A Novel Hemostatic Peptide Solution for Common Acute Gastrointestinal Bleeding Diseases: First Case Series Study on the Treatment Results of Endoscopic Hemostasis by Nonexpert Endoscopists.

INTRODUCTION: We investigated the hemostatic effect and safety of a hemostatic peptide solution for the treatment of gastrointestinal bleeding requiring emergency endoscopy. METHODS: We retrospectively examined the patient backgrounds, hemostatic results, and procedural safety in patients who were treated with a hemostatic peptide solution for hemostasis during emergency endoscopies for gastrointestinal bleeding. All hemostatic procedures were performed by nonexpert physicians with less than 10 years of endoscopic experience. All of the cases were treated at a single institution over the months from January 2022 to January 2023. RESULTS: Twenty-six consecutive patients (17 males and 9 females) with a median age of 74 (45-95) years were included. Their conditions requiring emergency endoscopy were melena in 8 patients, hematochezia in 2, hematemesis in 8, anemia in 6, and bleeding during esophagogastroduodenoscopy in 2. The sites of bleeding were the esophagus in 3 patients, the stomach in 17, the duodenum in 3, the small intestine in 2, and the colon in 1. Hemostasis was obtained with another hemostasis device used in conjunction with the hemostatic peptide solution in 13 cases and with the hemostatic peptide solution alone in 13 cases. The hemostasis success rate was 100%, with no complications. Rebleeding occurred within 1 week in 4 cases. CONCLUSION: Hemostasis with the hemostatic peptide solution was safe and provided a temporary high hemostatic effect in emergency gastrointestinal endoscopy.

Bioinformatic Identification of Potential RNA Alterations on the Atrial Fibrillation Remodeling from Human Pulmonary Veins.

Atrial fibrillation (AF) is the most frequent persistent arrhythmia. Many genes have been reported as a genetic background for AF. However, most transcriptome analyses of AF are limited to the atrial samples and have not been evaluated by multiple cardiac regions. In this study, we analyzed the expression levels of protein-coding and long noncoding RNAs (lncRNAs) in six cardiac regions by RNA-seq. Samples were donated from six subjects with or without persistent AF for left atria, left atrial appendages, right atria, sinoatrial nodes, left ventricles, right ventricles, and pulmonary veins (PVs), and additional four right atrial appendages samples were collected from patients undergoing mitral valve replacement. In total, 23 AF samples were compared to 23 non-AF samples. Surprisingly, the most influenced heart region in gene expression by AF was the PV, not the atria. The ion channel-related gene set was significantly enriched upon analysis of these significant genes. In addition, some significant genes are cancer-related lncRNAs in PV in AF. A co-expression network analysis could detect the functional gene clusters. In particular, the cancer-related lncRNA, such as SAMMSON and FOXCUT, belong to the gene network with the cancer-related transcription factor FOXC1. Thus, they may also play an aggravating role in the pathogenesis of AF, similar to carcinogenesis. In the least, this study suggests that (1) RNA alteration is most intense in PVs and (2) post-transcriptional gene regulation by lncRNA may contribute to the progression of AF. Through the screening analysis across the six cardiac regions, the possibility that the PV region can play a role other than paroxysmal triggering in the pathogenesis of AF was demonstrated for the first time. Future research with an increase in the number of PV samples will lead to a novel understanding of the pathophysiology of AF.

Molecular Pathogenesis of Cardiac Arrhythmia.

The heart is a necessary organ for sustaining life in mammals, and it is the first organ to function during early development [...].

Comparative Study of Transcriptome in the Hearts Isolated from Mice, Rats, and Humans.

