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Summary: In contrast to mammals, the avian cochlea, specifically the basilar papilla, can regenerate sensory hair cells, which involves fate conversion of supporting cells to hair cells. To determine the mechanisms for converting supporting cells to hair cells, we used single-cell RNA sequencing during hair cell regeneration in explant cultures of chick basilar papillae. We identified dynamic changes in the gene expression of supporting cells, and the pseudotime trajectory analysis demonstrated the stepwise fate conversion from supporting cells to hair cells. Initially, supporting cell identity was erased and transition to the precursor state occurred. A subsequent gain in hair cell identity progressed together with downregulation of precursor-state genes. Transforming growth factor β receptor 1-mediated signaling was involved in induction of the initial step, and its inhibition resulted in suppression of hair cell regeneration. Our data provide new insights for understanding fate conversion from supporting cells to hair cells in avian basilar papillae.

Sensorineural hearing loss is a common disability often caused by the loss of sensory hair cells in the cochlea. Hair cell (HCs) regeneration has long been the main target for the development of novel therapeutics for sensorineural hearing loss. In the mammalian cochlea, hair cell regeneration is limited, but the auditory epithelia of non-mammalian organisms retain the capacity for hair cell regeneration. In the avian basilar papilla (BP), supporting cells (SCs), which give rise to regenerated hair cells, are usually quiescent. Hair cell loss induces both direct transdifferentiation and mitotic division of supporting cells. Here, we established an explant culture model for hair cell regeneration in chick basilar papillae and validated it for investigating the initial phase of hair cell regeneration. The histological assessment demonstrated hair cell regeneration via direct transdifferentiation of supporting cells. Labeling with 5-ethynyl-2′-deoxyuridine (EdU) revealed the occurrence of mitotic division in the supporting cells at specific locations in the basilar papillae, while no EdU labeling was observed in newly generated hair cells. RNA sequencing indicated alterations in known signaling pathways associated with hair cell regeneration, consistent with previous findings. Also, unbiased analyses of RNA sequencing data revealed novel genes and signaling pathways that may be related to the induction of supporting cell activation in the chick basilar papillae. These results indicate the advantages of our explant culture model of the chick basilar papillae for exploring the molecular mechanisms of hair cell regeneration.

Hearing loss has become one of the most common disabilities worldwide. The synaptic connections between inner hair cells (IHCs) and spiral ganglion neurons have specialized synaptic constructions, termed ribbon synapses, which are important for auditory function. The ribbon synapses in the cochlea are quite vulnerable to various insults. As such, the maintenance of ribbon synapses is important for ensuring hearing function. Insulin-like growth factor 1 (IGF1) plays a critical role in the development and maintenance of the cochlea and has the potential to protect cochlear hair cells from various insults. In this study, we examined the role of IGF1 in the maintenance of ribbon synapses in cochlear explants of postnatal day four mice. We cultured cochlear explants with an IGF1 receptor antagonist, JB1, which is an IGF1 peptide analog. Results showed that exposure to JB1 for 24 h resulted in the loss of ribbon synapses. After an additional 24-h culture without JB1, the number of ribbon synapses spontaneously recovered. The application of exogenous IGF1 showed two different aspects of ribbon synapses. Low doses of exogenous IGF1 promoted the recovery of ribbon synapses, while it compromised the spontaneous recovery of ribbon synapses at high doses. Altogether, these results indicate that the paracrine or autocrine release of IGF1 in the cochlea plays a crucial role in the maintenance of cochlear ribbon synapses.

Various tissues possess tissue-specific stem/progenitor cells, including the inner ears. Stem/progenitor cells of the inner ear can be isolated as so-called otospheres from differentiated cells using a sphere forming assay. Although recent studies have demonstrated the characteristics of otospheres to some extent, most of the features of these cells are unknown. In this report, we describe the findings of transcriptome analyses with a cDNA microarray of otospheres derived from the cochleae of the inner ears of neonatal mice in order to clarify the gene expression profile of otic stem/progenitor cells. There were common transcription factors between otospheres and embryonic stem cells, which were supposed to be due to the stemness of otospheres. In comparison with the cochlear sensory epithelium, the otospheres shared characteristics with the cochlea, although several transcription factors specific for otospheres were identified. These transcription factors are expected to be essential for maintaining the characteristics of otospheres, and appear to be candidate genes that promote the direct conversion of cells into otic stem/progenitor cells.

