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Objectives: Nocturia is considered a clinical problem when nocturnal urinary frequency is two or more times. For affected patients, development of depression, falling, and increased mortality rate are matters of concern. The present study investigated the efficacy and safety of lemborexant for insomnia patients with nocturia. Methods: Insomnia patients (Athens Insomnia Scale [AIS] ≥ 6) who typically awoke twice or more during the night to urinate and were examined at our institutions from June 2021 to December 2022 were enrolled. Each was administrated 5 mg of lemborexant, one tablet, daily for 4 weeks. Total AIS score, nocturia frequency, individual frequency‐volume chart findings, and N‐QOL score were examined before and after administration. Results: Of the 37 patients recruited, 5 were excluded, thus 32 were enrolled and subjected to analyses. Following lemborexant therapy, the mean AIS total score was significantly decreased from 11.4 to 7.8 (p < 0.01) as was mean number of nocturia episodes from 3.4 to 2.3 (p < 0.001). Furthermore, the mean single voided urine volume at night was significantly increased from 182.5 to 225.3 mL (p < 0.001)and mean period of undisturbed sleep was significantly extended from 105.3 to 174.8 min (p < 0.001), while mean total N‐QOL score was significantly improved from 49.6% to 64.8% (p < 0.001). As for adverse events, mild somnolence was observed in three cases. Conclusions: Lemborexant may be effective and safe for use in insomniac patients with nocturia. [ABSTRACT FROM AUTHOR]

Skeletal isomerization of ergosterol peroxide, a primary oxidation product of ergosterol, was investigated under thermal and iron(II)‐mediated conditions. Thermal isomerization resulted in not only the isolation of the predicted 7‐hydroxy‐5,6‐epoxides but also the discovery of the unprecedented 7/9/5‐ring‐fused ergostane for the first time. The iron(II)‐mediated isomerization proceeded at ambient temperature, resulting in the formation of the expected 5,6‐epoxysterols and a ring‐opened bicyclic diketone. The diketone was further converted into novel ergostane under thermal conditions and into (+)‐sarocladione under acidic conditions. All transformations from ergosterol to sarocladione, including the isolation of the unstable diketone intermediate, were achieved at ambient temperature, confirming the biosynthetic pathway of sarocladione. Several mushroom ingredients with a 5,6‐epoxy group were synthesized stereoselectively from the isomerization products, leading to the confirmation or revision of the structures of natural products. The β‐amyloid aggregation inhibitory activity of synthetic sterols was evaluated for the first time to gain insights into the potential for dementia prevention. This study is valuable both for supplying rare sterols found in mushrooms for biological studies and for shedding light on the oxidative metabolic pathways of ergosterol. [ABSTRACT FROM AUTHOR]

Laboratory‐based studies have shown that psychological stress caused by response to various stressors triggers acute changes in the cardiovascular system. A better understanding is needed of the emerging evidence on temporal associations between psychological stress and cardiovascular responses in natural settings. This study examined the association of psychological stress and heart rate variability (HRV) in daily life, at high resolution over 2 weeks, taking the effect of physical activity into account. Participants (n = 34) completed ecological momentary assessments (EMA) 6 times per day, reporting levels of perceived stress, low‐arousal negative affect (LNA), and high‐arousal negative affect. Chest‐mounted heart‐rate monitors were worn to assess HRV. Multilevel models were used to examine the association between psychological stress levels and preceding/subsequent HRV. Reduced time domain HRV measures (mean and standard deviation of R‐wave to R‐wave intervals) during the prior hour predicted higher levels of perceived stress. Frequency domain HRV measures higher low to high frequency (LF/HF) and lower HF to total power (HF nu) ratios during the preceding 10 min predicted higher perceived stress levels, suggesting the dominance of sympathetic nervous system activity. EMA reports of higher perceived stress levels were associated with reduced time domain HRV measures during the following 10 min. On the other hand, higher LNA were related to increased HRV measures, such as lower LF/HF and higher HF nu during the following hour. The dynamic associations observed may have therapeutic implications for 'just‐in‐time' interventions in the management of daily stress and cardiovascular health. [ABSTRACT FROM AUTHOR]

Inclusion body myositis (IBM) is an idiopathic inflammatory myopathy, but cardiac involvement has rarely been reported. Although bicuspid aortic valve (BAV) is one of the most common congenital heart diseases, the relationship between IBM and valvular heart disease remains unknown. We herein report the first case of a 68‐year‐old male patient with IBM coexisting with severe aortic stenosis due to BAV that was successfully treated with aortic valve replacement. To date, only 10 cases of IBM with cardiac manifestation, including our case, have been reported, and we review the current literature on cardiac involvement in patients with IBM. [ABSTRACT FROM AUTHOR]

Objective: To assess the effectiveness of pre‐ and postoperative supervised pelvic floor muscle training (PFMT) on the recovery of continence and pelvic floor muscle (PFM) function after robot‐assisted laparoscopic radical prostatectomy (RARP). Patients and Methods: We carried out a single‐blind randomised controlled trial involving 54 male patients scheduled to undergo RARP. The intervention group started supervised PFMT 2 months before RARP and continued for 12 months after surgery with a physiotherapist. The control group was given verbal instructions, a brochure about PFMT, and lifestyle advice. The primary outcome was 24‐h pad weight (g) at 3 months after RARP. The secondary outcomes were continence status (assessed by pad use), PFM function, and the Expanded Prostate Cancer Index Composite (EPIC) score. Results: Patients who participated in supervised PFMT showed significantly improved postoperative urinary incontinence (UI) compared with the control group (5.0 [0.0–908.0] g vs 21.0 [0.0–750.0] g; effect size: 0.34, P = 0.022) at 3 months after RARP based on 24‐h pad weight. A significant improvement was seen in the intervention compared with the control group (65.2% continence [no pad use] vs 31.6% continence, respectively) at 12 months after surgery (effect size: 0.34, P = 0.030). Peak pressure during a maximum voluntary contraction was higher in the intervention group immediately after catheter removal and at 6 months, and a longer duration of sustained contraction was found in the intervention group compared with the control group. We were unable to demonstrate a difference between groups in EPIC scores. Conclusion: Supervised PFMT can improve postoperative UI and PFM function after RARP. Further studies are needed to confirm whether intra‐anal pressure reflects PFM function and affects continence status in UI in men who have undergone RARP. [ABSTRACT FROM AUTHOR]

Aryl hydrocarbon receptor (AhR) is a ligand‐dependent transcription factor. We previously reported spontaneous ileocecal tumorigenesis in AhR‐deficient mice after the age of 10 weeks, which originated in the confined area between ileum and cecum. This study aimed to investigate the underlying mechanism that causes tumor development at this particular location. To observe mucosal architecture in detail, tissues of ileocecal region were stained with methylene blue. Gene expression profile in the ileocecal tissue was compared with cecum. Immunohistochemical analysis was performed with ileocecal tissues using antibodies against ileum‐specific Reg3β or cecum‐specific Pitx2. In AhR+/+ mice and AhR+/− mice, that do not develop lesions, methylene blue staining revealed the gradually changing shape and arrangement of villi from ileum to cecum. It was also observed in AhR‐deficient mice before developing lesions. Microarray‐based analysis revealed abundant antimicrobial genes, such as Reg3, in the ileocecal tissue while FGFR2 and Pitx2 were specific to cecum. Immunohistochemical analysis of AhR‐deficient mice indicated that lesions originated from the ileocecal junction, a boundary area between different epithelial types. Site‐specific gene expression analysis revealed higher expression of IL‐1β at the ileocecal junction compared with the ileum or cecum of 9–11‐week‐old AhR‐deficient mice. These findings indicate that AhR plays a vital function in the ileocecal junction. Regulating AhR activity can potentially manage the stability of ileocecal tissue possessing cancer‐prone characteristics. This investigation contributes to understanding homeostasis in different epithelial transitional tissues, frequently associated with pathological states. [ABSTRACT FROM AUTHOR]