The heart is a significant organ in mammalian life, and the heartbeat mechanism has been an essential focus of science. However, few studies have focused on species differences. Accordingly, challenges remain in studying genes that have universal functions across species and genes that determine species differences. Here, we analyzed transcriptome data in mouse, rat, and human atria, ventricles, and sinoatrial nodes (SA) obtained from different platforms and compared them by calculating specificity measure (SPM) values in consideration of species differences. Among the three heart regions, the species differences in SA were the greatest, and we searched for genes that determined the essential characteristics of SA, which was SHOX2 in our criteria. The SPM value of SHOX2 was prominently high across species. Similarly, by calculating SPM values, we identified 3 atrial-specific, 11 ventricular-specific, and 17 SA-specific markers. Ontology analysis identified 70 cardiac region- and species-specific ontologies. These results suggest that reanalyzing existing data by calculating SPM values may identify novel tissue-specific genes and species-dependent gene expression. This study identified the importance of SHOX2 as an SA-specific transcription factor, a novel cardiac regional marker, and species-dependent ontologies.

Preferential Expression of Ca2+-Stimulable Adenylyl Cyclase III in the Supraventricular Area, including Arrhythmogenic Pulmonary Vein of the Rat Heart.

Ectopic excitability in pulmonary veins (PVs) is the major cause of atrial fibrillation. We previously reported that the inositol trisphosphate receptor in rat PV cardiomyocytes cooperates with the Na+-Ca2+ exchanger to provoke ectopic automaticity in response to norepinephrine. Here, we focused on adenylyl cyclase (AC) as another effector of norepinephrine stimulation. RT-PCR, immunohistochemistry, and Western blotting revealed that the abundant expression of Ca2+-stimulable AC3 was restricted to the supraventricular area, including the PVs. All the other AC isotypes hardly displayed any region-specific expressions. Immunostaining of isolated cardiomyocytes showed an enriched expression of AC3 along the t-tubules in PV myocytes. The cAMP-dependent response of L-type Ca2+ currents in the PV and LA cells is strengthened by the 0.1 mM intracellular Ca2+ condition, unlike in the ventricular cells. The norepinephrine-induced automaticity of PV cardiomyocytes was reversibly suppressed by 100 µM SQ22536, an adenine-like AC inhibitor. These findings suggest that the specific expression of AC3 along t-tubules may contribute to arrhythmogenic automaticity in rat PV cardiomyocytes.

E44Q mutation in NaV1.7 in a patient with infantile paroxysmal knee pain: electrophysiological analysis of voltage-dependent sodium current.

Gain-of-function mutations in voltage-gated sodium channels (NaV1.7, NaV1.8, and NaV1.9) are known causes of inherited pain disorders. Identification and functional assessment of new NaV1.7 mutations could help elucidate the phenotypic spectrum of NaV1.7 channelopathies. We identified a novel NaV1.7 mutation (E44Q in exon 2) that substitutes a glutamic acid residue for glutamine in the cytoplasmic N-terminus of NaV1.7 in a patient with paroxysmal pain attacks during childhood and his family who experienced similar pain episodes. To study the sodium channel's function, we performed electrophysiological recordings. Voltage-clamp recordings revealed that the mutation increased the amplitude of the non-inactivating component of the sodium current, which might facilitate channel opening. These data demonstrate that E44Q is a gain-of-function mutation in NaV1.7, which is consistent with our patient's pain phenotype.

Small-volume vitrification and rapid warming yield high survivals of one-cell rat embryos in cryotubes†.

To cryopreserve cells, it is essential to avoid intracellular ice formation during cooling and warming. One way to achieve this is to convert the water inside the cells into a non-crystalline glass. It is currently believed that to accomplish this vitrification, the cells must be suspended in a very high concentration (20-40%) of a glass-inducing solute, and subsequently cooled very rapidly. Herein, we report that this belief is erroneous with respect to the vitrification of one-cell rat embryos. In the present study, one-cell rat embryos were vitrified with 5 µL of EFS10 (a mixture of 10% ethylene glycol (EG), 27% Ficoll, and 0.45 M sucrose) in cryotubes at a moderate cooling rate, and warmed at various rates. Survival was assessed according to the ability of the cells to develop into blastocysts and to develop to term. When embryos were vitrified at a 2613 °C/min cooling rate and thawed by adding 1 mL of sucrose solution (0.3 M, 50 °C) at a warming rate of 18 467 °C/min, 58.1 ± 3.5% of the EFS10-vitrified embryos developed into blastocysts, and 50.0 ± 4.7% developed to term. These rates were similar to those of non-treated intact embryos. Using a conventional cryotube, we achieved developmental capabilities in one-cell rat embryos by rapid warming that were comparable to those of intact embryos, even using low concentrations (10%) of cell-permeating cryoprotectant and at low cooling rates.

