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Kawasaki disease (KD) causes vascular injury and lifelong remodeling. Excessive intimal proliferation has been observed, resulting in coronary artery lesions (CALs). However, the mechanisms underlying vascular remodeling in CAL and statin treatment have not been comprehensively elucidated. This study aimed to investigate the effects of statins on vascular remodeling using a KD mouse model. Candida albicans water‐soluble substance (CAWS) was intraperitoneally injected in 5‐week‐old male apolipoprotein‐E‐deficient mice. They were categorized as follows (n = 4): control, CAWS, CAWS+statin, and late‐statin groups. The mice were euthanized at 6 or 10 weeks after injection. Statins (atorvastatin) were initiated after CAWS injection, except for the late‐statin group, for which statins were internally administered 6 weeks after injection. Elastica van Gieson staining and immunostaining were performed for evaluation. Statins substantially suppressed the marked neointimal hyperplasia induced by CAWS. Additionally, CAWS induced TGFβ receptor II and MAC‐2 expression around the coronary arteries, which was suppressed by the statins. KD‐like vasculitis might promote the formation of aneurysm by destroying elastic laminae and inducing vascular stenosis by neointimal proliferation. The anti‐inflammatory effects of statins might inhibit neointimal proliferation. Therefore, statin therapy might be effective in adult patients with KD with CAL by inhibiting vascular remodeling. [ABSTRACT FROM AUTHOR]

Objectives: This study investigated the effects of prostate surgery on storage symptoms in male patients with lower urinary tract symptoms (LUTS) from benign prostatic enlargement (BPE). This study aimed to identify patient characteristics associated with improved, unchanged, and deteriorated post‐surgical storage symptoms and to identify the risk factors for non‐improvement or deterioration. Methods: A retrospective analysis of 586 prostate surgeries performed between 2016 and 2022 at Yokosuka Kyosai Hospital was conducted on patients with LUTS and at least one storage symptom preoperatively. Patients with active urinary tract infection, prostate/bladder cancer, urethral strictures, or dementia were excluded. The study enrolled 230 patients and assessed storage symptoms using the International Prostate Symptom Score (IPSS). Results: Overall, storage symptoms improved, remained unchanged, and deteriorated in 87.0%, 5.7%, and 7.4% of patients, respectively. The patients in the deteriorated group were significantly older, whereas those in the no‐change group had smaller prostate volumes. Patient‐reported outcome scores (IPSS, IPSS‐QoL, and BII) were significantly higher in the improved group. The predictors of non‐improvement included low IPSS storage score, cardiovascular disease, and diabetes mellitus. Predictors of deterioration included advanced age and low IPSS storage score. Conclusions: Patients with severe LUTS showed greater postoperative improvement in storage symptoms. A low IPSS storage score predicted non‐improvement and deterioration. Advanced age, low IPSS storage score, and a history of cardiovascular disease and diabetes mellitus were identified as key predictors. Awareness of these factors may guide preoperative counseling and improve decision‐making in prostate surgery, ensuring more personalized and effective treatment strategies. [ABSTRACT FROM AUTHOR]

In contrast to the well‐established oxidative C=C double bond cleavage to give the corresponding carbonyl compounds, little is known about reductive C=C double bond cleavage. Here we report that C−C single bond cleavage in 1,2‐diaryl‐1,2‐diborylethanes proceeds by reduction with sodium metal to yield α‐boryl benzylsodium species. In combination with our previous reductive diboration of stilbenes, the overall transformation represents reductive cleavage of the C=C double bonds of stilbene to yield α‐boryl‐α‐sodiated toluenes. This reductive two‐step C=C double bond cleavage is applicable to ring‐opening or ring‐expansion reactions of polycyclic aromatic hydrocarbons. [ABSTRACT FROM AUTHOR]

Achaete‐scute family bHLH transcription factor 2 (ASCL2) is highly expressed in hepatoblastoma (HB) tissues, but its role remains unclear. Thus, biological changes in the HB cell line HepG2 in response to induced ASCL2 expression were assessed. ASCL2 expression was induced in HepG2 cells using the Tet‐On 3G system, which includes doxycycline. Cell viability, proliferation activity, mobility, and stemness were evaluated using 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide, colony‐formation, migration, invasion, and sphere‐formation assays. Quantitative reverse‐transcription polymerase chain reaction was used to assess the expression of markers for proliferation (CCND1 and MYC), epithelial‐mesenchymal transition (EMT; SNAI1, TWIST1, and ZEB1), mesenchymal‐epithelial transition (CDH1), and stemness (KLF4, POU5F1, and SOX9). Compared with the non‐induced HepG2 cells, cells with induced ASCL2 expression showed significant increases in viability, colony number, migration area (%), and sphere number on days 7, 14, 8, and 7, respectively, and invasion area (%) after 90 h. Furthermore, induction of ASCL2 expression significantly upregulated CCND1, MYC, POU5F1, SOX9, and KLF4 expression on days 2, 2, 3, 3, and 5, respectively, and increased the ratios of SNAI1, TWIST1, and ZEB1 to CDH1 on day 5. ASCL2 promoted the formation of malignant phenotypes in HepG2 cells, which may be correlated with the upregulation of the Wnt signaling pathway‐, EMT‐, and stemness‐related genes. ASCL2 activation may therefore be involved in the progression of HB. [ABSTRACT FROM AUTHOR]

Metal‐catalyzed asymmetric alkylation of indoles with α‐diazoesters is well‐known, however, the underlying mechanisms of this reaction, particularly the origin of stereoselectivity, remain uncertain. For the Pd catalysis, we address this cutting‐edge challenge from two complementary viewpoints – i) the molecular level regarding a single catalytically active Pd center; and ii) nano‐level Pd species investigating the factors favoring the appearance of the preferred catalytic centers. The formation of the active catalytic species was monitored by structural methods (NMR and ESI‐MS), and metal particles were characterized with electron microscopy (SEM, EDX). On the molecular level, chiral bipyridine‐N,N'‐dioxides proved to be competent chiral controllers. The kinetic and DFT computational data revealed a crucial role of water in the rate and selectivity determining steps and showed that the enantioselectivity of the process is controlled by the protodepalladation step. On the nano‐scale, the important effect of catalyst precursor on the overall reaction performance was shown. [ABSTRACT FROM AUTHOR]

Transplantation surgery continues to evolve and improve through advancements in transplant technique and technology. With the increased availability of ultrasound machines as well as the continued development of Enhanced Recovery after Surgery (ERAS) protocols, regional anesthesia has become an essential component of providing analgesia and minimizing opioid use perioperatively. Many centers currently utilize peripheral and neuraxial blocks during transplantation surgery, but these techniques are far from standardized practices. The utilization of these procedures is often dependent on transplantation centers' historical methods and perioperative cultures. To date, no formal guidelines or recommendations exist which address the use of regional anesthesia in transplantation surgery. In response, the Society for the Advancement of Transplant Anesthesia (SATA) identified experts in both transplantation surgery and regional anesthesia to review available literature concerning these topics. The goal of this task force was to provide an overview of these publications to help guide transplantation anesthesiologists in utilizing regional anesthesia. The literature search encompassed most transplantation surgeries currently performed and the multitude of associated regional anesthetic techniques. Outcomes analyzed included analgesic effectiveness of the blocks, reduction in other analgesic modalities—particularly opioid use, improvement in patient hemodynamics, as well as associated complications. The findings summarized in this systemic review support the use of regional anesthesia for postoperative pain control after transplantation surgeries. Part 1 of the manuscript focused on regional anesthesia performed in thoracic transplantation surgeries, and part 2 in abdominal transplantations. Specifically, regional anesthesia in liver, kidney, pancreas, intestinal, and uterus transplants or applicable surgeries are discussed. [ABSTRACT FROM AUTHOR]