Inner ear mechanosensory hair cells transduce sound and balance information. Auditory hair cells emerge from a Sox2-positive sensory patch in the inner ear epithelium, which is progressively restricted during development. This restriction depends on the action of signaling molecules. Fibroblast growth factor (FGF) signalling is important during sensory specification: attenuation of Fgfr1 disrupts cochlear hair cell formation; however, the underlying mechanisms remain unknown. Here we report that in the absence of FGFR1 signaling, the expression of Sox2 within the sensory patch is not maintained. Despite the down-regulation of the prosensory domain markers, p27(Kip1), Hey2, and Hes5, progenitors can still exit the cell cycle to form the zone of non-proliferating cells (ZNPC), however the number of cells that form sensory cells is reduced. Analysis of a mutant Fgfr1 allele, unable to bind to the adaptor protein, Frs2/3, indicates that Sox2 maintenance can be regulated by MAP kinase. We suggest that FGF signaling, through the activation of MAP kinase, is necessary for the maintenance of sensory progenitors and commits precursors to sensory cell differentiation in the mammalian cochlea.

Shiga toxin (Stx)-producing Escherichia coli (STEC) causes serious gastrointestinal illness, including hemorrhagic colitis and hemolytic uremic syndrome. Two types of Stxs (Stx1 and Stx2) are known and both are encoded by bacteriophages (Stx phages), but the production of Stx2 is known to be a major risk factor for severe STEC infections. The production of Stx2, but not Stx1, is tightly coupled with the induction of Stx phages, and Stx2 production levels vary between STEC strains even within the same serotype. Here, we analyzed the genomic diversity of all Stx phages in 71 strains representing the entire O145:H28 lineage, one of the often highly pathogenic STECs, and the relationship between the variations in Stx phage genomes and the levels of Stx2 production by host strains. Our analysis reveals highly dynamic natures of Stx phages in O145:H28, including the independent acquisition of similar Stx phages by different sublineages, the recent transfer of Stx phage between different sublineages, and the frequent gain and loss of Stx phages in some sublineages. We also show the association of the Stx2 phage types with the Stx2 production levels of host strains: strains carrying short-tailed Stx2 phages exhibited significantly higher Stx2 production levels than those carrying long-tailed Stx2 phages. Detailed analyses of the Stx2 phage genomes revealed that both of short- and long-tailed phages exhibited sequence diversification and they were divided into two groups, respectively, based on the sequence similarity of the phage early region encoding genes responsible for phage induction, short-tailed phages contained early regions clearly different in genetic organization from those in long-tailed phages. Therefore, the variations in the early regions between short-and long-tailed Stx2 phages appeared to be linked to a striking difference in Stx2 production levels in their host strains. These results broaden our understanding of the diversification and dynamism of Stx phages in O145:H28 and the association of Stx2 phage types with the Stx2 production level in this STEC lineage.

Abstract Materials informatics in the development of organic light-emitting diode (OLED) related materials have been performed and exhibited the effectiveness for finding promising compounds with a desired property. However, the molecular structure optimization of the promising compounds through the conventional approach, namely the fine-tuning of molecules, still involves a significant amount of trial and error. This is because it is challenging to endow a single molecule with all the properties required for practical applications. The present work focused on fine-tuning triazine-based electron-transport materials using machine learning (ML) techniques. The prediction models based on localized datasets containing only triazine derivatives showed high prediction accuracy. The descriptors from density functional theory calculations enhanced the prediction of the glass transition temperature. The proposed multistep virtual screening approach extracted the promising triazine derivatives with the coexistence of higher electron mobility and glass transition temperature. Nine selected triazine compounds from 3,670,000 of the initial search space were synthesized and used as the electron transport layer for practical OLED devices. Their observed properties matched the predicted properties, and they enhanced the current efficiency and lifetime of the device. This paper provides a successful model for the ML assisted fine-tuning that effectively accelerates the development of practical materials.

