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Abstract Background Ischemic stroke in young adults can be caused by a variety of etiologies including the monogenic disorders. Visceral heterotaxy is a condition caused by abnormal left–right determinations during embryonic development. We aimed to determine the cause of a young ischemic stroke patient with visceral heterotaxy. Case presentation We performed neurological, radiological, and genetic evaluations in a 17-year-old male patient presenting ischemic stroke and visceral heterotaxy to determine the underlying cause of this rare disease combination. Brain magnetic resonance imaging (MRI) showed evidence of embolic stroke, abdominal computed tomography (CT) showed visceral heterotaxy, and echocardiogram showed cardiac anomaly with right-to-left-shunt (RLS). Whole genome sequencing (WGS) revealed a heterozygous missense variant (NM_018055.5: c.1016 T > C, p.(Met339Val)) in the NODAL gene, which is essential to the determination of the left–right body axis. Conclusions Our study highlights the importance of evaluating genetic etiology in young ischemic stroke and the need for stroke risk management in visceral heterotaxy patients with RLS. To the best of our knowledge, we report the first genetically-confirmed case of visceral heterotaxy with young embolic stroke reported to date.

Abstract Cardiac glycosides, known as inhibitors of Na+,K+-ATPase, have anti-cancer effects such as suppression of cancer cell proliferation and induction of cancer cell death. Here, we examined the signaling pathway elicited by cardiac glycosides in the human hepatocellular carcinoma HepG2 cells and human epidermoid carcinoma KB cells. Three kinds of cardiac glycosides (ouabain, oleandrin, and digoxin) inhibited the cancer cell proliferation and decreased the expression level of thyroid adenoma-associated protein (THADA). Interestingly, the knockdown of THADA inhibited cancer cell proliferation, and the proliferation was significantly rescued by re-expression of THADA in the THADA-knockdown cells. In addition, the THADA-knockdown markedly decreased the expression level of L-type amino acid transporter LAT1. Cardiac glycosides also reduced the LAT1 expression. The LAT1 inhibitor, JPH203, significantly weakened the cancer cell proliferation. These results suggest that the binding of cardiac glycosides to Na+,K+-ATPase negatively regulates the THADA-LAT1 pathway, exerting the anti-proliferative effect in cancer cells.

ObjectivesStandardized criteria for disease activity and end of treatment of systemic treatment of atopic dermatitis have not been established. The objective of this study is to explore the experience using upadacitinib retrospectively, to find clues to weaning from systemic treatment, and to determine the algorithm for setting treatment goals and terminating systemic treatment.MethodsFourteen patients treated with upadacitinib between 1 November 2021 and 31 December 2023 were enrolled in the study. Topical anti-inflammatory treatments were combined. Treatment outcomes were established according to the European Task Force of Atopic Dermatitis guidelines. To evaluate disease status and control, we adopted the Treat to target strategy. Changes in serum biomarkers (TARC and IgE) were also observed.ResultsAll patients achieved EASI 50 after 52 weeks. At 76 weeks, 80% and 30% of patients achieved EASI 75 and EASI 90, respectively. Four patients completed upadacitinib, five patients discontinued treatment, and five patients remained on treatment. Two patients achieved complete remission without topical anti-inflammatory treatment. Two patients discontinued due to adverse events. Patients with better treatment adherence, mainly topical treatment, tended to be able to withdraw from UPA. IgE increased from baseline in 11 patients (78.6%) and TARC increased in 14 patients (100%). These biomarkers decreased from the peak 24–48 weeks after initiating treatment, after the improvement of eczema.ConclusionCombining systemic and topical treatments effectively induces remission in AD patients. Transitioning off systemic treatment begins by achieving remission maintained solely with topical therapy, emphasizing the importance of adherence.

Abstract Previous work has shown that motor skill learning stimulates and requires generation of myelinating oligodendrocytes (OLs) from their precursor cells (OLPs) in the brains of adult mice. In the present study we ask whether OL production is also required for non-motor learning and cognition, using T-maze and radial-arm-maze tasks that tax spatial working memory. We find that maze training stimulates OLP proliferation and OL production in the medial prefrontal cortex (mPFC), anterior corpus callosum (genu), dorsal thalamus and hippocampal formation of adult male mice; myelin sheath formation is also stimulated in the genu. Genetic blockade of OL differentiation and neo-myelination in Myrf conditional-knockout mice strongly impairs training-induced improvements in maze performance. We find a strong positive correlation between the performance of individual wild type mice and the scale of OLP proliferation and OL generation during training, but not with the number or intensity of c-Fos+ neurons in their mPFC, underscoring the important role played by OL lineage cells in cognitive processing.

Abstract Mutations in the human ATP13A2 (PARK9), a lysosomal ATPase, cause Kufor-Rakeb Syndrome, an early-onset form of Parkinson’s disease (PD). Here, we demonstrate that ATP13A2 functions as a lysosomal H+,K+-ATPase. The K+-dependent ATPase activity and the lysosomal K+-transport activity of ATP13A2 are inhibited by an inhibitor of sarco/endoplasmic reticulum Ca2+-ATPase, thapsigargin, and K+-competitive inhibitors of gastric H+,K+-ATPase, such as vonoprazan and SCH28080. Interestingly, these H+,K+-ATPase inhibitors cause lysosomal alkalinization and α-synuclein accumulation, which are pathological hallmarks of PD. Furthermore, PD-associated mutants of ATP13A2 show abnormal expression and function. Our results suggest that the H+/K+-transporting function of ATP13A2 contributes to acidification and α-synuclein degradation in lysosomes.

Abstract Bitterness is an important physiological function in the defense responses to avoid toxic foods. The taste receptor 2 family is well known to mediate bitter taste perception in Type II taste cells. Here, we report that the polycystic kidney disease 2-like 1 (PKD2L1) channel is a novel sensor for the bitter aftertaste in Type III taste cells. The PKD2L1 channel showed rebound activation after the washout of quinine, a bitter tastant, in electrophysiological whole-cell recordings of the PKD2L1-expressing HEK293T cells and Ca2+-imaging analysis of Type III taste cells isolated from wild-type PKD2L1 mice. In the short-term two-bottle preference and lick tests in vivo, the wild-type mice avoided normal water while the PKD2L1-knockout mice preferred normal water after they ingested the quinine-containing water. These results may explain the new mechanism of the quinine-triggered bitter aftertaste perception in Type III taste cells.