An efficient carrier injection at the electrode/organic semiconductor interface of organic light‐emitting diodes (OLEDs) is challenging. It is well‐known that an electric dipole at the electrode/semiconductor interface improves the carrier injection from the electrode because of a vacuum‐level shift. In this study, poly (vinylidene fluoride‐trifluoroethylene) [P(VDF/TrFE)] is used as a polar polymer with spontaneous polarization. P(VDF/TrFE) is spin‐coated on an indium tin oxide (ITO) electrode surface as a hole injection layer for OLEDs. The P(VDF/TrFE) layer enhances the hole injection from the ITO electrode by causing a vacuum‐level shift. As a result, the device driving voltage can be lowered. In addition, annealing temperature dependence is observed. To investigate the origin of the hole injection effect, the P(VDF/TrFE)‐layered ITO surface and the thin film structure of the P(VDF/TrFE) layer are measured. The P(VDF/TrFE) layers at different annealing temperatures show no difference in surface properties but show significant differences in the thin film structure. The hole injection of OLEDs is significantly enhanced because of the structural change in ultrathin P(VDF/TrFE) layer. [ABSTRACT FROM AUTHOR]

Mixing i‐PrI and DABCO in solvent EtCN gave two quaternary ammonium salts (QASs) quantitatively, one of which is monocationic (QAS‐1) and the other is dicationic (QAS‐2). These QASs were found to catalyze hydrosilylation of alkynes with hydrosilanes (HAH) without the aid of metal and metalloid catalysts. This organocatalysis can be applied to a variety of alkynes: terminal/internal aryl and alkyl alkynes with/without a functional group. With dihydrosilanes (H2Si), the HAH occurred with high E‐selectivity through syn addition, which was exclusively observed when using terminal alkyl alkynes, irrespective of a hydrosilane used. A scalable HAH is also feasible. The H−Si unit remaining in alkenylsilanes derived from H2Si is available for dehydrogenative alkynylation and N‐heteroarylation under zinc–pyridine catalysis. This synthetic application delivers unique silicon compounds that have, for instance, alkyl, aryl, alkenyl, and alkynyl groups in a single molecule. Mechanistic studies suggested that alkynes activated by QASs irreversibly react with hydrosilanes that become more nucleophilic by the coordination of EtCN. A radical pathway is unlikely. The QAS catalysts can be recovered and reused at least 5 times. [ABSTRACT FROM AUTHOR]

Objective: To investigate the trial of spontaneous urination without catheter (TWOC) outcomes for men with acute urinary retention, determine successful TWOC predictors, and evaluate the impact of add‐on medication therapy on TWOC. Methods: This retrospective study included men with acute urinary retention and post‐void residual (PVR) >250 mL who underwent TWOC between July 2009 and July 2019. Patients were divided into a medicated group who received alpha1 blocker on urinary retention diagnosis and a naïve group who did not. The trial was defined as unsuccessful if the PVR was >150 mL or if the patient experienced difficulty emptying their bladder with abdominal discomfort or pain, and a transurethral catheter was reinserted. Results: Among 576 men with urinary retention, 269 (46.7%) constituted the medicated group and 307 (53.3%) the naïve. The naïve group comprised more elderly patients (P = 0.010) with higher Eastern Cooperative Oncology Group performance status (PS) (P = 0.001) and smaller prostate volume (P = 0.028) than the other. In the medicated group, 153 men received additional oral medication before TWOC to increase the success rate. There were significant age differences (P = 0.041) in the medicated group and significant median PS differences (P = 0.010) in the naïve group between the successful and unsuccessful outcomes of TWOC. The multivariate logistic regression model demonstrated that age <80 years in medicated patients (P = 0.042, odds ratio [OR] 1.701) and PS <2 in naïve patients (P = 0.001, OR 2.710) were significant independent predictors of successful TWOC outcomes. Conclusions: This is the first study classifying patients with urinary retention according to medication status. Both medicated and naïve groups had different patient backgrounds and TWOC outcome predictors, suggesting a discrepant etiology behind urinary retention. Hence, acute urinary retention management in men should vary based on medication status for male lower urinary tract symptoms when urinary retention is diagnosed. [ABSTRACT FROM AUTHOR]

Transplantation surgery continues to evolve and improve through advancements in transplant technique and technology. With the increased availability of ultrasound machines as well as the continued development of enhanced recovery after surgery (ERAS) protocols, regional anesthesia has become an essential component of providing analgesia and minimizing opioid use perioperatively. Many centers currently utilize peripheral and neuraxial blocks during transplantation surgery, but these techniques are far from standardized practices. The utilization of these procedures is often dependent on transplantation centers' historical methods and perioperative cultures. To date, no formal guidelines or recommendations exist which address the use of regional anesthesia in transplantation surgery. In response, the Society for the Advancement of Transplant Anesthesia (SATA) identified experts in both transplantation surgery and regional anesthesia to review available literature concerning these topics. The goal of this task force was to provide an overview of these publications to help guide transplantation anesthesiologists in utilizing regional anesthesia. The literature search encompassed most transplantation surgeries currently performed and the multitude of associated regional anesthetic techniques. Outcomes analyzed included analgesic effectiveness of the blocks, reduction in other analgesic modalities—particularly opioid use, improvement in patient hemodynamics, as well as associated complications. The findings summarized in this systemic review support the use of regional anesthesia for postoperative pain control after transplantation surgeries. Part 1 of the manuscript focuses on regional anesthesia performed in thoracic transplantation surgeries, and part 2 in abdominal transplantations. [ABSTRACT FROM AUTHOR]

A 52‐year‐old female never‐smoker with an abnormal shadow in the right lung detected on radiography was referred to our institution. Contrast‐enhanced computed tomography revealed an irregular nodule in the upper lobe of the right lung, suggestive of a pulmonary vascular abnormality. Angiography revealed a direct communication between the right internal mammary artery (IMA) and the right upper lobe pulmonary artery branches, with dilated and tortuous vascular proliferation. As multiple branch arteries were seen flowing into the upper lobe from the IMA, transcatheter selective embolization of these vessels and right upper lobectomy by video‐assisted thoracoscopic surgery were performed. Contrary to the clinical diagnosis, the pathological finding was a pulmonary adenocarcinoma of the right upper lobe. Additional lymph node dissection was performed later. We report an extremely rare and unprecedented case of pulmonary adenocarcinoma fed by the right IMA, with a literature review. [ABSTRACT FROM AUTHOR]