Giant cell myocarditis (GCM) is a rare but fatal disease that can lead to cardiac failure. Survival with a cardiac standstill requires mechanical circulatory support or a biventricular assist device (BiVAD) and prolonged survival is extremely rare. Drug‐induced hypersensitivity syndrome (DIHS) is a severe cutaneous adverse reaction. Some cases of DIHS are reportedly associated with the onset of GCM. We present a case of a 28‐year‐old woman who developed GCM during steroid tapering after DIHS. She went into continuous cardiac standstill but survived for 74 days under BiVAD support. Our case is noteworthy because the histopathologic specimens obtained on three occasions contributed to the diagnosis of this particular condition over time. We also reviewed previous literature on concomitant cases of GCM and DIHS. We found that two are potentially associated and most cases of GCM occur within 3 months of DIHS during steroid tapering. [ABSTRACT FROM AUTHOR]

Objective: High‐fat diets cause obesity in male mice; however, the underlying mechanisms remain controversial. Here, three contrasting ideas were assessed: hedonic overdrive, reverse causality, and passive overconsumption models. Method s : A total of 12 groups of 20 individually housed 12‐week‐old C57BL/6 male mice were exposed to 12 high‐fat diets with varying fat content from 40% to 80% (by calories), protein content from 5% to 30%, and carbohydrate content from 8.4% to 40%. Body weight and food intake were monitored for 30 days after 7 days at baseline on a standard low‐fat diet. Results: After exposure to the diets, energy intake increased first, and body weight followed later. Intake then declined. The peak energy intake was dependent on both dietary protein and carbohydrate, but not the dietary fat and energy density, whereas the rate of decrease in intake was only related to dietary protein. On high‐fat diets, the weight of food intake declined, but despite this average reduction of 14.4 g in food intake, they consumed, on average, 357 kJ more energy than at baseline. Conclusions: The hedonic overdrive model fit the data best. The other two models were not supported. [ABSTRACT FROM AUTHOR]

Objective: Malignant salivary glands tumors (MSGTs) are a quite rare and heterogeneous group of tumors. Management of these lesions remains controversial and challenging. Thus, finding new prognostic factors that can help to guide the decision‐making process, appears to be paramount. The aim of this study was to evaluate the prognostic performance of preoperative sarcopenia to stratify MSGTs patients at high risk of disease progression. Study Design: Retrospective study. Setting: A single‐institution analysis (Maxillo‐facial Surgery Unit, University of Naples Federico II). Methods: The study consists of a retrospective analysis of 74 patients surgically treated for MSGTs. For all patients, the skeletal muscle index (SMI) was calculated and sarcopenia was defined as SMI < 41 in females and <43 in males. The correlation between sarcopenia and tumor variables was analyzed. The prognostic performance of sarcopenia was evaluated through survival Kaplan‐Meier curves. Results: Sarcopenia resulted statistically related to age (P <.001), tumor size (P <.001), lymph node metastases (P <.001), and American Joint Committee on Cancer tumor, node, metastasis stage (P <.001). Kaplan‐Meier survival curves show that 47.3% of sarcopenic patients died before their final follow‐up. Conclusion: Data obtained from our study seem to confirm the correlation between sarcopenia and other high‐risk features. The early detection of sarcopenia in patients with negative prognostic factors could be used to implement the support therapeutic strategies aimed at restore the clinical conditions of the patients. Sarcopenia may be routinely investigated before surgery to suggest the implementation of precautionary therapeutic strategies to improve the standard treatment response, reducing possible complications. [ABSTRACT FROM AUTHOR]

A spin space group provides a suitable way of fully exploiting the symmetry of a spin arrangement with a negligible spin–orbit coupling. There has been a growing interest in applying spin symmetry analysis with the spin space group in the field of magnetism. However, there is no established algorithm to search for spin symmetry operations of the spin space group. This paper presents an exhaustive algorithm for determining the spin symmetry operations of commensurate spin arrangements. The present algorithm searches for spin symmetry operations from the symmetry operations of a corresponding nonmagnetic crystal structure and determines their spin‐rotation parts by solving a Procrustes problem. An implementation is distributed under a permissive free software license in spinspg Version 0.1.1, available at https://github.com/spglib/spinspg. [ABSTRACT FROM AUTHOR]

Purpose: The Database Task Force of the Japan Society for Pharmacoepidemiology began its annual surveys of databases available for clinico and pharmacoepidemiological studies in 2010. In this report, we summarize the characteristics of the databases available in Japan based on the results of our 2021 survey to illustrate the recent developments in the infrastructure for database research in Japan. Methods: We included 20 major databases from the academia, government, or industry that were accessible to third parties. We used a web‐based questionnaire to ask the database providers about their characteristics, such as their organization, data source(s), numbers of individuals enrolled, age distribution, code(s) used, and average follow‐up periods. Results: We received responses from all 20 databases approached: eight hospital‐based databases, six insurer‐based databases, four pharmacy‐based databases, and two in the "other" category. Among them, 17 contained information from medical claims, pharmacy claims, and/or Diagnosis Procedure Combination data. Most insurer databases contained health check‐up data that could be attached to the claims component. Some hospital‐based databases had data from electronic medical records. Most insurer‐based databases collected data from the insurers of working‐age employees and therefore had limited coverage of older people. Most databases coded their medication data using the Japanese reimbursement codes, and many provided Anatomical Therapeutic Chemical Classification codes. Conclusions: The number of databases available for clinico and pharmacoepidemiological research and the proportion of the population they cover are increasing in Japan. The differences in their characteristics mean that the appropriate database must be selected for a particular study purpose. [ABSTRACT FROM AUTHOR]

Background and Aim: Convolutional neural network (CNN) systems that automatically detect abnormalities from small‐bowel capsule endoscopy (SBCE) images are still experimental, and no studies have directly compared the clinical usefulness of different systems. We compared endoscopist readings using an existing and a novel CNN system in a real‐world SBCE setting. Methods: Thirty‐six complete SBCE videos, including 43 abnormal lesions (18 mucosal breaks, 8 angioectasia, and 17 protruding lesions), were retrospectively prepared. Three reading processes were compared: (A) endoscopist readings without CNN screening, (B) endoscopist readings after an existing CNN screening, and (C) endoscopist readings after a novel CNN screening. Results: The mean number of small‐bowel images was 14 747 per patient. Among these images, existing and novel CNN systems automatically captured 24.3% and 9.4% of the images, respectively. In this process, both systems extracted all 43 abnormal lesions. Next, we focused on the clinical usefulness. The detection rates of abnormalities by trainee endoscopists were not significantly different across the three processes: A, 77%; B, 67%; and C, 79%. The mean reading time of the trainees was the shortest during process C (10.1 min per patient), followed by processes B (23.1 min per patient) and A (33.6 min per patient). The mean psychological stress score while reading videos (scale, 1–5) was the lowest in process C (1.8) but was not significantly different between processes B (2.8) and A (3.2). Conclusions: Our novel CNN system significantly reduced endoscopist reading time and psychological stress while maintaining the detectability of abnormalities. CNN performance directly affects clinical utility and should be carefully assessed. [ABSTRACT FROM AUTHOR]

