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Albuminuria is a major risk factor of cardiovascular events, however, the impact of albuminuria on clinical outcomes of patients undergoing transcatheter aortic valve replacement (TAVR) has not been fully investigated. This retrospective study included 206 patients who underwent TAVR for severe aortic stenosis. Patients were divided into two groups according to the preoperative urinary albumin-to-creatinine ratio (ACR): high (ACR ≥ 30 mg/g) and low (ACR30 mg/g). The incidence of 1-month worsening renal function (WRF), defined as a decrease in estimated glomerular filtration rate (eGFR) ≥10% from baseline after TAVR, was investigated. Patients with high ACR had acute kidney injury (8.5% vs. 1.0%, p = 0.01) and 1-month WRF (29.2% vs. 12.0%, p = 0.002) more frequently than those with low ACR. High ACR was independently associated with 1-month WRF (odds ratio, 3.72; 95% confidence interval, 1.72-8.08; p0.001). Albuminuria can be a useful predictor of deterioration of renal function at various time points after TAVR.

The relationship between carotid artery ultrasound findings and clinical outcomes in patients who undergo percutaneous coronary intervention (PCI) has not been completely elucidated.This single-center retrospective study investigated 691 patients who underwent PCI and carotid ultrasound testing. Maximum carotid intima-media thickness (CIMT) was defined as the greatest CIMT at the maximally thick point among the common carotid artery, carotid bulb, and internal carotid artery. A carotid plaque was defined as vessel wall thickening with a CIMT ≥ 1.5 mm. The characteristics of carotid plaque (heterogeneity, calcification, or irregular/ulcerated surface) were evaluated visually. Patients were divided into those with and without heterogeneous carotid plaque (maximum CIMT ≥ 1.5 mm and heterogeneous texture). The endpoint was the incidence of a major adverse cardiovascular event (MACE) defined as a composite of cardiovascular (CV) death, myocardial infarction, and ischemic stroke.Among 691 patients, 309 were categorized as having a heterogeneous plaque. Patients with heterogeneous plaques were at a higher risk of MACE than those without (p=0.002). A heterogeneous plaque was independently associated with MACE after adjusting for covariates (hazard ratio [HR], 1.71; 95% confidence interval [CI], 1.01-2.90; p=0.046). Calcified or irregular/ulcerated plaques were correlated with a higher incidence of MACE, but both were not independently associated with MACE (HR, 1.35; 95% CI, 0.69-2.64, p=0.38 and HR, 0.98; 95% CI, 0.57-1.69; p=0.95, respectively).The presence of a heterogeneous carotid plaque in patients who underwent PCI predicted future CV events. These patients may require more aggressive medical therapy and careful follow-up.

The relationship between handgrip strength (HGS) and clinical outcomes after percutaneous coronary intervention (PCI) has not yet been thoroughly investigated.This was a single-center, observational study. A total of 469 patients who underwent PCI and whose periprocedural HGS was measured were included. Patients were divided into two groups: the low HGS group (men, ＜28 kg; women, ＜18 kg) and the high HGS group (men, ≥ 28 kg; women, ≥ 18 kg). The primary outcome was the composite endpoint of all-cause death, myocardial infarction (MI), and heart failure readmission.There were 151 patients in the low HGS group and 318 patients in the high HGS group. The age of patients in the low HGS group was significantly higher (median [interquartile range]: 78 [71-82] vs. 70 [61-75] years, p＜0.001), while the body mass index and serum albumin level were significantly lower (body mass index: 22.5 [20.2-24.3] vs. 24.3 [22.3-26.6] kg/mLow HGS was independently associated with adverse outcomes after PCI.