Azelnidipine treatment reduces the expression of Cav1.2 protein.

AIMS: Azelnidipine, a third-generation dihydropyridine calcium channel blocker (DHP CCB), has a characteristic hypotensive effect that persists even after it has disappeared from the plasma, which is thought to be due to its high hydrophobicity. However, because azelnidipine is unique, it might have other unknown effects on L-type Cav1.2 channels that result in the long-lasting decrease of blood pressure. The aim of this study was to investigate the potential quantitative modification of Cav1.2 by azelnidipine. MAIN METHODS: HEK293 cells were used to express Cav1.2 channels. Immunocytochemical analysis was performed to detect changes in the surface expression of the pore-forming subunit of the Cav1.2 channel, Cav1.2α1c. Western blotting analysis was performed to evaluate changes in expression levels of total Cav1.2α1c and Cavß2c. KEY FINDINGS: The surface expression of Cav1.2α1c was markedly reduced by treatment with azelnidipine, but not with other DHP CCBs (amlodipine and nicardipine). Results obtained with a dynamin inhibitor and an early endosome marker suggested that the reduction of surface Cav1.2α1c was not likely caused by internalization. Azelnidipine reduced the total amount of Cav1.2α1c protein in HEK293 cells and rat pulmonary artery smooth muscle cells. The reduction of Cav1.2α1c was rescued by inhibiting proteasome activity. In contrast, azelnidipine did not affect the amount of auxiliary Cavß2c subunits that function as a chaperone of Cav1.2. SIGNIFICANCE: This study is the first to demonstrate that azelnidipine reduces the expression of Cav1.2α1c, which might partly explain its long-lasting hypotensive effect.

Comparative study of hyperpolarization-activated currents in pulmonary vein cardiomyocytes isolated from rat, guinea pig, and rabbit.

Pulmonary vein (PV) cardiomyocytes have the potential to generate spontaneous activity, in contrast to working myocytes of atria. Different electrophysiological properties underlie the potential automaticity of PV cardiomyocytes, one being the hyperpolarization-activated inward current (Ih), which facilitates the slow diastolic depolarization. In the present study, we examined pharmacological characteristics of the Ih of PV cardiomyocytes in rat, guinea pig and rabbit. The results showed that guinea pig and rat PV cardiomyocytes possessed sizeable amplitudes of the Ih, and the Ih of guinea pig was suppressed by Cs+, a blocker of the hyperpolarization-activated cation current. However, the Ih of rat was not suppressed by Cs+, but by Cd2+, a blocker of the Cl- current. The current density of the Ih of rabbit PV cardiomyocytes was significantly smaller than those of other species. This suggests that the ion channels that carry the Ih of PV cardiomyocytes differ among the animal species.

Utility of autologous fibrin glue and polyglycolic acid sheet for preventing delayed bleeding associated with antithrombotic therapy after gastric ESD.

