus, withdrawal for a relatively short period would help recovery from osteoclast suppression. This study investigated the relationship between drug holidays and recovery from osteoclast suppression. Materials and methods: Seven patients who received high-dose denosumab and underwent segmental mandibulectomy for medication-related osteonecrosis of the jaw were enrolled in this study. Osteoclast suppression (+) was defined as the absence of cathepsin K-positive cells or cathepsin K-positive mononuclear or small multinucleated cells observed on the bone surface of both mesial and distal specimens. When normal osteoclasts were found, osteoclast suppression was defined as (−); when both suppressed cathepsin K-positive cells and normal morphological osteoclasts were found, it was defined as (±). Results: Osteoclast suppression was: (+) in four patients, three without a drug holiday and one with a 9-month drug holiday; (±) in one patient with an 8-month drug holiday, and (−) in two patients with drug holidays for 13 and 20 months. Conclusion: These findings suggest that a long-term drug holiday, such as 12 months, is required for recovery from osteoclast suppression in patients with cancer receiving high-dose denosumab.

Induced pluripotent stem cell-derived mesenchymal stem cells (iMSCs) hold great promise as a cell source for transplantation into injured tissues to alleviate inflammation. However, the therapeutic efficacy of iMSC transplantation for ischemic stroke remains unknown. In this study, we evaluated the therapeutic effects of iMSC transplantation on brain injury after ischemia-reperfusion using a rat transient middle cerebral artery occlusion model and compared its therapeutic efficacy with that of bone marrow mesenchymal stem cells (BMMSCs). We showed that iMSCs and BMMSCs reduced infarct volumes after reperfusion and significantly improved motor function on days 3, 7, 14, 28, and 56 and cognitive function on days 28 and 56 after reperfusion compared with the vehicle group. Furthermore, immunological analyses revealed that transplantation of iMSCs and BMMSCs inhibited microglial activation and expression of proinflammatory cytokines and suppressed oxidative stress and neuronal cell death in the cerebral cortex at the ischemic border zone. No difference in therapeutic effect was observed between the iMSC and BMMSC groups. Taken together, our results demonstrate that iMSC therapy can be a practical alternative as a cell source for attenuation of brain injury and improvement of neurological function because of the unlimited supply of uniform therapeutic cells.

Abstract Medication-related osteonecrosis of the jaw (MRONJ) is a refractory osteonecrosis caused by antiresorptive agents such as bisphosphonate and denosumab (DMB). In MRONJ surgery, computed tomography (CT) is generally used to determine the extent of bone resection. However, in some recent MRONJ cases, no abnormal findings were detected on CT. Therefore, we aimed to clarify the characteristics of MRONJ without osteolysis. This retrospective and observational study included 18 patients diagnosed with MRONJ between October 2020 and October 2022 at Department of Dentistry and Oral Surgery, Kansai Medical University Medical Center. In four of 18 patients with MRONJ, no abnormal findings such as osteolysis, separation of sequestrum, and periosteal reaction were observed on CT images at the first visit. All four patients with non-osteolytic MRONJ had malignant tumors and received high-dose DMB, and in the four patients there were no preceding dental infections such as apical lesions or periodontal disease and the trigger of MRONJ was unknown. Surgery was performed in three of the four patients. The extent of bone resection was determined using magnetic resonance imaging and intraoperative gross findings. In the future, it is necessary to establish a method for diagnosing non osteolytic MRONJ and determining the extent of bone resection.

Background Perivascular inflammation contributes to the development of atherosclerosis and microcirculatory dysfunction. Pericoronary adipose tissue (PCAT) attenuation, measured by coronary computed tomography angiography, is a potential indicator of coronary inflammation. However, the relationship between PCAT attenuation, microcirculatory dysfunction, and periprocedural myocardial injury (PMI) remains unclear. Methods and Results Patients with chronic coronary syndrome who underwent coronary computed tomography angiography before percutaneous coronary intervention were retrospectively identified. PCAT attenuation and adverse plaque characteristics were assessed using coronary computed tomography angiography. The extent of microcirculatory dysfunction was evaluated using the angio‐based index of microcirculatory resistance before and after percutaneous coronary intervention. Overall, 125 consecutive patients were included, with 50 experiencing PMI (PMI group) and 75 without PMI (non‐PMI group). Multivariable analysis showed that older age, higher angio‐based index of microcirculatory resistance, presence of adverse plaque characteristics, and higher lesion‐based PCAT attenuation were independently associated with PMI occurrence (odds ratio [OR], 1.07 [95% CI, 1.01–1.13]; P=0.02; OR, 1.06 [95% CI, 1.00–1.12]; P=0.04; OR, 6.62 [95% CI, 2.13–20.6]; P=0.001; and OR, 2.89 [95% CI, 1.63–5.11]; P

Summary: The subnuclear distribution of centromeres is cooperatively regulated by condensin II and the linker of nucleoskeleton and cytoskeleton (LINC) complex. However, other nuclear membrane structures and nuclear proteins are probably involved in centromere dynamics and distribution. Here, we focused on the nuclear pore complex (NPC), which is known to regulate gene expression, transcription memory, and chromatin structure in addition to transport between the cytoplasm and nucleoplasm. We report here that some nucleoporins (Nups), including Nup85, Nup133, CG1, Nup93b, and NUA, are involved in centromere scattering in Arabidopsis thaliana. In addition, the centromere dynamics after metaphase in nup mutants were found to be similar to that of the condensin II mutant. Furthermore, both biochemical and genetic approaches showed that the Nups interact with the LINC complex. These results suggest that Nups regulate centromere scattering cooperatively with condensin II and the LINC complex.