Background: Tumor size is an important prognostic factor in lung cancer in dogs, and the canine lung carcinoma stage classification (CLCSC) recently has been proposed to subdivide tumor sizes. It is unclear if the same classification scheme can be used for small‐breed dogs. Objectives: To investigate whether the tumor size classification of CLCS is prognostic for survival and progression outcomes in small‐breed dogs with surgically resected pulmonary adenocarcinomas (PACs). Animals: Fifty‐two client‐owned small‐breed dogs with PAC. Methods: Single‐center retrospective cohort study conducted between 2005 and 2021. Medical records of dogs weighing <15 kg with surgically resected lung masses histologically diagnosed as PAC were examined. Results: The numbers of dogs with tumor size ≤3 cm, >3 cm to ≤5 cm, >5 cm to ≤7 cm, or >7 cm were 15, 18, 14, and 5, respectively. The median progression‐free interval (PFI) and overall survival time (OST) were 754 and 716 days, respectively. In univariable analysis, clinical signs, lymph node metastasis, margin, and histologic grade were associated with PFI, and age, clinical signs, margin, and lymph node metastasis were associated with OST. Tumor size classification of CLCS was associated with PFI in all categories, and tumor size >7 cm was associated with OST. In multivariable analysis, tumor size >5 cm to ≤7 cm and margin were associated with PFI, and age was associated with OST. Conclusions and Clinical Importance: The tumor size classification of CLCS would be an important prognostic factor in small‐breed dogs with surgically resected PACs. [ABSTRACT FROM AUTHOR]

Aims/Introduction: Research on the incidence and underlying mechanisms of rapid renal function decline in patients with type 2 diabetes mellitus with preserved renal function and normoalbuminuria is limited. This study aimed to investigate the involvement of hemoglobin level as a risk factor for rapid decliners among patients with type 2 diabetes with preserved renal function and normoalbuminuria. Materials and Methods: This was a retrospective observational study of 242 patients with type 2 diabetes with a baseline estimated glomerular filtration rate of ≥60 mL/min/1.73 m2 and normoalbuminuria (<30 mg/gCr), followed up for >1 year. The annual rate of estimated glomerular filtration rate decline during the follow‐up period was calculated using least square regression analysis; rapid decliners defined at ≥3.3%/year. Risk factors associated with rapid decliners were identified using a logistic regression analysis of variables previously identified as risk factors of rapid decliners. Results: The median follow‐up period was 6.7 years, and 34 patients showed rapid decliners. On multivariate analysis, lower baseline hemoglobin level was a risk factor of rapid decliners (odds ratio 0.69, 95% confidence interval 0.47–0.99; P = 0.045). Furthermore, the baseline hemoglobin levels were correlated positively with iron and ferritin levels, implying that an impaired iron metabolism might cause lower hemoglobin levels in rapid decliners. Conclusions: In patients with type 2 diabetes with preserved renal function and normoalbuminuria, lower hemoglobin levels were a risk factor for rapid decliners, where disturbed iron metabolism might precede the development of diabetic kidney disease. [ABSTRACT FROM AUTHOR]

Indenone azines, in which the exocyclic C=C bond in dibenzopentafulvalene is replaced by an azine moiety (C=N−N=C), have been synthesized as novel electron‐accepting π‐conjugated scaffolds. Structural modulation at the 7,7′‐positions of indenone azines enabled stereoselective syntheses of diastereomers in which the configurations of the two C=N bonds are E,E or Z,Z. X‐ray crystallographic analyses revealed that all the indenone azines exhibit high coplanarity in contrast to the twisted frameworks of dibenzopentafulvalene derivatives, resulting in the formation of densely π‐stacked structures. Electrochemical measurements and quantum chemical calculations revealed the electron‐accepting character of indenone azines comparable to isoindigo dyes. In particular, the intramolecular hydrogen bonds of 7,7′‐dihydroxy‐substituted derivatives impart enhanced electron‐accepting character and significantly red‐shifted photoabsorption. This study demonstrates that indenone azines represent a promising candidate as electron‐accepting building blocks for optoelectronic materials. [ABSTRACT FROM AUTHOR]

Here, we report a case of mediastinal mesenchymal tumor with a pericytic neoplasm feature that responded to radiation therapy. A 43‐year‐old man visited our hospital with a complaint of esophageal obstruction and chest pain. Chest computed tomography revealed a middle mediastinal tumor and a mesenchymal tumor was diagnosed with a pericytic neoplasm feature by video‐assisted thoracoscopic biopsy. The definitive treatment for soft tissue tumor is surgical resection; however, the mediastinal tumor was unresectable because of esophageal and tracheal invasion. Radiation therapy was administered and there was a partial tumor response and 2 years disease‐free status. With a review of the literature, we discuss the clinical and pathological characteristics of this rare tumor and its treatment. [ABSTRACT FROM AUTHOR]

Mechanical distortion of working skeletal muscle induces sympathoexcitation via thin fibre afferents, a reflex response known as the skeletal muscle mechanoreflex. However, to date, the receptor ion channels responsible for mechanotransduction in skeletal muscle remain largely undetermined. Transient receptor potential vanilloid 4 (TRPV4) is known to sense mechanical stimuli such as shear stress or osmotic pressure in various organs. It is hypothesized that TRPV4 in thin‐fibre primary afferents innervating skeletal muscle is involved in mechanotransduction. Fluorescence immunostaining revealed that 20.1 ± 10.1% of TRPV4 positive neurons were small dorsal root ganglion (DRG) neurons that were DiI‐labelled, and among them 9.5 ± 6.1% of TRPV4 co‐localized with the C‐fibre marker peripherin. In vitro whole‐cell patch clamp recordings from cultured rat DRG neurons demonstrated that mechanically activated current amplitude was significantly attenuated after the application of the TRPV4 antagonist HC067047 compared to control (P = 0.004). Such reductions were also observed in single‐fibre recordings from a muscle–nerve ex vivo preparation where HC067047 significantly decreased afferent discharge to mechanical stimulation (P = 0.007). Likewise, in an in vivo decerebrate rat preparation, the renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) responses to passive stretch of hindlimb muscle were significantly reduced by intra‐arterial injection of HC067047 (ΔRSNA: P = 0.019, ΔMAP: P = 0.002). The findings suggest that TRPV4 plays an important role in mechanotransduction contributing to the cardiovascular responses evoked by the skeletal muscle mechanoreflex during exercise. Key points: Although a mechanical stimulus to skeletal muscle reflexively activates the sympathetic nervous system, the receptors responsible for mechanotransduction in skeletal muscle thin fibre afferents have not been fully identified.Evidence suggests that TRPV4 is a mechanosensitive channel that plays an important role in mechanotransduction within various organs.Immunocytochemical staining demonstrates that TRPV4 is expressed in group IV skeletal muscle afferents. In addition, we show that the TRPV4 antagonist HC067047 decreases the responsiveness of thin fibre afferents to mechanical stimulation at the muscle tissue level as well as at the level of dorsal root ganglion neurons. Moreover, we demonstrate that intra‐arterial HC067047 injection attenuates the sympathetic and pressor responses to passive muscle stretch in decerebrate rats.These data suggest that antagonism of TRPV4 attenuates mechanotransduction in skeletal muscle afferents.The present study demonstrates a probable physiological role for TRPV4 in the regulation of mechanical sensation in somatosensory thin fibre muscle afferents. [ABSTRACT FROM AUTHOR]

Circulating tumor cells (CTCs) derived from any tumor tissue could contribute to metastasis and resistance to cancer treatments. In this study, we performed single‐cell next‐generation sequencing of CTCs and evaluated their usefulness for characterizing tumor biology and the mechanisms of metastasis in neuroblastomas (NB). We aimed to isolate CTCs from 10 patients with NB at diagnosis before any treatments and four patients at relapse. GD2+CD90+CD45−CD235a−DAPI− cells were isolated as neuroblastoma CTCs using fluorescence‐activated cell sorting. In five patients with advanced stages (M stage), DNA and RNA sequencing of CTCs at single‐cell level were performed. NB CTCs were isolated from eight of the 10 patients at diagnosis and three of the four patients at relapse. More CTCs could be isolated from patients with advanced stages. In one patient, ALK mutation (p.F1174L), was identified in both tumor tissue and a CTC. In patients with MYCN amplification, this gene was amplified in 12 of 13 CTCs. Using single‐cell RNA sequencing, angiogenesis‐related and cell cycle‐related genes together with CCND1 and TUBA1A genes were found to be upregulated in CTCs. In one patient, CTCs were divided into two subgroups showing different gene expression profiles. In one subgroup, cell cycle‐related and proliferation‐related genes were differentially upregulated compared with the other group. In conclusion, next‐generation sequencing of CTCs at single‐cell level might help to characterize the tumor biology and the mechanisms of metastasis in NB. [ABSTRACT FROM AUTHOR]

