Adherence and Effectiveness of MoviPrepⓇ in Bowel Preparation for Colonoscopy: A Multicenter Study from the Hiroshima GI Endoscopy Research Group.

Objectives: Bowel preparation is burdensome because of long cleansing times and large dose volumes of conventional polyethylene glycol (PEG) lavage solution NiflecⓇ (Nif). MoviPrep (Mov)Ⓡ is a hyperosmolar preparation of PEG, electrolytes, and ascorbic acid; despite the smaller dose volume of 2 L, it can be challenging for many patients. We examined a more effective and acceptable bowel preparation method without compromising cleanliness and effectiveness, combining low-residue diet and laxative (Modified Brown Method) in Mov administered 1 day pre-colonoscopy. Methods: This multicenter, randomized, open-label, parallel-group comparative study, conducted at Hiroshima University Hospital and 7 affiliated hospitals in May 2015-March 2016, evaluated adherence to and effectiveness of Mov in bowel preparation. Participants (n=380) were allocated to receive 1 of 3 pre-colonoscopy regimens: Nif+Modified Brown Method (Group A), Mov+Modified Brown Method (Group B), or Mov+Laxative (Group C). Results: Total intake volume showed no significant difference among the groups. Bowel preparation time was significantly shorter in Group B (112.4±44.8 min, n=118) than in Groups A (131.3±59 min, n=105) and C (122.6±48.1 min, n=115). Sleep disturbance (37%) was significantly higher in Group B than Group A; distension (11%) was significantly lower in Group C than in Groups A and B (p<0.05, respectively). No severe adverse events occurred in any group. Conclusions: Mov+Modified Brown method provided significantly shorter bowel preparation time, with no significant difference in total intake volume among the regimens. Mov+Laxative yielded significantly less distension than the other groups, with bowel preparation equivalent to that of the Nif+Modified Brown method.

Discrimination is not impaired when more cortical space between two electro-tactile markers increases perceived duration.

The purpose of the present study was to examine how duration processing is affected by space between two electro-tactile stimuli marking inter-stimulus time intervals. The results of two experiments, where the method of constant stimuli was used, indicated that discrimination remained at the same level when delivering two markers to different fingers (of the same hand) resulted in longer perceived duration than delivering them to the same finger. Indeed, in Experiment 1, intervals were overestimated while discrimination remained at the same level when the leading and tailing markers were delivered to the index and ring fingers, respectively, compared with when both markers were delivered to the index finger. In Experiment 2, while there were individual differences in spatial effect on perceived duration when the leading and tailing markers were delivered to the middle and little fingers, respectively, discrimination remained at the same level even with participants overestimating intervals. This indicates that variability in duration processing is constant within the same cortical hemisphere when more space between two stimuli marking time results in longer perceived duration.

H-DBAS: alternative splicing database of completely sequenced and manually annotated full-length cDNAs based on H-Invitational.

The Human-transcriptome DataBase for Alternative Splicing (H-DBAS) is a specialized database of alternatively spliced human transcripts. In this database, each of the alternative splicing (AS) variants corresponds to a completely sequenced and carefully annotated human full-length cDNA, one of those collected for the H-Invitational human-transcriptome annotation meeting. H-DBAS contains 38,664 representative alternative splicing variants (RASVs) in 11,744 loci, in total. The data is retrievable by various features of AS, which were annotated according to manual annotations, such as by patterns of ASs, consequently invoked alternations in the encoded amino acids and affected protein motifs, GO terms, predicted subcellular localization signals and transmembrane domains. The database also records recently identified very complex patterns of AS, in which two distinct genes seemed to be bridged, nested or degenerated (multiple CDS): in all three cases, completely unrelated proteins are encoded by a single locus. By using AS Viewer, each AS event can be analyzed in the context of full-length cDNAs, enabling the user's empirical understanding of the relation between AS event and the consequent alternations in the encoded amino acid sequences together with various kinds of affected protein motifs. H-DBAS is accessible at http://jbirc.jbic.or.jp/h-dbas/.

Neural correlates of tactile simultaneity judgement: a functional magnetic resonance imaging study.