Background and study aims Delayed bleeding is one of the most serious adverse events of gastric endoscopic submucosal dissection (ESD), especially in patients taking antithrombotic therapy. This study aimed to evaluate the utility and safety of a shielding method with autologous fibrin glue and polyglycolic acid (PGA) sheets for patients undergoing gastric ESD who are receiving antithrombotic therapy. Patients and methods One hundred twenty-three patients who were treated with gastric ESD while receiving antithrombotic therapy between December 2014 and September 2017 were enrolled in this study. Patients who received the shielding method were classified into the shielding group. Others were classified into the conventional group. Various clinico-pathological factors were retrospectively compared between the two groups. Results The shielding group consisted of 38 patients, and the conventional group consisted of the remaining 85 patients. In the shielding group, the rate of continuation of antithrombotic therapy was significantly higher (68.4 % vs 41.2 %). Incidence of delayed bleeding was lower in the shielding group (2.6 %, 1/38) than in the conventional group (14.1 %, 12/85). In the propensity score-adjusted logistic regression analysis, the delayed bleeding rate in the shielding group tended to be lower than in the conventional group ( P  = 0.070). Allogeneic transfusion was performed in eight patients (8/85, 9.4 %) in the conventional group and none in the shielding group ( P  = 0.047). No adverse event associated with endoscopic shielding were observed in the shielding group. Conclusions This study suggests that a shielding method with autologous fibrin glue and PGA sheet effectively prevents delayed bleeding after gastric ESD in patients receiving antithrombotic therapy.

Molecular identification of HSPA8 as an accessory protein of a hyperpolarization-activated chloride channel from rat pulmonary vein cardiomyocytes.

Pulmonary veins (PVs) are the major origin of atrial fibrillation. Recently, we recorded hyperpolarization-activated Cl- current (ICl, h) in rat PV cardiomyocytes. Unlike the well-known chloride channel protein 2 (CLCN2) current, the activation curve of ICl, h was hyperpolarized as the Cl- ion concentration ([Cl-] i ) increased. This current could account for spontaneous activity in PV cardiomyocytes linked to atrial fibrillation. In this study, we aimed to identify the channel underlying ICl, h Using RT-PCR amplification specific for Clcn2 or its homologs, a chloride channel was cloned from rat PV and detected in rat PV cardiomyocytes using immunocytochemistry. The gene sequence and electrophysiological functions of the protein were identical to those previously reported for Clcn2, with protein activity observed as a hyperpolarization-activated current by the patch-clamp method. However, the [Cl-] i dependence of activation was entirely different from the observed ICl, h of PV cardiomyocytes; the activation curve of the Clcn2-transfected cells shifted toward positive potential with increased [Cl-] i , whereas the ICl, h of PV and left ventricular cardiomyocytes showed a leftward shift. Therefore, we used MS to explore the possibility of additional proteins interacting with CLCN2 and identified an individual 71-kDa protein, HSPA8, that was strongly expressed in rat PV cardiomyocytes. With co-expression of HSPA8 in HEK293 and PC12 cells, the CLCN2 current showed voltage-dependent activation and shifted to negative potential with increasing [Cl-] i Molecular docking simulations further support an interaction between CLCN2 and HSPA8. These findings suggest that CLCN2 in rat heart contains HSPA8 as a unique accessory protein.

Mechanisms Underlying Spontaneous Action Potential Generation Induced by Catecholamine in Pulmonary Vein Cardiomyocytes: A Simulation Study.

Cardiomyocytes and myocardial sleeves dissociated from pulmonary veins (PVs) potentially generate ectopic automaticity in response to noradrenaline (NA), and thereby trigger atrial fibrillation. We developed a mathematical model of rat PV cardiomyocytes (PVC) based on experimental data that incorporates the microscopic framework of the local control theory of Ca2+ release from the sarcoplasmic reticulum (SR), which can generate rhythmic Ca2+ release (limit cycle revealed by the bifurcation analysis) when total Ca2+ within the cell increased. Ca2+ overload in SR increased resting Ca2+ efflux through the type II inositol 1,4,5-trisphosphate (IP3) receptors (InsP3R) as well as ryanodine receptors (RyRs), which finally triggered massive Ca2+ release through activation of RyRs via local Ca2+ accumulation in the vicinity of RyRs. The new PVC model exhibited a resting potential of -68 mV. Under NA effects, repetitive Ca2+ release from SR triggered spontaneous action potentials (APs) by evoking transient depolarizations (TDs) through Na+/Ca2+ exchanger (APTDs). Marked and variable latencies initiating APTDs could be explained by the time courses of the α1- and ß1-adrenergic influence on the regulation of intracellular Ca2+ content and random occurrences of spontaneous TD activating the first APTD. Positive and negative feedback relations were clarified under APTD generation.