Background: Stroke is a leading cause of severe disability in the United States, but there is no effective method for patients to accurately detect the signs of stroke at home. We developed a mobile app, Destroke, that allows remote performance of a modified NIH stroke scale (NIHSS) by patients. Aims: To assess the feasibility of a mobile app for stroke monitoring and education by patients with a history of stroke. Materials and methods: We enrolled 25 patients with a history of stroke in a prospective open-label study to evaluate the feasibility of the Destroke app in patients with stroke. Nineteen patients completed all study assessments, with a median time from stroke onset to enrollment of 5.6 years (range 0.1–12 years). We designed a modified NIHSS that assessed 12 out of 16 tasks on the NIHSS. Patients completed this test eight times over a 28-day period. We conducted pre-study surveys that assessed demographic information, stroke and cardiovascular history, baseline NIHSS, and experience using mobile technologies, and mid- and post-study surveys that assessed patient satisfaction on app usage and confidence in stroke detection. Results: Ten men and nine women participated in this study (median age of 64 (33–76)), representing ten US states and Washington D.C. Median baseline NIHSS was 0 (0–4). 15 patients reported using health apps. On a 5-point Likert scale, patients rated the app as 4.2 on being able to understand and use the app and 4.3 on using the app when instructed by their doctor. For eight patients with poor confidence in detecting the signs of a stroke before the study, six showed higher confidence after the study. Conclusions: The use of an at-home stroke monitoring app is feasible by patients with a history of stroke and improves confidence in detecting the signs of stroke.

Study Design A retrospective study of prospectively collected clinical data. Purpose To identify preoperative psychological factors associated with patient satisfaction after surgery for lumbar spinal stenosis (LSS). Overview of Literature Associations between depressive symptoms, anxiety, and worse surgical outcome or patient dissatisfaction have been reported in LSS patients. However, the influence of preoperative pain catastrophizing and fear-avoidance beliefs on postoperative satisfaction is not well understood. Methods LSS patients who underwent decompression surgery with or without fusion were included. Clinical outcomes were measured before surgery and 6 months postoperatively using the Zurich Claudication Questionnaire (ZCQ); Visual Analog Scale (VAS) of low back pain, leg pain, and leg numbness; Japanese Orthopaedic Association Back Pain Evaluation Questionnaire; and the Medical Outcomes Study 36-item Short-Form General Health Survey (SF-36). The Hospital Anxiety and Depression Scale (HADS), Pain Catastrophizing Scale, and Pain Anxiety Symptoms Scale were used to evaluate psychological status before surgery. Patients were classified as satisfied or dissatisfied with surgery based on a ZCQ satisfaction subscale cutoff score of 2.5. Results The satisfied and dissatisfied groups contained 128 and 29 patients, respectively. Six months postoperatively, outcome scores for the dissatisfied group were unchanged or worse than preoperative scores (p>0.05). Multivariate logistic regression analysis showed significant associations between dissatisfaction and preoperative low back pain VAS score ≥median (odds ratio [OR], 0.27; 95% confidence interval [CI], 0.10–0.74; p=0.01), preoperative mental health SF-36 score ≥median (OR, 0.26; 95% CI, 0.08–0.89; p=0.03), and preoperative anxiety HADS score ≥median (OR, 3.95; 95% CI, 1.16–13.46; p=0.03). Conclusions Preoperative less severe low back pain, lower mental health, and higher anxiety are associated with patient dissatisfaction with lumbar surgery, not depression, pain catastrophizing, or fear-avoidance beliefs. Pre- and postoperative psychological status should be assessed carefully and managed appropriately.

Abstract Signet-ring cell carcinoma (SRCC) is a unique subtype of gastric cancer that is impaired for cell–cell adhesion. The pathogenesis of SRCC remains unclear. Here, we show that expression of kinesin-associated protein 3 (KAP3), a cargo adaptor subunit of the kinesin superfamily protein 3 (KIF3), a motor protein, is specifically decreased in SRCC of the stomach. CRISPR/Cas9-mediated gene knockout experiments indicated that loss of KAP3 impairs the formation of circumferential actomyosin cables by inactivating RhoA, leading to the weakening of cell–cell adhesion. Furthermore, in KAP3 knockout cells, post-Golgi transport of laminin, a key component of the basement membrane, was inhibited, resulting in impaired basement membrane formation. Together, these findings uncover a potential role for KAP3 in the pathogenesis of SRCC of the stomach.