Simultaneity judgement (SJ) is a temporal discrimination task in which the targets span an ultimately short time range (zero or not). Psychophysical studies suggest that SJ is adequate to probe the perceptual components of human time processing in pure form. Thus far, time-relevant neural correlates for tactile SJ are unclear. We performed functional magnetic resonance imaging (fMRI) to investigate the neural correlates of tactile SJ using tactile number judgement as a time-irrelevant control task. As our main result, we demonstrated that the right inferior parietal lobule (IPL) is an SJ-specific region. The right IPL was detected by both parametric and non-parametric statistical analyses, and its activation intensity fulfilled a strict statistical criterion. In addition, we observed that some left-dominant regions (e.g., the striatum) were specifically activated by successive stimuli during SJ. Meanwhile, no region was specifically activated by simultaneous stimuli during SJ. Accordingly, we infer that the neural process for tactile SJ is as follows: the striatum estimates the time interval between tactile stimuli; based on this interval, the right IPL discriminates the successiveness or simultaneity of the stimuli. Moreover, taking detailed behavioural results into account, we further discuss possible concurrent or alternative mechanisms that can explain the fMRI results.

Presence of poorly differentiated component correlated with submucosal invasion in the early diffuse-type gastric cancer.

BACKGROUND/AIMS: Diffuse-type gastric carcinoma is associated with a poor prognosis. However, the clinical behavior of diffuse-type gastric cancer is not fully understood. The aim of this study is to distinguish the behaviors of early diffuse-type gastric carcinomas by sub classifying tumors according to their histologic features. METHODOLOGY: A total of 114 cases of diffuse-type early gastric cancer were studied retrospectively. We analyzed and compared the resected cancer specimens according to the histologic components: as poorly differentiated adenocarcinoma component-present (poor+) versus poorly differentiated adenocarcinoma component-absent (poor-). Helicobacter pylori status was evaluated by Giemsa staining and IgG serology. We assessed the degree of cancer invasion and compared background status of gastritis in accordance with the updated Sydney System criteria and serologic markers. RESULTS: In comparison to the poor+ cancers, the poor- cancers had a significantly larger portion of cells confined to the mucosa (p=0.002). Only 8 of the 114 cases were regarded as H. pylori-negative. Although we could not detect any serologic markers specific for gastritis with poor+ cancer, but the serum levels of gastrin was slightly higher in patients with poor+ cancers than in those with poor- cancers. CONCLUSIONS: The biologic behavior of poor+ gastric carcinoma is worse than that of poor- carcinoma. There is a close relation between H. pylori infection and carcinogenesis of poorly differentiated adenocarcinoma.

Multiple Looks of Auditory Empty Durations Both Improve and Impair Temporal Sensitivity.

Discrimination of two neighboring empty durations that are marked by three successive sounds is improved when the presentation of the first (standard, S) duration is repeated before that of the second (comparison, C), as SSSSC. This improvement in sensitivity, called the multiple-look effect, has been explained by a statistical model regarding variability. This model assumes that the perceived duration of the standard is averaged across observations (within a trial within an individual). The increasing of the number of observations thus reduces the standard error of the mean perceived duration. Alternatively, the multiple-look effect is attributed to the listener's prediction based on regular rhythm. Listeners perceive regular rhythm during the repetition of the standard, predict the timing of subsequent sounds, and detect a sound that is displaced from the predicted timing. These models were tested in the present experiment in which the main factor was a temporal separation between the standard and the comparison; i.e., these durations were adjacent to each other as SSSSC or separated by a temporal blank as SSSS_C. The results differed between stimulus structures. First, the multiple-look effect was replicated in the SSSSC condition (yielding a higher performance than SC), but disappeared in SSSS_C (having no difference with S_C). Second, no multiple-look effect occurred in CSSSS (no difference with CS), and moreover, an impairment effect was observed in C_SSSS (a lower performance than C_S). Finally, discrimination was improved in SSSS_CCCC compared with SSSSCCCC, the effect being kept even when sounds were aligned at irregular intervals. These findings are not consistent with those expected from the statistical model because the temporal separation should have produced no effects if the number of standards had been a sole parameter determining the multiple-look effect. The prediction-based model can explain the first finding; inserting a blank between the standard and the comparison violates the listener's prediction based on regular rhythm, thus reducing the multiple-look effect. However, it did not expect the other findings and required revisions. Notably, the second finding indicates that the formation of regular rhythm can impair temporal discrimination. In other words, an inversed multiple-look effect occurs.