Objectives: Parkinson's disease caused by the loss of dopaminergic neurons induces not only motor dysfunction but also lower urinary tract dysfunction. Patients with Parkinson's disease have recently been reported to experience both urge urinary incontinence (overactive bladder) and stress urinary incontinence, the latter of which occurs when the pressure of the bladder exceeds that of the urethra. Vibegron is a highly selective novel β3‐adrenoceptor agonist approved for the treatment of overactive bladder. However, how β3‐adrenoceptor agonists affect urethral function remains unclear. In a clinical report, the urethral function of patients with Parkinson's disease was shown to be degraded. The present study aimed to investigate the effects of vibegron on lower urinary tract activity in a rat model of Parkinson's disease. Methods: In a rat model of Parkinson's disease induced by unilateral 6‐hydroxydopamine injection into the substantia nigra pars compacta, we examined the effects of vibegron on bladder and urethral activity. Results: Cystometric analysis revealed that, compared with vehicle injection, intravenous injection of 3 mg/kg vibegron significantly increased the inter‐contraction interval (p <.05) and reduced voiding pressure (p <.01). However, no significant effects on urethral function were observed. Conclusions: The results of the present study provide corroborating evidence that bladder dysfunction is suppressed by the administration of vibegron in Parkinson's disease model rats, confirming that vibegron is effective for treating overactive bladder without further worsening urethral function. These findings may contribute to a better understanding of the mechanisms of β3‐adrenoceptor agonists. [ABSTRACT FROM AUTHOR]

A crystal symmetry search is crucial for computational crystallography and materials science. Although algorithms and implementations for the crystal symmetry search have been developed, their extension to magnetic space groups (MSGs) remains limited. In this paper, algorithms for determining magnetic symmetry operations of magnetic crystal structures, identifying magnetic space‐group types of given MSGs, searching for transformations to a Belov–Neronova–Smirnova (BNS) setting, and symmetrizing the magnetic crystal structures using the MSGs are presented. The determination of magnetic symmetry operations is numerically stable and is implemented with minimal modifications from the existing crystal symmetry search. Magnetic space‐group types and transformations to the BNS setting are identified by a two‐step approach combining space‐group‐type identification and the use of affine normalizers. Point coordinates and magnetic moments of the magnetic crystal structures are symmetrized by projection operators for the MSGs. An implementation is distributed with a permissive free software license in spglib v2.0.2: https://github.com/spglib/spglib. [ABSTRACT FROM AUTHOR]

Background/Aim: During sports activities, teeth‐related contact can cause injury to both ally and opponent players, which can lead to potential infections and aesthetic problems. However, the extent of such injuries remains unclear. This study aimed to clarify the frequency and situation of head injuries caused by teeth (HICBT) occurring under the supervision of schools in Japan. Material and Methods: HICBT records were extracted from the Japan Sport Council data on head injuries occurring reported during the 7‐year period from 2012 to 2018 under the supervision of schools in Japan. Results: Of the total 463,527 head injury cases during the study period, 4495 cases (approximately 1%) were HICBT. Of the HICBT cases, 3650 (81.20%) were related to sports and athletic activity. Such injuries were reported to occur most often during basketball with a rate of 57.07% and 50.43%; soccer/futsal was the next most common sport with a rate of 13.38% and 24.01% in junior high school and high school students. Tag games were responsible for a similar number of HICBT cases at 22.73% and 39.03% in kindergartens and elementary school students. Conclusions: A total of 4495 cases of HICBT were identified, accounting for about 1% of all head injuries under the supervision of schools in Japan during the study period. This result reminds us that our teeth could be the weapon against the players during sports events. HICBTs occurring during basketball and soccer/futsal, in which mouthguards are not mandatory, were conspicuous among junior and senior high school students. Active use of mouthguards in various sports will protect players as well as their teammates and opponents. Sports dentists should encourage the revision of rules, such as mandating the use of mouthguards, in popular sports with a high incidence of HICBT, such as basketball and soccer/futsal. [ABSTRACT FROM AUTHOR]

Background/Aims: A light‐cured intermediate material is useful for fabricating a hard insert and a buffer space mouthguard (H&SMG). However, it requires improvement in its mechanical properties and shock‐absorbing capacity. The aim of this study was to evaluate the mechanical properties of two prototype light‐cured intermediate materials reinforced with glass fibers, and the impact absorption capacity and durability of H&SMGs made with the prototype intermediate materials. Materials and Methods: Two prototype materials containing long and microlength glass fibers in a light‐cured intermediate material, Innerframe LC®, for H&SMG, were fabricated and tested. A three‐point bending test was performed for evaluation of the mechanical properties. In addition, a shock absorption test was conducted using a customized pendulum impact testing machine to evaluate the H&SMGs' impact absorption capacity and durability. Results: Long and microlength glass fibers significantly improved flexural modulus and strength. H&SMGs made with these two glass fiber‐containing materials had high impact absorption capacity against both low and high impact forces, while the mouthguards made with long glass fiber materials had the best results. Conclusion: Long and microlength glass fibers with the prototype materials improved the mechanical properties of Innerframe LC® and the impact absorption capacity and durability of H&SMGs. H&SMGs made with the long glass fiber prototype materials had the best performance. [ABSTRACT FROM AUTHOR]

Dietary choices have a profound impact on the aging process. In addition to the total amount of energy intake, macronutrient composition influences both health and lifespan. However, the exact mechanisms by which dietary macronutrients influence onset and progression of age‐associated features remain poorly understood. Cellular senescence is a state of stable growth arrest characterized by the secretion of numerous bioactive molecules with pro‐inflammatory properties. Accumulation of senescent cells is considered one of the basic mechanisms of aging and an important contributor to chronic inflammation and tissue degeneration. Whether dietary macronutrients affect the accumulation and the phenotype of senescent cells with age is still unknown. Here, we show that feeding on diets with varying ratios of dietary macronutrients for 3 months has a significant effect on different senescence‐associated markers in the mouse liver. High protein intake is associated with higher expression levels of the two classical senescence‐associated growth arrest genes, p21 and p16. Furthermore, the expression of many pro‐inflammatory secretory markers was increased in diets enriched in protein and further enhanced by increases in fat content. These results provide preliminary evidence that dietary macronutrients have a significant influence on senescence markers and merit further investigation. [ABSTRACT FROM AUTHOR]

Introduction: There is no standard for insoluble particulate matters in dialysate. We evaluated the insoluble particulate matters in online prepared substitution fluid. Methods: We evaluated particle diameters and constituent elements of particles in online prepared substitution fluid and the final endotoxin retentive filter (ETRF). Results: The measurement results with particles in the online prepared substitution fluid and particles attached to the final ETRF revealed that Ca‐containing particles accounted for 11 particles and Si‐containing particles accounted for 19 particles of 30 particles detected in the online prepared substitution fluid and the final ETRF. Conclusion: We presume that insoluble particulates in online prepared substitution fluid were Ca and Mg precipitated from dialysate and Si precipitated from dialysis water. Even if two ETRFs were connected in series, these particles were formed in the final ETRF. [ABSTRACT FROM AUTHOR]

Background and objective: Remodelling of pulmonary arteries (PA) contributes to the progression of pulmonary hypertension (PH). Periostin, a matricellular protein, has been reported to be involved in the development of PH. We examined the role of periostin in the pathogenesis of PH using different types of experimental PH. Methods: PH was induced by vascular endothelial growth factor receptor antagonist (Sugen5416) plus hypoxic exposure (SuHx) and venous injection of monocrotaline‐pyrrole (MCT‐P) in wild‐type (WT) and periostin−/− mice. Pulmonary haemodynamics, PA remodelling, expression of chemokines and fibroblast growth factor (FGF)‐2, accumulation of macrophages to small PA and the right ventricle (RV) were examined in PH‐induced WT and periostin−/− mice. Additionally, the role of periostin in the migration of macrophages, human PA smooth muscle (HPASMCs) and endothelial cells (HPMVECs) was investigated. Results: In PH induced by SuHx and MCT‐P, PH and accumulation of M2 macrophage to small PA were attenuated in periostin−/− mice. PA remodelling post‐SuHx treatment was also mild in periostin−/− mice compared to WT mice. Expression of macrophage‐associated chemokines and FGF‐2 in lung tissue, and accumulation of CD68‐positive cells in the RV were less in SuHx periostin−/− than in SuHx WT mice. Periostin secretion in HPASMCs and HPMVECs was enhanced by transforming growth factor‐β. Periostin also augmented macrophage, HPASMCs and HPMVECs migration. Separately, serum periostin levels were significantly elevated in patients with PH compared to healthy controls. Conclusion: Periostin is involved in the development of different types of experimental PH, and may also contribute to the pathogenesis of human PH. [ABSTRACT FROM AUTHOR]