Abstract Background Sarcopenia is associated with poor prognosis in patients with colorectal cancer (CRC), but the mechanisms contributing to this association remain unclear. We hypothesized that skeletal muscle status is associated with tumor‐infiltrating lymphocytes (TILs) in patients with CRC. Therefore, this study investigated the clinical effect of sarcopenia and its relationship with the local immune system in CRC patients. Methods A total of 256 consecutive patients with CRC who underwent curative resection between 2008 and 2014 were enrolled. Sarcopenia was determined according to the skeletal muscle index (SMI), which was assessed using L3 skeletal muscle mass on axial computed tomography images, and its relationship with patient clinicopathological characteristics and survival was evaluated. Additionally, TILs (CD3+, CD8+, CD4+, and FOXP3+ T cells) were assayed by immunohistochemistry. The relationship between TILs and skeletal muscle status was evaluated. Results Patients with a lower SMI showed significantly shorter recurrence‐free and overall survival compared with those with a higher SMI. Low expression of TILs was associated with significantly shorter recurrence‐free survival. SMI was significantly correlated with the number of CD3+ and CD8+ cells in the ordinal logistic regression analysis. Patients with low skeletal muscle status and low CD3+ and CD8+ cells had an unfavorable prognosis compared with patients with high skeletal muscle status and high CD3+ and CD8+ cells. Conclusion Our data showed an association between skeletal muscle status and local immune cells, and this association may play a pivotal role in the clinical outcome of patients with CRC.

Abstract Background Although end-of-life patients have a variety of oral-related symptoms, the involvement of dentists and dental hygienists in the palliative care teams is limited. This study investigates the current state of palliative care education in universities that train dentists and dental hygienists and the need for dentistry in the clinical setting of palliative medicine in Japan. Methods First, we investigated the involvement of dentistry in hospitals with palliative care units from a website. The number of reports on palliative care presented by dental hygienists at academic conferences around 2016, when the public medical insurance system in Japan covered oral care for patients with terminal illnesses, were examined. We also surveyed the syllabuses of the university that trained nurses, dentists, and dental hygienists to determine their education regarding palliative care. Results Of the 376 hospitals with palliative care units, 176 (46.8%) had dentistry in the hospital. Additionally, 321 hospitals (85.4%), which included those without dentistry, responded that they provided oral care by dentists and dental hygienists in the palliative care unit. There were only two presentations on palliative care in the annual meetings of the two major academic societies by dental hygienists between 2012 and 2016. However, this number increased rapidly to 47 between 2017 and 2020. The syllabus surveys showed that, compared to nursing universities, universities that trained dentists or dental hygienists had lesser education in palliative care. Furthermore, education in the universities that trained dental hygienists was mostly related to the oral care of patients with terminal illnesses, while the physical and mental conditions of end-of-life patients were not well educated. Conclusion Considering that society requires the involvement of dental hygienists in the field of palliative care, it is necessary to enhance basic and clinical education of palliative care in universities that train dentists and dental hygienists to provide good oral care to patients with terminal illnesses and contribute to improving their quality of life.

Background/purpose: Tongue pressure plays an important role in swallowing function. The purpose of this study is to investigate whether decreased tongue pressure is associated with dysphagia and the development of pneumonia in the elderly requiring long-term care. Materials and methods: Tongue pressure measurement and swallowing videoendoscopic (VE) examination were performed in 60 hospitalized elderly people (33 males and 27 females, with an average age of 84.3 years) to investigate the relationship with the clinical course. Factors related with dysphagia was analyzed by Fisher's exact test and one-way ANOVA, followed by multivariate logistic regression. The relationship between each variable and survival were analyzed by cox regression. Results: Twenty-one patients had dysphagia by VE examination. Multivariate analysis showed that smaller BMI and reduced tongue pressure were significantly correlated with dysphagia. Smaller number of remaining teeth and dysphagia were significantly related to pneumonia-related death. No patients with tongue pressure of larger than 20 kpa died by pneumonia within one year, while in those with tongue pressure of smaller than 20 kpa, one-year cumulative survival rate by pneumonia was 44.3%. Conclusion: Decreased tongue pressure was significantly associated with dysphagia and may increase the risk of pneumonia-related death in the elderly requiring long-term care.