In this study, we focused on assessing the symmetry of shapes and quantifying an index of ‘order’ in three-dimensional shapes using curvature, which is important in product design. Specifically, the target three-dimensional shape was divided into two segments, and the Jensen–Shannon distance was calculated for the distribution of the Casorati curvatures in both segments to determine the similarity between them. This was proposed as an indicator of the ‘order’ exhibited by the shape. To validate the effectiveness of the proposed index, sensory evaluation experiments were conducted on three shapes: extruded, rotated, and vase. For the rotated shape, the coefficient of determination between the proposed index and the sensory evaluation value of ‘order’ on a 5-point Likert scale was found to be less than 0.1. The reason for the poor correlation coefficient of determination may be attributed to the bias in human perception, where individuals tend to perceive mirror symmetry with respect to the plane that includes the vertical axis when recognizing the mirror symmetry of an object. In contrast, for the extruded and vase shapes, the coefficients of determination were 0.36 and 0.66, respectively, supporting the validity of the proposed index. Nonetheless, the coefficient of determination decreased slightly for familiar extruded shapes and asymmetric vase shapes. In future research, our aim is to quantify ‘aesthetic preference’ by combining the ‘order’ and ‘complexity’ indexes.

Purpose: This study aimed to investigate the accuracy and clinical significance of an artificial intelligence (AI)-based automated Alberta Stroke Program Early Computed Tomography (ASPECT) scoring software of head CT for the indication of intravenous recombinant tissue plasminogen activator (rt-PA) therapy. Methods: This study included two populations of acute ischemic stroke: one comprised patients who had undergone head CT within 48 h of presentation (Population #1, n = 448), while the other included patients within 4.5 h from onset (Population #2, n = 132). The primary endpoint was the concordance rate of ASPECTS of the neurologists and AI software against the benchmark score. The secondary endpoints were to validate the accuracy of the neurologist and AI software in assessing the ability to rule out extensive infarction (ASPECTS of 0–5) in population #2. Results: The reading accuracy of AI software was comparable to that of the board-certified vascular neurologists. The detection rate of cardiogenic cerebral embolism was better than that of atherothrombotic cerebral infarction. By excluding extensive infarction, AI-software showed a higher specificity and equivalent sensitivity compared to those of experts. Conclusions: The AI software for ASPECTS showed convincing agreement with expert evaluation and would be supportive in determining the indications of intravenous rt-PA therapy.

Abstract Objective To survey the content of occupational safety and health (OSH) disclosed in corporate social responsibility (CSR)-related reports and integrated reports in 2020 and to compare the changes between 2012 and 2020 according to industry and company size. Results Among all companies, 441 (20.3%) issued CSR-related reports and 590 (28.1%) issued integrated reports. The number (percentage) of companies that issued either CSR-related reports or integrated reports was 880 (40.5%). The percentages of both CSR-related reports and integrated reports increased with increased company size. The number (percentage) of companies reporting OSH in CSR-related reports was 391 (88.7%) and that in integrated reports was 493 (83.6%). The percentage of OSH reporting in CSR-related reports and integrated reports was high in secondary industries and low in tertiary industries.

Abstract The aim of this clinical report was to describe the improvement of masticatory disorders with the use of digital technology to simultaneously perform prosthodontic treatment of natural teeth and edentulous areas. Computer‐guided implant surgery was performed, and crown prostheses and implant superstructures were fabricated simultaneously using digital technology.

Abstract The emergence of hepatitis C virus (HCV) with resistance-associated substitution (RAS), produced by mutations in the HCV genome, is a major problem in direct acting antivirals (DAA) treatment. This study aimed to clarify the mutational spectrum in HCV-RNA and the substitution pattern for the emergence of RASs in patients with chronic HCV infection. HCV-RNA from two HCV replicon cell lines and the serum HCV-RNA of four non-liver transplant and four post-liver transplant patients with unsuccessful DAA treatment were analyzed using high-accuracy single-molecule real-time long-read sequencing. Transition substitutions, especially A>G and U>C, occurred prominently under DAAs in both non-transplant and post-transplant patients, with a mutational bias identical to that occurring in HCV replicon cell lines during 10-year culturing. These mutational biases were reproduced in natural courses after DAA treatment. RASs emerged via both transition and transversion substitutions. NS3-D168 and NS5A-L31 RASs resulted from transversion mutations, while NS5A-Y93 RASs was caused by transition substitutions. The fidelity of the RNA-dependent RNA polymerase, HCV-NS5B, produces mutational bias in the HCV genome, characterized by dominant transition mutations, notably A>G and U>C substitutions. However, RASs are acquired by both transition and transversion substitutions, and the RASs-positive HCV clones are selected and proliferated under DAA treatment pressure.

Background. Although HBV infection is a serious health issue worldwide, the landscape of HBV genome dynamics in the host has not yet been clarified. This study aimed to determine the continuous genome sequence of each HBV clone using a single-molecule real-time sequencing platform, and clarify the dynamics of structural abnormalities during persistent HBV infection without antiviral therapy. Patients and Methods. Twenty-five serum specimens were collected from 10 untreated HBV-infected patients. Continuous whole-genome sequencing of each clone was performed using a PacBio Sequel sequencer; the relationship between genomic variations and clinical information was analyzed. The diversity and phylogeny of the viral clones with structural variations were also analyzed. Results. The whole-genome sequences of 797,352 HBV clones were determined. The deletion was the most common structural abnormality and concentrated in the preS/S and C regions. Hepatitis B e antibody (anti-HBe)-negative samples or samples with high alanine aminotransferase levels have significantly diverse deletions than anti-HBe-positive samples or samples with low alanine aminotransferase levels. Phylogenetic analysis demonstrated that various defective and full-length clones evolve independently and form diverse viral populations. Conclusions. Single-molecule real-time long-read sequencing revealed the dynamics of genomic quasispecies during the natural course of chronic HBV infections. Defective viral clones are prone to emerge under the condition of active hepatitis, and several types of defective variants can evolve independently of the viral clones with the full-length genome.

Abstract A 54‐year‐old woman presented to our hospital with a fever and cough. The patient had a medical history of follicular lymphoma treated with obinutuzumab. She was infected with an omicron variant of coronavirus disease 2019 and developed viral pneumonia. Antibiotics, molnupiravir, sotrovimab, and prednisolone were administered but were ineffective. The patient's symptoms and pneumonia persisted. She could not produce antibodies against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) because she was administered obinutuzumab. Finally, when we administered 300 mg of tixagevimab and cilgavimab, pneumonia immediately improved. However, the infection was prolonged for more than 4 months. Patients treated with anti‐CD20 monoclonal antibodies may have a prolonged SARS‐CoV‐2 infection. In such cases, tixagevimab/cilgavimab may be effective.

