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The pressure-induced amorphization (PIA) of ice and clathrate hydrates occurs at temperatures significantly below their melting and decomposition points. The PIA of type I clathrate hydrates containing methane and ethane as guest molecules was investigated using Raman and infrared (IR) spectroscopy. With isothermal compression at 100 K, methane hydrate (MH) underwent PIA at 2-3.5 GPa, whereas ethane hydrate (EH) underwent PIA at 4.0-5.5 GPa. The type I clathrate structure consists of small (5 12 ) and large (5 12 6 2 ) cages. The Raman results revealed that the collapsed small and large cages in the amorphous forms of MH and EH were not distinguishable. The collapsed cages, including the methane and ethane molecules, were similar to the small and large cages, respectively. Their water networks were folded or expanded during the PIA process so that the cavity sizes of the collapsed cages were compatible with those of the guest molecules. Peaks in the IR spectra of crystalline MH assignable to the ro-vibrational transition of methane in large cages were observed in the C-H stretching wavenumber region below 40 K. The ro-vibrational IR band disappeared after amorphization, suggesting that the rotational motion of the methane molecule in the large cage was frozen by the collapse, as reported in previous dielectric spectroscopic and simulation studies. This study contributes to a better understanding of the changes in the local structure around guest molecules during PIA and the dynamics of the guest molecules.

Pregnancy of unknown location (PUL) is a condition in which a pregnancy test, such as elevation of serum or urine β-human chorionic gonadotrophin (hCG) level, is rendered positive; however, intrauterine or extrauterine pregnancy cannot be confirmed by transvaginal sonography (TVS). Diagnostic dilation and curettage (D&C) or laparoscopy may be performed to search for the pregnancy location. We experienced a case of PUL in which D&C was performed and histological examination revealed a tiny complete hydatidiform mole within the uterine contents. A retrospective review of the clinical course of this case, such as the evaluation of serum β-hCG levels and TVS findings, suggested that this medical entity could be explained by a tiny hydatidiform mole. In PUL, during D&C, when abnormal villi are detected, even if the lesion is tiny, a suspicion of a hydatidiform mole should be considered by the pathologists, and immunostaining and/or chromosome testing/molecular genotyping should be subsequently performed. Whether a tiny hydatidiform mole poses a risk of persistent gestational trophoblastic disease requires further study based on the accumulation of cases. D&C for PUL patients may be a useful procedure to determine such diagnoses and pick up cases., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Kobayashi et al.)

Cryptdin-4 (crp4) is an enteric α-defensin derived from mice, and is a main mediator of immunity to oral infections and a determinant of the composition of the intestinal microbiota. Structurally, crp4 exists in two states: the oxidized form (crp4oxi), constrained by three invariant disulfide bonds, and the reduced form (crp4red) with six free thiol groups, both of which exist in the intestinal tract. In this study, the antibacterial mechanisms of crp4 in both forms under aerobic and anaerobic conditions were investigated using Escherichia coli ( E. coli ), an anaerobic facultative bacterium, as a model. Fluorescent dye studies revealed that both crp4oxi and crp4red exhibited antimicrobial activity against cells cultured under aerobic conditions via rapid membrane depolarization. Furthermore, the antioxidant treatment experiments suggested that only crp4oxi exhibited antimicrobial activity by the induction and accumulation of reactive oxygen species (ROS). However, under anaerobic culture conditions, the ability of both forms to disrupt the function of bacterial membranes decreased and activity was greatly reduced, but crp4red maintained some antimicrobial activity. This activity may be due to the inhibition of intracellular functions by DNA binding. Altogether, these data indicate that, according to its redox structure and the environmental redox conditions, crp4 could perform different antimicrobial activities via different mechanisms.

Background: Because of revisions to insurance reimbursement costs, medical fees have changed for investigations and percutaneous coronary intervention (PCI) treatment of chronic coronary syndrome (CCS). In this retrospective study, we investigated these changes and their effects on mortality and cardiovascular events., Methods and results: We included 1,483 patients who underwent elective PCI for CCS between April 2010 and September 2019. The primary outcomes were changes in PCI procedure fees and all included hospitalization fees due to the biennial revisions of reimbursement costs across 5 time periods (~2 years each). Secondary outcomes were rates of survival and freedom from major adverse cerebral and cardiovascular events (MACCE) in each time period. Patient characteristics were generally unchanged over the study period; however, treatment procedures changed significantly, with changes in the approach site (from transfemoral to transradial access; P<0.0001) and final device (from bare-metal stents to drug-eluting stents; P<0.0001), and an increase in the use of imaging modalities (P<0.0001). Medical fee parameters (primary outcomes) decreased significantly from 2010 to 2019 (P<0.001): PCI procedure fees decreased by 25%, whereas all included hospitalization fees decreased by 20%. There were no significant differences in survival or freedom-from-MACCE rates between periods., Conclusions: Because of revisions to reimbursement prices, there were rapid and significant decreases in PCI procedure and hospitalization fees for CCS. These changes had no effect on mortality or cardiovascular events.

Pancreatic cancer is highly metastatic and has poor prognosis, mainly due to delayed detection, often after metastasis has occurred. A novel method to enable early detection and disease intervention is strongly needed. Here we unveil for the first time that pancreatic cancer cells (PANC-1) and secreted exosomes express MUC1 bearing cancer-relevant dynamic epitopes recognized specifically by an anti-MUC1 antibody (SN-131), which binds specifically core 1 but not core 2 type O -glycans found in normal cells. Comprehensive assessment of the essential epitope for SN-131 indicates that PANC-1 cells produce dominantly MUC1 with aberrant O -glycoforms such as Tn, T, and sialyl T (ST) antigens. Importantly, SN-131 showed the highest affinity with MUC1 bearing ST antigen at the immunodominant DTR motif ( K D = 1.58 nM) independent of the glycosylation states of other Ser/Thr residues in the MUC1 tandem repeats. The X-ray structure revealed that SN-131 interacts directly with Neu5Ac and root GalNAc of the ST antigen in addition to the proximal peptide region. Our results demonstrate that targeting O -glycosylated "dynamic neoepitopes" found in the membrane-tethered MUC1 is a promising therapeutic strategy for improving the treatment outcome of patients with pancreatic cancer., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Nuclear magnetic resonance (NMR)-based metabolomics, which comprehensively measures metabolites in biological systems and investigates their response to various perturbations, is widely used in research to identify biomarkers and investigate the pathogenesis of underlying diseases. However, further applications of high-field superconducting NMR for medical purposes and field research are restricted by its high cost and low accessibility. In this study, we applied a low-field, benchtop NMR spectrometer (60 MHz) employing a permanent magnet to characterize the alterations in the metabolic profile of fecal extracts obtained from dextran sodium sulfate (DSS)-induced ulcerative colitis model mice and compared them with the data acquired from high-field NMR (800 MHz). Nineteen metabolites were assigned to the 60 MHz 1 H NMR spectra. Non-targeted multivariate analysis successfully discriminated the DSS-induced group from the healthy control group and showed high comparability with high-field NMR. In addition, the concentration of acetate, identified as a metabolite with characteristic behavior, could be accurately quantified using a generalized Lorentzian curve fitting method based on the 60 MHz NMR spectra.