Abstract Background The COVID-19 pandemic and associated lockdown had a considerable impact on eating disorders (EDs). We evaluated the clinical features of Japanese ED patients before and after the first COVID-19 outbreak-related state of emergency (April 7, 2020). Methods We studied 148 patients who were divided into two groups based on when they arrived at our clinic: before (Before group: n = 86) or after (After group: n = 62) the start of the first state of emergency. All patients completed the Japanese versions of the Eating Disorder Inventory (EDI) and Parental Bonding Instrument (PBI). Results The After group was substantially younger than the Before group (p = .0187). Regardless of the ED type, patients who developed an ED during the first state of emergency tended to be significantly younger than those who developed one before. Differences in EDI characteristics were observed between the two groups. The PBI care subscale was notably higher (p = .0177) in the After group. The PBI maternal care subscale was the only statistically significant factor associated with age (β = -0.35, p < .0001). Conclusions Home confinement associated with the COVID-19 pandemic and the ensuing increase in parent-child closeness may have influenced the decreased age of ED patients at their initial consultation. Treatment interventions should consider the differences in the clinical features of EDs.

The proportional recovery rule (PRR) posits that most stroke survivors can expect to reduce a fixed proportion of their motor impairment. As a statistical model, the PRR explicitly relates change scores to baseline values – an approach that arises in many scientific domains but has the potential to introduce artifacts and flawed conclusions. We describe approaches that can assess associations between baseline and changes from baseline while avoiding artifacts due either to mathematical coupling or to regression to the mean. We also describe methods that can compare different biological models of recovery. Across several real datasets in stroke recovery, we find evidence for non-artifactual associations between baseline and change, and support for the PRR compared to alternative models. We also introduce a statistical perspective that can be used to assess future models. We conclude that the PRR remains a biologically relevant model of stroke recovery.

The mechanosensory hair cells of the inner ear are required for hearing and balance and have a distinctive apical structure, the hair bundle, that converts mechanical stimuli into electrical signals. This structure comprises a single cilium, the kinocilium, lying adjacent to an ensemble of actin-based projections known as stereocilia. Hair bundle polarity depends on kinociliary protocadherin-15 (Pcdh15) localization. Protocadherin-15 is found only in hair-cell kinocilia, and is not localized to the primary cilia of adjacent supporting cells. Thus, Pcdh15 must be specifically targeted and trafficked into the hair-cell kinocilium. Here we show that kinocilial Pcdh15 trafficking relies on cell type-specific coupling to the generic intraflagellar transport (IFT) transport mechanism. We uncover a role for fibroblast growth factor receptor 1 (FGFR1) in loading Pcdh15 onto kinociliary transport particles in hair cells. We find that on activation, FGFR1 binds and phosphorylates Pcdh15. Moreover, we find a previously uncharacterized role for clathrin in coupling this kinocilia-specific cargo with the anterograde IFT-B complex through the adaptor, DAB2. Our results identify a modified ciliary transport pathway used for Pcdh15 transport into the cilium of the inner ear hair cell and coordinated by FGFR1 activity. [ABSTRACT FROM AUTHOR]