Objective: Oligodendrocyte progenitor cell differentiation is regulated by nutritional signals in the adult median eminence (ME), but the consequences on local myelination are unknown. The aim of this study was to characterize myelin plasticity in the ME of adult mice in health or in response to chronic nutritional challenge and determine its relevance to the regulation of energy balance. Methods: We assessed new oligodendrocyte (OL) and myelin generation and stability in the ME of healthy adult male mice using bromodeoxyuridine labelling and genetic fate mapping tools. We evaluated the contribution of microglia to ME myelin plasticity in PLX5622-treated C57BL/6J mice and in Pdgfra-Cre/ERT2;R26R-eYFP;Myrffl/fl mice, where adult oligodendrogenesis is blunted. Next, we investigated how high-fat feeding or caloric restriction impact ME OL lineage progression and myelination. Finally, we characterized the functional relevance of adult oligodendrogenesis on energy balance regulation. Results: We show that myelinating OLs are continuously and rapidly generated in the adult ME. Paradoxically, OL number and myelin amounts remain remarkably stable in the adult ME. In fact, the high rate of new OL and myelin generation in the ME is offset by continuous turnover of both. We show that microglia are required for continuous OL and myelin production, and that ME myelin plasticity regulates the recruitment of local immune cells. Finally, we provide evidence that ME myelination is regulated by the body’s energetic status and demonstrate that ME OL and myelin plasticity are required for the regulation of energy balance and hypothalamic leptin sensitivity. Conclusions: This study identifies a new mechanism modulating leptin sensitivity and the central control of energy balance and uncovers a previously unappreciated form of structural plasticity in the ME.

Pulmonary hypertension (PH) is a severe and progressive disease that causes elevated right ventricular systolic pressure, right ventricular hypertrophy and ultimately right heart failure. However, the underlying pathophysiologic mechanisms are poorly understood. We previously showed that 3,4-l-dihydroxylphenyalanine (DOPA) sensitizes vasomotor response to sympathetic tone via coupling between the adrenergic receptor alpha1 (ADRA1) and a G protein-coupled receptor 143 (GPR143), a DOPA receptor. We investigated whether DOPA similarly enhances ADRA1-mediated contraction in pulmonary arteries isolated from rats, and whether GPR143 is involved in the PH pathogenesis. Pretreating the isolated pulmonary arteries with DOPA 1 μM enhanced vasoconstriction in response to phenylephrine, an ADRA1 agonist, but not to U-46619, a thromboxane A2 agonist or endothelin-1. We generated Gpr143 gene-deficient (Gpr143-/y) rats, and confirmed that DOPA did not augment phenylephrine-induced contractile response in Gpr143-/y rat pulmonary arteries. We utilized a rat model of monocrotaline (MCT)-induced PH. In the MCT model, the right ventricular systolic pressure was attenuated in the Gpr143-/y rats than in WT rats. Phenylephrine-induced cell migration and proliferation were also suppressed in Gpr143-/y pulmonary artery smooth muscle cells than in WT cells. Our result suggests that GPR143 is involved in the PH pathogenesis in the rat models of PH.

Abstract Background Fibrous sclerosing tumours and hypertrophic lesions in IgG4-related disease (IgG4-RD) are formed in various organs throughout the body, but disease in the oral region is not included among individual organ manifestations. We report a case of ossifying fibrous epulis that developed from the gingiva, as an instance of IgG4-RD. Case presentation A 60-year-old Japanese man visited the Department of Oral and Maxillofacial Surgery, Gunma University Hospital, with a chief complaint of swelling of the left mandibular gingiva. A 65 mm × 45 mm pedunculated tumour was observed. The bilateral submandibular lymph nodes were enlarged. The intraoperative pathological diagnosis of the enlarged cervical lymph nodes was inflammation. Based on this diagnosis, surgical excision was limited to the intraoral tumour, which was subsequently pathologically diagnosed as ossifying fibrous epulis. Histopathologically, the ossifying fibrous epulis exhibited increased levels of fibroblasts and collagen fibres, as well as infiltration by numerous plasma cells. The IgG4/IgG cell ratio was > 40%. Serologic analysis revealed hyper-IgG4-emia (> 135 mg/dL). The patient met the comprehensive clinical diagnosis criteria and the American College of Rheumatology and European League Against Rheumatism classification criteria for IgG4-RD. Based on these criteria, we diagnosed the ossifying fibrous epulis in our patient as an IgG4-related disease. A pathological diagnosis of IgG4-related lymphadenopathy was established for the cervical lymph nodes. Concomitant clinical findings were consistent with type II IgG4-related lymphadenopathy. Conclusions A routine serological test may be needed in cases with marked fibrous changes (such as epulis) in the oral cavity and plasma cells, accompanied by tumour formation, to determine the possibility of individual-organ manifestations of IgG4-related disease.

Background: The relationship between abnormal cortical plasticity and parkinsonian symptoms remains unclear in Parkinson's disease (PD). Objective: We studied the relationship between their symptoms and degree of Long-term potentiation (LTP)-like effects induced by quadripulse magnetic stimulation (QPS) over the primary motor cortex, which has a small inter-individual variability in humans. Methods: Participants were 16 PD patients (drug-naïve or treated with L-DOPA monotherapy) and 13 healthy controls (HC). LTP-like effects by QPS were compared between three conditions (HC､PD with or without L-DOPA). In PD, correlation analyses were performed between clinical scores (MDS-UPDRS, MMSE and MoCA-J) and the degree of LTP-like effects induced by QPS. Results: In PD, QPS-induced LTP-like effect was reduced and restored by L-DOPA. The degree of the LTP was negatively correlated with MDS-UPDRS Part I and III scores, but not with MMSE and MoCA-J. In the sub-scores, upper limb bradykinesia and rigidity showed a negative correlation with the LTP-like effect whereas the tremor had no correlation. Conclusions: Our results suggest that motor cortical plasticity relate with mechanisms underlying bradykinesia and rigidity in the upper limb muscles. LTP induced by QPS may be used as an objective marker of parkinsonian symptoms.

[Purpose]: We used a near-infrared ray catheter (NIRC) in a child with cloacal exstrophy presenting with hematometra and assessed whether the NIRC could help with complicated adhesiolysis during hemi-hysterectomy in children. [Method]: A 6-French pig tail-type NIRC was inserted into the left ureter with guidance from a cystoscope. Laparoscopic hemi-hysterectomy with fluorescence observation was performed using the VISERA ELITE 2 system. [Result]: NIRC insertion into the left ureter was not as difficult as expected despite the eccentric position of the left ureter orifice. When we found an enlarged left uterus and fallopian tube, adhesion was extremely severe around them due to chronic inflammation caused by hematometra. When near-infrared rays were applied, a fluorescent ureteral catheter that emitted bright green excitation light was observed on the dorsal side of the enlarged left uterus and fallopian tube. Under ureteral navigation with an NIRC, dissection of the adhesions was performed safely and smoothly. Hemi-hysterectomy and adnexectomy were performed successfully. The patient was doing well 2 years postoperatively without any complications. [Conclusion]: An NIRC can provide useful real-time visualization of the ureter course and reduce the risk of ureteral damage in children with advanced adhesions.