Background: There are ongoing efforts to examine the effect of 5-HT1A receptor partial agonists as an add-on therapy for several symptoms of schizophrenia. By conducting a systematic review and meta-analysis, we evaluated whether augmentation with 5-hydroxtrypatamine (5-HT)1A partial agonists of the azapirone class improves psychotic symptoms and attention/processing speed, a key domain of cognition, in patients with schizophrenia., Methods: A literature search was performed from 1987 to February 25, 2022, to identify randomized controlled trials. The standardized mean difference (SMD) with 95% confidence intervals (CI) was calculated when there were 2 or more studies. Seven studies, involving 435 patients, met the inclusion criteria., Results: Random-effects model meta-analyses revealed that add-on therapy with buspirone or tandospirone had a significant beneficial effect on overall psychotic symptoms (SMD = -1.13, 95% CI = -1.98 to -0.27) and positive symptoms (SMD = -0.72, 95% CI =-1.31 to -0.12), while the effect on negative symptoms did not reach statistical significance (SMD = -0.93, 95% CI = -1.90 to 0.04). A significant positive effect was also observed on attention/processing speed (SMD = 0.37, 95% CI = 0.12 to 0.61)., Conclusions: These findings support the idea that some compounds that stimulate 5-HT1A receptors provide an effective pharmacologic enhancer in the treatment of schizophrenia. Further clinical trials are warranted to determine the benefits of the adjunctive use of 5-HT1A partial agonists in ameliorating symptoms and improving functional outcomes in patients with schizophrenia or other psychiatric disorders., (© The Author(s) 2023. Published by Oxford University Press on behalf of CINP.)

Nonalcoholic steatohepatitis (NASH) is a chronic liver disease characterized by fibrosis that develops from fatty liver. Disruption of intestinal microbiota homeostasis, dysbiosis, is associated with fibrosis development in NASH. An antimicrobial peptide α-defensin secreted by Paneth cells in the small intestine is known to regulate composition of the intestinal microbiota. However, involvement of α-defensin in NASH remains unknown. Here, we show that in diet-induced NASH model mice, decrease of fecal α-defensin along with dysbiosis occurs before NASH onset. When α-defensin levels in the intestinal lumen are restored by intravenous administration of R-Spondin1 to induce Paneth cell regeneration or by oral administration of α-defensins, liver fibrosis is ameliorated with dissolving dysbiosis. Furthermore, R-Spondin1 and α-defensin improved liver pathologies together with different features in the intestinal microbiota. These results indicate that decreased α-defensin secretion induces liver fibrosis through dysbiosis, further suggesting Paneth cell α-defensin as a potential therapeutic target for NASH., (© 2023. The Author(s).)

Competing Interests: The authors declare no conflict of interest.

Sleep is essential for our health. Short sleep is known to increase disease risks via imbalance of intestinal microbiota, dysbiosis. However, mechanisms by which short sleep induces dysbiosis remain unknown. Small intestinal Paneth cell regulates the intestinal microbiota by secreting antimicrobial peptides including α-defensin, human defensin 5 (HD5). Disruption of circadian rhythm mediating sleep-wake cycle induces Paneth cell failure. We aim to clarify effects of short sleep on HD5 secretion and the intestinal microbiota. Fecal samples and self-reported sleep time were obtained from 35 healthy middle-aged Japanese (41 to 60-year-old). Shorter sleep time was associated with lower fecal HD5 concentration ( r  = 0.354, p  = 0.037), lower centered log ratio (CLR)-transformed abundance of short-chain fatty acid (SCFA) producers in the intestinal microbiota such as [Ruminococcus] gnavus group ( r  = 0.504, p  = 0.002) and Butyricicoccus ( r  = 0.484, p  = 0.003), and lower fecal SCFA concentration. Furthermore, fecal HD5 positively correlated with the abundance of these genera and SCFA concentration. These findings suggest that short sleep relates to disturbance of the intestinal microbiota via decreased HD5 secretion.

Objective: The purpose of this study was to investigate if leg cycling could reduce lower extremity spasticity in patients with cerebral palsy (CP). In addition, we investigated whether the intervention could cause changes in the modulation of presynaptic inhibition., Methods: This study was a quasi-experimental study, with pretest-posttest for 1 group. Participants in this experiment were eight adult patients with CP with lower extremity spasticity. Spasticity parameters assessed were the amplitude of soleus maximum Hoffmann's reflex (H max ) and maximum angular velocity (MAV) of knee flexion measured using the pendulum test. D1 inhibition, which seems to be related to the presynaptic inhibition, was recorded by measuring soleus Hoffmann's reflex (H-reflex) with conditioned electric stimuli to the common peroneal nerve., Results: D1 inhibition was significantly enhanced immediately by the cycling intervention. The amplitude of the soleus H max was significantly depressed, and there was significant difference in H max /maximum M-wave. The MAV was increased due to inhibition of the stretch reflex., Conclusion: Leg cycling suppressed stretch reflex and H-reflex, and caused plasticity of inhibitory circuits in patients with CP with lower extremity spasticity. These findings strongly suggest that lower extremity spasticity can be improved by cycling movements., Competing Interests: The authors have no conflicts of interest in relation to this manuscript., (©2023 Japanese Society of Physical Therapy.)

Intestinal epithelial cells separate subepithelial tissues from luminal environment formed with food, incoming pathogens, and resident intestinal microbiota, etc., and elicit various intestinal function. Enteroid, a three-dimensional culture system of small intestinal epithelial cells, has been widely used for analyzing the intestinal function, further a transgenic enteroid was developed to investigate the molecular mechanisms. However, conventional transgenic enteroid production method, which transfer gene into single stem cells, has limitations including low efficiency and time-consuming. Here we show that by gene transfer into small intestinal isolated crypts maintaining stem cell niche, a transgenic enteroid was obtained quickly and efficiently. Isolated crypts were transfected by lentiviral vector without separating into single cells, and transgenic enteroid composed of all lineages of intestinal epithelial cells was generated at day 7 with yield of 56%, maintaining the intestinal function in drug transport and innate immunity. Our efficient and simple transgenic enteroid generation method enables high-throughput investigation of intestinal epithelial cells and contributes to understanding intestinal function., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Approximately 30% or more of the total proteins annotated from sequenced bacteria genomes are annotated as hypothetical or uncharacterized proteins. However, elucidation on the function of these proteins is hindered by the lack of simple and rapid screening methods, particularly with novel or hard-to-transform bacteria. In this report, we employed cell-penetrating peptide (CPP) -peptide nucleotide acid (PNA) conjugates to elucidate the function of such uncharacterized proteins in vivo within the native bacterium. Paenibacillus , a hard-to-transform bacterial genus, was used as a model. Two hypothetical genes showing amino acid sequence similarity to ι-carrageenases, termed cgi A and cgi B, were identified from the draft genome of Paenibacillus sp. strain YYML68, and CPP-PNA probes targeting the mRNA of the acyl carrier protein gene, acp P, and the two ι-carrageenase candidate genes were synthesized. Upon direct incubation of CPP-PNA targeting the mRNA of the acp P gene, we successfully observed growth inhibition of strain YYML68 in a concentration-dependent manner. Similarly, both the function of the candidate ι-carrageenases were also inhibited using our CPP-PNA probes allowing for the confirmation and characterization of these hypothetical proteins. In summary, we believe that CPP-PNA conjugates can serve as a simple and efficient alternative approach to characterize proteins in the native bacterium.

To investigate the relationship between the gut and skin (gut-skin axis), head skin hemodynamic responses to gut stimulation including the injection of acetic acid in nude mice were measured by spectroscopic video imaging, which was calculated using a modified Beer-Lambert formula. The relationship with blood proteins was also analyzed. The blood volume changes in three mice injected with acetic acid were highly reproducible in the mathematical model equation. Four proteins correlated with blood volume changes were all related to immunity. These results suggest that intestinal pH can alter the blood volume in the skin and induce immune-related responses., (Creative Commons Attribution license.)