The impact of preoperative albuminuria on the prognosis after transcatheter aortic valve implantation (TAVI) has not been studied. A total of 228 patients who underwent TAVI for severe aortic stenosis (AS) and for whom preoperative urinary data was available were retrospectively investigated. Patients were divided into two groups according to the urinary albumin-to-creatinine ratio (ACR): high (ACR≥ 30 mg/g) and low (ACR30 mg/g). The urinary total protein-to-creatinine ratio (PCR) and dipstick proteinuria were also evaluated. The primary outcome was the composite outcome of all-cause death and readmission for heart failure. In total, 117 patients had a high ACR and 111 patients had a low ACR. During the median follow-up period of 467 days, patients with a high ACR had a higher incidence of the primary outcome than those with a low ACR (p0.001). Patients with a high PCR or positive dipstick proteinuria were also at a higher risk for the primary outcome (p0.001 and p=0.008, respectively). Multivariable Cox proportional hazards analysis showed a high ACR was independently associated with a primary outcome (hazard ratio, 4.98; 95% confidence interval, 1.84-13.49; p=0.002). In conclusion, preoperative albuminuria is an independent predictor of cardiac events in patients with severe AS undergoing TAVI.

CRISPR/Cas9-mediated gene knock-in in in vivo neurons using in utero electroporation is a powerful technique, but the knock-in efficiency is generally low. We previously demonstrated that co-transfection with RAD51, a key molecule of the initial step of homology-directed repair (HDR), expression vector increased EGFP knock-in efficiency in the β-actin site up to 2.5-fold in the pyramidal neurons in layer 2/3 of the somatosensory cortex of mouse brain. To further improve the efficiency, we examined the effect of inhibition of DNA ligase IV (LIG4) that is an essential molecule for non-homologous end joining (NHEJ). Co-transfection with small hairpin RNA for LIG4 (shlig4) expression vector increased the EGFP knock-in efficiency in the β-actin site up to 3.6-fold compared to the condition without shlig4. RAD51 and shlig4 expression vector co-transfection further increased the knock-in efficiency up to 4.7-fold of the control condition. These results suggest that the inhibition of LIG4 is more effective than RAD51 overexpression, and it enhances the effect of RAD51 overexpression on HDR-mediated gene knock-in in vivo neurons.

Mitral isthmus (MI) ablation for mitral flutter is technically difficult, and incomplete block line is not uncommon. The objective of this study is to investigate the effect of the ridge line of left pulmonary vein isolation (LPVI) from left atrial appendage (LAA) on completion rate of mitral isthmus (MI) block line and recurrence rate of atrial tachycardia (AT) or atrial flutter (AFL) after the first MI ablation.We identified 611 patients who underwent first MI ablation for mitral flutter during the study period. Finally, 559 patients were enrolled and divided into two groups according to the method of ridge line ablation of LPVI (LAA group, n = 467, conventional group, n = 92). Outcome measures were the completion of MI block line by first MI ablation, the recurrence of AT/AFL, and repeat MI ablation after the first MI ablation.The first MI block line completion rate was significantly higher in the LAA group than the conventional group (95% vs. 85%, p 0.001). The recurrence rate of AT/AFL after 3 months from first MI ablation was significantly lower in the LAA group. The requirement of additional MI ablation tended to be lower in the LAA group.Our novel approach of ablating LPV-LAA ridge from the LAA side during PVI can increase the success rate of MI block line completion, and reduce the recurrence rate of AT/AFL and the need for additional MI block line ablation. Graphical abstract Ablation of the left pulmonary vein-left atrial appendage ridge from the left atrial appendage side during PVI increased the success rate of mitral isthmus block line completion.

IQSEC3, a gephyrin-binding GABAergic (gamma-aminobutyric acidergic) synapse-specific guanine nucleotide exchange factor, was recently reported to regulate activity-dependent GABAergic synapse maturation, but the underlying signaling mechanisms remain incompletely understood.We generated mice with conditional knockout (cKO) of Iqsec3 to examine whether altered synaptic inhibition influences hippocampus-dependent fear memory formation. In addition, electrophysiological recordings, immunohistochemistry, and behavioral assays were used to address our question.We found that Iqsec3-cKO induces a specific reduction in GABAergic synapse density, GABAergic synaptic transmission, and maintenance of long-term potentiation in the hippocampal CA1 region. In addition, Iqsec3-cKO mice exhibited impaired fear memory formation. Strikingly, Iqsec3-cKO caused abnormally enhanced activation of ribosomal P70-S6K1-mediated signaling in the hippocampus but not in the cortex. Furthermore, inhibiting upregulated S6K1 signaling by expressing dominant-negative S6K1 in the hippocampal CA1 of Iqsec3-cKO mice completely rescued impaired fear learning and inhibitory synapse density but not deficits in long-term potentiation maintenance. Finally, upregulated S6K1 signaling was rescued by IQSEC3 wild-type, but not by an ARF-GEF (adenosine diphosphate ribosylation factor-guanine nucleotide exchange factor) inactive IQSEC3 mutant.Our results suggest that IQSEC3-mediated balanced synaptic inhibition in hippocampal CA1 is critical for the proper formation of hippocampus-dependent fear memory.