[Dynamic Attending Binds Time and Rhythm Perception].

Relations between time and rhythm perception are discussed in this review of psychophysical research relevant to the multiple-look effect and dynamic-attending theory. Discrimination of two neighboring intervals that are marked by three successive sounds is improved when the presentation of the first (standard, S) interval is repeated before that of the second (comparison, C), as SSSSC. This improvement in sensitivity, called the multiple-look effect, occurs because listeners (1) perceive regular rhythm during the repetition of the standard interval, (2) predict the timing of subsequent sounds, and (3) detect sounds that are deviated from the predicted timing. The dynamic-attending theory attributes such predictions to the entrainment of attentional rhythms. An endogenous attentional rhythm is synchronized with the periodic succession of sounds marking the repeated standard. The standard and the comparison are discriminated on the basis of whether the ending marker of the comparison appears at the peak of the entrained attentional rhythm. This theory is compatible with the findings of recent neurophysiological studies that relate temporal prediction to neural oscillations.

Monocyte chemoattractant protein-1 transfection induces angiogenesis and tumorigenesis of gastric carcinoma in nude mice via macrophage recruitment.

PURPOSE: Monocyte chemoattractant protein-1 (MCP-1) is a chemokine that has various roles in tumor development and progression. We previously reported that expression of MCP-1 is associated with macrophage infiltration and tumor vessel density in human gastric carcinomas. The present study was undertaken to obtain direct evidence that MCP-1 participates in recruitment of macrophages and induction of angiogenesis. EXPERIMENTAL DESIGN: We did transfection experiments to analyze the role of MCP-1 in tumorigenicity and angiogenesis in gastric carcinoma in nude mice. The human MCP-1 gene cloned into the BCMGS-Neo expression vector was transfected into the human gastric carcinoma TMK-1 cell line. We examined tumor volumes with the ectopic s.c. xenograft model and tumorigenicity with the orthotopic gastric xenograft model. We determined intratumor microvessel counts and tumor-infiltrating macrophage counts by immunohistochemical staining. RESULTS: There was no difference in in vitro proliferation between MCP-1-transfected TMK-1 cells and mock-transfected (control) cells; however, MCP-1 transfectants induced tumor growth in ectopic xenografts and increased tumorigenicity and induced lymph node metastases and ascites in orthotopic xenografts. In both ectopic and orthotopic xenograft models, strong infiltration of macrophages was observed within and around the tumors after implantation of MCP-1 transfectants whereas fewer macrophages were seen after inoculation of control cells. The microvessel density was significantly higher in tumors produced by MCP-1 transfectants than in control tumors. CONCLUSIONS: MCP-1 produced by gastric carcinoma cells may regulate angiogenesis via macrophage recruitment. MCP-1 may be a potential target for antiangiogenic therapy for gastric carcinoma.

Perceptual versus motor spatiotemporal interactions in duration reproduction across two hands.

The possibility of spatiotemporal interactions in motor action that are comparable with the perceptual kappa effect was tested in the present study. In the kappa effect, the empty duration between two successive stimuli is overestimated when the spatial distance between these stimuli is increased. Indeed, when participants reproduced the standard (empty) duration, delivering two tactile stimuli to different hands resulted in a longer reproduced duration than delivering both stimuli to the same hand, regardless of how long the standard was. However, when a spatial factor during motor action (reproduction) was manipulated by letting participants use an identical hand or different hands for two button pushes reproducing the standard, the different-hand condition yielded a shorter reproduced duration than the identical-hand condition when the standard was 1000 ms or more. More specifically, this decrement in the reproduced duration grew linearly with the standard, suggesting that a given space increases the "rate" of an internal timer during motor action. Because each tick of the timer was accelerated, the total error causing an earlier push of the second button was increased with the standard. A pacemaker-counter model was adopted to explain the differences between the perceptual and the motor spatiotemporal interactions.