Background: Sleep is one of the most important health-related factors. This cross-sectional study focused on sleep quality relates to systemic symptoms, including dental symptoms. Methods: Resource data were compiled from 7995 men and women aged 30 to 69 years, which is the core of the Japanese working population. The subjects were divided into four groups based on their answers to two questions, one on sleep time and one on sleep sufficiency, and groups were compared with other items in the questionnaire by means of a contingency table analysis (χ2 test). Results: Relationships were found between the sleep groups and basic attributes, the presence of subjective symptoms, and the presence of hospital visits. The items with significant relationships included 14 symptoms, such as lower back pain (p < 0.01) and four diseases, including high blood pressure (p < 0.01). A multinomial logistic regression was conducted with the sleep groups as objective variables. In the poor sleep group, significant odds ratios were found for four items, including hours of work (odds ratio: 2.53) and feeling listless (2.01). Conclusions: The results allowed multiple symptoms and diseases related to sleep quality to be identified, and different trends in the response rates of the groups were found. These results suggest that the useful classification of sleep quality groups according to health problems contributes to understanding the effects of different symptoms.

Introduction: Free-water (FW) imaging, a new analysis method for diffusion magnetic resonance imaging (MRI), can indicate neuroinflammation and degeneration. We evaluated FW in Alzheimer's disease (AD) using tau/inflammatory and amyloid positron emission tomography (PET)., Methods: Seventy-one participants underwent multi-shell diffusion MRI, 18 F-THK5351 PET, 11 C-Pittsburgh compound B PET, and neuropsychological assessments. They were categorized into two groups: healthy controls (HCs) ( n = 40) and AD-spectrum group (AD-S) ( n = 31) using the Centiloid scale with amyloid PET and cognitive function. We analyzed group comparisons in FW and PET, correlations between FW and PET, and correlation analysis with neuropsychological scores., Results: In AD-S group, there was a significant positive correlation between FW and 18 F-THK5351 in the temporal lobes. In addition, there were negative correlations between FW and cognitive function in the temporal lobe and cingulate gyrus, and negative correlations between 18 F-THK5351 and cognitive function in the same regions., Discussion: FW imaging could be a biomarker for tau in AD alongside clinical correlations., Competing Interests: None declared. Author disclosures are available in the supporting information., (© 2022 The Authors. Alzheimer's & Dementia: Translational Research & Clinical Interventions published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

The AFX stent graft (Endologix) has an active seal mechanism that can conform to an irregular vascular lumen. We modified the candy-plug technique using an AFX VERA suprarenal extension with restricted purse-string sutures to shape it into a candle-like contraption. We treated 2 patients with patent, dilated false lumens (FLs) after central aortic repair using this technique. This plug was deployed into the FL to block retrograde blood flow proximally. Partial or complete thrombosis of the FL was observed in both patients 6 months after surgery. This technique was feasible for FL occlusion., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Clusterin is a heavily glycosylated protein that is upregulated in various cancer and neurological diseases. The findings by the Hancock and Iliopoulos group that levels of the tryptic glycopeptide derived from plasma clusterin, 372 Leu-Ala-Asn-Leu-Thr-Gln-Gly-Glu-Asp-Gln-Tyr-Tyr-Leu-Arg 385 with a biantennary disialyl N -glycan (A2G2S2 or FA2G2S2) at Asn374 differed significantly prior to and after curative nephrectomy for clear cell renal cell carcinoma (RCC) patients motivated us to verify the feasibility of this glycopeptide as a novel biomarker of RCC. To determine the precise N -glycan structure attached to Asn374, whether A2G2S2 is composed of the Neu5Acα2,3Gal or/and the Neu5Acα2,6Gal moiety, we synthesized key glycopeptides having one of the two putative isomers. Selective reaction monitoring assay using synthetic glycopeptides as calibration standards allowed "top-down glycopeptidomics" for the absolute quantitation of targeted label-free glycopeptides in a range from 313.3 to 697.5 nM in the complex tryptic digests derived from serum samples of RCC patients and healthy controls. Our results provided evidence that the Asn374 residue of human clusterin is modified dominantly with the Neu5Acα2,6Gal structure and the levels of clusterin bearing an A2G2S2 with homo Neu5Acα2,6Gal terminals at Asn374 decrease significantly in RCC patients as compared with healthy controls. The present study elicits that a new strategy integrating the bottom-up glycoproteomics with top-down glycopeptidomics using structure-defined synthetic glycopeptides enables the confident identification and quantitation of the glycopeptide targets pre-determined by the existing methods for intact glycopeptide profiling., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

The direct and selective functionalization of inert C-H bonds via intramolecular hydrogen atom transfer (HAT) is an increasingly powerful tool in organic synthesis. Herein, we designed an efficient and facile iodine atom transfer in fluorinated alkyl iodides via 1,5-HAT. Our process enables site-selective iodination of unreactive C(sp 3 )-H bonds to afford di- and tri-fluorinated alkyl iodides in good yields. Furthermore, our process shows excellent atom economy and high functional group tolerance, including methyl, methoxy, chloro, cyano, and silyl moieties.

Background: Patients with schizophrenia show impairments of social cognition, which cause poor real-world functional outcomes. Transcranial direct current stimulation (tDCS) delivered to frontal brain areas has been shown to partially alleviate disturbances of social cognition. In this study, we aimed to determine whether multisession tDCS targeting the superior temporal sulcus (STS), a brain region closely related to social cognition, would improve social cognitive performance in patients with schizophrenia., Methods: This was an open-label, single-arm trial to investigate the benefits and safety of multisession tDCS over the left STS. Fifteen patients received tDCS (2 mA × 20 min) two times per day for 5 consecutive days. Anodal and cathodal electrodes were placed over the left STS and right supraorbital regions, respectively. Assessments with the Social Cognition Screening Questionnaire (SCSQ), the Hinting Task (HT), the Brief Assessment of Cognition in Schizophrenia (BACS), and the Positive and Negative Syndrome Scale (PANSS) were conducted at baseline and 1 month after the final stimulation., Results: Significant improvements were found on theory of mind, as measured using the SCSQ ( d = 0.53) and the HT ( d = 0.49). These changes on social cognition were not correlated with those of neurocognition, as measured using the BACS or psychotic symptoms, as measured using the PANSS. There were no adverse events of serious/moderate levels attributable to tDCS., Conclusion: These results suggest that administration of multisession tDCS with anode stimulation targeting the left STS provides a novel strategy to improve functional outcomes in patients with schizophrenia., Ethics Statement: The National Center of Neurology and Psychiatry Clinical Research Review Board (CRB3180006) approved this study., Trial Registration: This study was registered within the Japan Registry of Clinical Trials (jRCTs032180026)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yamada, Sueyoshi, Yokoi, Inagawa, Hirabayashi, Oi, Shirama and Sumiyoshi.)