Abstract Dementia is a syndrome characterised by cognitive impairments, with a loss of learning/memory abilities at the earlier stages and executive dysfunction at the later stages. However, recent studies have suggested that impairments in both learning/memory abilities and executive functioning might co-exist. Cognitive impairments have been primarily evaluated using neuropsychological assessments, such as the Mini-Mental State Examination (MMSE). Recently, neuroimaging techniques such as magnetoencephalography (MEG), which assess changes in resting-state brain activity, have also been used as biomarkers for cognitive impairment. However, it is unclear whether these changes reflect dysfunction in executive function as well as learning and memory. In this study, parameters from the MEG for brain activity, MMSE for learning/memory, and Frontal Assessment Battery (FAB) for executive function were compared within 207 individuals. Three MEG parameters were used as representatives of resting-state brain activity: median frequency, individual alpha frequency, and Shannon’s spectral entropy. Regression analysis showed that median frequency was predicted by both the MMSE and FAB scores, while individual alpha frequency and Shannon’s spectral entropy were predicted by MMSE and FAB scores, respectively. Our results indicate that MEG spectral parameters reflect both learning/memory and executive functions, supporting the utility of MEG as a biomarker of cognitive impairment.

Sakamoto et al. demonstrate an improved optical clearing method, iTOMEI, for plant imaging. The new method can achieve fast clearing and effective removal of autofluorescence signals, and at the same time preserve signals from desired fluorescence proteins.

Abstract Background The advanced lung cancer inflammation index (ALI), which comprehensively evaluates the patient body composition and inflammation/nutritional status, is reportedly associated with the patient outcome in lung cancer. However, the clinical significance in colorectal cancer (CRC) patients after curative resection remains unclear. Methods A total of 813 CRC patients after curative resection between April 2005 and June 2019 in a single institution were retrospectively enrolled. The association of the preoperative ALI (calculated as follows: body mass index × albumin value/neutrophil‐to‐lymphocyte ratio) with clinicopathological factors, postoperative complications, and survival was analyzed. Results A low ALI was significantly associated with male gender, older age, a higher depth of tumor invasion, progressed TNM stage, and preoperative carcinoembryonic antigen (CEA) positivity. Both postoperative complications and severe complications occurred more frequently in the ALI‐low group than in the ALI‐high group (P

Abstract Aim This study investigated whether preoperative serum transferrin, a rapid‐turnover protein, was associated with prognosis after colorectal cancer (CRC) resection. Methods We evaluated preoperative transferrin, which was calculated as iron and unsaturated iron‐binding capacity, in 501 patients who underwent surgery for Stage I–III CRC. Transferrin level was directly proportional to total iron‐binding capacity (TIBC), and TIBC

Background/purpose: Although mandibular advancement oral appliances (OAs) are the most widely used and accepted therapeutic modality for obstructive sleep apnea (OSA), whether these maxillary and mandibular appliances should be semi-fixed or fixed remains uncertain. This randomized crossover pilot study compared the efficacy, side effects, and patient preference of semi-fixed and fixed OAs for the treatment of OSA. Materials and methods: Patients with mild to moderate OSA were recruited and randomly assigned to either the semi-fixed or fixed OA group, whereby they used their assigned OA for the first 4 weeks, followed by assessments for sleep parameters (including the Apnea-Hypopnea Index [AHI]) and temporomandibular joint pain as a side effect. After a two-week washout period, patients were switched to the alternative OA for 4 weeks, followed by repeated assessments. Patient preference was assessed at the end of the completed treatment period. Results: Fifteen patients were enrolled and completed the full study protocol. Both types of OAs were efficient in reducing the patient's AHI in comparison to baseline (i.e., without OA). However, there was no significant difference in AHI reduction between the semi-fixed and fixed OA devices. Regarding the side effect of temporomandibular joint pain and patient preference, the semi-fixed OA device was superior to the fixed OA device on both measures. Conclusion: While both semi-fixed and fixed OAs are effective in treating patients with OSA, semi-fixed OAs are superior in regards to both patient preference and reduced side effects. Thus, semi-fixed OAs may be the preferred therapeutic modality for OSA.

The nuclear lamina regulates chromatin organization and gene positioning. Here the authors show that CROWDED NUCLEI proteins contribute to the meshwork lamina structure in Arabidopsis nuclei and regulate copper tolerance by promoting lamina association and expression of copper response genes.

Abstract Introduction Pain has been identified as a risk factor for cognitive dysfunction, which in turn affects pain perception. Although pain, cognitive dysfunction, and their interaction are clinically important, the neural mechanism connecting the two phenomena remains unclear. Methods The resting-state brain activity of 38 participants was measured using magnetoencephalography before and after the patients underwent selective nerve root block (SNRB) for the treatment of their pain. We then assessed the extent to which these data correlated with the subjective levels of pain experienced by the patients across SNRB based on the visual analogue scale and the cognitive status of the patients measured after SNRB using the Japanese versions of the Mini-Mental State Examination (MMSE-J). Results Slow oscillations (delta) in the right precentral gyrus, right middle temporal gyrus, and left superior frontal gyrus were negatively correlated with the subjective level of pain, and fast oscillations (gamma) in the right insular cortex and right middle temporal gyrus before SNRB were negatively correlated with the MMSE-J score afterwards. These correlations disappeared after SNRB. Conclusion The presently observed changes in neural activity, as indicated by oscillation changes, might represent the transient bridge between pain and cognitive dysfunction in patients with severe pain. Our findings underscore the importance of treating pain before a transient diminishment of cognitive function becomes persistent.