Perceived empty duration between sounds of different lengths: Possible relation with repetition and rhythmic grouping.

We investigated how perceived duration of empty time intervals would be modulated by the length of sounds marking those intervals. Three sounds were successively presented in Experiment 1. Each sound was short (S) or long (L), and the temporal position of the middle sound's onset was varied. The lengthening of each sound resulted in delayed perception of the onset; thus, the middle sound's onset had to be presented earlier in the SLS than in the LSL sequence so that participants perceived the three sounds as presented at equal interonset intervals. In Experiment 2, a short sound and a long sound were alternated repeatedly, and the relative duration of the SL interval to the LS interval was varied. This repeated sequence was perceived as consisting of equal interonset intervals when the onsets of all sounds were aligned at physically equal intervals. If the same onset delay as in the preceding experiment had occurred, participants should have perceived equality between the interonset intervals in the repeated sequence when the SL interval was physically shortened relative to the LS interval. The effects of sound length seemed to be canceled out when the presentation of intervals was repeated. Finally, the perceived duration of the interonset intervals in the repeated sequence was not influenced by whether the participant's native language was French or Japanese, or by how the repeated sequence was perceptually segmented into rhythmic groups.

Phase and Frequency-Dependent Effects of Transcranial Alternating Current Stimulation on Motor Cortical Excitability.

Transcranial alternating current stimulation (tACS) can entrain ongoing brain oscillations and modulate the motor system in a frequency-dependent manner. Recent animal studies have demonstrated that the phase of a sinusoidal current also has an important role in modulation of neuronal activity. However, the phase effects of tACS on the human motor system are largely unknown. Here, we systematically investigated the effects of tACS phase and frequency on the primary motor cortex (M1) by using motor evoked potentials (MEPs) with transcranial magnetic stimulation (TMS). First, we compared the phase effects (90°, 180°, 270° or 360°) of 10 and 20 Hz tACS on MEPs. The 20 Hz tACS significantly increased M1 excitability compared with the 10 Hz tACS at 90° phase only. Second, we studied the 90° phase effect on MEPs at different tACS frequencies (5, 10, 20 or 40 Hz). The 20 vs. 10 Hz difference was again observed, but the 90° phase in 5 and 40 Hz tACS did not influence M1 excitability. Third, the 90° phase effects of 10 and 20 Hz tACS were compared with sham stimulation. The 90° phase of 20 Hz tACS enhanced MEP amplitudes compared with sham stimulation, but there was no significant effect of 10 Hz tACS. Taken together, we assume that the differential 90° phase effects on 20 Hz and 10 Hz tACS can be attributed to the neural synchronization modulated by tACS. Our results further underline that phase and frequency are the important factors in the effects of tACS on M1 excitability.

Expression of vascular endothelial growth factor (VEGF)-C and VEGF-D in early gastric carcinoma: correlation with clinicopathological parameters.

In this study, we investigated whether expression of vascular endothelial growth factor (VEGF)-C and/or VEGF-D correlates with clinicopathological features of human gastric carcinoma. We immunohistochemically examined the expression of VEGF-C and VEGF-D in 140 archival surgical specimens of submucosally invasive gastric carcinoma. Of these specimens, 32 (22.9%) and 12 (8.6%) showed intense VEGF-C and VEGF-D immunoreactivity in cancer cells, respectively. VEGF-C immunoreactivity was associated with histological type, lymphatic invasion, lymph node metastasis, and microvessel density. No association was identified between VEGF-D immunoreactivity and clinicopathological variables. These results suggest that VEGF-C is a dominant regulator of lymphangiogenesis in early-stage human gastric carcinoma.

Involvement of proinflammatory cytokines IL-1beta and IL-6 in progression of human gastric carcinoma.