Study Design Cross-sectional study. Purpose The purpose of this study was to investigate the effects of psychotic symptoms such as anxiety and fear in patients undergoing lumbar spinal canal stenosis. Overview of Literature Recently, patients with spinal disorders have not only been evaluated objectively for their disease, but also for patient-reported outcomes (PROs) including pain, physical function, and quality of life (PROs). Since depression has been previously associated with surgical outcomes, several studies have indicated that psychological problems may worsen the effects of pain and make treatment increasingly difficult. Methods A questionnaire survey was conducted on 346 lumbar spinal stenosis (LSS) patients who visited our hospital from 2010 to 2016. The content of the questionnaire included questions on PROs (Japanese Orthopedic Association Back Pain Evaluation Questionnaire [JOABPEQ], Roland–Morris Disability Questionnaire, Japanese version [RDQ], and Zurich Claudication Questionnaire [ZCQ]) and psychological evaluation (Self-rating Questionnaire of Depression, Pain Catastrophizing Scale, Pain Anxiety Symptoms Scale-20 [PASS-20], Hospital Anxiety and Depression Scale, and Brief Scale for Psychiatric Problems in Orthopedic Patients). IBM SPSS Statistics (IBM Corp., Armonk, NY, USA) was used for statistical analysis and Spearman’s rank correlation coefficient, Mann-Whitney U-test, and multiple regression analysis were also performed. Results No significant correlations were found between psychological factors and PROs (r>0.4). However, patients with abnormal scores for preoperative psychological items on questionnaires other than the PASS-20 also had lower scores for lumbar spine dysfunction and social life dysfunction on the JOABPEQ subscales along with higher scores for the RDQ, symptom severity and physical function on the ZCQ compared to those with normal psychological scores (p

Introduction: Sarcopenia, a condition characterized by decreased skeletal muscle mass, has increasingly been attracting attention in Japan, which has an aged society. The association between chronic low back pain (CLBP) and muscle mass is important. This study aimed to investigate the effect of exercise therapy for CLBP with or without sarcopenia. Methods: This study was a prospective cohort study. Patients who were aged >65 years during 2017-2018 and had CLBP, with pain lasting >12 weeks and pain intensity being 3, were included in the study. The patients were divided into two groups: sarcopenia (S) and nonsarcopenia (NS) groups. The numerical rating scale (NRS) for pain intensity, Roland-Morris Disability Questionnaire (RMDQ), Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ), Hospital Anxiety and Depression Scale (HADS), trunk muscle strength, a European Quality of Life instrument, and an NRS of treatment satisfaction were assessed. All patients underwent a high-intensity exercise therapy during 2 weeks of hospitalization and were followed up for 1 and 3 months. Results: Twenty-eight patients with CLBP were included. The prevalence rate of sarcopenia was 42.9%. The NRS and RMDQ scores and gait function were clinically improved at the end points in all patients with or without sarcopenia. Moreover, high treatment satisfaction was achieved. The quality of life, treatment satisfaction, psychological disorder subscale score of the JOABPEQ, and HADS score tended to be lower in the S group than in the NS group. Conclusions: Our short-term exercise therapy was effective for low back pain, disability, and gait disturbance in elderly patients with CLBP with or without sarcopenia. However, the prevalence of sarcopenia was high in elderly patients with CLBP. Although low back pain and disability in patients in the S group were improved by exercise therapy, their quality of life and treatment satisfaction might be lower than those of patients without sarcopenia.

Introduction: The aims of the present study were 1) to examine the association between neck and shoulder pain (NSP) and lifestyle in the general population and 2) to examine if sagittal spino-pelvic malalignment is more prevalent in NSP. Methods: A total of 107 volunteers (mean age, 64.5 years) were recruited in this study from listings of resident registrations in Kihoku region, Wakayama, Japan. Feeling pain or stiffness in the neck or shoulders was defined as an NSP. The items studied were: 1) the existence or lack of NSP and their severity (using VAS scale), 2) Short Form-36 (SF-36), 3) Self-Rating Questionnaire for Depression (SRQ-D), 4) Pain Catastrophizing Scale (PCS), 5) a detailed history consisting of 5 domains as being relevant to the psychosocial situation of patients with chronic pain, 6) A VAS of pain and numbness to the arm, and from thoracic region to legs. The radiographic parameters evaluated were also measured. Participants with a VAS score of 40 mm or higher and less were divided into 2 groups. Association of SF-36, SRQ-D, and PCS with NSP were assessed using multiple regression analysis. Results: In terms of QoL, psychological assessment and a detailed history, bodily pain in SF-36, SRQ-D, and family stress were significantly associated with NSP. A VAS of pain and numbness to the arm, and from thoracic region to legs, was significantly associated with NSP. There were no statistical correlations between the VAS and radiographic parameters of the cervical spine. Among the whole spine sagittal measurements, multiple logistic regression analysis showed that sacral slope (SS) and sagittal vertical axis (SVA) were significantly associated with NSP. Conclusion: In this study, we showed the factors associated with NSP. Large SS and reduced SVA were significantly associated with NSP, while cervical spine measurements were not.