Aims. This study is aimed at clarifying the relationship between visit-to-visit variability of glycated hemoglobin (HbA1c) and the risk of diabetic kidney disease (DKD) and to identifying the most useful index of visit-to-visit variability of HbA1c. Methods. This clinic-based retrospective longitudinal study included 699 Japanese type 2 diabetes mellitus patients. Visit-to-visit variability of HbA1c was calculated as the internal standard deviation of HbA1c (HbA1c-SD), the coefficient of variation of HbA1c (HbA1c-CV), the HbA1c change score (HbA1c-HVS), and the area under the HbA1c curve (HbA1c-AUC) with 3-year serial HbA1c measurement data, and the associations between these indices and the development/progression of DKD were examined. Results. Cox proportional hazards models showed that the HbA1c-SD and HbA1c-AUC were associated with the incidence of microalbuminuria, independently of the HbA1c level. These results were verified and replicated in propensity score (PS) matching and bootstrap analyses. Moreover, the HbA1c-SD and HbA1c-AUC were also associated with oxidized human serum albumin (HSA), an oxidative stress marker. Conclusions. Visit-to-visit variability of HbA1c was an independent risk factor of microalbuminuria in association with oxidative stress among type 2 diabetes mellitus patients. HbA1c-AUC, a novel index of HbA1c variability, may be a potent prognostic indicator in predicting the risk of microalbuminuria.

A lipoma is a benign tumor, where the parenchyma is composed of adipose tissue. Lipomas comprise 0.1%–5% of all benign tumors in the oral cavity. A 43-year-old man, with a known masticatory disorder, visited the Department of Oral Surgery at our hospital because of a facial swelling. The swelling, which had worsened over 15 years, was not painful, but the patient had discomfort while eating and talking. A detailed examination revealed a smooth, elastic, soft, circular, and yellowish pink pedunculated tumor-like lesion, with a diameter of approximately 40 mm, on the right buccal mucosa. An oval-shaped neoplastic lesion with a well-defined border of 40 mm×20 mm was noted on MRI. Based on these results, the lesion was characterized as being a benign lipoma. The tumor was resected under local anesthesia. The pedunculated tumor was excised with an electric knife, and the wound was sutured. No trismus or paresthesia was noted on the postoperative follow-up.

Hepatocyte growth factor (HGF) has neuroprotective effects against ischemia-induced injuries. Dental pulp stem cell (DPSC) transplantation attenuates tissue injury in the brain of rats with post-transient middle cerebral artery occlusion. We sought to determine whether DPSCs that overexpress HGF can enhance their therapeutic effects on brain damage post-ischemia/reperfusion injury. Treatment with DPSCs overexpressing HGF reduced infarct volumes compared to unmodified DPSC treatment at 3 and 7 days post-transient middle cerebral artery occlusion. The use of unmodified DPSCs and DPSCs overexpressing HGF was associated with improved motor function compared to that with administration of vehicle at 7 days post-transient middle cerebral artery occlusion. DPSCs overexpressing HGF significantly inhibited microglial activation and pro-inflammatory cytokine production along with suppression of neuronal degeneration. Post-reperfusion, DPSCs overexpressing HGF attenuated the decreases in tight junction proteins, maintained blood-brain barrier integrity, and increased microvessel density in peri-infarct areas. The administration of DPSCs overexpressing HGF during the acute phase of stroke increased their neuroprotective effects by modulating inflammation and blood-brain barrier permeability, thereby promoting improvements in post-ischemia/reperfusion brain injury. Keywords: focal cerebral ischemia, hepatocyte growth factor, dental pulp stem cells, gene transfer, ex vivo therapy, intravenous transplantation, neuroprotection

Leguminous plants host nitrogen-fixing bacteria in root nodules, but cease symbiosis when sufficient nitrogen is available. Here, the authors show that the Lotus japonicus transcription factor NRSYM1 activates the production of CLE-RS2 in nitrogen-sufficient conditions to prevent nodulation

The three-dimensional (3D) arrangement of cells in tissues provides an anatomical basis for analyzing physiological and biochemical aspects of plant and animal cellular development and function. In this study, we established a protocol for tissue clearing and 3D imaging in rice. Our protocol is based on three improvements: clearing with iTOMEI (clearing solution suitable for plants), developing microscopic conditions in which the Z step is optimized for 3D reconstruction, and optimizing cell-wall staining. Our protocol successfully 3D imaged rice shoot apical meristems, florets, and root apical meristems at cellular resolution throughout whole tissues. Using fluorescent reporters of auxin signaling in rice root tips, we also revealed the 3D distribution of auxin signaling events that are activated in the columella, quiescent center, and multiple rows of cells in the stele of the root apical meristem. Examination of cells with higher levels of auxin signaling revealed that only the central row of cells was connected to the quiescent center. Our method provides opportunities to observe the 3D arrangement of cells in rice tissues.