This work has successfully demonstrated a system for monitoring pink-beam X-rays exiting from a beamline front-end, which has a specific spatial distribution based on each energy component. In this study, the X-rays scattered from a single-crystal chemical-vapor-deposited diamond film were converted into a cross-sectional image using pinhole optics, followed by digitization with a direct detection complementary metal-oxide-semiconductor 2D detector. By using single crystals instead of poly-crystals, good quality images were obtained with no diffraction bright spots. As a result of applying photon energy discrimination using the droplet analysis to the image information, the spatial distribution of each energy component of the undulator radiation was successfully visualized. The result was found to be in good agreement with the theoretically calculated result obtained using the synchrotron radiation calculation code SPECTRA. The new synchrotron radiation beam monitor proposed in this paper can serve as a powerful beam diagnostic tool for diffraction-limited rings that require strict light source stability. [ABSTRACT FROM AUTHOR]

Dietary macronutrient composition influences both hepatic function and aging. Previous work suggested that longevity and hepatic gene expression levels were highly responsive to dietary protein, but almost unaffected by other macronutrients. In contrast, we found expression of 4005, 4232, and 4292 genes in the livers of mice were significantly associated with changes in dietary protein (5%–30%), fat (20%–60%), and carbohydrate (10%–75%), respectively. More genes in aging‐related pathways (notably mTOR, IGF‐1, and NF‐kappaB) had significant correlations with dietary fat intake than protein and carbohydrate intake, and the pattern of gene expression changes in relation to dietary fat intake was in the opposite direction to the effect of graded levels of caloric restriction consistent with dietary fat having a negative impact on aging. We found 732, 808, and 995 serum metabolites were significantly correlated with dietary protein (5%–30%), fat (8.3%–80%), and carbohydrate (10%–80%) contents, respectively. Metabolomics pathway analysis revealed sphingosine‐1‐phosphate signaling was the significantly affected pathway by dietary fat content which has also been identified as significant changed metabolic pathway in the previous caloric restriction study. Our results suggest dietary fat has major impact on aging‐related gene and metabolic pathways compared with other macronutrients. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to assess the safety risks associated with using nonsteroidal anti‐inflammatory drugs (NSAIDs) in elderly patients (≥65 years) compared with younger patients (<65 years) with osteoarthritis (OA) and/or chronic low back pain (CLBP). Methods: A retrospective analysis was conducted on anonymized claims data of patients prescribed NSAIDs for OA and/or CLBP from 2009 to 2018 using hospital‐based administrative database—Medical Data Vision (MDV). The key outcome was the incidence of developing gastrointestinal (GI), renal, and acute myocardial infarction (AMI) that are well‐known events associated with NSAID use. Results: Of 288,715 patients included, 23.7%, 60.5%, and 15.8% had OA, CLBP, or both, respectively. Elderly patients used non‐oral NSAIDs more frequently than oral NSAIDs (57.8% and 38.7%, respectively), whereas younger patients showed comparable use (50.7% and 52.8%, respectively). The incidence of events per 10,000 person‐years (95% CI) was higher in the elderly than in younger patients: GI, 29.68(27.67–31.68) vs. 16.61(14.60–18.63); renal, 124.77(120.56–128.99) vs. 39.88(36.72–43.03); and AMI, 27.41(25.48–29.35) vs. 10.90(9.27–12.53), respectively. After adjusting for covariates, the increase in risk for these events was seen in patients >70 years compared with younger patients (18–30 years) and was remarkable in patients >80 years with 2‐fold, 10‐fold, and 7‐fold higher risk for developing GI, renal, and AMI events, respectively. Conclusion: Risk for developing NSAID‐associated events was higher in the elderly; particularly, renal and AMI events that remarkably increased in patients >80 years. To reduce them, NSAIDs should be prescribed at the lowest effective dose for the shortest duration possible. [ABSTRACT FROM AUTHOR]

Summary: As haematologists, we always seek to follow standardised guidelines for practice and apply the best treatment within our means for our patients with blood diseases. However, treatment can never follow an exact recipe. Opinions differ as to the best approach; sometimes more than one treatment approach results in identical outcomes, or treatments differ only by the manner in which they fail. Furthermore, the haematologist is faced with constraints relating to the local economic environment. Patients too are not the same the world over. Early presentation is commoner in the developed world, as is the patient's understanding of the disease process. This in turn has an impact on the way patients are managed, the rigorousness of patient adhesion to the treatment schedule and the outcome. Here we take a look at the precursor B‐cell acute lymphoblastic leukaemia in an adolescent in a range of different settings from low‐ to high income countries with widely differing challenges for diagnosis, therpy and follow‐up. For these reasons, given the same starting conditions, patients will be treated differently according to the institute and the country they are in. Experts from around the world have been tasked to describe their management plan and rationale for a specific disease presentation. Here they explore the management of precursor B‐cell acute lymphoblastic leukaemia (pre‐B ALL) in five different institutions worldwide with a focus on those with more or less strained economies. We end with a conclusion from an expert in the field comparing and contrasting these different management styles and considering their merits and limitations. [ABSTRACT FROM AUTHOR]

Fulminant myocarditis is an inflammatory disease of the cardiac muscle that severely deteriorates cardiac function and often causes haemodynamic collapse in a manner similar to acute coronary syndrome. In rare cases, the myocardium of the right ventricle is dominantly damaged. In cases of lymphocytic myocarditis, a common type of fulminant myocarditis, cardiac function is often recovered after peak myocardial inflammation subsides; however, some cases show irreversible myocardial damage. Herein, we report the case of a 43‐year‐old woman with irreversible, right‐side dominant ventricular myocardial damage; she presented with various cardiopulmonary conditions including complete atrioventricular block, ventricular tachycardia, right heart failure, right ventricular thrombosis, and pulmonary embolism. The patient was successfully treated with medications and a cardiac resynchronization therapy‐defibrillator device. [ABSTRACT FROM AUTHOR]

The Committee for the Development of Guidelines for Infection Control in the Urological Field, including Urinary Tract Management of the Japanese Urological Association, together with its systematic review team and external reviewers, have prepared a set of practice guidelines, an abridged version of which is published herein. These guidelines cover the following topics: (i) foundations of infection control, standard precautions, route‐specific precautions, and occupational infection control (including vaccines); (ii) the relationship between urologists and infection control; (iii) infection control in urological wards and outpatient clinics; (iv) response to hepatitis B virus reactivation; (v) infection control in urological procedures and examinations; (vi) prevention of infections occurring in conjunction with medical procedures and examinations; (vii) responses to urinary tract tuberculosis and bacillus Calmette–Guérin; (viii) aseptic handling, cleaning, disinfection, and sterilization of urinary tract endoscopes (principles of endoscope manipulation, endoscope lumen cleaning, and disinfection); (ix) infection control in the operating room (principles of hand washing, preoperative rubbing methods, etc.); (x) prevention of needlestick and blood/bodily fluid exposure and response to accidental exposure; (xi) urinary catheter‐associated urinary tract infection and purple urinary bag syndrome; and (xii) urinary catheter‐associated urinary tract infections in conjunction with home care. In addressing these topics, the relevant medical literature was searched to the extent possible, and content was prepared for the purpose of providing useful information for clinical practice. [ABSTRACT FROM AUTHOR]