Comparison of 3D endoscopy and conventional 2D endoscopy in gastric endoscopic submucosal dissection: an ex vivo animal study.

BACKGROUND AND OBJECTIVES: Conventional endoscopy provides two-dimensional (2D) information without depth information. This study compared three-dimensional (3D) endoscopy and 2D endoscopy using an endoscopic submucosal dissection (ESD) training model to evaluate the utility of 3D endoscopy. METHODS: Porcine stomach specimens (7 × 7 cm) were prepared from commercially available resected porcine stomachs and a 10-mm hypothetical lesion was marked at the center of each specimen. Specimens were individually placed in an ESD training model, and subjected to either 2D or 3D ESD. En bloc resection rate, perforation rate, incision time, dissection time, and levels of five eyestrain symptoms (fatigue, pain, blurred vision, head-heaviness, and headache; 100-mm visual analog scale) were compared between the 2D and 3D procedures. In a crossover design, 8 endoscopists each performed two 2D and two 3D procedures. RESULTS: All 32 lesions were resected en block, but perforation occurred in one 2D procedure. Incision time was significantly shorter in 3D ESD than in 2D ESD (102.8 ± 42.1 s vs. 135.8 ± 65.7 s, p < 0.05). Dissection time was also significantly shorter in 3D ESD than in 2D ESD (366.3 ± 187.6 s vs. 517.8 ± 282.3 s, p < 0.05). Differences in levels of all symptoms except blurred vision between before and after ESD were larger in 3D ESD than in 2D ESD. CONCLUSIONS: Incision time and dissection time were significantly shorter in 3D ESD compared with 2D ESD, but eyestrain was increased. Depth information from 3D images appears to facilitate rapid and stable ESD maneuvers.

Operational effectiveness of three-dimensional flexible endoscopy: an ex vivo study using a new model.

BACKGROUND AND OBJECTIVES: Two-dimensional (2D) images lack depth information and thus provide probabilistic recognition that do not completely match the actual three-dimensional (3D) information. Here, we investigated the operability of 3D endoscopes. METHODS: A 3D operation model was developed by passing 20 silk threads through upper and lower plates at 2-mm intervals in front and back rows separated by 1 mm. We evaluated accuracy and time of operating an electrosurgical knife. A successful operation was defined as pulling only a front-row thread; an unsuccessful operation was defined as pulling no thread (miss) or simultaneously pulling front- and back-row threads. Endoscopists (four experts, six trainees) repeated the operation under 2D and 3D conditions until individually accumulating 10 successful attempts under each condition. RESULTS: Operation accuracy was significantly higher for 3D compared with 2D in all endoscopists (88.5% vs. 61.3%; p < 0.01) and in both experience groups (trainees: 84.5% vs. 61.2%; experts: 95.2% vs. 61.5%; both p < 0.01). Operation time was significantly shorter for 3D compared with 2D in all endoscopists (12.5 ± 4.1 s vs. 14.8 ± 4.7 s; p < 0.01) and in both experience groups (trainees: 12.8 ± 4.2 s vs. 15.2 ± 4.9 s; experts: 12.1 ± 4.0 s vs. 14.3 ± 4.3 s; both p < 0.01). DISCUSSION: Compared with 2D endoscopy, 3D endoscopy significantly improved operation accuracy and shortened operation time, suggesting that 3D endoscopy enables accurate operation by depth information, aiding spatial recognition.