Kinesin superfamily proteins are microtubule-based molecular motors driven by the energy of ATP hydrolysis. Among them, the kinesin-4 family is a unique motor that inhibits microtubule dynamics. Although mutations of kinesin-4 cause several diseases, its molecular mechanism is unclear because of the difficulty of visualizing the high-resolution structure of kinesin-4 working at the microtubule plus-end. Here, we report that KLP-12, a C. elegans kinesin-4 ortholog of KIF21A and KIF21B, is essential for proper length control of C. elegans axons, and its motor domain represses microtubule polymerization in vitro. The crystal structure of the KLP-12 motor domain complexed with tubulin, which represents the high-resolution structural snapshot of the inhibition state of microtubule-end dynamics, revealed the bending effect of KLP-12 for tubulin. Comparison with the KIF5B-tubulin and KIF2C-tubulin complexes, which represent the elongation and shrinking forms of microtubule ends, respectively, showed the curvature of tubulin introduced by KLP-12 is in between them. Taken together, KLP-12 controls the proper length of axons by modulating the curvature of the microtubule ends to inhibit the microtubule dynamics.

Background Posterior reversible encephalopathy syndrome (PRES) is a disease characterised by reversible subcortical vasogenic oedema, neurological symptoms and abnormal findings on head imaging. It is recognised as one of the most prominent organ disorders in hypertensive emergencies but is rarely associated with thrombotic microangiopathy (TMA).Case presentation A woman in her 40s with untreated hypertension had occasional headaches in the past 4 months. The headaches worsened during the 3 weeks prior to admission. On the day of admission, the patient presented with severe headache accompanied by frequent vomiting. MRI of the head revealed oedematous changes in the brainstem, including the subcortical, cerebellum and pons. Fundus examination revealed hypertensive retinopathy with papilloedema. Blood tests indicated thrombocytopenia, renal dysfunction and haemolytic anaemia, and a blood smear confirmed fragmented erythrocytes. Coombs’ test, and tests for ADAMTS13 activity and infectious and autoimmune diseases were negative. The patient was diagnosed with PRES, secondary to malignant hypertension (MH) and associated with TMA. Antihypertensive therapy promptly improved the clinical symptoms, blood pressure, and the abnormal MRI and blood test findings. The patient was discharged from the hospital 20 days after admission.Conclusions We report a rare case of PRES that was associated with TMA and triggered by MH. Antihypertensive therapy was effective in alleviating the associated adverse clinical symptoms. Differentiation of underlying diseases is essential for early intervention, since treatment depends on factors causing TMA.

This article provides a synopsis of current progress made in fundamental studies of lower urinary tract dysfunction (LUTD) after spinal cord injury (SCI) above the sacral level. Animal models of SCI allowed us to examine the effects of SCI on the micturition control and the underlying neurophysiological processes of SCI-induced LUTD. Urine storage and elimination are the two primary functions of the LUT, which are governed by complicated regulatory mechanisms in the central and peripheral nervous systems. These neural systems control the action of two functional units in the LUT: the urinary bladder and an outlet consisting of the bladder neck, urethral sphincters, and pelvic-floor striated muscles. During the storage phase, the outlet is closed, and the bladder is inactive to maintain a low intravenous pressure and continence. In contrast, during the voiding phase, the outlet relaxes, and the bladder contracts to facilitate adequate urine flow and bladder emptying. SCI disrupts the normal reflex circuits that regulate co-ordinated bladder and urethral sphincter function, leading to involuntary and inefficient voiding. Following SCI, a spinal micturition reflex pathway develops to induce an overactive bladder condition following the initial areflexic phase. In addition, without proper bladder–urethral-sphincter coordination after SCI, the bladder is not emptied as effectively as in the normal condition. Previous studies using animal models of SCI have shown that hyperexcitability of C-fiber bladder afferent pathways is a fundamental pathophysiological mechanism, inducing neurogenic LUTD, especially detrusor overactivity during the storage phase. SCI also induces neurogenic LUTD during the voiding phase, known as detrusor sphincter dyssynergia, likely due to hyperexcitability of Aδ-fiber bladder afferent pathways rather than C-fiber afferents. The molecular mechanisms underlying SCI-induced LUTD are multifactorial; previous studies have identified significant changes in the expression of various molecules in the peripheral organs and afferent nerves projecting to the spinal cord, including growth factors, ion channels, receptors and neurotransmitters. These findings in animal models of SCI and neurogenic LUTD should increase our understanding of pathophysiological mechanisms of LUTD after SCI for the future development of novel therapies for SCI patients with LUTD.

Generative design is a system that automates part of the design process, but it cannot evaluate psychological issues related to shapes, such as “beauty” and “liking”. Designers therefore evaluate and choose the generated shapes based on their experience. Among the design features, “complexity” is considered to influence “aesthetic preference”. Although feature descriptors calculated from curvature can be used to quantify “complexity”, the selection guidelines for curvature and feature descriptors have not been adequately discussed. Therefore, this study aimed to conduct a systematic classification of curvature and a feature descriptor of 3D shapes and to apply the results to the “complexity” quantification. First, we surveyed the literature on curvature and feature descriptors and conducted a systematic classification. To quantify “complexity”, we used five curvatures (Gaussian curvature, mean curvature, Casorati curvature, shape index, and curvature index) and a feature descriptor (entropy of occurrence probability) obtained from the classification and compared them with the sensory evaluation values of “complexity”. The results showed that the determination coefficient between the quantified and sensory evaluation values of “complexity” was highest when the mean curvature was used. In addition, the Casorati curvature tended to show the highest signal-to-noise ratio (i.e., a high determination coefficient irrespective of the parameters set in the entropy calculation). These results will foster the development of generative design of 3D shapes using psychological evaluation.

Microtubules are dynamic polymers consisting of αβ-tubulin heterodimers. The initial polymerization process, called microtubule nucleation, occurs spontaneously via αβ-tubulin. Since a large energy barrier prevents microtubule nucleation in cells, the γ-tubulin ring complex is recruited to the centrosome to overcome the nucleation barrier. However, a considerable number of microtubules can polymerize independently of the centrosome in various cell types. Here, we present evidence that the minus-end-binding calmodulin-regulated spectrin-associated protein 2 (CAMSAP2) serves as a strong nucleator for microtubule formation by significantly reducing the nucleation barrier. CAMSAP2 co-condensates with αβ-tubulin via a phase separation process, producing plenty of nucleation intermediates. Microtubules then radiate from the co-condensates, resulting in aster-like structure formation. CAMSAP2 localizes at the co-condensates and decorates the radiating microtubule lattices to some extent. Taken together, these in vitro findings suggest that CAMSAP2 supports microtubule nucleation and growth by organizing a nucleation centre as well as by stabilizing microtubule intermediates and growing microtubules.