Abstract A micromachine constructed to possess various chemical and mechanical functions is one of the ultimate targets of technology. Conventional lithographic processes can be used to form complicated structures. However, they are basically limited to rigid and static structures with poor surface properties. Here, we demonstrate a novel method for assembling responsive and functional microstructures from diverse particles modified with DNA strands. The DNA strands are designed to form hairpins at room temperature and denature when heated. Structures are assembled through the simultaneous manipulation and heating of particles with “hot” optical tweezers, which incorporates the particles one by one. The flexible connection formed by DNA strands allows the responsive deformation of the structures with local controllability of the structural flexibility. We assembled a microscopic robot arm actuated by an external magnet, a hinge structure with a locally controlled connection flexibility and a three-dimensional double helix structure. The method is simple and can also be applied to build complex biological tissues from cells.

Among seven homologs of cytochrome b561 in a model organism C. elegans, Cecytb-2 was confirmed to be expressed in digestive organs and was considered as a homolog of human Dcytb functioning as a ferric reductase. Cecytb-2 protein was expressed in Pichia pastoris cells, purified, and reconstituted into a phospholipid bilayer nanodisc. The reconstituted Cecytb-2 in nanodisc environments was extremely stable and more reducible with ascorbate than in a detergent-micelle state. We confirmed the ferric reductase activity of Cecytb-2 by analyzing the oxidation of ferrous heme upon addition of ferric substrate under anaerobic conditions, where clear and saturable dependencies on the substrate concentrations following the Michaelis–Menten equation were observed. Further, we confirmed that the ferric substrate was converted to a ferrous state by using a nitroso-PSAP assay. Importantly, we observed that the ferric reductase activity of Cecytb-2 became enhanced in the phospholipid bilayer nanodisc.

The panel patterns of soccer balls that change with each World Cup have a significant impact on the balls’ aerodynamic and flight characteristics. In this study, the aerodynamic forces of eleven types of soccer ball with different panel patterns were measured in a wind tunnel experiment. We characterized the panel shapes of soccer balls by the length, cross-sectional area, and the panel grooves’ volume. The results confirmed that the drag and drag crisis characteristics are dependent on the groove length and volumes. Flow separation points were visualized by an oil film experiment and particle image velocimetry (PIV) measurement to understand the drag crisis of the soccer balls. The results showed that the panel shape of the ball significantly changes the position of the separation point near the critical region, where the drags crisis occurs. In the critical region, laminar and turbulent flows coexist on the ball. On the other hand, the effect of panel shape on the separation point position is small in subcritical and supercritical states.

Stroke is the most prevalent cardiovascular disease worldwide, and is still one of the leading causes of death and disability. Stem cell-based therapy is actively being investigated as a new potential treatment for certain neurological disorders, including stroke. Various types of cells, including bone marrow mononuclear cells, bone marrow mesenchymal stem cells, dental pulp stem cells, neural stem cells, inducible pluripotent stem cells, and genetically modified stem cells have been found to improve neurological outcomes in animal models of stroke, and there are some ongoing clinical trials assessing their efficacy in humans. In this review, we aim to summarize the recent advances in cell-based therapies to treat stroke.

The soccer ball panel pattern, which changes every World Cup, greatly affects the ball’s aerodynamics and flight characteristics. In this study, the fluid force of 11 soccer balls with different panel patterns was measured by wind tunnel tests. The drag crises with different Reynolds numbers were confirmed depending on the panel shape. To understand this, the shapes of panel grooves were measured and the relationship between them was investigated. The flow separation point was also visualized by the oil film method and the particle image velocimetry (PIV) analysis. The separation points were confirmed to be different depending on the panel groove by the oil film method in a supercritical Reynolds region. The flow separation points were found to be almost the same position in the subcritical and supercritical state and to be partly different around the Reynolds number of drag crisis.

The oxidant/antioxidant imbalance plays a pivotal role in the lung. Uric acid (UA), an endogenous antioxidant, is highly present in lung tissue, however, its impact on lung function under pathophysiological conditions remains unknown. In this work, pharmacological and genetic inhibition of UA metabolism in experimental mouse models of acute and chronic obstructive pulmonary disease (COPD) revealed that increased plasma UA levels improved emphysematous phenotype and lung dysfunction in accordance with reduced oxidative stress specifically in female but not in male mice, despite no impact of plasma UA induction on the pulmonary phenotypes in nondiseased mice. In vitro experiments determined that UA significantly suppressed hydrogen peroxide (H2O2)-induced oxidative stress in female donor-derived primary human bronchial epithelial (NHBE) cells in the absence of estrogen, implying that the benefit of UA is limited to the female airway in postmenopausal conditions. Consistently, our clinical observational analyses confirmed that higher blood UA levels, as well as the SLC2A9/GLUT9 rs11722228 T/T genotype, were associated with higher lung function in elderly human females. Together, our findings provide the first unique evidence that higher blood UA is a protective factor against the pathological decline of lung function in female mice, and possibly against aging-associated physiological decline in human females.