Objective: Maternal high-fat diet (HFD) increases offspring obesity, yet the impacts of different levels of maternal dietary fat have seldom been addressed. In mice, the impact of graded maternal dietary fat on offspring adiposity and offspring's later susceptibility to HFD were assessed.Methods: Lactating mice were fed diets with graded fat content from 8.3% to 66.6%. One male and one female pup from each litter were weaned onto a low-fat diet for 15 weeks. HFD (41.7%) was then introduced to half of the offspring for 12 weeks.Results: Offspring body weight and adiposity were positively related to maternal dietary fat content and were higher when mothers were exposed to HFD. The maternal diet effect was nonlinear and sex dependent. A maternal dietary fat of 41.7% and above exaggerated the offspring body weight gain in males but was not significant in females. Maternal 8.3% fat and 25% fat diets led to the highest daily energy expenditure and respiratory exchange ratio in offspring. Offspring fed a low-fat diet had higher daily energy expenditure and respiratory exchange ratio than those fed an HFD.Conclusions: Increasing maternal dietary fat during lactation, and HFD in later life, had significant and interacting impacts on offspring obesity. Maternal diet had a bigger impact on male offspring. The effects of maternal dietary fat content were nonlinear. [ABSTRACT FROM AUTHOR]

In this study, the bond behavior of corroded reinforced concrete was investigated by conducting pull‐out tests on concrete specimens with variable induced crack widths and different splitting modes. To simulate cracks due to corrosion and focus on their effect on bond strength degradation, a novel method using expansion agent filled pipes is proposed. With the increase of the crack width over elapsed time from filling the aluminum pipe with an expansion agent, a target crack width was obtained. The results confirm that the type of splitting greatly influences the reduction in bond strength with deterioration of bond strength more severe in "Side‐split" than in "Single‐split." Furthermore, using the surface crack width as a variable, empirical formulas to predict bond strength degradation due to corrosion of rebar are proposed. These prediction models give a good correlation when compared to the available literature. [ABSTRACT FROM AUTHOR]

Objective: To determine if a clinical presentation indistinguishable from migraine can occur due to an underlying condition or pathology, that is, "symptomatic migraine." Background: It is currently not clear whether migraine truly can be caused by an underlying condition or pathology. Characterization of the etiology and clinical features of possible symptomatic migraine is of significant clinical importance and further may help elucidate the pathophysiology of migraine. Methods: We devised operational diagnostic criteria for "symptomatic migraine" and "possible symptomatic migraine" requiring strong evidence for a causal relation between underlying cause and migraine symptoms adhering strictly to diagnostic criteria. PubMed was searched for case reports of symptomatic migraine from inception to March 2020. Only articles published in English or German were included. No restrictions were placed on study design. Relevant references in the articles were also included. Papers were systematically reviewed by two independent reviewers for detailed clinical features of migraine as well as the proposed underlying conditions and the effects of treatment of these conditions. Results: Our search retrieved 1726 items. After screening, 109 papers comprising 504 cases were reviewed in detail. Eleven patients with migraine with aura (MWA) fulfilled our working criteria for symptomatic migraine, and 39 patients fulfilled our criteria for possible symptomatic migraine. The most common etiologies of symptomatic migraine were arteriovenous malformations, carotid stenosis, dissection or aneurysm, brain infarctions, meningioma, and various intra‐axial tumors. Conclusions: Symptomatic MWA, indistinguishable from idiopathic MWA, may occur due to cortical lesions or microembolization. We found no clear evidence supporting the existence of symptomatic migraine without aura although we did identify possible cases. Our findings are limited by the available literature, and we suggest that prospective studies are needed. [ABSTRACT FROM AUTHOR]

Ptychographic coherent diffraction imaging (CDI) allows the visualization of both the structure and chemical state of materials on the nanoscale, and has been developed for use in the soft and hard X‐ray regions. In this study, a ptychographic CDI system with pinhole or Fresnel zone‐plate optics for use in the tender X‐ray region (2–5 keV) was developed on beamline BL27SU at SPring‐8, in which high‐precision pinholes optimized for the tender energy range were used to obtain diffraction intensity patterns with a low background, and a temperature stabilization system was developed to reduce the drift of the sample position. A ptychography measurement of a 200 nm thick tantalum test chart was performed at an incident X‐ray energy of 2.500 keV, and the phase image of the test chart was successfully reconstructed with approximately 50 nm resolution. As an application to practical materials, a sulfur polymer material was measured in the range of 2.465 to 2.500 keV including the sulfur K absorption edge, and the phase and absorption images were successfully reconstructed and the nanoscale absorption/phase spectra were derived from images at multiple energies. In 3 GeV synchrotron radiation facilities with a low‐emittance storage ring, the use of the present system will allow the visualization on the nanoscale of the chemical states of various light elements that play important roles in materials science, biology and environmental science. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Respiratory syncytial virus (RSV) is a major cause of hospitalization for bronchiolitis and pneumonia in infancy. In Japan, limited data are publicly available on RSV epidemiology and clinical characteristics among infants.This retrospective study described RSV incidence, seasonality, patient characteristics, resource use, and clinical outcomes among Japanese children <2 years from January 2017 through December 2018. The RSV cases were identified using the Japanese Medical Data Center database.In the database, 9,711 and 8,509 RSV patients <2 years were identified in 2017 and 2018, respectively. Of these, 25% required hospitalization. Ninety percent of hospitalized patients did not have a known RSV risk factor. Nineteen percent of hospitalized patients experienced dehydration, and 12% had acute respiratory failure. Hospitalization lasted 1 week on average and 7% required some type of mechanical ventilation. The peak of hospitalizations occurred at 2 months. The incidence of RSV hospitalization in children <2 years was 23.2 per 1,000 person‐years, which increased to 35.4 per 1,000 for infants <6 months. This age group accounted for 40% of all RSV‐associated hospitalizations among children <2 years.Roughly one‐fourth of all RSV patients <2 years were hospitalized. Ninety percent of these did not have an underlying risk condition. This underscores that RSV can cause serious disease among all young children. Three to four out of every 100 Japanese children <6 months were hospitalized for RSV, and this age group accounted for ~40% of all RSV‐associated hospitalizations. Novel and broad‐based RSV prevention strategies, especially those targeting young infants, are needed. [ABSTRACT FROM AUTHOR]

Overexpression of human dynactin‐associated protein isoform a (dynAPa) transforms NIH3T3 cells. DynAPa is a single‐pass transmembrane protein with a carboxy‐terminal region exposed to the outside of cells. According to the NCBI RefSeq database, there may be two other splicing variants of the encoding gene (dynAPb and c). DynAPa and c differ in some amino‐terminal residues (NH2‐MVA in dynAPa and NH2‐MEYQLL in dynAPc). DynAPb has the same amino‐terminal residues as dynAPc, but lacks 55 residues in the intracellular region. All three isoforms have the same carboxy‐terminal region, including the transmembrane domain. Expression of mRNAs of three splicing variants was found in human cancer cell lines ACHN and Caki‐1. The subcellular localization and in vitro cell transformation ability of the three isoforms were examined using NIH3T3 cells overexpressing each respective isoform. All isoforms were found to be localized to the Golgi apparatus and plasma membrane, where the carboxy‐terminal region was exposed to the outside of cells. Cell transformation was tested using focus formation due to loss of contact inhibition of cell proliferation, and colony formation was examined on soft agar and spheroid formation in ultralow U‐bottomed wells. DynAPa robustly formed foci and colonies on soft agar and spheroid, whereas these abilities were considerably decreased for dynAPb and completely lost in dynAPc. These findings warrant dissection studies to identify the dynAP domain that is required for cell transformation. [ABSTRACT FROM AUTHOR]