N‐methyl‐d‐aspartate receptors (NMDARs) are pivotal players in the synaptic transmission and synaptic plasticity underlying learning and memory. Accordingly, dysfunction of NMDARs has been implicated in the pathophysiology of Alzheimer disease (AD). Here, we used histoblot and sodium dodecylsulphate‐digested freeze‐fracture replica labelling (SDS‐FRL) techniques to investigate the expression and subcellular localisation of GluN1, the obligatory subunit of NMDARs, in the hippocampus of P301S mice. Histoblots showed that GluN1 expression was significantly reduced in the hippocampus of P301S mice in a laminar‐specific manner at 10 months of age but was unaltered at 3 months. Using the SDS‐FRL technique, excitatory synapses and extrasynaptic sites on spines of pyramidal cells and interneuron dendrites were analysed throughout all dendritic layers in the CA1 field. Our ultrastructural approach revealed a high density of GluN1 in synaptic sites and a substantially lower density at extrasynaptic sites. Labelling density for GluN1 in excitatory synapses established on spines was significantly reduced in P301S mice, compared with age‐matched wild‐type mice, in the stratum oriens (so), stratum radiatum (sr) and stratum lacunosum‐moleculare (slm). Density for synaptic GluN1 on interneuron dendrites was significantly reduced in P301S mice in the so and sr but unaltered in the slm. Labelling density for GluN1 at extrasynaptic sites showed no significant differences in pyramidal cells, and only increased density in the interneuron dendrites of the sr. This differential alteration of synaptic versus extrasynaptic NMDARs supports the notion that the progressive accumulation of phospho‐tau is associated with changes in NMDARs, in the absence of amyloid‐β pathology, and may be involved in the mechanisms causing abnormal network activity of the hippocampal circuit. [ABSTRACT FROM AUTHOR]

Objective: To investigate the outcome, determine the predictors for the success of, and evaluate the efficacy of pharmacokinetic therapy on trial catheter removal for women with urinary retention. Methods: Inclusion criteria were female patients with acute urinary retention defined as painful, palpable, or percussive bladder, when the patient is unable to pass any urine, accompanied by postvoid residual (PVR) > 250 ml, and who underwent trial catheter removal between July 2009 and July 2019. Before trial catheter removal, alpha‐blockers alone or alpha‐blockers and parasympathomimetics (bethanechol or distigmine bromide) were used to facilitate spontaneous voiding in some cases. Results: Fifty‐nine of 104 (56.7%) women with urinary retention were catheter‐free post trial. There was no significant difference between successful and non‐successful trials in average age (p =.392), median ECOG (Eastern Cooperative Oncology Group) performance status (p =.374), diabetes mellitus (p =.842), dementia (p =.801), previous history of cerebrovascular events (p =.592), or intrapelvic surgery (p =.800). Oral medications were administered for 39/59 (66.1%) in the success group and 30/45 (66.7%) patients in the non‐success groups (p =.598). Serum albumin (3.2 ± 0.7 g/dl and 2.8 ± 0.8 g/dl, p =.039) and total protein values (6.5 ± 0.8 g/dl and 6.0 ± 1.0 g/dl, p =.038) at diagnosis of urinary retention were higher in the success group than the non‐success group, respectively. Multivariate logistic regression found that a serum albumin >3 g/dl was an independent predictor of successful trial catheter removal for women with urinary retention (p =.030, odds ratio [OR] 3.3, 95% confidence interval [CI] of OR 1.1–9.9). Age < 70 years old was a likely predictor of successful trial catheter removal (p =.066, OR 4.8, 95% CI of OR 0.9–25.0). Conclusions: This is the first retrospective study to investigate the predictive factors for successful trial catheter removal in women with urinary retention. A serum albumin value >3 mg/dl at diagnosis of urinary retention was a significant independent predictor of catheter‐free status after trial catheter removal, and age < 70 years‐old was a possible contributor. There was no evidence that oral medication contributed to catheter‐free status. [ABSTRACT FROM AUTHOR]

A bicyclo[3.3.0]octane‐3,7‐dione, bearing four phenylsulfanyl (PhS) groups at the diagonal α‐positions of the carbonyls, was synthesized as a key intermediate useful for exploring the regioselective transformations of symmetrical Weiss diketone. Tetra‐PhS‐substituted bicyclo[3.3.0]octane‐3,7‐dione was prepared by deprotonation of the Weiss diketone, using LDA in the presence of PhSSO2Ph. The tetra‐PhS‐substituted derivative thus obtained served as a scaffold for further regioselective base‐promoted enolization. Furthermore, the tetra‐PhS‐substituted Weiss diketone underwent an unexpected base‐promoted rearrangement to form isomeric tetra‐PhS‐substituted bicyclo[3.3.0]octane‐3,7‐dione through migration of PhS groups, likely through an interrupted Favorskii rearrangement. [ABSTRACT FROM AUTHOR]

Occludin, tricellulin, and marvelD3 belong to the tight junction (TJ)‐associated MARVEL protein family. Occludin and tricellulin jointly contribute to TJ strand branching point formation and epithelial barrier maintenance. However, whether marvelD3 has the same function remains unclear. Furthermore, the roles of the carboxy‐terminal cytoplasmic tail, which is conserved in occludin and tricellulin, on the regulation of TJ strand morphology have not yet been explored in epithelial cells. We established tricellulin/occludin/marveld3 triple‐gene knockout (tKO) MDCK II cells and evaluated the roles of marvelD3 in the TJ strand structure and barrier function using MDCK II cells and a mathematical model. The complexity of TJ strand networks and paracellular barrier did not change in tKO cells compared to that in tricellulin/occludin double‐gene knockout (dKO) cells. Exogenous marvelD3 expression in dKO cells did not increase the complexity of TJ strand networks and epithelial barrier tightness. The expression of the carboxy‐terminal truncation mutant of tricellulin restored the barrier function in the dKO cells, whereas occludin lacking the carboxy‐terminal cytoplasmic tail was not expressed on the plasma membrane. These data suggest that marvelD3 does not affect the morphology of TJ strands and barrier function in MDCK II cells and that the carboxy‐terminal cytoplasmic tail of tricellulin is dispensable for barrier improvement. [ABSTRACT FROM AUTHOR]

Claudin‐based tight junctions (TJs) are formed at the most apical part of cell–cell contacts in epithelial cells. Previous studies suggest that scaffolding proteins ZO‐1 and ZO‐2 (ZO proteins) determine the location of TJs by interacting with claudins, but this idea is not conclusive. To address the role of the ZO proteins binding to claudins at TJs, a COOH‐terminal PDZ domain binding motif‐deleted claudin‐3 mutant, which lacks the ZO protein binding, was stably expressed in claudin‐deficient MDCK cells. The COOH‐terminus‐deleted claudin‐3 was localized at the apicolateral region similar to full‐length claudin‐3. Consistently, freeze‐fracture electron microscopy revealed that the COOH‐terminus‐deleted claudin‐3‐expressing cells reconstituted belts of TJs at the most apical region of the lateral membrane and restored functional epithelial barriers. These results suggest that the interaction of claudins with ZO proteins is not a prerequisite for TJ formation at the most apical part of cell–cell contacts. [ABSTRACT FROM AUTHOR]