UNLABELLED: Gastric carcinoma occurs in response to chronic inflammation of gastric mucosa infected with Helicobacter pylori. It is not known how cytokines affect the growth and progression of gastric carcinoma. MATERIALS AND METHODS: We measured tissue concentrations of the proinflammatory cytokines interleukin (IL)-1beta and IL-6 in gastric carcinoma and investigated the correlation between the levels of these cytokines and clinicopathological features. Biopsy specimens of tumors or adjacent normal mucosa were obtained from 42 Japanese patients with gastric carcinoma. Tissue levels of IL-1beta and IL-6 were measured by enzyme-linked immunosorbent assay. RESULTS: IL-1beta levels were significantly higher in the neoplasm than in the corresponding normal mucosa. The IL-6 levels in the neoplasm correlated significantly with the depth of invasion and lymphatic invasion. High levels of IL-1beta and IL-6 were characteristic of non-scirrhous type gastric carcinoma. CONCLUSION: These results suggest that IL-1beta and IL-6 are involved in the growth and progression of human gastric carcinoma.

Regulation of vascular endothelial growth factor (VEGF)-C and VEGF-D expression by the organ microenvironment in human colon carcinoma.

Vascular endothelial growth factor (VEGF)-C and VEGF-D are potent lymphangiogenic factors produced by tumour and stromal cells. The purpose of this study was to investigate the expression of VEGF-C and VEGF-D in the organ microenvironment. We implanted human KM12 colon carcinoma cell lines into the subcutis and caecal wall of nude mice. The expression of VEGF-C and VEGF-D mRNAs and proteins were examined by reverse transcriptase-polymerase chain reaction and immunohistochemistry, respectively. Under culture conditions, VEGF-C mRNA was not detected in KM12 cells; however, VEGF-C expression was detected after implantation of KM12 cells into nude mice. VEGF-C and VEGF-D protein contents were higher in orthotopic (caecal wall) tumours than in ectopic (subcutis) tumours. Small vessels expressing VEGF receptor-3 were observed in the peripheral portions of caecal tumours. In metastatic liver tumours, VEGF-C and VEGF-D proteins were produced in lower amounts than those in caecal tumours. These data suggest that the expression of lymphangiogenic factors is influenced by the organ microenvironment. Therefore, experimental studies of colon cancer lymphangiogenesis should be performed with orthotopic implantation models.

Single nucleotide polymorphism in the hypoxia-inducible factor-1alpha gene in colorectal carcinoma.

Colorectal carcinoma is one of the most common malignancies in the world, and its incidence has increased in recent years. We have reported that expression of hypoxia-inducible factor (HIF)-1alpha correlates with expression of vascular endothelial growth factor (VEGF), tumor stage, lymphatic invasion, venous invasion, and liver metastasis. It has also been reported that a single nucleotide polymorphism (SNP) in exon 12 of HIF-1alpha gene is present in renal cell carcinoma and head and neck squamous cell carcinoma patients. We investigated the C1772T polymorphism in colorectal cancer patients and healthy control subjects to clarify the mechanism of HIF-1alpha activation in colorectal carcinoma. The exon 12 genotype was not associated with sex or age. The distribution of HIF-1alpha genotypes in controls was 89 C/C (89%), 11 C/T (11%), and 0 T/T (0%). The distribution of HIF-1alpha genotypes in colorectal cancer patients was 100 C/C (100%), 0 C/T (0%), and 0 T/T (0%). The difference in genotype distribution between patients and control subjects was significant (p<0.0005). These results suggest that the C1772T polymorphism in HIF-1alpha is not involved in progression or metastasis of colorectal carcinoma.

About the time-shrinking illusion in the tactile modality.

The aim of this study was to examine the occurrence of a so-called time-shrinking illusion in the tactile modality, while it had been tested so far mainly with auditory and visual stimuli. We examined whether the perception of an empty time interval marked by two brief tactile stimuli, S (240 ms), would be influenced by the presence of a preceding time interval, P (160, 240, or 320 ms). Results showed that S was underestimated when P was shorter than S. This underestimation appeared as a kind of perceptual assimilation between P and S, but S was not overestimated when P was longer. The underestimation was rather interpreted as a manifestation of the time-shrinking illusion.