Alternative splicing of pre‐mRNAs can regulate gene expression levels by coupling with nonsense‐mediated mRNA decay (NMD). In order to elucidate a repertoire of mRNAs regulated by alternative splicing coupled with NMD (AS‐NMD) in an organism, we performed long‐read RNA sequencing of poly(A)+ RNAs from an NMD‐deficient mutant strain of Caenorhabditis elegans, and obtained full‐length sequences for mRNA isoforms from 259 high‐confidence AS‐NMD genes. Among them are the S‐adenosyl‐L‐methionine (SAM) synthetase (sams) genes sams‐3 and sams‐4. SAM synthetase activity autoregulates sams gene expression through AS‐NMD in a negative feedback loop. We furthermore find that METT‐10, the orthologue of human U6 snRNA methyltransferase METTL16, is required for the splicing regulation in␣vivo, and specifically methylates the invariant AG dinucleotide at the distal 3′ splice site (3′SS) in␣vitro. Direct RNA sequencing coupled with machine learning confirms m6A modification of endogenous sams mRNAs. Overall, these results indicate that homeostasis of SAM synthetase in C. elegans is maintained by alternative splicing regulation through m6A modification at the 3′SS of the sams genes. SYNOPSIS: Alternative splicing (AS) of pre‐mRNAs can regulate gene expression levels by coupling with nonsense‐mediated mRNA decay (NMD). Here, assessment of the organismal substrate repertoire of this process reveals SAM synthetase (sams) gene expression regulation via m6A modification in C. elegans. Long‐read sequencing of poly(A)+ RNAs from an NMD‐deficient mutant strain reveals 259 high‐confidence AS‐NMD genes, including the SAM synthetase (sams) genes.SAMS activity negatively autoregulates AS‐NMD of the sams genes in␣vivo.Direct RNA sequencing coupled with machine learning reveals m6A modification of endogenous sams mRNAs at the distal 3′ splice sites.Methyltransferase METT‐10 catalyzes m6A modification specifically at the distal 3′ splice site of sams pre‐mRNA in␣vitro.METT‐10 regulates alternative splicing of the sams genes in␣vivo. [ABSTRACT FROM AUTHOR]

Cancer‐associated fibroblasts (CAFs) regulate cancer progression through the modulation of extracellular matrix (ECM) and cancer cell adhesion. While undergoing a series of phenotypic changes, CAFs control cancer–stroma interactions through integrin receptor signaling. Here, we isolated CAFs from patients with non‐small‐cell lung cancer (NSCLC) and examined their gene expression profiles. We identified collagen type XI α1 (COL11A1), integrin α11 (ITGA11), and the ITGA11 major ligand collagen type I α1 (COL1A1) among the 390 genes that were significantly enriched in NSCLC‐associated CAFs. Increased ITGA11 expression in cancer stroma was correlated with a poor clinical outcome in patients with NSCLC. Increased expression of fibronectin and collagen type I induced ITGA11 expression in CAFs. The cellular migration of CAFs toward collagen type I and fibronectin was promoted via ERK1/2 signaling, independently of the fibronectin receptor integrin α5β1. Additionally, ERK1/2 signaling induced ITGA11 and COL11A1 expression in cancer stroma. We, therefore, propose that targeting ITGA11 and COL11A1 expressing CAFs to block cancer–stroma interactions may serve as a novel, promising anti‐tumor strategy. [ABSTRACT FROM AUTHOR]

Objective: To evaluate voiding behavior characteristics in intact and sham mice, and to examine whether intact mice show changes in "normal" micturition with aging. Methods: A total of 72 8‐week‐old mice were divided into two groups – intact and sham – and the latter group was subjected to a sham of partial bladder outlet obstruction surgery. Urination frequency was evaluated (through metabolic cages) at 1, 2, 3, 6 and 12 months after the surgery (or at the equivalent time points for the intact mice). To address possible mechanisms for aging and surgical effects on urinary behavior, quantitative real‐time polymerase chain reaction assays were carried out. Primary data were evaluated using scatter plots and descriptive statistics. Results: In sham mice, urination frequency showed strong variation at the earlier post‐surgical time points (especially at 1 month), with variation decreasing with time. Quantitative real‐time polymerase chain reaction showed that the serotonin 2C receptor‐encoding mRNA accumulated to >28‐fold higher levels at 24 months compared with 3 months in intact mice. A major limitation of the quantitative real‐time polymerase chain reaction experiments was that we did not separate whole bladder into muscle and mucosa. Conclusions: Although a sham operation is typically used in partial bladder outlet obstruction experiments to provide control animals, the sham group might itself show increased variation in micturition frequency at early times after surgery, compared with intact animals. [ABSTRACT FROM AUTHOR]

Background: Pulmonary vein (PV) antrum isolation (PVAI) has proven to be a useful strategy for radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF) worldwide. However, non‐PV foci, especially from the superior vena cava (SVC), play an important role in initiating and maintaining AF. Methods: In all, 427 consecutive patients with non‐valvular AF who were admitted to our hospitals to undergo RFCA of AF using an EnSite™ system were evaluated. The length from the top of the sinus node to the top of the myocardial sleeve of SVC (L‐SVC), longer and shorter diameter of SVC of 1 cm above of junction of right atrium and SVC, and local activation time (LAT) of SVC were measured. Then, the SVC firing was evaluated by an intravenous administration of isoproterenol and adenosine triphosphate. Results: L‐SVC, longer and shorter diameter of SVC, and LAT of SVC were significantly longer in the SVC firing group than non‐SVC firing group (P <.05). Moreover, in accordance with the L‐SVC, the frequency of the SVC firing significantly increased (P <.001). A univariate analysis and multivariate statistical analysis revealed that L‐SVC longer than 37.0 mm (odds ratio 6.39) and longer diameter of SVC (odds ratio 6.78) were independent risk factors for SVC firing in patients with AF who underwent RFCA of AF. Conclusions: In view of these findings, L‐SVC longer than 37.0 mm longer diameter SVC longer than 17.0 mm may be one of the important predictors of SVC firing in patients with AF. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a neurodegenerative disorder caused by the selective loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc). Lewy bodies (LBs), another histological hallmark of PD, are observed in patients with familial or sporadic PD. The therapeutic potential of reducing the accumulation of α‐synuclein, a major LB component, has been investigated, but it remains unknown whether the formation of LBs results in the loss of DA neurons. PARK4 patients exhibit multiplication of the α‐synuclein gene (SNCA) without any pathological mutations, but their symptoms develop relatively early. Therefore, study of PARK4 might help elucidate the mechanism of α‐synuclein aggregation. In this study, we investigated the dynamics of α‐synuclein during the early stage of immature DA neurons, which were differentiated from human‐induced pluripotent stem cells (hiPSCs) derived from either a PARK4 patient with SNCA triplication or a healthy donor. We observed increased α‐synuclein accumulation in PARK4 hiPSC‐derived DA neurons relative to those derived from healthy donor hiPSCs. Interestingly, α‐synuclein accumulation disappeared over time in the PARK4 patient‐derived DA neurons. Moreover, an SNCA‐specific antisense oligonucleotide could reduce α‐synuclein levels during the accumulation stage. These observations may help reveal the mechanisms that regulate α‐synuclein levels, which may consequently be useful in the development of new therapies for patients with sporadic or familial PD. [ABSTRACT FROM AUTHOR]