Xenopus laevis tadpoles possess regenerative capacity in their hindlimb buds at early developmental stages (stages ~52–54); they can regenerate complete hindlimbs with digits after limb bud amputation. However, they gradually lose their regenerative capacity as metamorphosis proceeds. Tadpoles in late developmental stages regenerate fewer digits (stage ~56), or only form cartilaginous spike without digits or joints (stage ~58 or later) after amputation. Previous studies have shown that administration of fibroblast growth factor 10 (FGF10) in late‐stage (stage 56) tadpole hindlimb buds after amputation can improve their regenerative capacity, which means that the cells responding to FGF10 signaling play an important role in limb bud regeneration. In this study, we performed single‐cell RNA sequencing (scRNA‐seq) of hindlimb buds that were amputated and administered FGF10 by implanting FGF10‐soaked beads at a late stage (stage 56), and explored cell clusters exhibiting a differential gene expression pattern compared with that in controls treated with phosphate‐buffered saline. The scRNA‐seq data showed expansion of fgf8‐expressing cells in the cluster of the apical epidermal cap of FGF10‐treated hindlimb buds, which was reported previously, indicating that the administration of FGF10 was successful. On analysis, in addition to the epidermal cluster, a subset of myeloid cells and a newly identified cluster of steap4‐expressing cells showed remarkable differences in their gene expression profiles between the FGF10‐ or phosphate‐buffered saline‐treatment conditions, suggesting a possible role of these clusters in improving the regenerative capacity of hindlimbs via FGF10 administration. [ABSTRACT FROM AUTHOR]

Xenopus laevis tadpoles have a strong regenerative ability and can regenerate their whole tails after tail amputation. Lineage‐restricted tissue stem cells are thought to provide sources for the regenerating tissues by producing undifferentiated progenitor cells in response to tail amputation. However, elucidating the behavioral dynamics of tissue stem cells during tail regeneration is difficult because of their rarity, and there are few established methods of isolating these cells in amphibians. Here, to detect and analyze rare tissue stem cells, we attempted to enrich tissue stem cells from tail regeneration buds. High Hoechst dye efflux capacity is thought to be a common characteristic of several types of mammalian tissue stem cells; these stem cells, designated as the "side population (SP)," may be enriched by flow cytometry (SP method). To evaluate the effectiveness of stem cell enrichment using the SP method in regenerating X. laevis tadpole tails, we performed single‐cell RNA sequencing (scRNA‐seq) of SP cells from regeneration buds and analyzed the frequency of satellite cells, which are muscle stem/progenitor cells expressing pax7. The pax7‐expressing cells were enriched in the SP compared with whole normal tails and regeneration buds. Furthermore, hes1‐expressing cells, which are assumed to be neural stem/progenitor cells, were also enriched in the SP. Our findings suggest that the SP method is efficient for successfully enriching tissue stem cells in regenerating X. laevis tadpole tails, indicating that the combination of the SP method and scRNA‐seq is useful for studying tissue stem cells that contribute to tail regeneration. [ABSTRACT FROM AUTHOR]

Background: The recommended doxorubicin (DOX) dose for small dogs is 1 mg/kg. Recent data suggest that DOX‐induced gastrointestinal (GI) toxicosis can be reduced with maropitant treatment. Objectives: To investigate the incidence of adverse events (AEs) in small‐breed dogs administered a single 25 mg/m2 DOX followed by administration of maropitant (DOX25). The primary aim was to assess myelo‐ and GI toxicoses for 2 weeks after DOX administration. The secondary aim was to compare the incidence and grades of AEs found in the DOX25 group with a historical control group (DOX 1 mg/kg without administration of antiemetic or antidiarrheal medications). Animals: Nineteen small‐breed tumor‐bearing dogs. Methods: A prospective, observational study of tumor‐bearing dogs, weighing 5 to 10 kg, administered a single 25 mg/m2 dose of DOX IV, followed by administration of maropitant for the next 5 days. Results: Inappetence, vomiting, and diarrhea were found in 7/19, 2/19, and 6/19 of the DOX25 dogs, respectively. Neutropenia and thrombocytopenia was 12/19 and 3/19, respectively. Most AEs were grades 1 and 2, except for grades 3 and 4 inappetence and neutropenia in 3 and 4 dogs, respectively. Furthermore, febrile neutropenia occurred in 3/19 dogs in the DOX25 group. All AEs between the DOX25 and historical control groups were not significantly different. Conclusions and Clinical Importance: Vomiting and diarrhea were deemed acceptable with 25 mg/m2 DOX followed by maropitant treatment in 5 to 10 kg dogs; however, additional supportive care might be needed for dogs with inappetence and neutropenia. [ABSTRACT FROM AUTHOR]

Pulmonary hypoplasia is diagnosed during the perinatal period and is a cause of death in newborns. However, these developmental abnormalities are diagnosed in adulthood in some cases. A 70‐year‐old male smoker was diagnosed with stage IIIA pulmonary adenocarcinoma in the right upper lobe with right middle lobe hypoplasia. He subsequently underwent right upper and middle lobectomy with lymph node dissection by video‐assisted thoracoscopic surgery. In addition to an invasive adenocarcinoma in the right upper lobe, pathological examination of the hypoplastic lobe revealed neuroendocrine hyperplasia, as well as tumorlets and a typical carcinoid. Eight cases of pulmonary neuroendocrine tumors that developed from pulmonary hypoplasia have been reported to date. Interestingly, all but one case occurred in the right middle lobe. Neuroendocrine cell hyperplasia has been reported to develop in hypoplastic lungs postnatally; therefore, we speculated that the lesion was the origin of these neuroendocrine tumors. Moreover, the pathological findings suggested that atelectasis was involved in the pathogenesis of this rare condition. In adults, when lobar hypoplasia is diagnosed, neuroendocrine tumors should be anticipated. [ABSTRACT FROM AUTHOR]

Background: Kawasaki disease (KD) is an acute febrile illness with systemic vasculitides, mostly affecting infants and young children. The etiology of KD is still unclear; however, altered gut microbiota have been recently implicated as a contributing factor for the development of vasculitis. Methods: We conducted an age‐ and gender‐matched case‐control study on 50 patients and 200 control subjects to search for potential factors leading to intestinal dysbiosis associated with KD. Data were analyzed using conditional multivariable logistic regression. Results: Previous antibiotic administration was associated with the patients who developed KD (odds ratio [OR] 11.7, 95% confidence interval [CI] 4.7−29.1, P < 0.0001), but not other variables, including breastfeeding and group nursery. In subgroup analyses, cesarean birth was indicated as an associated factor in addition to previous antibiotic administration in infants under 12 months of age (OR: 8.0, 95% CI: 1.8−34.4, P = 0.005), but not in older children. Conclusions: The association between previous antibiotic administration and the onset of KD was demonstrated. Antibiotics may contribute to the development of KD by affecting the intestinal microbiota in infants and young children. [ABSTRACT FROM AUTHOR]