This study proposes a postsynaptic density (PSD) lattice model comprising a non-microtubule tubulin-based backbone structure and its associated proteins, including various PSD scaffold/adaptor proteins and other PSD proteins., A purification protocol was developed to identify and analyze the component proteins of a postsynaptic density (PSD) lattice, a core structure of the PSD of excitatory synapses in the central nervous system. “Enriched”- and “lean”-type PSD lattices were purified by synaptic plasma membrane treatment to identify the protein components by comprehensive shotgun mass spectrometry and group them into minimum essential cytoskeleton (MEC) and non-MEC components. Tubulin was found to be a major component of the MEC, with non-microtubule tubulin widely distributed on the purified PSD lattice. The presence of tubulin in and around PSDs was verified by post-embedding immunogold labeling EM of cerebral cortex. Non-MEC proteins included various typical scaffold/adaptor PSD proteins and other class PSD proteins. Thus, this study provides a new PSD lattice model consisting of non-microtubule tubulin-based backbone and various non-MEC proteins. Our findings suggest that tubulin is a key component constructing the backbone and that the associated components are essential for the versatile functions of the PSD.

Six mutations in the salt-inducible kinase 1 (SIK1) have been identified in developmental and epileptic encephalopathy (DEE-30) patients, and two of the mutations are nonsense mutations that truncate the C-terminal region of SIK1. In a previous study, we generated SIK1 mutant (SIK1-MT) mice recapitulating the C-terminal truncated mutations using CRISPR/Cas9-mediated genome editing and found an increase in excitatory synaptic transmission and enhancement of neural excitability in neocortical neurons in SIK1-MT mice. NMDA was injected into SIK1-MT males to induce epileptic seizures in the mice. The severity of the NMDA-induced seizures was estimated by the latency and the number of tail flickering and hyperflexion. Activated brain regions were evaluated by immunohistochemistry against c-fos, Iba1, and GFAP. As another epilepsy model, pentylenetetrazol was injected into the adult SIK1 mutant mice. Seizure susceptibility induced by both NMDA and PTZ was enhanced in SIK1-MT mice. Brain regions including the thalamus and hypothalamus were strongly activated in NMDA-induced seizures. The epilepsy-associated mutation of SIK1 canceled the pharmacological effects of the ACTH treatment on NMDA-induced seizures. These results suggest that SIK1 may be involved in the neuropathological mechanisms of NMDA-induced spasms and the pharmacological mechanism of ACTH treatment.