Background The aims of the present study were to investigate the relationships between prior direct oral anticoagulant (DOAC) therapy and infarct volume and the site of arterial occlusion in patients with acute ischemic stroke and non‐valvular atrial fibrillation. Methods and Results From March 2011 through November 2016, consecutive patients with acute ischemic stroke in the middle cerebral artery territory and non‐valvular atrial fibrillation were recruited. The infarct volume was assessed semi‐automatically using initial diffusion‐weighted imaging, and the arterial occlusion site was evaluated on magnetic resonance angiography. The effect of prior DOAC treatment on the site of arterial occlusion was assessed by multivariate ordinal logistic regression analysis. A total of 330 patients (149 women; median age 79 [quartiles 71–86] years; median National Institutes of Health Stroke Scale score 11 [4–21]) were enrolled. Of these, 239 were on no anticoagulant, 40 were undertreated with a vitamin K antagonist (VKA), 22 were sufficiently treated with VKA (PT‐INR ≥1.6), and 29 were on a DOAC before the acute ischemic stroke. The infarct volume on admission differed among the groups (median 14.5 [2.0–59.8] cm3 in patients with no anticoagulation, 24.8 [2.1–63.0] in undertreated VKA, 1.3 [0.3–13.5] in sufficient VKA, and 2.3 [0.5–21.0] in DOAC, P=0.001). Multivariate analysis showed that prior DOAC treatment was independently and negatively associated with more proximal artery occlusion (odds ratio [OR] 0.34, P=0.015), compared with no anticoagulant. Conclusions DOAC treatment before the event was associated with smaller infarct volume and decreased risk of greater proximal artery occlusion in acute ischemic stroke patients with non‐valvular atrial fibrillation, compared with no anticoagulation.

Xylem vessels are important for water conduction in vascular plants. The VASCULAR-RELATED NAC-DOMAIN (VND) family proteins, master regulators of xylem vessel cell differentiation in Arabidopsis thaliana, can upregulate a set of genes required for xylem vessel cell differentiation, including those involved in secondary cell wall (SCW) formation and programmed cell death (PCD); however, it is not fully understood how VND activity levels influence these processes. Here, we examined the Arabidopsis VND7-VP16-GR line, in which VND7 activity is post-translationally activated by treatments with different concentrations of dexamethasone (DEX), a synthetic glucocorticoid. Our observations showed that 1 nM DEX induced weak SCW deposition, but not PCD, whereas 10 or 100 nM DEX induced both SCW deposition and PCD. The decreased chlorophyll contents and SCW deposition were apparent after 24 h of 100 nM DEX treatment, but became evident only after 48 h of 10 nM DEX treatment. Moreover, the lower DEX concentrations delayed the upregulation of VND7 downstream genes, and decreased their induction levels. They collectively suggest that the regulation of VND activity is important not only to initiate xylem vessel cell differentiation, but also regulate the quality of the xylem vessels through VND-activity-dependent upregulation of the PCD- and SCW-related genes.

Methods for preventing medication-related osteonecrosis of the jaw (MRONJ) in cancer patients who have received high-dose bisphosphonate (BP) or denosumab (Dmab) have not yet been established. Tooth extraction after starting medication has been believed to be a major risk factor for MRONJ, and therefore this procedure tends to be avoided. This study investigated the risk factors for MRONJ, with a special reference to the correlation between tooth extraction and development of MRONJ. One hundred and thirty-five cancer patients who were administrated high-dose BP or Dmab were enrolled in the study. Demographic factors, general condition, treatment factors, and dental findings were examined retrospectively using medical records and panoramic X-ray findings. The cumulative occurrence rate of MRONJ was calculated using the Kaplan-Meier method, and the correlation between these variables and development of MRONJ was analyzed by univariate and multivariate Cox regression analysis. MRONJ developed in 18 of 135 patients. The 1-, 2-, and 3-year cumulative occurrence rates were 8.6%, 21.5%, and 29.2%, respectively. The duration of medication before first visit to the dental unit and the presence of a tooth with clinical symptoms were significantly correlated with the development of MRONJ. The rate of MRONJ occurrence in patients who had teeth with clinical symptoms, but who did not undergo tooth extraction, became higher 2 years later than that in patients who underwent extraction of teeth with symptoms, although not significant. Early dental examination and effective preventative care to avoid infection/inflammation are important for preventing MRONJ.