Abstract Background A dural metastasis is one of the essential differential diagnoses of meningioma. In general, carcinomas of the breast and lung in females and prostate in males have been the most commonly reported primary lesions of dural metastases. However, dural metastasis of gallbladder carcinoma is extremely rare. Here, we report a unique case of a dural matter metastasis of gallbladder carcinoma as the first manifestation, which was autopsy-defined as small cell carcinoma. Case presentation A 78-year-old man came to our hospital complaining of left hemianopia. Brain computed tomography (CT) revealed a sizeable parasagittal dural-based extra-axial tumor. However, the findings for meningioma were atypical by magnetic resonance imaging, suggesting a meningioma mimic. A contrast-enhanced CT scan of the abdomen revealed a large gallbladder carcinoma. The patient opted for the best supportive care and died 2 months later. The post-mortem examination revealed small cell carcinoma in gallbladder carcinoma. Moreover, an immunologically similar carcinoma was detected in the dural metastasis. Conclusions To the best of our knowledge, this is the first case of a dural metastasis of gallbladder small cell carcinoma. A systemic examination is essential for clinicians when atypical findings of meningioma are observed, suggesting a meningioma mimic. We present this rare case with a review of the literature.

We investigate the magnetic-field effects on the Mott transition in the kagome lattice Hubbard model using the cellular dynamical mean-field theory combined with the continuous-time quantum Monte Carlo simulations. By calculating the magnetization and the momentum-resolved one-particle spectrum, we clarify that an applied magnetic field drives the first-order metal-insulator transition in a metallic phase around the zero-field Mott transition point. It is found that near the field-induced transition, the quasiparticle weight (effective mass) is increased (decreased) with increasing field, showing a sharp contrast to the results of the single-site dynamical mean-field study. The calculation of spin correlation functions elucidates that the nearest-neighbor antiferromagnetic correlations get enhanced with increasing field toward the transition point, indicating that the magnetic field stabilizes the insulating state with strong antiferromagnetic correlations. [ABSTRACT FROM AUTHOR]

Background and PurposeThe potential for adaptive plasticity in the post-stroke brain is difficult to estimate, as is the demonstration of central nervous system (CNS) target engagement of drugs that show promise in facilitating stroke recovery. We set out to determine if paired associative stimulation (PAS) can be used (a) as an assay of CNS plasticity in patients with chronic stroke, and (b) to demonstrate CNS engagement by memantine, a drug which has potential plasticity-modulating effects for use in motor recovery following stroke.MethodsWe examined the effect of PAS in fourteen participants with chronic hemiparetic stroke at five time-points in a within-subjects repeated measures design study: baseline off-drug, and following a week of orally administered memantine at doses of 5, 10, 15, and 20 mg, comprising a total of seventy sessions. Each week, MEP amplitude pre and post-PAS was assessed in the contralesional hemisphere as a marker of enhanced or diminished plasticity. Strength and dexterity were recorded each week to monitor motor-specific clinical status across the study period.ResultsWe found that MEP amplitude was significantly larger after PAS in baseline sessions off-drug, and responsiveness to PAS in these sessions was associated with increased clinical severity. There was no observed increase in MEP amplitude after PAS with memantine at any dose. Motor threshold (MT), strength, and dexterity remained unchanged during the study.ConclusionPaired associative stimulation successfully induced corticospinal excitability enhancement in chronic stroke subjects at the group level. However, this response did not occur in all participants, and was associated with increased clinical severity. This could be an important way to stratify patients for future PAS-drug studies. PAS was suppressed by memantine at all doses, regardless of responsiveness to PAS off-drug, indicating CNS engagement.

A novel extract powder purified from the boiled water of adzuki bean paste production was developed to better utilize this resource. The compounds contributing to pigmentation of purified adzuki bean extract powders were investigated in order to compare their antioxidant activity in vitro with (+)-catechin. When a normal extract was exposed to the air under heat treatment, the colour of adzuki bean extract became more strongly reddish, which was associated with polyphenol polymerization. Anthocyanins also contributed to the pigmentation of the purified adzuki bean extracts. Especially, two anthocyanin compounds, peonidin-3-rutinoside and malvidin-3-O-glucoside were newly identified in the adzuki bean extract. The reducing powder, iron chelating activity and free-radical scavenging capacity of the adzuki bean extract were greater than that of (+)-catechin while its total antioxidant value was lower. Thus, adzuki bean extract powders are promising alternatives to replace synthetic antioxidants and potential dyes.