Background:Six mutations in the salt inducible kinase 1 (SIK1) coding gene have been identified in the early infantile epileptic encephalopathy (EIEE-30) patients accompanied by autistic symptoms, such as repetitive behavior and social behavioral deficits. Among these mutations, two are nonsense mutations that truncate the C-terminal region. It has been shown that the C-terminal truncated form of SIK1 protein affects the subcellular distribution of SIK1 protein, tempting to speculate the relevance to the pathophysiology of the disorders.Methods:We generated SIK1 mutant (SIK1-MT) mice recapitulating the C-terminal truncated mutations using CRISPR/Cas9-mediated genome editing. We performed cellular assays to examine the subcellular localization of SIK1-MT. We also performed patch clamp electrophysiological recording and behavioral tests to evaluate the neuronal functions and behaviors in SIK1-MT mice. Pharmacological experiments using risperidone were also performed to examine the potential therapeutics of the disorder.Results:SIK1-MT protein was distributed in the nucleus and cytoplasm, whereas the distribution of wild-type SIK1 was restricted to the nucleus. We found the disruption of excitatory and inhibitory (E/I) synaptic balance due to an increase in excitatory synaptic transmission and enhancement of neural excitability in the pyramidal neurons in layer 5 of the medial prefrontal cortex in SIK1-MT mice. We also found the increased repetitive behavior and social behavioral deficits in SIK1-MT mice. The risperidone administration attenuated the neural excitability and excitatory synaptic transmission, but the disrupted E/I synaptic balance was unchanged because it also reduced the inhibitory synaptic transmission. Risperidone also eliminated the repetitive behavior, but not social behavioral deficits.Limitations:We failed to identify drugs that can cure the social behavioral deficits in this mouse model.Conclusions:In the present study, we generated model mice for EIEE-30 recapitulating C-terminal truncated SIK1 mutation discovered in human patients. We found that the C-terminal deletion of SIK1 affects the subcellular distribution of SIK1, resulting in the elevated excitability of neuronal networks and autistic behaviors in the mutant mice. Repetitive behavior, but not social deficits, was restored by risperidone, probably due to the decrease of both excitatory and inhibitory synaptic functions by the drug.

Fusion images of diffusion-weighted whole-body imaging with background body signal suppression and T2-weighted image (DWIBS/T2) demonstrate a strong signal for malignancies, with a high contrast against the surrounding tissues, and enable anatomical analysis. In the present study, DWIBS/T2 was compared with 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) for diagnosing cancer in the abdomen. Patient records, including imaging results of examination conducted between November 2012 and May 2014, were analyzed retrospectively. In total, 10 men (age, 73.6±9.6 years) and 8 women (age, 68.9±7.1 years) were enrolled into the current study. Of the enrolled patients, 2 were diagnosed with hepatocellular carcinoma, 1 with cholangiocellular carcinoma, 1 with liver metastasis, 2 with pancreatic ductal adenocarcinoma, 1 with renal cell carcinoma and 1 with malignant lymphoma. Benign lesions were also analyzed, including adenomyomatosis of the gallbladder (5 patients), intraductal papillary mucinous neoplasm (4 patients) and right adrenal adenoma (1 case). All the patients with cancer showed positive results on DWIBS/T2 images. However, only 7 out of 8 patients were positive with PET/CT. One patient with right renal cellular carcinoma was positive with DWIBS/T2, but negative with PET/CT. All the patients with benign lesions were negative with DWIBS/T2 and PET/CT. In conclusion, DWIBS/T2 was more sensitive in diagnosing cancer of organs in the abdominal cavity compared with PET/CT. Furthermore, negative results with DWIBS/T2 and PET/CT were useful for the diagnosis of benign lesions, such as adenomyomatosis of the gallbladder and intraductal papillary mucinous neoplasm.

Diffusion-weighted whole-body imaging with background body signal suppression (DWIBS) images show significant contrast for cancer tissues against non-cancerous tissues. Fusion of a DWIBS and a T2-weighted image (DWIBS/T2) can be used to obtain functional, as well as anatomic, information. In the present study, the performance of DWIBS/T2 in the diagnosis of abdominal solid cancer was evaluated. The records of 14 patients were retrospectively analyzed [5 patients with hepatocellular carcinoma (HCC), 4 with metastatic liver cancer, 3 with pancreatic cancer, 1 with renal cellular carcinoma and 1 with malignant lymphoma of the para-aortic lymph node]. T1WI and T2WI scans did not detect pancreatic cancer in certain cases, whereas DWIs and DWIBS/T2 clearly demonstrated pancreatic cancer in all cases. In addition, metastatic liver cancer and HCC were successfully detected with abdominal US and CECT; however, US did not detect pancreatic cancer in 1 case, while CECT and DWIBS/T2 detected pancreatic cancer in all cases. In conclusion, the diagnostic performance of DWIBS/T2 was the same as that of abdominal US and CECT in detecting primary and metastatic liver cancer. DWIBS/T2 enabled the diagnosis of pancreatic cancer in cases where it was not detected with US, T1WI or T2WI.