Objectives: We devised a novel physician-modified endograft (PMEG) with hydrogel-reinforced fenestrations to provide a more secure connection with the bridging graft than fenestrations alone. We applied this novel PMEG in a clinical setting and evaluated the clinical and technical results., Methods: In this study, patients with complex thoraco-abdominal aortic pathologies involving the renal, superior mesenteric or coeliac artery were included. However, patients with pararenal abdominal aneurysm were excluded. Regardless of anatomical suitability, all patients referred to our hospital were enrolled. All patients were treated via compassionate use of PMEG. All PMEGs were used following the same procedure using hydrogel-reinforced fenestrations. A retrospective analysis was conducted on consecutive patients who were treated between October 2018 and April 2021., Results: Out of 40 patients, 29 and 11 were men and women, respectively. The median patient age was 73.6 (range: 49-87) years. Among the patients, 36 (90%) had true aneurysms, whereas the others had false lumen aneurysms and penetrating atherosclerotic ulcer. Despite anatomical challenges, all branches were successfully reconstructed. The mean operative time was 333 (standard deviation 98) min. Postoperative computed tomography angiography did not reveal type I and IIIc endoleaks from the hydrogel-reinforced fenestrations. The 30-day survival rate was 97.5%. One patient died due to brain haemorrhage on postoperative day 5. During follow-up, computed tomography revealed no migration of any bridging graft., Conclusions: We confirmed the effectiveness of the hydrogel as a sealing material and the secure connection between hydrogel-reinforced fenestrations and side branches in vivo., Clinical Trial Registration Number: 5287., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Aims: A mineralocorticoid receptor antagonist (MRA) is effective in patients with chronic heart failure; however, the effects of the early initiation of an MRA in patients with acute heart failure (AHF) have not been elucidated., Methods and Results: In this multicentre, randomized, double-blind, placebo-controlled, parallel-group study, we focused on the safety and effectiveness of the treatment with eplerenone, a selective MRA in 300 patients with AHF, that is, 149 in the eplerenone group and 151 in the placebo group in 27 Japanese institutions. The key inclusion criteria were (i) patients aged 20 years or older and (ii) those with left ventricular ejection fraction of ≤40%. The primary outcome was a composite of cardiac death or first re-hospitalization due to cardiovascular disease within 6 months. The mean age of the participants was 66.8 years, 27.3% were women, and the median levels of brain natriuretic peptide were 376.0 pg/mL. The incidences of the primary outcome were 19.5% in the eplerenone group and 17.2% in the placebo group [hazard ratio (HR): 1.09, 95% confidence interval (CI): 0.642-1.855]. In prespecified secondary outcomes, HR for the composite endpoint, cardiovascular death, or first re-hospitalization due to heart failure within 6 months was 0.55 (95% CI: 0.213-1.434). The safety profile for eplerenone was as expected., Conclusion: The early initiation of eplerenone in patients with AHF could safely be utilized. The reduction of the incidence of a composite of cardiovascular death or first re-hospitalization for cardiovascular diseases by eplerenone is inconclusive because of inadequate power., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Renal denervation is a promising new non-pharmacological treatment for resistant hypertension. However, there is a lack of data from Asian patients. The REQUIRE trial investigated the blood pressure-lowering efficacy of renal denervation in treated patients with resistant hypertension from Japan and South Korea. Adults with resistant hypertension (seated office blood pressure ≥150/90 mmHg and 24-hour ambulatory systolic blood pressure ≥140 mmHg) with suitable renal artery anatomy were randomized to ultrasound renal denervation or a sham procedure. The primary endpoint was change from baseline in 24-hour ambulatory systolic blood pressure at 3 months. A total of 143 patients were included (72 renal denervation, 71 sham control). Reduction from baseline in 24-hour ambulatory systolic blood pressure at 3 months was not significantly different between the renal denervation (-6.6 mmHg) and sham control (-6.5 mmHg) groups (difference: -0.1, 95% confidence interval -5.5, 5.3; p = 0.971). Reductions from baseline in home and office systolic blood pressure (differences: -1.8 mmHg [p = 0.488] and -2.0 mmHg [p = 0.511], respectively), and medication load, did not differ significantly between the two groups. The procedure-/device-related major adverse events was not seen. This study did not show a significant difference in ambulatory blood pressure reductions between renal denervation and a sham procedure in treated patients with resistant hypertension. Although blood pressure reduction after renal denervation was similar to other sham-controlled studies, the sham group in this study showed much greater reduction. This unexpected blood pressure reduction in the sham control group highlights study design issues that will be addressed in a new trial. CLINICAL TRIAL REGISTRATION: NCT02918305 ( http://www.clinicaltrials.gov )., (© 2021. The Author(s).)

[Purpose] This study aimed to investigate the absolute intra-rater and inter-rater reliabilities during the measurement of muscle hardness, which is used to evaluate physical therapy. Moreover, we examined the effects of using different equipment types and their positioning on the intra-rater and inter-rater reliabilities. [Participants and Methods] Participants of this study comprised 12 healthy adult male individuals. Two experts and two beginners measured the muscle hardness of the lumbar erector spinae and rectus femoris using three types of hardness meters at two positions, including when the muscle was relaxed and stretched. [Results] Intra-rater fixed bias was observed during some measurements by both experts and beginners. Inter-rater fixed bias was observed during measurements by some experts and not the beginners. [Conclusion] In this study, the measurement of muscle hardness demonstrated a need to reconsider the measurement position and acclimation time. These examinations require the consideration of relative and absolute reliabilities., (2022©by the Society of Physical Therapy Science. Published by IPEC Inc.)

Objectives: Concentrations of soluble amyloid precursor proteins-α (sAPPα) and -β (sAPPβ) in cerebrospinal fluid (CSF) may reflect the neuropathology of Alzheimer's disease (AD). We previously reported that the concentrations of both sAPPα and sAPPβ were significantly higher in patients with mild cognitive impairment (MCI) due to AD (MCI-AD) than in control subjects without cognitive impairment. The present study analyzed whether these sAPPs are useful in the differential diagnosis of MCI., Methods: A modified and sensitive method was used to analyze concentrations of sAPPα and sAPPβ in CSF of patients with MCI-AD (n = 30) and MCI due to other causes (MCI-others) (n = 24). Phosphorylated tau (p-tau) and amyloid β-protein 42 (Aβ42) were also analyzed using standard methods., Results: CSF concentrations of sAPPα and sAPPβ were significantly higher in the MCI-AD than in the MCI-others group (p < 0.001). Furthermore, concentrations of both sAPPα and sAPPβ were highly correlated with the concentration of p-tau, consistent with our previous report., Conclusions: Measurement of both sAPPs in CSF using sensitive methods can be helpful in the precise differential diagnosis of patients with MCI., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Paneth cells are intestinal epithelial cells that release antimicrobial peptides, such as α-defensin as part of host defense. Together with mesenchymal cells, Paneth cells provide niche factors for epithelial stem cell homeostasis. Here, we report two subtypes of murine Paneth cells, differentiated by their production and utilization of fucosyltransferase 2 (Fut2), which regulates α(1,2)fucosylation to create cohabitation niches for commensal bacteria and prevent invasion of the intestine by pathogenic bacteria. The majority of Fut2 - Paneth cells were localized in the duodenum, whereas the majority of Fut2 + Paneth cells were in the ileum. Fut2 + Paneth cells showed higher granularity and structural complexity than did Fut2 - Paneth cells, suggesting that Fut2 + Paneth cells are involved in host defense. Signaling by the commensal bacteria, together with interleukin 22 (IL-22), induced the development of Fut2 + Paneth cells. IL-22 was found to affect the α-defensin secretion system via modulation of Fut2 expression, and IL-17a was found to increase the production of α-defensin in the intestinal tract. Thus, these intestinal cytokines regulate the development and function of Fut2 + Paneth cells as part of gut defense., Competing Interests: The authors declare no competing interest., (Copyright © 2022 the Author(s). Published by PNAS.)