Intracerebral hemorrhage (ICH), a form of brain bleeding and minor subtype of stroke, leads to significant mortality and long-term disability. There are currently no validated approaches to promote functional recovery after ICH. Research in stroke recovery and rehabilitation has largely focused on ischemic stroke, but given the stark differences in the pathophysiology between ischemic and hemorrhagic stroke, it is possible that strategies to rehabilitate the brain in distinct stroke subtypes will be different. Here, we review our current understanding of recovery after primary intracerebral hemorrhage with the intent to provide a framework to promote novel, stroke-subtype specific approaches.

BackgroundsSeveral domains of cognitive function, including learning memory and executive function, are impaired in mood disorders. Also, the relationship between disturbances of these two cognitive domains has been suggested. In line with the recent initiative to establish a standard measure of cognitive decline in bipolar disorder, the present study was conducted to (1) test the criterion-related validity and test–retest reliability of the California Verbal Learning Test (CVLT)-II Japanese version, and (2) determine if type of word learning tasks (i.e., with or without a category structure) affects severity of verbal memory deficits in patients with subsyndromal bipolar disorder.MethodsThirty-six patients with bipolar disorder with mild symptoms and 42 healthy volunteers participated in the study. We first compared effect sizes for memory deficits in patients among the CVLT-II, Brief Assessment of Cognition in Schizophrenia (BACS), and Hopkins Verbal Memory Tests-Revised (HVLT-R). We next evaluated the correlations between scores of the CVLT-II vs. those of the BACS and HVLT-R. Bipolar patients were re-assessed with the same (standard) or alternate forms of the CVLT-II and HVLT-R 1 month later.ResultsScores on the CVLT-II 1–5 Free Recall and Long-delay Free Recall, as well as the HVLT-R Immediate Recall, but not the BACS List Learning were significantly lower for patients compared to control subjects. The effect sizes for cognitive decline due to the illness were comparable when measured by the CVLT-II and HVLT-R, ranging from 0.5 to 0.6. CVLT-II scores were significantly correlated with those of the HVLT-R and BACS. Test–retest reliability of the CVLT-II was acceptable, and no significant practice effect was observed when the alternate form was used. There was no consistent relationship between mood symptoms and performance on the CVLT-II.ConclusionThese results suggest the CVLT-II Japanese version is able to discriminate between bipolar disorder patients and healthy controls with good sensitivity and validity. Data in this study also indicate that the degree of verbal memory deficits in bipolar disorder may be influenced by memory organizational strategy.

Backgrounds. Magnifying endoscopy with blue laser imaging (ME-BLI) for diagnosis of early gastric cancer (EGC) is as effective as magnifying endoscopy with narrow-band imaging (ME-NBI). However, there are different EGCs in microstructure visualization between ME-BLI and ME-NBI. This study aimed to clarify the pathological features of the EGCs, in which microstructure visualization was different between ME-NBI and ME-BLI. Methods. EGCs were classified into groups A (irregular microsurface pattern (MSP) in ME-BLI and absent MSP in ME-NBI), B (irregular MSP in two modalities), or C (absent MSP in two modalities), according to the vessel plus surface classification. We compared the pathological features of EGCs between the three groups. Results. 17, four, and five lesions could be evaluated in detail in groups A, B and C, respectively. Well-differentiated adenocarcinomas with shallow crypts were more frequent in group A than in group B (58.8 and 0%, resp.). The mean crypt depth of group A was significantly shallower than that of group B (56 ± 20, 265 ± 64 μm, resp., P=0.0002). Conclusions. ME-BLI could better visualize the microstructures of the EGCs with shallow crypts compared with ME-NBI. Therefore, ME-BLI could enable a more accurate diagnosis of EGC with shallow crypts.