To improve the management of patients with acute cholangitis, the present study compared laboratory test variables between acute cholangitis patients with or without common bile duct (CBD) dilatation [CBDdil(+) and CBDdil(-), respectively]. The medical records of patients diagnosed with acute cholangitis and subjected to endoscopic retrograde cholangiopancreatography between February 2008 and May 2015 were retrospectively analyzed. The present study consisted of 40 men (aged 69.4±8.8 years) and 37 women (aged 68.8±11.6 years). It was observed that CBDdil(-) patients were slightly younger than CBDdil(+) patients (P=0.0976), and levels of C-reactive protein (CRP) were significantly higher in CBDdil(-) patients than in CBDdil(+) patients (P=0.0392). In addition, logistic regression analysis indicated that CRP levels were associated with the presence of CBD dilatation (P=0.0392). These data indicate that patients with acute cholangitis without CBD dilatation tend to be younger and have higher levels of CRP. Thus, in acute cholangitis patients without CBD dilatation, diagnosis should be determined using clinical symptoms and laboratory data.

The present study investigated the potential utility of contrast-enhanced abdominal ultrasonography (CEUS), using Sonazoid™, in colorectal cancer (CRC). Three patients were subjected to CEUS with Sonazoid™. Surgical specimens were immunostained for CD31. Numbers of blood vessels positive for CD31 were analyzed in each of five fields at ×400 magnification and averaged to determine blood vessel density. Blood vessel density was compared between non-tumorous and tumorous areas. Prior to the administration of Sonazoid™, CRC was illustrated as irregular-shaped wall thickening. One minute after the administration of Sonazoid™, the majority of the thickened wall was enhanced, while some parts of the thickened wall remained unenhanced. Blood vessel densities of non-tumorous and tumorous areas in patient two were 25.2±2.5 and 5.2±1.1 (P

The present study aimed to identify novel predictors of upper gastrointestinal (GI) bleeding by assessing change ratios of blood test variables. Records of 1,023 patients (431 men and 592 women) who underwent endoscopy between October 2014 and September 2015 at the National Hospital Organization Shimoshizu Hospital (Yotsukaido, Japan) were retrospectively analyzed. Patients whose blood test variables for the time-point of endoscopy and three months previously were available were enrolled and subsequently categorized into a group with and another one without upper GI bleeding (n=32 and 84, respectively), and the respective change ratios were calculated for each group. One-way analysis of variance revealed that in patients with upper GI bleeding, change ratios of white blood cell count and alkaline phosphatase were significantly higher than those in patients without, while change ratios of hemoglobin (Hb), total protein and albumin were significantly reduced. Logistic regression analysis demonstrated that the change ratio of Hb was significantly correlated with upper GI bleeding. Receiver-operator characteristic analysis revealed that an 18.7% reduction of Hb was the threshold value for the prediction of upper GI bleeding. In conclusion, the present study revealed that a ≥18.7% reduction in Hb over three months has predictive value for upper GI bleeding.

Diffusion-weighted whole-body imaging with background body signal suppression (DWIBS) yields positive results for cancer against the surrounding tissues. The combination of DWIBS and T2-weighted images (DWIBS/T2) in the diagnosis of gastrointestinal tract cancers was retrospectively analyzed in the present study. Patients were subjected to magnetic resonance imaging after cancer was diagnosed through specimens obtained via biopsy or endoscopic mucosal resection. Sixteen patients were assessed between July, 2012 and June, 2013 and the correlation between detection with DWIBS/T2 and T staging was analyzed. Regarding patients who underwent surgery, the correlation between detection with DWIBS/T2 and the diameter or depth of invasion was analyzed. All cancers that had advanced to >T2 stage were detectable by DWIBS/T2, whereas all cancers staged as T2) or invading beyond the muscularis propria.