Purpose: We applied indocyanine green fluorescence angiography (ICG-FA) to a child with intestinal volvulus and assessed if ICG-FA could help judge bowel resection. Method: ICG with a dose of 0.5 mg/kg was injected and decision of intestinal resection was made by means of the degrees of fluorescent intensity in fluorescence system. Result: An 8-year-old girl was diagnosed as intestinal volvulus due to mesenteric defect with 200 cm of the strangulated intestine. ICG-FA revealed no fluorescence was observed at the entire strangulated intestine, thus we planned to re-evaluate the viability of intestine. ICG-FA at second look operation showed three patterns of fluorescent intensity including WHITE; strong fluorescence at mesentery and intestinal wall, GRAY; weak mosaic fluorescence at bowel wall, and BLACK; no fluorescence. We decided to resect 100 cm of BLACK fluorescent bowel and preserve WHITE and GRAY fluorescent intestine with double-barreled stoma. The 3rd ICG-FA reveled GRAY pattern changed to WHITE fluorescence, thus stoma was closed successfully. The patient is doing well 2 years after surgery without any complication Conclusion: ICG-FA can provide useful real-time visualization of intestinal perfusion intraoperatively, and help surgeon judge the necessity and its area of bowel resection.

Abstract The detection of underlying atrial fibrillation (AF) has become increasingly possible by insertable cardiac monitoring (ICM). During hospitalization for cryptogenic stroke, factors related to the early and late development of AF have not been studied. CHALLENGE ESUS/CS is a multicenter registry of cryptogenic stroke patients undergoing transesophageal echocardiography. Twelve-lead electrocardiogram, continuous cardiac monitoring, and 24-h Holter electrocardiogram were all used for the detection of AF. Early and late detection of AF was determined with an allocation ratio of 1:1 among patients with AF. A total of 677 patients (68.7 ± 12.8 years; 455 men) were enrolled, and 64 patients developed AF during hospitalization. Four days after admission was identified as the approximate median day to classify early and late phases to detect AF: ≤ 4 days, 37 patients; > 4 days, 27 patients. Multiple logistic regression analysis showed that spontaneous echo contrast (SEC) (OR 5.91; 95% CI 2.19–15.97; p 3 cm in diameter (OR 3.28; 95% CI 1.35–7.97; p = 0.009) was associated with AF > 4 days. SEC and large infarctions were important predictors of in-hospital AF detection, particularly in the early and late stages, respectively; thus, they could serve as indications for recommending ICM.

Background: Both pre-supplementary motor area (pre-SMA) and SMA-proper (SMA) must play important roles in visuomotor sequence learning. However, functional differences between the pre-SMA and SMA have not been well studied in humans. Objective: To elucidate the functional differences between the pre-SMA and SMA in sequence learning in humans. Methods: To induce LTP/LTD, we administered quadripulse transcranial magnetic stimulation (QPS) with an inter-stimulus interval of 5 or 50 ms (QPS-5/50) over the pre-SMA or SMA in healthy volunteers. The sham stimulation was also done as a control. We studied the effects of LTP/LTD in the pre-SMA/SMA on a new sequence learning and the performance of well-learned sequence by using sequence learning task called the “2 × 10 task”. Effects on the simple choice reaction time task were also studied for comparison. Results: QPS-5 over the pre-SMA increased the error rate without any changes in movement speed. When administered over the SMA, QPS-5 decreased, and QPS-50 increased the rate of reaction time reduction across trials without changes in the error rate. QPS over neither the pre-SMA nor SMA affected the performances of a well-learned sequence or a simple choice reaction time task. Conclusions: Our findings that QPS over the pre-SMA correlated with sequence learning performance and that over the SMA with execution speed are consistent with the previous results in animals and humans. Our results lend further support to the utility of QPS for modulating motor learning in humans.

Gastric chief cells differentiate from mucous neck cells and develop their mature state at the base of oxyntic glands with expression of secretory zymogen granules. After parietal cell loss, chief cells transdifferentiate into mucous cell metaplasia, designated spasmolytic polypeptide-expressing metaplasia (SPEM), which is considered a candidate precursor of gastric cancer. We examined the range of microRNA (miRNA) expression in chief cells and identified miRNAs involved in chief cell transdifferentiation into SPEM. Among them, miR-148a was strongly and specifically expressed in chief cells and significantly decreased during the process of chief cell transdifferentiation. Interestingly, suppression of miR-148a in a conditionally immortalized chief cell line induced up-regulation of CD44 variant 9 (CD44v9), one of the transcripts expressed at an early stage of SPEM development, and DNA methyltransferase 1 (Dnmt1), an established target of miR-148a. Immunostaining analyses showed that Dnmt1 was up-regulated in SPEM cells as well as in chief cells before the emergence of SPEM in mouse models of acute oxyntic atrophy using either DMP-777 or L635. In the cascade of events that leads to transdifferentiation, miR-148a was down-regulated after acute oxyntic atrophy either in xCT knockout mice or after sulfasalazine inhibition of xCT. These findings suggest that the alteration of miR-148a expression is an early event in the process of chief cell transdifferentiation into SPEM. Keywords: SPEM, miRNA, CD44 Variant 9, miR-148a, Transdifferentiation, Metaplasia, Gastric, DNMT1, Plasticity

Background Cerebrovascular diseases are common comorbidities in patients with cancer. Although active cancer causes ischemic stroke by multiple pathological conditions, including thromboembolism attributable to Trousseau syndrome, the relationship between stroke and inactive cancer is poorly known. The aim of this study was to elucidate the different underlying pathogeneses of cryptogenic stroke in active and inactive patients with cancer, with detailed investigation by transesophageal echocardiography. Methods and Results CHALLENGE ESUS/CS (Mechanisms of Embolic Stroke Clarified by Transesophageal Echocardiography for Embolic Stroke of Undetermined Source/Cryptogenic Stroke) registry is a multicenter registry including data of patients initially diagnosed as having cryptogenic stroke and undergoing transesophageal echocardiography. Patients were divided into active cancer, inactive cancer, and noncancer groups, and their clinical features were compared. Of the total 667 enrolled patients (age, 68.7±12.8 years; 455 men), 41 (6.1%) had active cancer, and 51 (7.5%) had a history of inactive cancer. On multinomial logistic regression analysis, infarctions in multiple vascular territories (odds ratio [OR], 2.73; 95% CI, 1.39–5.40) and CRP (C‐reactive protein) (OR, 1.10; 95% CI, 1.01–1.19) were independently associated with active cancer, whereas age (OR, 1.05; 95% CI, 1.01–1.08), contralateral carotid stenosis from the index stroke lesion (OR, 4.05; 95% CI, 1.60–10.27), calcification of the aortic valve (OR, 2.10; 95% CI, 1.09–4.05), and complicated lesion of the aortic arch (OR, 2.13; 95% CI, 1.11–4.10) were significantly associated with inactive cancer. Conclusions Patients with cancer were not rare in cryptogenic stroke. Although patients with active cancer had more multiple infarctions, patients with inactive cancer had more atherosclerotic embolic sources potentially causing arteriogenic strokes. Registration URL: https://www.umin.ac.jp/ctr/; Unique identifier: UMIN000032957.