Background: Amyloid-β (Aβ) and tau protein accumulation in the brain is thought to be one of the causes of Alzheimer's disease (AD). Recent study found that the glymphatic system was waste drainage system in the brain and promoting the elimination of Aβ and tau protein., Objective: We evaluated the relationships between the glymphatic system activity and the Aβ and tau protein deposition., Methods: Subjects were 21 patients with AD and 36 healthy subjects who underwent diffusion tensor imaging (DTI) scan and the positron emission tomography (PET) using with the Aβ tracer: 11C-PiB and the tau/inflammatory tracer: 18F-THK5351. We computed diffusion tensor image analysis along the perivascular space (DTI-ALPS) index as the proxy of glymphatic system activity, and estimated the relationships between the DTI-ALPS index and Aβ and tau protein/inflammatory deposition., Results: We found significant negative correlations between DTI-ALPS index and the standard uptake value ratio (SUVR) of 11C-PiB in the bilateral temporal and left parietal cortices and left posterior cingulate gyrus in all subjects. Further, we detected significant negative correlations between DTI-ALPS index and the SUVR of 18F-THK5351 in the bilateral temporal cortices and right parietal cortex in all participants, too., Conclusion: Our data suggested that DTI-ALPS index was a good biomarker for the evaluation of Aβ and tau deposition and neuroinflammation, and this marker might be effective to estimate the glymphatic system activity.

Despite emerging importance of tumor cells-derived exosomes in cancer metastasis, the heterogeneity of exosome populations has largely hampered systemic characterization of their molecular composition, biogenesis, and functions. This study communicates a novel method for predicting and targeting pre-metastatic sites based on an exosome model "fluorescent cancer glyconanosomes" displaying N-glycans of cultured tumor cells. Glycoblotting by antiadhesive quantum dots provides a nice tool to shed light on the pivotal functions of the glycocalyx reconstructed from four cancer cell types without bias due to other compositions of exosomes. In vivo imaging revealed that circulation, clearance, and organotropic biodistribution of cancer glyconanosomes in mice depend strongly on cancer cell-type-specific N-glycosylation patterns, the compositions of key glycotypes, particularly dominant abundances of high mannose-type N-glycans and the position-specific sialylation. Notably, organ biodistribution of cancer glyconanosomes is reproducible artificially by mimicking cancer cell-type-specific N-glycosylation patterns, demonstrating that nanosomal glycoblotting method serves as promising tools for predicting and targeting pre-metastatic sites determined by the glycocalyx of extracellular vesicles disseminated from the primary cancer site., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Certain symptoms associated with mild sickness and lethargy have not been categorized as definitive diseases. Confirming such symptoms in captive monkeys ( Macaca fascicularis , known as cynomolgus monkeys) can be difficult; however, it is possible to observe and analyze their feces. In this study, we investigated the relationship between stool state and various omics data by considering objective and quantitative values of stool water content as a phenotype for analysis. By examining the food intake of the monkeys and assessing their stool, urine, and plasma, we attempted to obtain a comprehensive understanding of the health status of individual monkeys and correlate it with the stool condition. Our metabolomics data strongly suggested that many lipid-related metabolites were correlated with the stool water content. The lipidomic analysis revealed the involvement of saturated and oxidized fatty acids, metallomics revealed the contribution of selenium (a bio-essential trace element), and intestinal microbiota analysis revealed the association of several bacterial species with the stool water content. Based on our results, we hypothesize that the redox imbalance causes minor health problems. However, it is not possible to make a definite conclusion using multi-omics alone, and other hypotheses could be proposed.

This study aimed to create a biomaterial from titanium dioxide (TiO 2 ), which has been known to have photocatalytic and bone formation promoting effects. I expected that anatase titanium dioxide-based implants could promote bone augmentation and induce bone formation. Powdery anatase TiO 2 was compression molded and sintered at 700, 800, 900, and 1000 °C to prepare sintered compact samples. X-ray diffraction and scanning electron microscopy were used to observe the surface of these samples. Furthermore, mouse osteoblast-like cells (MC3T3-E1 cell line) were seeded on the samples sintered at different temperatures, and cell proliferation was observed to evaluate the cell proliferation of the samples. The sample sintered at 700 °C was composed of anatase TiO 2 . The samples sintered at 800 °C and 900 °C were confirmed to consist of a mixture of anatase and rutile TiO 2 crystalline phases. Moreover, the sample sintered at 700 and 800 °C, which contained anatase TiO 2 , showed remarkable photocatalytic activity. Those samples sintered at 1000 °C were transformed to the rutile TiO 2 . The cell proliferation after 7-14-days culturing revealed that cells cultured on the 700 °C sample decreased in number immediately after initiation of culturing. The cells cultured on TiO 2 sintered at 900 °C markedly proliferated over time with an increase in the alkaline phosphatase activity, showing good MC3T3-E1 cell compatibility of the samples. The sample sintered at 1000 °C, which is rutile TiO 2 , showed the highest increase.

Aim: Intensive rehabilitation effectively improves physical functions in patients with acute stroke, but the frequency of intervention and its cost-effectiveness are poorly studied. This study aimed to examine the effect of early high-frequency rehabilitation intervention on inpatient outcomes and medical expenses of patients with stroke., Methods: The study retrospectively included 1759 patients with acute stroke admitted to the Kobe City Medical Center General Hospital between 2013 and 2016. Patients with a transient ischemic attack, subarachnoid hemorrhage, and those who underwent urgent surgery were excluded. Patients were divided into two groups according to the frequency of rehabilitation intervention: the high-frequency intervention group (>2 times/day, n = 1105) and normal-frequency intervention group (<2 times/day, n = 654). A modified Rankin scale score ≤2 at discharge, immobility-related complications and medical expenses were compared between the groups., Results: The high-frequency intervention group had a significantly shorter time to first rehabilitation (median [interquartile range], 19.0 h [13.1-38.4] vs. 24.7 h [16.1-49.4], P < 0.001) and time to first mobilization (23.3 h [8.7-47.2] vs. 22.8 h [5.7-62.3], P = 0.65) than the normal-frequency intervention group. Despite higher disease severity, the high-frequency intervention group exhibited favorable outcomes at discharge (modified Rankin scale, ≤2; adjusted odds ratio, 1.89; 95% confidence interval, 1.25-2.85; P = 0.002). No significant differences were observed between the two groups concerning the rate of immobility-related complications and total medical expenses during hospitalization., Conclusions: High-frequency intervention was associated with improved outcomes and decreased medical expenses in patients with stroke. Our results may contribute to reducing medical expenses by increasing the efficiency of care delivery. Geriatr Gerontol Int 2021; 21: 623-628., (© 2021 Japan Geriatrics Society.)

Bronchial artery aneurysm (BAA) is a rare disease, for which early treatment is recommended due to the risk of rupture often resulting in severe consequences. We report a case of successful treatment of an asymptomatic BAA by selective branch embolization combined with thoracic endovascular aortic repair (TEVAR). A 68-year-old man was accidentally found to have a bronchial artery aneurysm by computed tomography. The distance from the origin of the bronchial artery to the aneurysm was only 6 mm, at which branches were found. The BAA was completely excluded by selective branch coil embolization and deployment of a thoracic stent graft to cover the orifice of the BAA. Angiography confirmed that there was no endoleak. Selective branch embolization of BAA combined with TEVAR is effective to completely occlude the blood stream to BAA.