ERK5 Phosphorylates Kv4.2 and Inhibits Inactivation of the A-Type Current in PC12 Cells.

Extracellular signal-regulated kinase 5 (ERK5) regulates diverse physiological responses such as proliferation, differentiation, and gene expression. Previously, we demonstrated that ERK5 is essential for neurite outgrowth and catecholamine biosynthesis in PC12 cells and sympathetic neurons. However, it remains unclear how ERK5 regulates the activity of ion channels, which are important for membrane excitability. Thus, we examined the effect of ERK5 on the ion channel activity in the PC12 cells that overexpress both ERK5 and the constitutively active MEK5 mutant. The gene and protein expression levels of voltage-dependent Ca2+ and K⁺ channels were determined by RT-qPCR or Western blotting. The A-type K⁺ current was recorded using the whole-cell patch clamp method. In these ERK5-activated cells, the gene expression levels of voltage-dependent L- and P/Q-type Ca2+ channels did not alter, but the N-type Ca2+ channel was slightly reduced. In contrast, those of Kv4.2 and Kv4.3, which are components of the A-type current, were significantly enhanced. Unexpectedly, the protein levels of Kv4.2 were not elevated by ERK5 activation, but the phosphorylation levels were increased by ERK5 activation. By electrophysiological analysis, the inactivation time constant of the A-type current was prolonged by ERK5 activation, without changes in the peak current. Taken together, ERK5 inhibits an inactivation of the A-type current by phosphorylation of Kv4.2, which may contribute to the neuronal differentiation process.

Mammalian γ2 AMPK regulates intrinsic heart rate.

AMPK is a conserved serine/threonine kinase whose activity maintains cellular energy homeostasis. Eukaryotic AMPK exists as αßγ complexes, whose regulatory γ subunit confers energy sensor function by binding adenine nucleotides. Humans bearing activating mutations in the γ2 subunit exhibit a phenotype including unexplained slowing of heart rate (bradycardia). Here, we show that γ2 AMPK activation downregulates fundamental sinoatrial cell pacemaker mechanisms to lower heart rate, including sarcolemmal hyperpolarization-activated current (I f) and ryanodine receptor-derived diastolic local subsarcolemmal Ca2+ release. In contrast, loss of γ2 AMPK induces a reciprocal phenotype of increased heart rate, and prevents the adaptive intrinsic bradycardia of endurance training. Our results reveal that in mammals, for which heart rate is a key determinant of cardiac energy demand, AMPK functions in an organ-specific manner to maintain cardiac energy homeostasis and determines cardiac physiological adaptation to exercise by modulating intrinsic sinoatrial cell behavior.

Deterioration of autonomic neuronal receptor signaling and mechanisms intrinsic to heart pacemaker cells contribute to age-associated alterations in heart rate variability in vivo.

We aimed to determine how age-associated changes in mechanisms extrinsic and intrinsic to pacemaker cells relate to basal beating interval variability (BIV) reduction in vivo. Beating intervals (BIs) were measured in aged (23-25 months) and adult (3-4 months) C57BL/6 male mice (i) via ECG in vivo during light anesthesia in the basal state, or in the presence of 0.5 mg mL(-1) atropine + 1 mg mL(-1) propranolol (in vivo intrinsic conditions), and (ii) via a surface electrogram, in intact isolated pacemaker tissue. BIV was quantified in both time and frequency domains using linear and nonlinear indices. Although the average basal BI did not significantly change with age under intrinsic conditions in vivo and in the intact isolated pacemaker tissue, the average BI was prolonged in advanced age. In vivo basal BIV indices were found to be reduced with age, but this reduction diminished in the intrinsic state. However, in pacemaker tissue BIV indices increased in advanced age vs. adults. In the isolated pacemaker tissue, the sensitivity of the average BI and BIV in response to autonomic receptor stimulation or activation of mechanisms intrinsic to pacemaker cells by broad-spectrum phosphodiesterase inhibition declined in advanced age. Thus, changes in mechanisms intrinsic to pacemaker cells increase the average BIs and BIV in the mice of advanced age. Autonomic neural input to pacemaker tissue compensates for failure of molecular intrinsic mechanisms to preserve average BI. But this compensation reduces the BIV due to both the imbalance of autonomic neural input to the pacemaker cells and altered pacemaker cell responses to neural input.