Lower gastrointestinal (GI) bleeding can be caused by colorectal polyps or cancer. The aim of the present study was to identify blood test variables and medications that can predict lower GI bleeding, which would allow for appropriate colonoscopy. The medical records of patients who underwent colonoscopy from September 2014 to September 2015 were retrospectively analyzed. The selected patients included 278 men (mean age, 67.0±11.5 years) and 249 women (mean age, 69.6±12.0 years). The diagnosis, medications, and blood test variables were compared between patients with and without bleeding. Logistic regression analysis was performed to determine the factors associated with lower GI bleeding. The presence of colorectal polyp and cancer was associated with lower GI bleeding (P=0.0044) with an odds ratio of 6.71 (P=0.0148). No lower GI bleeding was observed in patients taking non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, or anticoagulants. The C-reactive protein (CRP) levels were significantly higher in patients with lower GI bleeding (P=0.0227). The Hb levels were lower in patients with lower GI bleeding, however this finding was not statistically significant (P>0.05). No blood test variable was associated with lower GI bleeding. Elevated CRP was associated with lower GI bleeding, while there was no association between the medications and lower GI bleeding.

Differentiation between adenomyomatosis (ADM) and cancer of the gallbladder is necessary during diagnosis. Diffusion-weighted whole body imaging with background body signal suppression (DWIBS) images are able to indicate cancer and inflammation. The fusion of a DWIBS with a T2 weighted image (DWIBS/T2) facilitates both functional and anatomical investigations. In the present study, patient records and images from patients with surgically confirmed ADM from April 2012 to October 2014 were analyzed retrospectively. The enrolled patients, including 6 men (64.2±13.1 years) and 4 women (57.3±12.4 years) were subjected to DWIBS/T2 during routine clinical practice. The diagnosis of ADM was based on magnetic resonance cholangiopancreatography, transabdominal ultrasonography, and endoscopic ultrasonography; ADM was diagnosed definitively when cystic lesions were observed, indicating the Rokitansky-Aschoff sinus. A single patient was indicated to be positive by DWIBS/T2 imaging. The Rokitansky-Aschoff sinus revealed a relatively high signal intensity; however, it was not as strong as that of the spleen. The signal intensity was also high on an apparent diffusion coefficient map, suggesting T2 shine-through. The thickened wall displayed low signal intensity. The aforementioned results indicate that ADM may be negative upon DWIBS/T2 imaging; one false positive case was determined to be ADM, accompanied by chronic cholecystitis. The majority of patients with ADM displayed negative findings upon DWIBS/T2 imaging, and chronic cholecystitis may cause false positives.

General transcription factor II-I (Gtf2i) is a transcription factor and one of the genes implicated in Willams–Beuren syndrome, an autism spectrum disorder. In this study, we investigated splice variants of the Gtf2i gene in both the 5'untranslated region (5'UTR) and the coding region. To search for novel 5'UTRs of Gtf2i, we utilized the cap analysis gene expression database of the mouse. We identified seven novel Gtf2i transcripts with alternatively spliced 5'UTRs in the rat brain. We also identified four novel splice variants in the coding sequence of Gtf2i. Furthermore, we identified a selective usage of certain types of 5'UTR by coding variants. In situ hybridization demonstrated a differential pattern of expression of Gtf2i mRNAs with alternatively spliced 5'UTRs among neuronal cells, and the localization of one of the variants in neuronal dendrites in the rat brain. Immunohistochemistry also demonstrated a distribution of Gtf2i-immunoreactivity in the dendrites. These results suggest multiple pathways of expression of Gtf2i gene in the brain. The expression patterns may be under the control of alternative promoters coupled to the alternative splicing in the coding region. Differential localization of mRNA to neuronal dendrites suggests spatiotemporal-specific translation at the post-synaptic sites that is involved in transfer of synaptic activity to expression of specific sets of genes in the nucleus. Gtf2i is a transcription factor and implicated in Willams–Beuren syndrome. We identified seven novel Gtf2i transcripts with alternatively spliced 5'UTRs in the rat brain. In situ hybridization demonstrated a differential expression of Gtf2i mRNAs with different 5'UTRs in somas and dendrites of neuronal cells. Differential localization of mRNA to neuronal dendrites suggests spatiotemporal-specific translation at the postsynaptic sites. The scheme shows genomic structure showing the positions of the potential transcription start tags (rDEC695, rDEC3D7, rDEC1D3, rDEC104, rDEC072 and rDEBE25). Newly identified exons (1.1–1.6) are shown with the white boxes. The distances from rDEC695-5'end are indicated in bp.