[Purpose] Adults with cerebral palsy often use a cane as a walking aid because of their decreased gait ability. However, it is unclear whether this affects lower limb muscle activity during walking. The purpose of this study was to clarify the influence of using a cane during walking on the spatio-temporal parameters of walking, lower limb muscle activity, and lower limb muscle coactivation in adults with spastic cerebral palsy. [Participants and Methods] Eleven participants with cerebral palsy were included. The spatio-temporal parameters of walking, lower limb muscle activity, and coactivation of lower limb muscle were measured during a 10 m trial with no cane, one cane, and two canes. [Results] Walking speed was lower and the stride time longer when using two canes than when using no cane. All muscle activities significantly reduced when using two canes. No significant difference was observed between using no cane and one cane, except for walking speed. In addition, there was no significant difference in coactivation between the conditions. [Conclusion] This study revealed that when two canes were used, the walking speed was reduced, and lower limb muscle activity was reduced, reducing the burden. In contrast, the movement pattern was not suggested to have changed., (2021©by the Society of Physical Therapy Science. Published by IPEC Inc.)

Background: Individuals undergoing rehabilitation often experience nutritional problems such as malnutrition, but there are no clinical practice guidelines (CPGs) specifically tailored to the combination of rehabilitation and nutritional care for these patients. The Japanese Association for Rehabilitation Nutrition aimed to develop CPGs for rehabilitation nutrition to support clinical decision making in daily practice., Methods: A CPG committee and development process based on the Grading of Recommendations Assessment, Development and Evaluation system and the Minds Handbook for Clinical Practice Guideline Development 2014 was established. Four clinical questions were defined for patients undergoing rehabilitation for cerebrovascular disease, hip fracture, cancer, and acute illness. Literatures of randomised control trials (RCTs) up to April 2020 were searched for using the MEDLINE, EMBASE, CENTRAL, and Ichushi-web databases. After screening, full-text papers were assessed for eligibility for analysis. Subsequently, studies included in the systematic review were examined regarding their risk of bias, and underwent meta-analyses. A CPG development committee drafted the guidelines based on the systematic review report. Final recommendations were determined by the panel members., Results: Four recommendations were made based on 4 to 9 RCTs for each disease/condition. The certainty of the evidence ranged from very low to low. Overall, the enhanced nutritional care was weakly recommended for rehabilitation patients with cerebrovascular disease, hip fracture, cancer, and acute illnesses., Conclusions: This CPG provides tentative recommendations for nutritional care of individuals undergoing rehabilitation. Due to low certainty of evidence and small sample sizes of the included studies, more high-quality and larger RCTs are needed to develop more practical CPGs., Competing Interests: Declaration of competing interest All members of the CPG Committee declare having a conflict of interest (COI) prior to developing this CPG. This includes both financial and academic COIs. The financial COIs included: employment and/or advisory roles; shareholdings and their profits; patent royalties; honoraria; payment for the manuscript; scholarship; research funding; donations for the course of the university; and others, including travel expenses and gifts not connected to research. Academic COIs included: affiliations; side jobs; specialties; affiliated academic societies; authorship of published articles regarding rehabilitation nutrition CPG; and experience developing a CPG other than the current CPG. The following COIs were reported: 1) Financial COIs. Hidetaka Wakabayashi received honoraria from Clinico Co. Ltd. and Nestle Japan Co. Ltd. Kenji Omura received honoraria from Otsuka Pharmaceutical Factory Co. Ltd. Committee of Clinical Practice Guideline, Japanese Association of Rehabilitation Nutrition, involved a member employed by the Department of Disaster and Comprehensive Medicine, Fukushima Medical University, endowed by Kowa Yakuhin Co. Ltd. and Toshiba Corporation. The other authors have no financial conflicts of interest to declare. 2) Academic COIs. Shinta Nishioka, Ryo Momosaki, Atsushi Fujimoto, Hidetaka Wakabayashi, and five other members of the Committee of Clinical Practice Guidelines, Japanese Association of Rehabilitation Nutrition have authorship of published articles regarding nutritional rehabilitation CPGs. Yayoi Kanehisa, Hideki Aragane, Yuki Iida, Yoshimasa Ishii, Hidetaka Wakabayashi, and 11 other members of the Committee of Clinical Practice Guideline, Japanese Association of Rehabilitation Nutrition, and 2 external reviewers had prior experience of developing CPGs other than the current CPG. The other authors have no academic conflicts of interest to declare., (Copyright © 2021 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Psychological stress has been reported to relate to dysbiosis, imbalance of the intestinal microbiota composition, and contribute to the onset and exacerbation of depression, though, underlying mechanisms of psychological stress-related dysbiosis have been unknown. It has been previously established that α-defensins, which are effector peptides of innate enteric immunity produced by Paneth cells in the small intestine, play an important role in regulation of the intestinal microbiota. However, the relationship between disruption of intestinal ecosystem and α-defensin under psychological stress is yet to be determined. Here we show using chronic social defeat stress (CSDS), a mouse depression model that (1) the exposure to CSDS significantly reduces α-defensin secretion by Paneth cells and (2) induces dysbiosis and significant composition changes in the intestinal metabolites. Furthermore, (3) they are recovered by administration of α-defensin. These results indicate that α-defensin plays an important role in maintaining homeostasis of the intestinal ecosystem under psychological stress, providing novel insights into the onset mechanism of stress-induced depression, and may further contribute to discovery of treatment targets for depression.

An aberrant right subclavian artery (ARSA) is a rare arterial anomaly. Although a few cases of total endovascular repair for the ARSA aneurysm have been previously reported, anatomical limitations and the possibility of endoleaks remained. In this case, we created 4 holes on the stent graft for each cervical branch, with reference to the preoperative computed tomography findings. This approach might enable us to repair all types of thoracic aortic aneurysms with ARSA with each anatomical feature., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Backgrounds: Social cognition is defined as the mental operations underlying social behavior. Patients with schizophrenia elicit impairments of social cognition, which is linked to poor real-world functional outcomes. In a previous study, transcranial direct current stimulation (tDCS) improved emotional recognition, a domain of social cognition, in patients with schizophrenia. However, since social cognition was only minimally improved by tDCS when administered on frontal brain areas, investigations on the effect of tDCS on other cortical sites more directly related to social cognition are needed. Therefore, we present a study protocol to determine whether multi-session tDCS on superior temporal sulcus (STS) would improve social cognition deficits of schizophrenia., Methods: This is an open-label, single-arm trial, whose objective is to investigate the efficacy and safety of multi-session tDCS over the left STS to improve social cognition in patients with schizophrenia. The primary outcome measure will be the Social Cognition Screening Questionnaire. Neurocognition, functional capacity, and psychotic symptoms will also be evaluated by the Brief Assessment of Cognition in Schizophrenia, UCSD Performance-Based Skills Assessment-Brief, and Positive and Negative Syndrome Scale, respectively. Data will be collected at baseline, and 4 weeks after the end of intervention. If social cognition is improved in patients with schizophrenia by tDCS based on this protocol, we may plan randomized controlled trial.