Background: We have recently reported that the susceptibility vessel sign (SVS) at the proximal portion of the horizontal (M1) middle cerebral artery (MCA) on T2*-weighted MRI is a strong predictor for no early recanalization after intravenous recombinant tissue plasminogen activator (t-PA) therapy. However, it is unclear whether the presence of the SVS at other locations, such as distal M1, the vertical portion (M2) of the MCA, and distal branches (MCA distal), is a predictor for no early recanalization in acute ischemic stroke patients. Methods: The SVS was defined as a hypointense signal of the MCA on T2*-weighted MRI on admission. The locations of the SVS were classified as M1 proximal, M1 distal, and MCA distal. M1 proximal SVS was defined as an SVS at the origin of the M1. M1 distal SVS was any M1 SVS not including the origin of the M1. MCA distal SVS was an SVS further away from M1. Early recanalization was defined as a new appearance of at least one of the distal branches on MRA within 1 h after t-PA therapy. A good outcome at 3 months was defined as a modified Rankin Scale (mRS) score of 0-1. Results: Consecutive acute stroke patients admitted to our stroke center and treated with t-PA between October 2005 and October 2012 were enrolled. There were 158 patients [median age, 78 (71-84) years; 84 (53%) males; median National Institutes of Health Stroke Scale score, 16 (10-20)]. Internal carotid artery occlusion was seen in 18 (72%) of the 25 patients with M1 proximal SVS, in 3 (14%) of the 22 patients with M1 distal SVS, in 4 (9%) of the 44 patients with MCA distal SVS, and in 18 (27%) of the 67 patients with No SVS (p Conclusion: M1 proximal SVS on T2*-weighted MRI is a strong predictor for no early recanalization, and all patients with it had a poor outcome. However, M1 distal SVS and MCA distal SVS were not predictors for no early recanalization, and half of the patients had a poor outcome.

Background: Approximately 25% of acute stroke patients were excluded from intravenous thrombolysis using recombinant tissue plasminogen activator (IV-tPA) because of unknown onset time. Recent studies have shown that patients with unknown onset time would be able to receive IV-tPA when showing no ischemia on fluid-attenuated inversion recovery (negative FLAIR). The present study evaluated the safety and feasibility of IV-tPA in patients with unknown onset time and negative FLAIR compared to those with standard IV-tPA. Methods: Stroke patients with unknown onset time were prospectively enrolled. Only patients with an occlusion of the internal carotid artery (ICA) and/or middle cerebral artery (M1 and M2) with a Diffusion-Weighted Imaging-Alberta Stroke Program Early CT Score (DWI-ASPECTS) ≥5 were analyzed. IV-tPA was performed within 3 h from the ‘first found abnormal time' if the patient showed negative FLAIR. Standard IV-tPA patients were extracted from our registry as controls after having been matched by age and occluded artery to the negative FLAIR (N-F) group. Results: Twenty patients in the N-F group and 60 in the control group were included. National Institutes of Health Stroke Scale (NIHSS) scores [median 18 (interquartile range 13-20) vs. 17 (12-20), p = 0.609] and DWI-ASPECTS [9 (7-9) vs. 8 (5-9), p = 0.213] were similar between the 2 groups. ICA occlusion was seen in 35%, M1 in 50%, and M2 in 15% in both groups. None of the N-F group and 1 (2%) of the control group experienced symptomatic intracerebral hemorrhage (p = 1.000). Recanalization within 1 h after IV-tPA was achieved in 6 (30%) patients in the N-F group and 24 (40%) in the control group (p = 0.595). Recanalization at 24 h after IV-tPA was seen in 13 (65%) patients in the N-F group and 43 (72%) in the control group (p = 0.584). At 7 days, 8 (40%) in the N-F group and 28 (47%) in the control group had a dramatic recovery (defined as a ≥10-point reduction in the total NIHSS score or a score of 0 or 1) (p = 0.796). At 3 months, a favorable outcome (modified Rankin scale score, 0-2) was seen in 47% in the N-F group and 33% in the control group (p = 0.365). Conclusion: IV-tPA in negative FLAIR patients with unknown onset time appears safe and feasible.

We investigated the physical and chemical stabilities of sulfur and phosphorus molecules encapsulated in a mesoporous carbon (MPC) and two kinds of single-walled carbon nanotubes (SWCNTs) having different cylindrical pore diameters. The sublimation temperatures of sulfur molecules encapsulated in MPC and the two kinds of SWCNTs were measured by thermo-gravimetric measurements. It was found that the sublimation temperature of sulfur molecules encapsulated in SWCNTs having mean tube diameter of 1.5 nm is much higher than any other molecules encapsulated in larger pores. It was also found that the capacity fading of lithium-sulfur battery can be diminished by encapsulation of sulfur molecules in SWCNTs. We also investigated the electrochemical properties of phosphorus molecules encapsulated in SWCNTs (P@SWCNTs). It was shown that P@SWCNT can adsorb and desorb both Li and Na ions reversibly.