PALB2 is а high‐penetrance gene for hereditary breast cancer (BC). Our study aimed to investigate the spectrum of PALB2 mutations in Russian cancer patients. PALB2 sequencing revealed pathogenic variants in 3/190 (1.6%) young‐onset and/or familial and/or bilateral BC cases but none in 96 ovarian cancer (OC) or 172 pancreatic cancer patients. Subsequently, seven recurrent PALB2 pathogenic alleles were selected from this and previous Slavic studies and tested in an extended patient series. PALB2 pathogenic variants were detected in 5/585 (0.9%) "high‐risk" BC, 10/1508 (0.7%) consecutive BC and 5/1802 (0.3%) OC cases. Haplotyping suggested that subjects with Slavic alleles c.509‐510delGA (n = 10) and c.172‐175delTTGT (n = 4) as well as carriers of Finnish c.1592delT mutation (n = 4) originated from a single founder each, while PALB2 p.R414X allele (n = 4) had at least two independent founders. Somatic loss of heterozygosity (LOH) was revealed in 5/10 chemonaive BCs and in 0/2 BC samples obtained after neoadjuvant therapy. Multigene sequencing identified somatic PALB2 inactivating point mutation in one out of two tumors without PALB2 LOH but in none of four BCs with PALB2 LOH. Genomic instability, as determined by NGS, was observed in four out of five tumors with biallelic PALB2 inactivation but not in the BC sample with the preserved wild‐type PALB2 allele. PALB2 germ‐line mutations contribute to a small fraction of cancer cases in Russia. The majority although not all PALB2‐driven BCs have somatic inactivation of the remaining PALB2 allele and therefore potential sensitivity to platinum compounds and PARP inhibitors. What's new? Variations in the PALB2 gene are associated with increased risk of hereditary breast cancer. The effect of PALB2 germ‐line mutations on cancer predisposition, however, remains unknown. Here, in a Russian cohort, about 1 percent of high‐risk breast cancer patients carried PALB2 pathogenic variants, with a lower frequency of variants identified in consecutive breast cancer cases. Ovarian cancer risk was marginally elevated in PALB2 mutation carriers. In addition, while several recurrent PALB2 alleles originated from a single founder, p.R414X had at least two independent ancestors, suggesting a possible mutation hotspot. Somatic inactivation of the remaining PALB2 allele may affect therapeutic response. [ABSTRACT FROM AUTHOR]

Aims/Introduction: Sodium–glucose cotransporter 2 inhibitors (SGLT2i) improve renal outcome in patients with type 2 diabetes mellitus, but the mechanism is not fully understood. The aim of this retrospective study was to assess the association of achieved blood pressure with renal outcomes in Japanese type 2 diabetes mellitus patients with chronic kidney disease. Materials and Methods: We assessed 624 Japanese type 2 diabetes mellitus patients with chronic kidney disease taking SGLT2i for >1 year. The patients were classified as those with post‐treatment mean arterial pressure (MAP) of ≥92 mmHg (n = 344) and those with MAP of <92 mmHg (n = 280) for propensity score matching (1:1 nearest neighbor match with 0.04 of caliper value and no replacement). The end‐point was a composite of progression of albuminuria or a decrease in the estimated glomerular filtration rate by ≥15% per year. Results: By propensity score matching, a matched cohort model was constructed, including 201 patients in each group. The incidence of renal composite outcome was significantly lower among patients with MAP of <92 mmHg than among patients with MAP of ≥92 mmHg (n = 11 [6%] vs n = 26 [13%], respectively, P = 0.001). The change in estimated glomerular filtration rate was similar in the two groups; however, the change in the albumin‐to‐creatinine ratio was significantly larger in patients with MAP of <92 mmHg. Conclusions: In Japanese type 2 diabetes mellitus patients with chronic kidney disease, blood pressure after SGLT2i administration influences the renal composite outcome. Blood pressure management is important, even during treatment with SGLT2i. [ABSTRACT FROM AUTHOR]

Interaction of cancer cells with cancer‐associated fibroblasts (CAFs) plays critical roles in tumor progression. Recently we proposed a new tumor invasion mechanism in which invasive cancer cells individually migrate on elongate protrusions of CAFs (CAF fibers) in 3‐D collagen matrix. In this mechanism, cancer cells interact with fibronectin fibrils assembled on CAFs mainly through integrin‐α5β1. Here we tested whether this mechanism is applicable to the collective invasion of cancer cells, using two E‐cadherin‐expressing adenocarcinoma cell lines, DLD‐1 (colon) and MCF‐7 (breast). When hybrid spheroids of DLD‐1 cells with CAFs were embedded into collagen gel, DLD‐1 cells collectively but very slowly migrated through the collagen matrix in contact with CAFs. Epidermal growth factor and tumor necrosis factor‐α promoted the collective invasion, possibly by reducing the E‐cadherin junction, as did the transforming growth factor‐β inhibitor SB431542 by stimulating the outgrowth of CAFs. Transforming growth factor‐β itself inhibited the cancer cell invasion. Efficient collective invasion of DLD‐1 cells required large CAF fibers or their assembly as stable adhesion substrates. Experiments with function‐blocking Abs and siRNAs confirmed that DLD‐1 cells adhered to fibronectin fibrils on CAFs mainly through integrin‐α5β1. Anti‐E‐cadherin Ab promoted the single cell invasion of DLD‐1 cells by dissociating the E‐cadherin junction. Although the binding affinity of MCF‐7 cells to CAFs was lower than DLD‐1, they also collectively invaded the collagen matrix in a similar fashion to DLD‐1 cells. Our results suggest that the direct interaction with CAFs, as well as environmental cytokines, contributes to the collective invasion of cancers. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of chronic administration of an alpha‐1 blocker on micturition patterns in long‐term partial bladder outlet obstruction. Methods: Mice were divided into three groups: a normal group, in which animals were fed a standard diet; a partial bladder outlet obstruction group, in which the proximal urethra was tied and animals were fed a standard diet; and a partial bladder outlet obstruction + naftopidil group, in which the proximal urethra was tied and animals were fed a standard diet containing naftopidil. Micturition behavior was evaluated in all groups for 6 months after partial bladder outlet obstruction surgery. The parameters evaluated included voided volume, time per void, urination frequency and total urine volume. Quantitative assessment of gene expression was also carried out. Results: Total urine volume, as well as total and average voided volume during night, was significantly decreased in partial bladder outlet obstruction + naftopidil mice compared with partial bladder outlet obstruction animals. The levels of transcripts encoding 5‐hydroxytryptamine 2A and tissue inhibitor of metalloproteinase 2 were significantly decreased in the partial bladder outlet obstruction + naftopidil group compared with the partial bladder outlet obstruction group. Conclusions: Long‐term administration of an alpha‐1 blocker seems to reverse the disturbance of the micturition pattern caused by partial bladder outlet obstruction. Mechanistically, this effect might be mediated by changes in the expression of a serotonin receptor and/or in the activity of the fibrogenesis pathway. [ABSTRACT FROM AUTHOR]

Background: Persistent Helicobacter pylori infection induces gastric mucosal atrophy, which is a precancerous condition. Hydrogen sulfide (H2S), a gaseous biological transmitter, has been implicated in both the physiological functions of the gastrointestinal tract and its diseases. To understand gastric epithelial cell response against H pylori infection, we investigated the metabolic changes of gastric cancer cells co‐cultured with H pylori and observed the modulation of endogenous H2S production. Materials and Methods: Gastric cancer AGS cells were co‐cultured with an H pylori standard strain possessing bacterial virulence factor CagA (ATCC 43504) and a strain without CagA (ATCC 51932). Three hours after inoculation, the cells were subjected to metabolomics analysis using gas chromatography‐tandem mass spectrometry (GC‐MS/MS). Orthogonal projections to latent structures discriminant analysis (OPLS‐DA) and pathway analysis were performed. In addition, intracellular H2S levels were measured by using HSip‐1 fluorescent probe. Results: Results of OPLS‐DA showed a significant difference between the metabolism of untreated control cells and cells inoculated with the H pylori strains ATCC 51932 or ATCC 43504, mainly due to 45 metabolites. Pathway analysis with the selected metabolites indicated that methionine metabolism, which is related to H2S production, was the most frequently altered pathway. H pylori‐inoculated cells produced more endogenous H2S than control cells. Moreover, ATCC 43504‐inoculated cells produced less H2S than ATCC 51932‐inoculated cells. Conclusions: H pylori infection modulates endogenous H2S production in AGS cells, suggesting that H2S might be one of the bioactive molecules involved in the biological mechanisms of gastric mucosal disease including mucosal atrophy. [ABSTRACT FROM AUTHOR]