Discrimination of two neighboring intra- and intermodal empty time intervals marked by three successive stimuli.

We investigated the discrimination of two neighboring intra- or inter-modal empty time intervals marked by three successive stimuli. Each of the three markers was a flash (visual-V) or a sound (auditory-A). The first and last markers were of the same modality, while the second one was either A or V, resulting in four conditions: VVV, VAV, AVA and AAA. Participants judged whether the second interval, whose duration was systematically varied, was shorter or longer than the 500-ms first interval. Compared with VVV and AAA, discrimination was impaired with VAV, but not so much with AVA (in Experiment 1). Whereas VAV and AVA consisted of the same set of single intermodal intervals (VA and AV), discrimination was impaired in the VAV compared to the AVA condition. This difference between VAV and AVA could not be attributed to the participants' strategy to perform the discrimination task, e.g., ignoring the standard interval or replacing the visual stimuli with sounds in their mind (in Experiment 2). These results are discussed in terms of sequential grouping according to sensory similarity.

No time-stretching illusion when a tone is followed by a noise.

A sine tone is perceived as longer when it is preceded by a more intense noise than when presented in isolation. This is the time-stretching illusion. We conducted an experiment where the method of constant stimuli was used to examine whether a tone would also be stretched when it was followed by a noise. The duration of a tone was overestimated when it was preceded by a noise, but not when followed by a noise or when located between two consecutive noises. Moreover, the increasing of the noise intensity (from -6 to +6 dB) relative to the tone intensity resulted in larger overestimations, but only in the condition where a tone was preceded by a noise. In brief, the duration of a tone is stretched when this tone is preceded by a noise and if this tone is not followed by a noise.

Discrimination of brief gaps marked by two stimuli: effects of sound length, repetition, and rhythmic grouping.

We examined the effects of sound marker length, marker repetition, and rhythmic grouping on auditory gap discrimination. The discrimination ofthe duration of a gap between two markers was impaired by lengthening these markers (from 150 to 262.5 ms). Discrimination was impaired by lengthening the preceding marker relative to lengthening the following marker, while the impairment was not increased when both markers were lengthened compared with when only the preceding marker was lengthened. This indicates that the level of discrimination is not decided by a simple summation of the effects of the preceding and of the following marker's length. Moreover, discrimination of a gap between a short (S) and a long (L) marker and of a gap between a long and a short marker was improved by repeating the presentation of these gaps (ie by repeating the markers alternately as SLSLSL...): both types of discrimination led to near identical performance. Finally, under the repetition condition each type of discrimination was not related to the tendency for each individual to perceive the stimulus sequences as segmented into rhythmic chunks of a short tone followed by a long tone (as [SL][SL][SL]...), or those of a long tone followed by a short tone (as S][LS][LS][L...).

Illusory continuity without sufficient sound energy to fill a temporal gap: examples of crossing glide tones.

The gap transfer illusion is an auditory illusion where a temporal gap inserted in a longer glide tone is perceived as if it were in a crossing shorter glide tone. Psychophysical and phenomenological experiments were conducted to examine the effects of sound-pressure-level (SPL) differences between crossing glides on the occurrence of the gap transfer illusion. We found that the subjective continuity-discontinuity of the crossing glides changed as a function of the relative level of the shorter glide to the level of the longer glide. When the relative level was approximately between -9 and +2 dB, listeners perceived the longer glide as continuous and the shorter glide as discontinuous, that is, the gap transfer illusion took place. The glides were perceived veridically below this range, that is, gap transfer did not take place, whereas above this range the longer glide and the shorter glide were both perceived as continuous. The fact that the longer glide could be perceived as continuous even when the crossing shorter glide was 9 dB weaker indicates that the longer glide's subjective continuity cannot be explained within the conventional framework of auditory organization, which assumes reallocation of sound energy from the shorter to the longer glide. The implicated mechanisms are discussed in terms of the temporal configuration of onsets and terminations and the time-frequency distribution of sound energy.