Summary: Beginning of metastasis, cancer cells detach from the primary tumor and they can survive even under loss of anchorage; however, the detachment-elicited mechanisms have remained unknown. Here, we found that Na+,K+-ATPase α3-isoform (α3NaK) in human cancer cells is dynamically translocated from intracellular vesicles to the plasma membrane when the attached cells are detached and that this mechanism contributes to the survival of the detached (floating) cancer cells. α3NaK was detected in the plasma membrane of floating cancer cells in peritoneal fluids of patients, while it was in the cytoplasm of the cells in primary tumor tissues. On cancer cell detachment, we also found the focal-adhesion-kinase-dependent Ca2+ response that induces the α3NaK translocation via nicotinic acid adenine dinucleotide phosphate pathway. Activation of AMP-activated protein kinase was associated with the translocated α3NaK in the plasma membrane. Collectively, our study identifies a unique mechanism for survival of detached cancer cells, opening up new opportunities for development of cancer medicines.

We report a 65-year-old man who was diagnosed with focal status epilepticus generating a dreamy state, delusions with anxiety, complex audiovisual hallucinations, elementary auditory hallucinations, and metamorphopsia with a growing large lateral temporal lobe lesion. After administrating anti-seizure drugs, all the symptoms disappeared, and brain magnetic resonance imaging revealed ipsilateral hippocampal sclerosis. To the best of our knowledge, this is the first report to present all the symptoms in one epilepsy case. On the basis of semiology, electroencephalography, and brain magnetic resonance imaging, we speculated that epileptic activities that have originated from the lateral lesion might have propagated to the ipsilateral mesial temporal lobe, causing hippocampal sclerosis.

Software-defined networks are vulnerable to attacks by compromised switches because commonly used programmable software switches are risky than traditional hardware ones. Although several countermeasures have been proposed to address compromised switches, the accuracy of detecting a malicious behavior depends on the performance of network statistics gathering by a controller. In this paper, we propose that WhiteRabbit is an approach to verify the consistency of the forwarding state by gathering real-time network statistics gathering from switches with accurate time scheduling. WhiteRabbit can detect attacks by compromised switches without being influenced by the performance of statistics gathering of a controller. Given that the proposed utilizes moving average, it mitigates the effect on the verification accuracy from the impact of the switch performance, such as scheduling error. In our previous work, we demonstrated the feasibility of WhiteRabbit using a prototype system. However, we could not evaluate the impact of the difference between the scheduled and actual execution times in our previous work, because we performed the experiment in a minimal setup using Mininet. Thus, we measured the scheduling error and time required to gather statistics in a large-scale environment. We also confirmed that the scheduling error is lower than the time required to gather statistics. Additionally, considering that WhiteRabbit only depends on the scheduling error, we verified that the accuracy of WhiteRabbit is higher than prior arts on the tree topology constructed with 15 switches.

Abstract Background Microglia-derived lysosomal cathepsins are important inflammatory mediators to trigger signaling pathways in inflammation-related cascades. Our previous study showed that the expression of cathepsin C (CatC) in the brain is induced predominantly in activated microglia in neuroinflammation. Moreover, CatC can induce chemokine production in brain inflammatory processes. In vitro studies further confirmed that CatC is secreted extracellularly from LPS-treated microglia. However, the mechanisms of CatC affecting neuroinflammatory responses are not known yet. Methods CatC over-expression (CatCOE) and knock-down (CatCKD) mice were treated with intraperitoneal and intracerebroventricular LPS injection. Morris water maze (MWM) test was used to assess the ability of learning and memory. Cytokine expression in vivo was detected by in situ hybridization, quantitative PCR, and ELISA. In vitro, microglia M1 polarization was determined by quantitative PCR. Intracellular Ca2+ concentration was determined by flow cytometry, and the expression of NR2B, PKC, p38, IkBα, and p65 was determined by western blotting. Results The LPS-treated CatCOE mice exhibited significantly increased escape latency compared with similarly treated wild-type or CatCKD mice. The highest levels of TNF-α, IL-1β, and other M1 markers (IL-6, CD86, CD16, and CD32) were found in the brain or serum of LPS-treated CatCOE mice, and the lowest levels were detected in CatCKD mice. Similar results were found in LPS-treated microglia derived from CatC differentially expressing mice or in CatC-treated microglia from wild-type mice. Furthermore, the expression of NR2B mRNA, phosphorylation of NR2B, Ca2+ concentration, phosphorylation of PKC, p38, IκBα, and p65 were all increased in CatC-treated microglia, while addition of E-64 and MK-801 reversed the phosphorylation of above molecules. Conclusion The data suggest that CatC promotes microglia M1 polarization and aggravates neuroinflammation via activation of Ca2+-dependent PKC/p38MAPK/NF-κB pathway. CatC may be one of key molecular targets for alleviating and controlling neuroinflammation in neurological diseases.

Background: Total colonic aganglionosis (TCA) and long segment aganglionosis (LSA) are rare forms of Hirschsprung disease (HD). Laparoscopic resection of total or the longer segment of the colon has not been unestablished for these forms. Methods: We retrospectively reviewed five infants with TCA or LSA who underwent the blunt tip dissector (BD) assisted laparoscopic Soave pull-through procedure, and patients’ characteristics and procedure outcomes were analyzed. Results: One infant with TCA had Mowat–Wilson syndrome. Ileostomy for TCA and transanal catheter placement for LSA allowed full enteral feeding with good weight gain before operation. The BD manipulator used in the laparoscopic surgery was simple to use and powerful enough to create tension, expand operating space, and improve access to specific parts of the mesentery or pelvis. No intraoperative complications such as perforation or bleeding were noted; thus, the operation was completed uneventfully, without conversion to open surgery in all cases. All the patients had excellent cosmetic results, without late complications. Conclusions: The BD manipulator is safe and effective to facilitate laparoscopy-assisted Soave pull-through procedure in children with TCA and LSA. This approach may be applied to the other pediatric diseases, which require resection of the longer segment of the colon.