Systemic insulin administration evokes sympathoexcitatory actions, but the mechanisms underlying these observations are unknown. We reported that insulin sensitizes the response of thin‐fibre primary afferents, as well as the dorsal root ganglion (DRG) that subserves them, to mechanical stimuli. However, little is known about the effects of insulin on primary neuronal responses to chemical stimuli. TRPV1, whose agonist is capsaicin (CAP), is widely expressed on chemically sensitive metaboreceptors and/or nociceptors. The aim of this investigation was to determine the effects of insulin on CAP‐activated currents in small DRG neurons and CAP‐induced action potentials in thin‐fibre muscle afferents of normal healthy rodents. Additionally, we investigated whether insulin potentiates sympathetic nerve activity (SNA) responses to CAP. In whole‐cell patch‐clamp recordings from cultured mice DRG neurons in vitro, the fold change in CAP‐activated current from pre‐ to post‐application of insulin (n = 13) was significantly (P < 0.05) higher than with a vehicle control (n = 14). Similar results were observed in single‐fibre recording experiments ex vivo as insulin potentiated CAP‐induced action potentials compared to vehicle controls (n = 9 per group, P < 0.05). Furthermore, insulin receptor blockade with GSK1838705 significantly suppressed the insulin‐induced augmentation in CAP‐activated currents (n = 13) as well as the response magnitude of CAP‐induced action potentials (n = 9). Likewise, the renal SNA response to CAP after intramuscular injection of insulin (n = 8) was significantly (P < 0.05) greater compared to vehicle (n = 9). The findings suggest that insulin potentiates TRPV1 responsiveness to CAP at the DRG and muscle tissue levels, possibly contributing to the augmentation in sympathoexcitation during activities such as physical exercise. Key points: Evidence suggests insulin centrally activates the sympathetic nervous system, and a chemical stimulus to tissues activates the sympathetic nervous system via thin fibre muscle afferents.Insulin is reported to modulate putative chemical‐sensitive channels in the dorsal root ganglion neurons of these afferents.In the present study, it is demonstrated that insulin potentiates the responsiveness of thin fibre afferents to capsaicin at muscle tissue levels as well as at the level of dorsal root ganglion neurons. In addition, it is demonstrated that insulin augments the sympathetic nerve activity response to capsaicin in vivo.These data suggest that sympathoexcitation is peripherally mediated via insulin‐induced chemical sensitization.The present study proposes a possible physiological role of insulin in the regulation of chemical sensitivity in somatosensory thin fibre muscle afferents. [ABSTRACT FROM AUTHOR]

A novel approach to the direct construction of tricyclic nitrogen heterocycles based on gold‐catalyzed cascade cyclization of aminoallenynes is described. The expected biscyclization reaction of hydroxyisobutyryl‐protected aminoallenynes was efficiently promoted by a catalytic amount of BrettPhosAuNTf2 in the presence of iPrOH to produce 1,2‐dihydrobenzo[cd]indole derivatives in good yields. When the reaction was combined with Friedel–Crafts acylation or palladium‐catalyzed N‐arylation, the resulting tricyclic products were efficiently converted into nitrogen‐containing polycyclic aromatic compounds (N‐PACs) with highly conjugated π‐electron systems. A newly obtained hexacyclic indolium salt showed characteristic concentration‐dependent absorption and emission properties. [ABSTRACT FROM AUTHOR]

Oxidation of primary alcohol to the corresponding aldehyde remains a significant challenge, even with the state‐of‐the‐art chemistry. Here, a novel electrochemical system was developed for the exclusive production of aldehyde from primary alcohol using an anion‐exchange membrane (AEM) reactor. Oxidation proceeded on a gold catalyst under basic conditions, which largely enhanced the reaction rate. Despite the basic nature around the reaction sites, the oxidation of primary alcohols exclusively yielded the corresponding aldehyde, which was attributed to the unique three‐phase interfacial reaction sites in the AEM reactor. In addition to benzyl alcohol, the oxidation of allylic and aliphatic alcohols was also demonstrated. Comparison of constant potential electrolysis with the AEM reactor or a conventional batch‐type cell revealed the crucial role of the triple‐phase boundary for the selectivity of the oxidation of alcohol. [ABSTRACT FROM AUTHOR]

A thiophene‐fused 1,4‐diazapentalene (TAP) was rationally designed and synthesized as a C=N‐containing 4n π‐electron system that exhibits restored antiaromaticity impaired by the doping with C=N bonds. X‐ray crystallographic analysis and quantum chemical calculations revealed that the annulation of thiophene rings with the 1,4‐diazapentalene moiety resulted in a much higher antiaromaticity than the pristine 1,4‐diazapentalene. These effects can be ascribed to the reduced bond alternation of the eight‐membered‐ring periphery caused by stabilization of the less‐stable bond‐shifted resonance structure upon increasing the degree of substitution of imine moieties. Consequently, TAP underwent facile hydrogenation even under mild conditions because of its pronounced antiaromaticity and the high aromaticity of the corresponding hydrogenated product H2‐TAP. In addition, the electrophilic C=N moieties in TAP led to the formation of a dense π‐stacked structure. These results highlight the effect of partial replacement of C=C bonds with C=N bonds in antiaromatic π‐electron systems. [ABSTRACT FROM AUTHOR]

Several lines of evidence have clarified that the key transmission pathways of itching sensation travel from the periphery to the central nervous system (CNS). Despite the functional significance of gastrin‐releasing peptide (GRP) and its cognate receptor in the itch processing mechanism in the spinal dorsal horn (SDH), the roles of GRP‐expressing (GRP+) neurons in different regions remain unclear. This study aimed to determine whether GRP+ neurons in the CNS directly modulated itch processing. To specifically activate spinal and supraspinal GRP neurons by the designer receptors exclusively activated by designer drugs (DREADDs) system, CAG‐LSL‐Gq‐DREADD mice were crossed with GRP‐Cre mice, resulting in the development of GRP‐hM3Dq mice. Immunohistochemistry showed that hM3Dq was highly expressed in the SDH and brainstem closely related to sensory processing. The intraperitoneal, intrathecal, or intracerebroventricular administration of clozapine‐N‐oxide, an agonist of hM3Dq, strongly elicited dermatome‐dependent itch‐related scratching behavior, but did not change pain sensitivity. Importantly, GRP‐Gq‐DREADD‐mediated scratching behavior in GRP‐hM3Dq mice was not affected by the ablation of transient receptor potential vanilloid 1+ sensory C‐fibers, and it was also observed to a similar degree under chronic itch conditions. Furthermore, there were no significant sex differences in the scratching behavior elicited by GRP‐Gq‐DREADD, suggesting that itch‐dominant roles of central GRP+ neurons might be common in both sexes, at least under normal physiological conditions. These novel findings not only contribute to understanding the functional roles of central GRP+ neurons further, but also propose the development of future effective therapeutics for intractable itching. [ABSTRACT FROM AUTHOR]