Background and study aims: Linked color imaging (LCI) is a new image-enhanced endoscopy technique using a laser light source to enhance slight differences in mucosal color. The aim of this study was to compare the usefulness of LCI and conventional white light imaging (WLI) endoscopy for diagnosing Helicobacter pylori (H. pylori). Patients and methods: We retrospectively analyzed images from 60 patients examined with WLI and LCI endoscopy between October 2013 and May 2014. Thirty patients had H. pylori infections, and other thirty patients tested negative for H. pylori after eradication therapy. Four endoscopists evaluated the 2 types of images to determine which was better at facilitating a diagnosis of H. pylori infection. Results: H. pylori infection was identified with LCI by enhancing the red appearance of the fundic gland mucosa. The accuracy, sensitivity, and specificity for diagnosing H. pylori infection using WLI were 74.2 %, 81.7 %, and 66.7 %, respectively, while those for LCI were 85.8 %, 93.3 %, and 78.3 %, respectively. Thus, the accuracy and sensitivity for LCI were significantly higher than those for WLI (P = 0.002 and P = 0.011, respectively). The kappa values for the inter- and intraobserver variability among the 4 endoscopists were higher for LCI than for WLI. Conclusions: H. pylori infection can be identified by enhancing endoscopic images of the diffuse redness of the fundic gland using LCI. LCI is a novel image-enhanced endoscopy and is more useful for diagnosing H. pylori infection than is WLI.

Background/Aims. The aim of this study was to evaluate the endoscopic recognition of esophageal squamous cell carcinoma (ESCC) using four different methods (Olympus white light imaging (O-WLI), Fujifilm white light imaging (F-WLI), narrow band imaging (NBI), and blue laser imaging- (BLI-) bright). Methods. We retrospectively analyzed 25 superficial ESCCs that had been examined using the four different methods. Subjective evaluation was provided by three endoscopists as a ranking score (RS) of each image based on the ease of detection of the cancerous area. For the objective evaluation we calculated the color difference scores (CDS) between the cancerous and noncancerous areas with each of the four methods. Results. There was no difference between the mean RS of O-WLI and F-WLI. The mean RS of NBI was significantly higher than that of O-WLI and that of BLI-bright was significantly higher than that of F-WLI. Moreover, the mean RS of BLI-bright was significantly higher than that of NBI. Furthermore, in the objective evaluation, the mean CDS of BLI-bright was significantly higher than that of O-WLI, F-WLI, and NBI. Conclusion. The recognition of superficial ESCC using BLI-bright was more efficacious than the other methods tested both subjectively and objectively.

Protease-activated receptors (PARs) 1 and 2 are expressed in capsaicin-sensitive sensory neurons, being anti- and pro-nociceptive, respectively. Given the possible cross talk between PAR-2 and capsaicin receptors, we investigated if PAR-2 activation could facilitate capsaicin-evoked visceral pain and referred hyperalgesia in the mouse and also examined the effect of PAR-1 activation in this model. Intracolonic (i.col.) administration of capsaicin triggered visceral pain-related nociceptive behavior, followed by referred hyperalgesia. The capsaicin-evoked visceral nociception was suppressed by intraperitoneal (i.p.) TFLLR-NH2, a PAR-1-activating peptide, but not FTLLR-NH2, a control peptide, and unaffected by i.col. TFLLR-NH2. SLIGRL-NH2, a PAR-2-activating peptide, but not LRGILS-NH2, a control peptide, administered i.col., facilitated the capsaicin-evoked visceral nociception 6 – 18 h after administration, while i.p. SLIGRL-NH2 had no effect. The capsaicin-evoked referred hyperalgesia was augmented by i.col. SLIGRL-NH2, but not LRGILS-NH2, 6 – 18 h after administration, and unaffected by i.p. SLIGRL-NH2, and i.p. or i.col. TFLLR-NH2. Our data suggest that PAR-1 is antinociceptive in processing of visceral pain, whereas PAR-2 expressed in the colonic luminal surface, upon activation, produces delayed sensitization of capsaicin receptors, resulting in facilitation of visceral pain and referred hyperalgesia. Keywords:: protease-activated receptor, visceral pain, capsaicin, referred hyperalgesia