Cisplatin [cis-diamminedichloroplatinum (II)] is a platinum-based anticancer drug widely used for the treatment of various cancers. It forms interstrand and intrastrand cross-linking with DNA and block DNA replication, resulting in apoptosis. On the other hand, intrinsic and acquired cisplatin resistance restricts its therapeutic effects. Although some studies suggest that dramatic epigenetic alternations are involved in the resistance triggered by cisplatin, the mechanism is complicated and remains poorly understood. Recent studies reported that cytoskeletal structures regulate cisplatin sensitivity and that activities of membrane transporters contribute to the development of resistance to cisplatin. Therefore, we focus on the roles of actin filaments and membrane transporters in cisplatin-induced apoptosis. In this review, we summarize the relationship between actin cytoskeleton and membrane transporters in the cisplatin resistance of cancer cells.

Multiple system atrophy (MSA) is a progressive neurodegenerative disorder. Since patients with MSA often have sleep-related respiratory disorders including upper-airway obstruction and/or central sleep disturbance, appropriate evaluation of the upper airway especially during sleep may be indispensable. Fiberoptic laryngoscopy during diazepam-induced sleep has been reported for upper-airway obstruction verification. However, some patients cannot endure the uncomfortable sensation of the fiberscope. To address these issues, we devised a protocol of four four-dimensional computed tomography (4D-CT) for upper-airway evaluation during sleep. Here, we report the case of patient with MSA who was evaluated for upper-airway obstruction during sleep using 4D-CT. A 46-year-old man (height 1.60 m, weight 79 kg) was admitted to our neurological department for tracheal intubation because of a sudden onset of respiratory failure occurring at night. At the age of 45 years, he was diagnosed as MSA with predominant parkinsonism. As pulmonary disease had been excluded and his swallowing was normal, our differential diagnoses were central sleep apnea or obstructive sleep apnea related to his MSA or obstructive sleep apnea (SA) related to his obesity. A tracheostomy was done to maintain the airway after extubation. Polysomnography showed obstructive SA and not central SA. Awake fiberoptic laryngoscopy showed no upper airway obstruction but bilateral vocal abduction impairment (BVAI) during inspiration. To assess the spatial and temporal conditions of the upper respiratory tract—the patient could not tolerate sleep laryngoscopy—we carried out a 4D-CT. Reconstructed 4D-CT images of respiration during sleep showed clear abnormalities: glottis closure at the terminal stage of inspiration and subsequent velopharyngeal closure. As glottis closure does not occur normally in obesity patients, the cause of the respiratory failure in this patient was considered MSA-related sleep-induced airway obstruction. We decided to keep the tracheostoma, because BVAI in patients with MSA may be getting worse, although central apnea after tracheostomy may cause sudden central origin-related death; 4 months postoperatively, the patient had experienced no further airway-related complications. This report indicates that 4D-CT sequential upper-airway assessment during sleep is useful for determining the abnormalities causing obstructive SA in patients with MSA.

Abstract Background Perineurioma (PN) is a peripheral nerve disease that primarily develops in the limbs and trunk and very rarely occurs in the oral cavity. PN is classified into two types: intraneural perineurioma (INPN) and soft tissue perineurioma (extraneural perineurioma, ENPN). In this article, we report a patient with mandibular body INPN derived from the perineurium of the inferior alveolar nerve. Case presentation The patient was a 43-year-old male. He consulted our department for a detailed examination of the right mandibular body. A biopsy was performed at another hospital and he was diagnosed with a schwannoma. At his first visit, hypesthesia extending from the right lower lip to the mental region was recognized and enlargement of the right mandibular canal was confirmed with X-ray CT and MRI. Considering the possibility of future tumor growth, we extirpated the tumor under general anesthesia. Cystic tumor was seen continuously in the inferior alveolar nerve. Immunohistologically, the tumor cells were positive for Glut-1, weakly positive for EMA, and weakly positive for Claudin-1, and the histopathological diagnosis was INPN. In addition, absence of the BCR region of chromosome 22 and expression of the BCR-ABL fusion gene were observed by fluorescent in situ hybridization (FISH), and a chromosome 22 abnormality was confirmed. These findings indicated that the disease was a neoplastic lesion. Conclusion Expression of the BCR-ABL fusion gene in INPN that develops in the oral cavity is thought to be very rare, and to the best of our knowledge, ours is the first case to be reported in the literature. About three postoperative years have passed, but findings suggestive of recurrence have not been observed.

The total synthesis of two decahydroquinoline poison frog alkaloids ent-cis-195A and cis-211A were achieved in 16 steps (38% overall yield) and 19 steps (31% overall yield), respectively, starting from known compound 1. Both alkaloids were synthesized from the common key intermediate 11 in a divergent fashion, and the absolute stereochemistry of natural cis-211A was determined to be 2R, 4aR, 5R, 6S, and 8aS. Interestingly, the absolute configuration of the parent decahydroquinoline nuclei of cis-211A was the mirror image of that of cis-195A, although both alkaloids were isolated from the same poison frog species, Oophaga (Dendrobates) pumilio, from Panama.

Stroke is a major cause of death worldwide, leading to serious disability. Post-ischemic injury, especially in the cerebral ischemia-prone hippocampus, is a serious problem, as it contributes to vascular dementia. Many studies have shown that in the hippocampus, ischemia/reperfusion induces neuronal death through oxidative stress and neuronal zinc (Zn2+) dyshomeostasis. Glutathione (GSH) plays an important role in protecting neurons against oxidative stress as a major intracellular antioxidant. In addition, the thiol group of GSH can function as a principal Zn2+ chelator for the maintenance of Zn2+ homeostasis in neurons. These lines of evidence suggest that neuronal GSH levels could be a key factor in post-stroke neuronal survival. In neurons, excitatory amino acid carrier 1 (EAAC1) is involved in the influx of cysteine, and intracellular cysteine is the rate-limiting substrate for the synthesis of GSH. Recently, several studies have indicated that cysteine uptake through EAAC1 suppresses ischemia-induced neuronal death via the promotion of hippocampal GSH synthesis in ischemic animal models. In this article, we aimed to review and describe the role of GSH in hippocampal neuroprotection after ischemia/reperfusion, focusing on EAAC1.

Epidemiological, clinical, and biological studies convincingly demonstrate that chronic inflammation predisposes to the development of human cancers. In digestive organs, inflammation-associated cancers include colitis-associated colorectal cancers, Helicobacter pylori-associated gastric cancer, as well as Barrett’s esophagus and esophageal adenocarcinoma associated with chronic duodenogastric-esophageal reflux. Cancer is a genomic disease, and stepwise accumulation of genetic and epigenetic alterations of tumor-related genes leads to the development of tumor cells. Recent genome analyses show that genetic alterations, which are evoked by inflammation, are latently accumulated in inflamed epithelial cells of digestive organs. Production of reactive oxygen and aberrant expression of activation-induced cytidine deaminase, a nucleotide-editing enzyme, could be induced in inflamed gastrointestinal epithelial cells and play a role as a genomic modulator of inflammation-associated carcinogenesis. Understanding the molecular linkage between inflammation and genetic alterations will open up a new field of tumor biology and provide a novel strategy for the prevention of inflammation-associated tumorigenesis.