Effects of light wavelength on MEG ERD/ERS during a working memory task.

We investigated the effects of light wavelengths on cortical oscillatory activity associated with working memory processes. Cortical activity responses were measured using magnetoencephalography (MEG) while participants performed an auditory Sternberg memory task during exposure to light of different wavelength. Each trial of the memory task consisted of four words presented as a memory set and one word presented as a probe. All words were presented audibly. Participants were instructed to indicate whether the probe word was or was not presented within the memory set. A total of 90 trials were conducted under the light exposure. Event-related synchronization (ERS) and event-related desynchronization responses in the alpha frequency range during the task were analyzed. Results showed that, during memory encoding, ERS responses were significantly greater in the short-wavelength (blue) light condition than in the middle-wavelength (green) light condition, approximately 20-30min after the onset of light exposure. Behavioral performance was very high throughout the experiment and there was no difference between the light conditions. Although the light effects were not observed in behavior, the result of ERS suggests that 20-30min of exposure to blue light enhances cortical activity related to active memory maintenance and/or attention to auditory stimuli.

Effect of skip lymphovascular invasion on hepatic metastasis in colorectal carcinomas.

BACKGROUND: "Skip" lymphovascular invasion presenting as discontinuous foci of tumor cells within the colon wall is now excluded from consideration when determining T stage in the TNM classification. The purpose of this study was to assess the clinicopathological characteristics of colorectal cancer (CRC) patients with such skip lymphovascular invasion. METHODS: First, a retrospective questionnaire survey of the incidence of skip lymphovascular invasion was performed for a total of 1,868 patients with CRCs at ten institutions. Next, we comparatively assessed clinicopathological data for 896 CRC patients with or without skip lymphovascular invasion. RESULTS: The incidence of skip lymphovascular invasion was 1.1 % (20 out of 1,868). Most of the affected cases were rectal, pT2, and node negative, with moderately differentiated histology. Skip lymphovascular invasion was present in the muscularis propria and subserosa, with the tumors directly invading submucosa (pT1) or muscularis propria (pT2). Hepatic metastasis was greater in CRC with skip lymphovascular invasion (25 %) than in pT1/2 CRC (0 %; P < 0.001) or pT3 CRC without such invasion (13.8 %; P = 0.185). CONCLUSIONS: Our study suggests that skip lymphovascular invasion is associated with hepatic metastasis in CRC cases. Thus, definition of a T category including such invasion would be useful for clinical practice.

Effects of daytime light exposure on cognitive brain activity as measured by the ERP P300.

Exposure to light modulates not only human alertness but also cognitive functions. The present study examined the temporal dynamics of the effects of light exposure on cortical activity related to cognitive processes. Event-related potentials (ERPs) were measured while participants performed an auditory oddball task during exposure to short-, medium- or long-wavelength light or darkness. Experiments were conducted in the daytime. After a 10-min period of darkness, one of the three lights was presented for 28 min. In the control condition, darkness was maintained for the entire session. The ERP component observed approximately 300 ms after the onset of the target stimulus (P300) was analyzed. The amplitude of P300 was larger after 5-20 min of exposure to short-wavelength light than at equivalent time points in the darkness. No differences were observed in the amplitude of P300 between the medium- or long-wavelength light condition and darkness at any time point. These results suggest that the amount of attentional resource allocated to the oddball task was increased by daytime exposure to short-wavelength light, and that following approximately 5 min of exposure the impact of light on cortical activity related to cognitive processes was able to be detected.