Objective: To study the efficacy of phosphodiesterase‐5 inhibitor tadalafil in attenuating adverse events after low‐dose‐rate brachytherapy for prostate cancer. Methods: This was a randomized open‐label trial, conducted at two institutions. Prostate cancer patients undergoing low‐dose‐rate brachytherapy were randomly assigned to receive tadalafil (study group) or tamsulosin (control group). The primary endpoint was International Prostate Symptom Score for subjective evaluation of lower urinary tract symptoms. Uroflowmetry, postvoid residual urine volume, and Sexual Health Inventory for Men score were the secondary endpoints. Each clinical variable was evaluated during a follow‐up period of 1 year after low‐dose‐rate brachytherapy. Results: A total of 107 patients were enrolled in this study, with a final total of 96 patients analyzed. The mean total International Prostate Symptom Score changes at 1, 3, 6, 9, and 12 months after low‐dose‐rate brachytherapy were +7.4, +7.1, +4.7, +1.5, and +0.8, respectively, in the tamsulosin group, and +8.5, +9.2, +6.4, +4.1, and +1.6, respectively, in the tadalafil group. There were no statistically significant differences in International Prostate Symptom Score with the exception of the score at 9‐month follow‐up. Moreover, there were no statistically significant differences in any of the uroflowmetry or postvoid residual urine volume findings. The Sexual Health Inventory for Men score in the tadalafil group was significantly higher than that in the tamsulosin group at 6, 9, and 12 months after low‐dose‐rate brachytherapy. Conclusions: Tadalafil could be an effective option for the management of lower urinary tract symptoms after low‐dose‐rate brachytherapy. [ABSTRACT FROM AUTHOR]

To prevent infectious diseases induced by the adhesion of microorganisms and their metabolic products to dental implants, saliva protein adsorption, which induces the plaque deposition to the intraoral substrates should be inhibited. We used a water‐soluble 2‐methacryloyloxyethyl phosphorylcholine (MPC) polymer to modify the surface of hydroxyapatite (HAp) substrate, the main component of dental implant surface. The MPC polymer containing a catechol group at the terminal of polymer chain and amino groups in the side chain was synthesized by mimicking the mussel adhesive protein. The MPC polymer containing 2% of the primary amino groups showed effective adhesion to the HAp substrate. Mucin, the dental plaque protein, adsorbs on the HAp surface; however, the MPC polymer modification could reduce this adsorption amount by more than 98% compared to the original HAp substrate surface. Thus, the treatment of the MPC polymer has potential to reduce oral infection due to plaque deposition. [ABSTRACT FROM AUTHOR]

Dithieno[a,e]penalenes (DTPs) with various substituents were synthesized as a class of antiaromatic compounds. Annulation of thiophene rings imparts the pentalene moiety with high thermal stability even without bulky substituents, while retaining antiaromaticity. The higher magnitude of antiaromaticity in DTPs, in addition to the differences in the electronic structures of the fused aromatic rings, resulted in a narrower HOMO–LUMO gap than that of the corresponding dibenzo[a,e]pentalene analog, giving rise to red‐shifted electronic absorption that reaches the near‐infrared region. Moreover, systematic investigations on the solid‐state packing structure revealed that DTPs prefer offset face‐to‐face packing motifs rather than face‐centered π–π stacking. In particular, the thienyl‐substituted DTP bearing hydrophilic side chains exhibited thermochromic behavior in polar solvents, which was ascribed to the formation of aggregates. [ABSTRACT FROM AUTHOR]

The design of catalysts for asymmetric propargylations remains a challenging task, with only a handful of methods providing access to enantioenriched homopropargylic alcohols. In this work, guided by previously reported computational predictions, a set of atropisomeric bipyridine N,N'‐dioxides was tested as Lewis base catalysts for the asymmetric propargylation of aldehydes with trichloroallenylsilane. The catalysts are easily prepared in four simple steps starting from readily available methyl ketones. Aryl‐substituted derivatives proved to be highly active and showed a high level of enantiocontrol even at 1 mol% loading. The reaction scope includes a wide range of aromatic, heteroaromatic, and unsaturated aldehydes. New computations confirm that the key stereodetermining transition state structures for the synthesized catalysts are similar to those previously reported for the model structure. [ABSTRACT FROM AUTHOR]

Na,K‐ATPase is a ubiquitous molecule contributing to the asymmetrical distribution of Na+ and K+ ions across the plasma membrane and maintenance of the membrane potential, a prerequisite of neuronal activity. Na,K‐ATPase comprises three subunits (α, β, and FXYD). The α subunit has four isoforms in mice, with three of them (α1, α2, and α3) expressed in the brain. However, the functional and biological significances of the different brain isoforms remain to be fully elucidated. Recent studies have revealed the association of Atp1a3, a gene encoding α3 subunit, with neurological disorders. To map the cellular distributions of the α subunit isoforms and their coexpression patterns, we evaluated the mRNA expression of Atp1a1, Atp1a2, and Atp1a3 by in situ hybridization in the mouse brain. Atp1a1 and Atp1a3 were expressed in neurons, whereas Atp1a2 was almost exclusively expressed in glial cells. Most neurons coexpressed Atp1a1 and Atp1a3, with highly heterogeneous expression levels across the brain regions and neuronal subtypes. We identified parvalbumin (PV)‐expressing GABAergic neurons in the hippocampus, somatosensory cortex, and retrosplenial cortex as an example of a neuronal subtype expressing low Atp1a1 and high Atp1a3. The expression of Atp1b isoforms was also heterogeneous across brain regions and cellular subtypes. The PV‐expressing neurons expressed a high level of Atp1b1 and a low level of Atp1b2 and Atp1b3. These findings provide basic information on the region‐ and neuronal‐subtype‐dependent expression of Na,K‐ATPase α and β subunit isoforms, as well as a rationale for the selective involvement of neurons expressing high levels of Atp1a3 in neurological disorders. [ABSTRACT FROM AUTHOR]

Owing to its excellent physicochemical properties, poly(ether ether ketone) (PEEK) has been used clinically for medical implants. However, its surface properties should be improved to further enhance its compatibility with a living organism and infection resistance. Here, we examined the surface construction via a combined process, that is, the self‐initiated photoinduced graft polymerization of N,N‐dimethylaminoethyl methacrylate (DMA) on PEEK substrate followed by polymer quaternization using various bromoalkanes (Q‐PDMA‐g‐PEEK). Using a Fourier transform infrared spectroscopy and X‐ray photoelectron spectroscopy, the grafting and quaternarization of poly(DMA) (PDMA) on the PEEK substrate was confirmed. The degree of quaternizations was at least 60% even when the various bromoalkanes were reacted. The Q‐PDMA‐g‐PEEK with 1‐bromooctane (BrC8) (C8‐Q‐PDMA‐g‐PEEK) substrate exhibited the highest ζ‐potential of other Q‐PDMA‐g‐PEEK substrates. However, no significant differences were observed in the degree of quaternization, thickness of the polymer layer, and hydrophilicity of all modified PEEK substrates. In addition, from antibacterial test with Escherichia coli, the C8Q‐PDMA‐g‐PEEK substrate exhibited the highest antibacterial rate (80%) among Q‐PDMA‐g‐PEEK substrates examined. Therefore, we concluded that the surface ζ‐potential is the one an important parameter for manufacturing PEEK substrates with bactericidal properties. [ABSTRACT FROM AUTHOR]

The article discusses the sixth revised diagnostic guidelines for Kawasaki disease (KD) among children in Japan. The revisions from the fifth guidelines include fever duration to five days or more and increase in coronary artery lesions for incomplete KD. It concludes that patients who received early treatment increase while the incidence of coronary artery lesions decrease.