Voltage‐dependent inactivation of ion channels contributes to the regulation of the membrane potential of excitable cells. Mouse polycystic kidney disease 2‐like 1 (PKD2L1) forms voltage‐dependent nonselective cation channels, which are activated but subsequently inactivated in response to membrane depolarization. Here, we found that the mutation of an asparagine 533 residue (N533Q) in the outer pore loop region of PKD2L1 caused a marked increase in outward currents induced by depolarization. In addition, the tail current analysis demonstrated that the N533Q mutants are activated during depolarization but the subsequent inactivation does not occur. Interestingly, the N533Q mutants lacked the channel activation triggered by the removal of stimuli such as extracellular alkalization and heating. Our findings suggest that the N533 residue in the outer pore loop region of PKD2L1 has a key role in the voltage‐dependent channel inactivation.

Repetitive transcranial magnetic stimulation (rTMS) induces changes in cortical excitability for minutes to hours after the end of intervention. However, it has not been precisely determined to what extent cortical plasticity prevails spatially in the cortex. Recent studies have shown that rTMS induces changes in "interhemispheric" functional connectivity, the resting-state functional connectivity between the stimulated region and the symmetrically corresponding region in the contralateral hemisphere. In the present study, quadripulse stimulation (QPS) was applied to the index finger representation in the left primary motor cortex (M1), while the position of the stimulation coil was constantly monitored by an online navigator. After QPS application, resting-state functional magnetic resonance imaging was performed, and the interhemispheric functional connectivity was compared with that before QPS. A cluster of connectivity changes was observed in the stimulated region in the central sulcus. The cluster was spatially extended approximately 10 mm from the center [half width at half maximum (HWHM): approximately 3 mm] and was extended approximately 20 mm long in depth (HWHM: approximately 7 mm). A localizer scan of the index finger motion confirmed that the cluster of interhemispheric connectivity changes overlapped spatially with the activation related to the index finger motion. These results indicate that cortical plasticity in M1 induced by rTMS was relatively restricted in space and suggest that rTMS can reveal functional dissociation associated with adjacent small areas by inducing neural plasticity in restricted cortical regions.

Aim. Oro-cervical necrotizing fasciitis (OCNF) treatment requires early surgical debridement and opening of the wound, and therefore, early diagnosis is very important. The Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) score based on blood test data has recently been proposed as an auxiliary diagnostic tool. However, in some cases, it is difficult to diagnose OCNF. We performed a pooled analysis of patients with OCNF at Gunma University Hospital and literature cases, with the goal of designing a new auxiliary diagnostic tool for OCNF by adding physical characteristics of the oro-cervical region to blood test data in the first examination. Methods. Univariate and multivariate logistic regression was used to select predictors of OCNF. The LRINEC-Oro-Cervical (OC) score was then designed using correlation coefficients of items selected in logistic regression analysis. A cutoff value for the LRINEC-OC score was determined using receiver operating characteristic (ROC) curve analysis. Results. CRP, WBC, Cr, and skin flare in the cervical and precordial regions were extracted as independent factors (p

Naftopidil, an α1-adrenoceptor antagonist, has been shown to inhibit nocturnal polyuria in patients with lower urinary tract symptom. However, it remains unclear how naftopidil decreases nocturnal urine production. Here, we investigated the effects of naftopidil on arginine-vasopressin (AVP) plasma level and urine production and osmolality in rats centrally administered with noradrenaline (NA). NA (3 or 30 μg/kg) was administered into the left ventricle (i.c.v.) of male Wistar rats 3 h after naftopidil pretreatment (10 or 30 mg/kg, i.p.). Blood samples were collected from the inferior vena cava 1 h after NA administration or 4 h after peritoneal administration of naftopidil; plasma levels of AVP were assessed by ELISA. Voiding behaviors of naftopidil (30 mg/kg, i.p.)-administered male Wistar rats were observed during separate light- and dark cycles. Administration of NA decreased plasma AVP levels and elevated urine volume, which were suppressed by systemic pretreatment with naftopidil (30 mg/kg, i.p.). Urine osmolality decreased 1 h after NA administration. However, naftopidil by itself had no effect on plasma AVP levels or urodynamic parameters during light- and dark cycles. Our findings suggest that systemic administration of naftopidil could prevent central noradrenergic nervous system-mediated decline in AVP secretion and increase in urine production in rats.

We investigated the protective effects of a selective α1A-adrenoceptor antagonist, silodosin (Silod) on urinary bladder function in cyclophosphamide (CYP)-induced cystitis rats, with and without desensitization of the capsaicin (CAP)-sensitive afferent nerve pathway. Male Wistar rats (310–400 g) were pretreated with Silod (0, 100, or 300 μg/kg/day, p.o.) for 1 week before cystometry, and were administered either CYP (150 mg/kg, i.p.) or saline 2 days before the experiment. In another experiment, the rats were treated with CAP (125 mg/kg, s.c.) 4 days before the cystometry. The rat bladders were harvested, weighed, and evaluated histologically. The cystometric evaluation showed significant reductions in the intercontraction interval (ICI), single voided volume (SVV), and bladder compliance in CYP-treated rats compared to those in the vehicle-treated rats. High-dose Silod or CAP treatment significantly increased the ICI and SVV in the CYP rats. However, high-dose Silod treatment did not increase the ICI and SVV in CAP-treated CYP rats. Treatment with Silod did not improve the bladder weight, edema, and leukocyte infiltration resulting from the CYP-induced bladder inflammation. These data suggest that blockade of α1-adrenoceptors by Silod inhibited the CAP-sensitive afferent pathway in rats with cystitis.

A peritonsillar abscess is a common deep infection that is usually related to acute tonsillitis. Needle aspiration is often performed for diagnosis and treatment, but several complications, including puncture of the carotid artery, may occur, even when performed by properly trained physicians. The utility of transoral pharyngeal ultrasonography (TOPU) equipped with a biopsy adaptor for safe and full aspiration is presented. A 19-year-old man was admitted to our hospital because of a peritonsillar abscess. TOPU showed the abscess and a branch of the carotid artery, and an otolaryngologist performed puncture through the biopsy adaptor with the aid of the ultrasound image. Needle aspiration was accomplished by avoiding arterial puncture and monitoring the shrinkage of the abscess. TOPU-guided needle aspiration is useful in the safe drainage of peritonsillar abscesses.