Aims: In patients with heart failure, over-activation of the cardiac sympathetic nerve (CSN) function is associated with severity of heart failure and worse outcome. The effects of MitraClip therapy on the CSN activity in patients with mitral regurgitation (MR) remained unknown. In this study, we evaluated the impact of the MitraClip therapy on CSN activity assessed by 123 I-metaiodobezylguanidine (MIBG) scintigraphy., Methods and Results: We enrolled consecutive patients with moderate-to-severe (3+) or severe (4+) MR who were scheduled to undergo MitraClip procedure in this prospective observational study. MIBG scintigraphy was performed at baseline and 6 months after the MitraClip procedure to evaluate the heart-mediastinum ratio and washout rate (WR). Changes in these MIBG parameters were analysed. Of the 13 consecutive patients, 10 were successfully treated with MitraClip procedure and completed follow-up assessment. With regard to the MIBG parameters, changes in the early and delayed heart-mediastinum ratio from baseline to 6 months were not significant (2.16 ± 0.42 to 2.06 ± 0.34, P = 0.38 and 1.87 ± 0.39 to 1.83 ± 0.39, P = 0.43, respectively), whereas WR was significantly decreased (38.6 ± 3.9% to 32.6 ± 3.94%, P = 0.002)., Conclusions: The CSN activity of the WR on MIBG imaging was improved 6 months after MitraClip therapy in patients with 3+ or 4+ MR., (© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Paneth cells and Lgr5+ intestinal stem cells (Lgr5+ ISCs) constitute the stem cell niche and maintain small intestinal epithelial integrity by recognizing various niche factors derived from subepithelial cells and external antigens. Although it has been known that interferon-γ (IFN-γ), a Th1 cytokine, is associated with intestinal epithelial disruption during inflammation as a niche factor, dynamics of Paneth cells and Lgr5+ ISCs in response to IFN-γ remain to be understood. Here we show that CAG-tdTomato;Lgr5-EGFP (CT-LE) mice generated in this study enable to identify Paneth cells and Lgr5+ ISCs separately by fluorescence signals. Lgr5+ ISCs underwent cell death a little earlier than Paneth cells in response to IFN-γ by simultaneous tracking using CT-LE mice. In addition, the timing of cell death in most Paneth cells overlapped with Lgr5+ ISCs, suggesting that Paneth cell depletion is induced directly by IFN-γ. Taken together, we established a novel simultaneous stem cell niche tracking method and clarified the involvement of both Paneth cells and Lgr5+ ISCs in stem cell niche damage induced by IFN-γ, further contribute to understanding the mechanism for maintaining intestinal homeostasis by stem cell niche., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Backgrounds: Antidepressants are widely used to treat major depressive disorder. First-line treatments with antidepressants are only successful in one-third of patients; however, evidence from randomized controlled trials on second-line treatments is limited. Moreover, recently acceptability is suggested to be a good indicator of overall treatment success., Methods: This is a multi-center two-arm, three-phased randomized controlled trial performed in Japan from December 2013 to March 2017 comparing the acceptability of escitalopram and duloxetine as a second-line drug. Patients, who failed to respond to antidepressants such as sertraline, paroxetine, fluvoxamine, milnacipran or mirtazapine for at least 3 weeks, were randomized to either escitalopram (Group A) or duloxetine (Group B) in Step 1 (8 weeks). In Step 2 (8 weeks), the drug was switched to the other if the first drug failed. The discontinuation rate at the end of Step 1 was the primary endpoint and non-inferiority of escitalopram vs duloxetine was tested. In addition, change in clinical measures from baseline were also assessed at the end of Step 1, 2 and up to 52 weeks., Results: At the end of Step 1, Group A (n = 82) was significantly superior to Group B (n = 78) in discontinuation rate (4.9% to 19.2%, P = 0.007). The change in clinical indices from baseline were not different between the groups at either timepoint., Limitations: As the major reason for discontinuation in Group B was the "withdrawal of consent" the concrete reason could not be verified., Conclusions: As a second-line treatment drug, escitalopram was suggested to be non-inferior to duloxetine in acceptability., Trial Registration: UMINCTR(UMIN000012367), registered on December 1st, 2013 and last updated on April 4th, 2017., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objectives: Thoracic endovascular aortic repair (TEVAR) is typically performed with general anesthesia (GA) and surgical cutdown (G-TEVAR). As the latest generation of TEVAR delivery systems are smaller, we introduced percutaneous TEVAR with regional anesthesia (RA) (R-TEVAR) and an arteriotomy closure device. In this study, we compare the safety and efficacy of R-TEVAR to that of the G-TEVAR., Methods: This single-center observational study included consecutive patients who underwent either G-TEVAR between January 2015 and October 2018 (33 patients) or R-TEVAR (41 patients) between January 2018 and April 2020. RA was achieved using an ultrasound-guided nerve block., Results: The mean outer diameter of the delivery device was significantly smaller in R-TEVAR (18.5 vs. 22.7 Fr; p < 0.01) and the time from arriving into the operating room to beginning of surgery (34.1 vs. 68.5 min; p < 0.01), procedural time (46.4 vs. 103.6 min; p < 0.01), and operating room stay time (108.3 vs. 194.6 min; p < 0.01) were significantly shorter. The mean rate of change in blood pressure was significantly lower in the R-TEVAR group (7.7% vs. 32.2%; p < 0.01). One case of spinal cord ischemia occurred in the G-TEVAR group (0% vs. 3.0%; p = 0.262) and one case of inadequate hemostasis and conversion to surgical cutdown without GA occurred in the R-TEVAR group (2.4% vs. 0%; p = 0.366)., Conclusions: The R-TEVAR is safe and minimally invasive. Further, RA may provide additional benefits of mean blood pressure stability and early recognition of neurologic complications.

[Purpose] We aimed to investigate the central nervous system factors that affect muscle strength based on the differences in load and time using the discrete wavelet transform, which is capable of a time-frequency-potential analysis. [Participants and Methods] Surface electromyography (EMG) of the right upper bicep muscle in 16 healthy adult males were measured at 10% MVC (maximum voluntary isometric contraction), 30%, 50%, 70%, and 80% to 100% MVC. We used a discrete wavelet transform for the electromyographic analysis and calculated the median instantaneous frequency spectrum (MDF) and frequency band component content rate (FCR) at 1-ms intervals as well as their spectrum integrated values (I-EMG). [Results] MDF and FCR tended to be high throughout the measurements. Specifically, the high-frequency band component content rate was high at the time of low muscle strength; fast-twitch muscle fibers may be involved during these muscle contractions. We found significant changes in the I-EMG as the muscle strength increased from 10% MVC to 100% MVC. [Conclusion] Analyzing the surface electromyograph using discrete wavelet transform enabled us to assess the central nervous system factors that increase in the EMG amplitude integrated values and change in the median instantaneous frequency spectrum and in the frequency band component content rate., (2021©by the Society of Physical Therapy Science. Published by IPEC Inc.)