Initial bacterial adhesion to medical devices and subsequent biofilm formation are known as the leading causes of surgical site infection (SSI). Therefore, inhibition of bacterial adhesion and biofilm formation on the surface of medical devices can reduce the risk of SSIs. In this study, a highly hydrophilic, antibiofouling surface was prepared by coating the bioabsorbable suture surface with poly(2-methacryloyloxyethyl phosphorylcholine (MPC)-co-n-butyl methacrylate) (PMB). The PMB-coated and noncoated sutures exhibited similar mechanical strength and surface morphology. The effectiveness of the PMB coating on the suture to suppress adhesion and biofilm formation of methicillin-resistant Staphylococcus aureus and methicillin-susceptible Staphylococcus aureus was investigated both in vitro and in vivo. The bacterial adhesion test revealed that PMB coating significantly reduced the number of adherent bacteria, with no difference in the number of planktonic bacteria. Moreover, fluorescence microscopy and scanning electron microscopy observations of adherent bacteria on the suture surface after contact with bacterial suspension confirmed PMB coating-mediated inhibition of biofilm formation. Additionally, we found that the PMB-coated sutures exhibited significant antibiofouling effects in vivo. In conclusion, PMB-coated sutures demonstrated bacteriostatic effects associated with a highly hydrophilic, antibiofouling surface and inhibited bacterial adhesion and biofilm formation. Therefore, PMB-coated sutures could be a new alternative to reduce the risk of SSIs. [ABSTRACT FROM AUTHOR]

Aim: Ample evidence indicates that gastrin‐releasing peptide receptor (GRPR)–expressing neurons play a critical role in the transmission of acute itch. However, the pathophysiology of spinal mechanisms underlying intractable itch such as psoriasis remains unclear. In this study, we aimed to determine whether itch‐responsive GRPR+ neurons contribute to the spinal transmission of imiquimod (IMQ)‐induced psoriatic itch. Methods: To generate a psoriasis model, C57BL/6J mice received a daily topical application of 5% IMQ cream on their shaved back skin for 7‐10 consecutive days. GRP+ neurons were inhibited using Cre‐dependent expression of Gi‐designer receptors exclusively activated by designer drugs (DREADDs), while GRPR+ neurons were ablated by intrathecal administration of bombesin‐saporin. Results: Repeated topical application of IMQ elicited psoriasis‐like dermatitis and scratching behaviors. The mRNA expression levels of GRP and GRPR were upregulated in the cervical spinal dorsal horn (SDH) on days 7 and 10 after IMQ application. Either chemogenetic silencing of GRP+ neurons by Gi‐DREADD or ablation of GRPR+ neurons significantly attenuated IMQ‐induced scratching behaviors. Conclusion: The GRP‐GRPR system might be enhanced in the SDH, and itch‐responsive GRPR+ neurons largely contribute to intractable itch in a mouse model of psoriasis. [ABSTRACT FROM AUTHOR]

The hippocampus plays key roles in learning and memory and is a main target of Alzheimer's disease (AD), which causes progressive memory impairments. Despite numerous investigations about the processes required for the normal hippocampal functions, the neurotransmitter receptors involved in the synaptic deficits by which AD disables the hippocampus are not yet characterized. By combining histoblots, western blots, immunohistochemistry and high‐resolution immunoelectron microscopic methods for GABAB receptors, this study provides a quantitative description of the expression and the subcellular localization of GABAB1 in the hippocampus in a mouse model of AD at 1, 6 and 12 months of age. Western blots and histoblots showed that the total amount of protein and the laminar expression pattern of GABAB1 were similar in APP/PS1 mice and in age‐matched wild‐type mice. In contrast, immunoelectron microscopic techniques showed that the subcellular localization of GABAB1 subunit did not change significantly in APP/PS1 mice at 1 month of age, was significantly reduced in the stratum lacunosum‐moleculare of CA1 pyramidal cells at 6 months of age and significantly reduced at the membrane surface of CA1 pyramidal cells at 12 months of age. This reduction of plasma membrane GABAB1 was paralleled by a significant increase of the subunit at the intracellular sites. We further observed a decrease of membrane‐targeted GABAB receptors in axon terminals contacting CA1 pyramidal cells. Our data demonstrate compartment‐ and age‐dependent reduction of plasma membrane‐targeted GABAB receptors in the CA1 region of the hippocampus, suggesting that this decrease might be enough to alter the GABAB‐mediated synaptic transmission taking place in AD. [ABSTRACT FROM AUTHOR]

In the cerebellum, GluD2 is exclusively expressed in Purkinje cells, where it regulates synapse formation and regeneration, synaptic plasticity, and motor learning. Delayed cognitive development in humans with GluD2 gene mutations suggests extracerebellar functions of GluD2. However, extracerebellar expression of GluD2 and its relationship with that of GluD1 are poorly understood. GluD2 mRNA and protein were widely detected, with relatively high levels observed in the olfactory glomerular layer, medial prefrontal cortex, cingulate cortex, retrosplenial granular cortex, olfactory tubercle, subiculum, striatum, lateral septum, anterodorsal thalamic nucleus, and arcuate hypothalamic nucleus. These regions were also enriched for GluD1, and many individual neurons coexpressed the two GluDs. In the retrosplenial granular cortex, GluD1 and GluD2 were selectively expressed at PSD‐95‐expressing glutamatergic synapses, and their coexpression on the same synapses was shown by SDS‐digested freeze‐fracture replica labeling. Biochemically, GluD1 and GluD2 formed coimmunoprecipitable complex formation in HEK293T cells and in the cerebral cortex and hippocampus. We further estimated the relative protein amount by quantitative immunoblotting using GluA2/GluD2 and GluA2/GluD1 chimeric proteins as standards for titration of GluD1 and GluD2 antibodies. Intriguingly, the relative amount of GluD2 was almost comparable to that of GluD1 in the postsynaptic density fraction prepared from the cerebral cortex and hippocampus. In contrast, GluD2 was overwhelmingly predominant in the cerebellum. Thus, we have determined the relative extracerebellar expression of GluD1 and GluD2 at regional, neuronal, and synaptic levels. These data provide a molecular–anatomical basis for possible competitive and cooperative interactions of GluD family members at synapses in various brain regions. [ABSTRACT FROM AUTHOR]

Background: Kawasaki disease (KD) is a systemic inflammatory disease resulting in an acute febrile syndrome commonly affecting children younger than 5 years. Coronary arteritis in KD is occasionally non‐responsive to several treatments. Recently, adipose tissue‐derived stem cells (ADSCs) have been shown to have anti‐inflammatory, immunosuppressive, and tissue‐repair characteristics and are considered a useful treatment for inflammatory disease. The present study aimed to elucidate whether the administration of ADSCs can suppress KD‐associated vasculitis in vivo. Methods: Candida albicans water‐soluble fraction is often used to model KD via the induction of severe coronary arteritis. Kawasaki disease model mice were intravenously administered ADSCs and phosphate‐buffered saline (PBS). On day 29, the mice were sacrificed and hearts from mice in each group were dissected. This was followed by serum collection. Cardiac tissue sections were subjected to histopathological examination to evaluate the inflammatory area. The levels of pro‐inflammatory cytokines in the serum were analyzed at days 15 and 29. The survival rates of both groups were compared. Results: The mean inflammatory area in coronary arteritis was significantly lower in the ADSC group compared to the PBS group (P < 0.01). Furthermore, the levels of pro‐inflammatory cytokines, such as IL‐1β, IL‐12, IL‐17, RANTES, INF‐γ, and TNF‐α, in the ADSC group were significantly lower than those in the PBS group. Moreover, the ADSC group had a significantly higher survival rate than the PBS group. Conclusions: These findings highlight that ADSCs have anti‐inflammatory and immune regulatory functions that could provide novel cell‐based therapeutic strategies for severe KD. [ABSTRACT FROM AUTHOR]