A capacitance-based void fraction sensor has been developed for the rocket or airbreathing engines, which is simple and do not disturb the flow. Typical conventional sensors usually have two concave electrodes mounted on the outer wall of the dielectric tube. They are relatively low accuracy if they have a noise shield; the maximum measurement error is over 30% in our research. The aim of this study is to improve the measurement accuracy while keeping the advantage of simplicity, mountability and non-intrusive characteristics. A theoretical formulae and electromagnetic field analysis, EFA, are used to design the sensors and are compared to an experiment using air/silicon-oil mixture flow. As the result, a newly developed asymmetrical type sensor which consists of asymmetric flat electrodes with side walls shows good performance; the inaccuracy between true void fraction and measured void fraction is 6% for the stratified flow.

Background and Purpose: Our aim was to confirm the clinical relationship between the Kurashiki Prehospital Stroke Scale (KPSS) scored by paramedics and favorable outcomes in patients with modified Rankin scale (mRS) scores of 0–1 assessed 3 months after symptom onset. Methods: We enrolled patients with acute stroke and transient ischemic attack showing symptoms on admission. Paramedics transferred patients to our hospital after estimating stroke severity using the KPSS. After categorizing patients into either the mRS 0–1 group (favorable outcome) or the mRS 2–6 group (no favorable outcome), we compared the background data between the two groups. We assessed KPSS scores predictive of a favorable outcome. Multivariate regression modeling was conducted to identify factors independently associated with a favorable outcome. Results: The study cohort comprised 147 patients with a premorbid status of mRS 0–1: 69 patients (47%) of them were in the mRS 0–1 group and 78 (53%) in the mRS 2–6 group at the follow-up 3 months after symptom onset. The median KPSS score was lower in the mRS 0–1 group than in the mRS 2–6 group (1 vs. 4, p Conclusion: KPSS score

We have developed a new biodegradable scaffold that does not require any cell seeding to create an in-situ tissue-engineering vasculature (iTEV). Animal experiments were conducted to test its characteristics and long-term efficacy. An 8-mm tubular biodegradable scaffold, consisting of polyglycolide knitted fibers and an L-lactide and ε-caprolactone copolymer sponge with outer glycolide and ε-caprolactone copolymer monofilament reinforcement, was implanted into the inferior vena cava (IVC) of 13 canines. All the animals remained alive without any major complications until euthanasia. The utility of the iTEV was evaluated from 1 to 24 months postoperatively. The elastic modulus of the iTEV determined by an intravascular ultrasound imaging system was about 90% of the native IVC after 1 month. Angiography of the iTEV after 2 years showed a well-formed vasculature without marked stenosis or thrombosis with a mean pressure gradient of 0.51 ± 0.19 mmHg. The length of the iTEV at 2 years had increased by 0.48 ± 0.15 cm compared with the length of the original scaffold (2-3 cm). Histological examinations revealed a well-formed vessel-like vasculature without calcification. Biochemical analyses showed no significant differences in the hydroxyproline, elastin, and calcium contents compared with the native IVC. We concluded that the findings shown above provide direct evidence that the new scaffold can be useful for cell-free tissue-engineering of vasculature. The long-term results revealed that the iTEV was of good quality and had adapted its shape to the needs of the living body. Therefore, this scaffold would be applicable for pediatric cardiovascular surgery involving biocompatible materials.

BACKGROUND: Because H(2)O(2) is generated by various oxidase-catalyzed reactions, a highly sensitive determination method of H(2)O(2) is applicable to measurements of low levels of various oxidases and their substrates such as glucose, lactate, glutamate, urate, xanthine, choline, cholesterol and NADPH. We propose herein a new, highly sensitive method for the measurement of H(2)O(2) and glucose using fluorescence correlation spectroscopy (FCS). METHODOLOGY/PRINCIPAL FINDINGS: FCS has the advantage of allowing us to determine the number of fluorescent molecules. FCS measures the fluctuations in fluorescence intensity caused by fluorescent probe movement in a small light cavity with a defined volume generated by confocal illumination. We thus developed a highly sensitive determination system of H(2)O(2) by FCS, where horseradish peroxidase (HRP) catalyzes the formation of a covalent bond between fluorescent molecules and proteins in the presence of H(2)O(2). Our developed system gave a linear calibration curve for H(2)O(2) in the range of 28 to 300 nM with the detection limit of 8 nM. In addition, by coupling with glucose oxidase (GOD)-catalyzed reaction, the method allows to measure glucose in the range of 80 nM to 1.5 µM with detection limit of 24 nM. The method was applicable to the assay of glucose in blood plasma. The mean concentration of glucose in normal human blood plasma was determined to be 4.9 mM. CONCLUSIONS/SIGNIFICANCE: In comparison with commercial available methods, the detection limit and the minimum value of determination for glucose are at least 2 orders of magnitude more sensitive in our system. Such a highly sensitive method leads the fact that only a very small amount of plasma (20 nL) is needed for the determination of glucose concentration in blood plasma.