Introduction: Transcranial direct current stimulation (tDCS) is a potentially novel strategy for cognitive enhancement in patients with disorders. We present a study protocol for a randomised controlled trial designed to evaluate the safety and efficacy of tDCS combined with cognitive tasks on cognition in such patients., Method and Analysis: This is a two-arm, parallel-design, randomised, sham-controlled trial, in which participants and raters will be blinded at a single centre. Stratified randomisation will be conducted, and a randomisation sequence will be generated through the Electronic Data Capture system. Patients who met the Diagnostic and Statistical Manual of Mental Disorders-5 criteria for neurocognitive disorders will be recruited and randomised to receive either active (2 mA for 20 min) or sham (stimulation ramped up and down for 1 min) stimulation in 10 sessions over five consecutive days. A direct current will be transferred by a 35 cm 2 saline-soaked sponge electrode. An anode will be placed over the left dorsolateral prefrontal cortex, and a cathode will be placed over the right supraorbital cortex. Calculation tasks will be conducted in both arms as a cognitive task for 20 min during the stimulation. This task consists of basic arithmetic questions, such as single-digit addition, subtraction, multiplication and division. The primary outcome will be the mean change in the Alzheimer Disease Assessment Scale-cognition at Day 5 after baseline. Depressive symptoms, as measured by the geriatric depression scale, and quality of life, as measured by the Medical Outcomes Study 36-item Short-Form Health Survey, will also be assessed. Data will be collected at baseline, within 3 days following the final stimulation and 1 month thereafter. The estimated sample size is 46 per group based on the assumptions that an estimated mean difference is -1.61 and SD is 2.7. Mixed models for repeated measures will be used for the statistical analysis., Ethics and Dissemination: The National Center of Neurology and the Psychiatry Clinical Research Review Board (CRB3180006) approved this study. The results of this study will be published in a scientific peer-reviewed journal., Trial Registration Details: Japan Registry of Clinical Trials jRCTs032180016., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To determine the phase that facilitates flap observation of the ascending aorta in Stanford type A acute aortic dissection with perfused false lumen., Methods: We reconstructed retrospective Electrocardiogram-gated Computed Tomography Angiography images of the ascending aorta of all 20 patients to 20 phases of curved-multiplanar reconstruction in 5% increment. One radiologist created and randomized 10 cross-sectional images of each phase for every patient and two radiologists scored these images on a 5-point scale depending on the degree of flap stoppage. We calculated the average score for each phase of each case and compared them among the three groups., Results: Image scores were significantly better in the 65 %-100 % R-R interval group than those in the 5%-30 % (p < 2e-16) and 35 %-60 % R-R interval groups(p = 7.2e-10). Similar scores were observed in the Heart Rate > 70 group (p = 0.00039, 2.2e-14). Moreover a similar tendency was observed in the arrhythmia group (p = 0.0035, 0.294). No difference was found in the degree of flap stoppage in the 65 %-100 % R-R interval group between the Heart Rate > 70 and Heart Rate ≤ 70 groups (p = 0.466) and between the arrhythmia and non-arrhythmia groups (p = 0.1240)., Conclusion: In observing the ascending aorta, We obtained a good image at 65 %-100 % R-R interval and similar tendency was observed in the patients with arrhythmia., Competing Interests: The authors reported no declarations of interest., (© 2020 The Authors.)

Aim: The purpose of this study was to investigate the association between drinking habits and subjective symptoms of the oral cavity based on Japanese national statistical data., Methods: The subjects were 8,698 respondents of the Japan National Livelihood Survey 2013, in their 30s to 60s. The association between drinking habits and each survey item was investigated by contingency table analysis and binary logistic regression analysis., Results: The proportion of people with drinking habits was 55.3% among men and 20.3% among women, and the proportion of men with drinking habits above the age of 40 years was high. Contingency table analysis indicated an association between drinking habits and the following items in men: subjective symptoms ( p < 0.01), chewing difficulty ( p < 0.05), subjective impression of health ( p < 0.01), smoking habit ( p < 0.01), and income level ( p < 0.01). Analysis indicated an association between drinking habits and hospital visits ( p < 0.01) and smoking habits ( p < 0.01) in women. When comparing the response rates of symptoms and presence of disease stratified according to drinking habits, inflammatory and sensory system symptoms were common in those who had drinking habits, as were diabetes and gout. Binomial logistic regression analysis with drinking habit as the objective variable indicated statistically significant odds ratios for smoking habit (2.13; 95% CI: 1.65-2.75), difficulty in chewing (1.63; 95% CI: 1.01-2.62), and working hours (1.50; 95% CI: 1.10-2.04). This study identified a correlation between drinking habits and masticatory disorders, suggesting that the effects of drinking as a risk factor for dental diseases should be examined in greater detail in the future., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2020 Takeshi Kamoda et al.)

Objective: This study aimed to determine predictors associated with readmission of inpatients with borderline personality disorder., Methods: This observational study evaluated 83 inpatients with borderline personality disorder admitted to the National Center of Neurology and Psychiatry Hospital in Japan from January 2013 to January 2016. Data were retrospectively obtained from electronic medical records., Results: There was no significant difference in the daily antipsychotic dose equivalent to chlorpromazine at admission between the readmitted and nonreadmitted groups, which indicated that there was no between-group difference in the psychiatric disease severity at admission. Multivariate logistic regression analyses revealed that the use of antipsychotics equivalent to >400 mg of chlorpromazine at discharge was associated with readmission within 1 year., Conclusions: In conclusion, high-dose antipsychotic drug use at discharge may be a risk factor for readmission. The present findings may have important clinical implications since they alert physicians to a possible predictor for readmissions of patients with borderline personality disorder., (© 2020 The Authors. Neuropsychopharmacology Reports published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Neuropsycho Pharmacology.)

Paneth cells contribute to intestinal innate immunity by sensing bacteria and secreting α-defensin. In Institute of Cancer Research (ICR) mice, α-defensin termed cryptdin (Crp) in Paneth cells consists of six major isoforms, Crp1 to 6. Despite accumulating evidences that α-defensin functions in controlling the intestinal microbiota, topographical localization of Paneth cells in the small intestine in relation to functions of α-defensin remains to be determined. In this study, we examined the expression level of messenger RNA (mRNA) encoding six Crp-isoforms and Crp immunoreactivities using singly isolated crypts together with bactericidal activities of Paneth cell secretions from isolated crypts of duodenum, jejunum, and ileum. Here we showed that levels of Crp mRNAs in the single crypt ranged from 5 x 10 3 to 1 x 10 6 copies per 5 ng RNA. For each Crp isoform, the expression level in ileum was 4 to 50 times higher than that in duodenum and jejunum. Furthermore, immunohistochemical analysis of isolated crypts revealed that the average number of Paneth cell per crypt in the small intestine increased from proximal to distal, three to seven-fold, respectively. Both Crp1 and 4 expressed greater in ileal Paneth cells than those in duodenum or jejunum. Bactericidal activities in secretions of ileal Paneth cell exposed to bacteria were significantly higher than those of duodenum or jejunum. In germ-free mice, Crp expression in each site of the small intestine was attenuated and bactericidal activities released by ileal Paneth cells were decreased compared to those in conventional mice. Taken together, Paneth cells and their α-defensin in adult mouse appeared to be regulated topographically in innate immunity to control intestinal integrity., (Copyright © 2020 Nakamura, Yokoi, Fukaya, Ohira, Shinozaki, Nishida, Kikuchi and Ayabe.)

Objectives: Thoracic endovascular aortic repair (TEVAR) for the treatment of aortic arch disease remains challenging due to certain anatomical and haemodynamic features. The purpose of this study was to evaluate the midterm results of TEVAR with a second-generation fenestrated endograft for aortic arch disease., Methods: This non-randomized, interventional study was part of a multicentre clinical trial conducted between 2010 and 2011 and was designed to assess the effectiveness of a second-generation precurved fenestrated endograft for aortic arch disease. Midterm data collected during the fifth postoperative year from 205 patients treated with this endograft with the proximal landing of zone 0 or 1 were assessed regarding survival, reoperation and complications., Results: The initial and technical success rates were 94% and 91%, respectively. Ninety-seven percent of patients were treated using zone 0. The rate of in-hospital deaths was 3%. Overall survival was 71% at 5 years; thoracic aorta-related death-free survival rates at 1 and 5 years after surgery were 99.5% and 97.8%, respectively. Aneurysm-related event-free survival rates at 1 and 5 years after surgery were 86.8% and 77.1%, respectively. Reoperation-free survival rates at 5 years were 86.6%. The most frequent reason for reoperation was type Ia endoleak (5%), followed by type II endoleak (2%). Incidences of cerebral infarction, device migration, spinal cord ischaemia and supra-aortic branch stenosis were 6%, 1%, 1% and 1%, respectively., Conclusions: The precurved fenestrated endograft provided appropriate conformability to the aortic arch and made zone 0 landing possible with simplified, less-invasive manipulations. The midterm results of TEVAR with this endograft suggest this method is a valuable endovascular treatment option for aortic arch disease., Clinical Trial Registration Number: UMIN000007213., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)