Objectives: Pelvic organ prolapse (POP) is relatively common in the elderly population. Laparoscopic sacrocolpopexy (LSC) has been reported by several studies to be a less invasive treatment option as compared to open sacrocolpopexy. However, almost all prior reports focused on the complications or surgical obstacles. The present study was designed to examine POP patients of all ages and assess lower urinary tract function before and after LSC. Methods: This retrospective study examined the results of LSC performed in POP patients. Urodynamic studies were performed pre‐ and postoperatively in 50 patients, with the subjects divided into two groups containing those less than and those older than 65 years of age. We performed a pressure flow study. We examined bladder functions by evaluating bladder capacity, detrusor pressure at maximum flow (PdetQmax), maximum flow rate (Qmax), normal desire to void, strong desire to void, voided volume, and postvoid residual volume (PVR). Statistical analysis was performed using Wilcoxon signed rank test. Values of P <.05 were considered significant. Results: With regard to the pressure‐flow study parameters, there was a significant increase in the normal desire to void and bladder capacity only in the ≥65 age group. After the operation, there was a significant increase in the mean postoperative Qmax and voided volume, while there was a significant decrease in the PdetQmax and PVR as compared to the preoperative values only in the ≥65 age group. Conclusions: Results show that in elderly patients with POP, LSC might be a valid option with regard to potentially regaining urinary tract function. [ABSTRACT FROM AUTHOR]

A novel preparation of hemiaminal derivatives bearing both an amide group and a benzoate group was carried out in good yields by the treatment of BPO in N,N‐dimethylamides under warming condition at 80 °C or irradiation with a mercury lamp. Further treatment of the obtained hemiaminal derivatives with indoles in 1,1,1,3,3,3‐hexafluoro‐2‐propanol generated the corresponding C–C bonded indoles bearing an amide group in good yields. The formed indoles bearing an amide group were smoothly transformed into the corresponding indoles bearing an aminomethyl group. [ABSTRACT FROM AUTHOR]

Treatment of O‐(β‐arylethyl) arylimidates with 1,3‐diiodo‐5,5‐dimethylhydantoin (DIH) under irradiation with a tungsten lamp in 1,2‐dichloroethane gave the corresponding 2,4‐diaryl‐5‐iodoxazoles and 2,4‐diaryloxazoles in good to moderate yields, respectively, depending on the aryl group. It was proposed that the reactions proceeded through the formation of N‐iodoimidates by the reaction of O‐(β‐arylethyl) arylimidates with DIH, followed by the formation of iminyl radicals via homolytic N–I bond cleavage, the 1,5‐H shift by the iminyl radicals, the C–I bond formation of the formed carbon‐centered radicals with iodine, the nucleophilic cyclization by the imino groups to form 2,4‐diaryloxazolines, the oxidation of the formed 2,4‐diaryloxazolines to 2,4‐diaryloxazoles, and the iodination of the formed 2,4‐diaryloxazoles to 2,4‐diaryl‐5‐iodoxazoles with DIH. [ABSTRACT FROM AUTHOR]

Objectives: To the best of our knowledge, no study has examined the reliability of assessment methods for male pelvic floor muscle (PFM) function. Therefore, this study aimed to clarify the reliability of manometry with an anal sensor (Peritron cat 9300A) to assess PFM function in healthy men. Methods: Healthy male subjects (n = 21) without urinary leakage underwent testing to assess PFM function, and intra‐ and interrater reliability tests among examiners were performed. The PFM function included maximal anorectal squeeze pressure, endurance, mean anorectal squeeze pressure, gradient, and area under the curve during PFM voluntary contraction. Results: Participants had a median age of 38 years (range 26‐51), and a mean BMI of 23.2 ± 2.0 kg/m2. Satisfactory intra‐ and interrater reliability scores were found for resting pressure, anorectal squeeze pressure, and endurance. The intra‐rater reliability of resting pressure, anorectal squeeze pressure, and endurance were 0.71, 0.89, and 0.75 for examiner 1 and 0.72, 0.89, and 0.87 for examiner 2. The interrater reliability for resting pressure, anorectal squeeze pressure, and endurance were 0.58, 0.93, and 0.61, respectively. Conclusions: This is the first prospective study showing the favorable intra‐ and interrater reliability of manometry for PFM function in healthy men. Our findings demonstrated that manometry can provide both reliable and reproducible data regarding PFM function in continent men, suggesting Peritron cat 9300A can be used to evaluate the PFM function in men. [ABSTRACT FROM AUTHOR]

Objectives: To compare the optimal administration period of antimicrobial prophylaxis in patients undergoing transurethral enucleation of the prostate for benign prostatic hyperplasia. Methods: We carried out a randomized controlled trial to compare the differences in incidence of perioperative genitourinary tract infection between single and multiple (3 days) administrations of cefazolin for transurethral enucleation of the prostate in benign prostatic hyperplasia patients without pyuria or bacteriuria between January 2015 and December 2018. Results: This multicenter randomized controlled trial included 203 patients who underwent a transurethral enucleation of the prostate procedure. All received antimicrobial prophylaxis, and were randomized into those who received single‐dose (n = 101) or multiple‐dose (n = 102) therapy. The rate of genitourinary tract infection after transurethral enucleation of the prostate for all patients was 1.5%, whereas that in the single‐dose group was 1.0% and in the multiple‐dose group was 2.0%, which were not significantly different (P = 1.00). Conclusions: A single dose of antimicrobial prophylaxis as a prophylactic antibacterial drug is sufficient for patients undergoing transurethral enucleation of the prostate who do not have presurgical pyuria or bacteriuria. [ABSTRACT FROM AUTHOR]

Aim: The prevalence of mental disorders increases sharply during adolescence. Therefore, school teachers are in a good position to provide initial assistance to students with mental health problems. Although effects of a number of mental health literacy programs aimed at teachers have been reported, they have not yet been reviewed in a systematic manner. This study conducted a systematic review of the effectiveness of mental health literacy programs for teachers. Methods: PubMed, PsycINFO, CINAHL, ERIC, Web of Science and reference lists of included studies were searched in September 2018. Studies that quantitatively measured at least one of the main components of mental health literacy, including (a) knowledge of mental illnesses, (b) stigma towards mental illnesses, (c) confidence in helping students, and (d) behaviour of helping students, were included regardless of study design. Risk of bias was rated for each included study according to the Cochrane tool for randomized studies and the Cochrane tool, for raondomized studies, and the Risk of Bias Assessment Tool for Nonrandomized Studies (RoBANS), for nonrandomized studies. Results: Sixteen studies met the inclusion criteria, including 1 randomized controlled trial (RCT), 2 cluster RCTs, 1 controlled before‐and‐after study and 12 case series. Most of the studies claimed significant improvement of knowledge, attitudes, behaviour and/or confidence. However, the overall quality for all outcomes was relatively low; 15 studies had high/unclear risk of bias due to lack of allocation concealment, not controlling for confounders, and/or inadequate analysis for attrition. Conclusions: More high quality evidence is required before the effectiveness of mental health literacy programs for teachers can be established. [ABSTRACT FROM AUTHOR]