In a clinical setting, it is important to diagnose complications of acute cholecystitis accurately. Diffusion-weighted whole body imaging with background body signal suppression/T2-weighted image fusion (DWIBS/T2) provides high signal intensity with a strong contrast against surrounding tissues in anatomical settings. In the present study, patients who were being treated for acute cholecystitis and underwent DWIBS/T2 in the National Hospital Organization Shimoshizu Hospital between December 2012 and August 2015 were enrolled. A total of 10 men and 4 women underwent DWIBS/T2. Records, including DWIBS/T2 and computed tomography (CT) imaging, were retrospectively analyzed for patients with acute cholecystitis. CT images revealed thickened gallbladder walls in patients with acute cholecystitis, and high signal intensity was observed in DWIBS/T2 images for the thickened gallbladder wall. Inflammation of the pericholecystic space and the liver resulted in high intensity signals with DWIBS/T2 imaging, whereas CT imaging revealed a low-density area in the cholecystic space. Plain CT scanning identified a low-density area in the liver, which became more obvious with contrast-enhanced CT. DWIBS/T2 imaging showed the inflammation of the liver and pericholesyctic space as an area of high signal intensity. Detectability of inflammation of the pericholecystic space and the liver was the same for DWIBS/T2 and CT, which suggests that DWIBS/T2 has the same sensitivity as CT scanning for the diagnosis of complicated acute cholecystitis. However, the strong contrast shown by DWIBS/T2 allows for easier evaluation of acute cholecystitis than CT scanning.

We investigated a unique microzone of the cerebellum located in folium-p (fp) of rabbit flocculus. In fp, Purkinje cells were potently excited by stimulation of the hypothalamus or mesencephalic periaqueductal gray, which induced defense reactions. Using multiple neuroscience techniques, we determined that this excitation was mediated via beaded axons of orexinergic hypothalamic neurons passing collaterals through the mesencephalic periaqueductal gray. Axonal tracing studies using DiI and biotinylated dextran amine evidenced the projection of fp Purkinje cells to the ventrolateral corner of the ipsilateral parabrachial nucleus (PBN). Because, in defense reactions, arterial blood flow has been known to redistribute from visceral organs to active muscles, we hypothesized that, via PBN, fp adaptively controls arterial blood flow redistribution under orexin-mediated neuromodulation that could occur in defense behavior. This hypothesis was supported by our finding that climbing fiber signals to fp Purkinje cells were elicited by stimulation of the aortic nerve, a high arterial blood pressure, or a high potassium concentration in muscles, all implying errors in the control of arterial blood flow. We further examined the arterial blood flow redistribution elicited by electric foot shock stimuli in awake, behaving rabbits. We found that systemic administration of an orexin antagonist attenuated the redistribution and that lesioning of fp caused an imbalance in the redistribution between active muscles and visceral organs. Lesioning of fp also diminished foot shock-induced increases in the mean arterial blood pressure. These results collectively support the hypothesis that the fp microcomplex adaptively controls defense reactions under orexin-mediated neuromodulation.

We previously reported that various mRNAs were associated with postsynaptic density (PSD) purified from rat forebrain. Among the thousands of PSD-associated mRNAs, we highlight the biology of the general transcription factor II-I (Gtf2i) mRNA, focusing on the significance of its versatile splicing for targeting its own mRNA into dendrites, regulation of translation, and the effects of Gtf2i expression level as well as its relationship with neuropsychiatric disorders., Article, INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES.18(2):411(2017)

Upper gastrointestinal (GI) bleeding can be fatal. Blood test variables were reviewed in search of threshold values to detect the presence of occult upper GI bleeding. The records of 1,023 patients who underwent endoscopy at the National Hospital Organization Shimoshizu Hospital from October 2014, to September 2015, were retrospectively reviewed. Of those, 95 had upper GI bleeding. One-way analysis of variance was applied to blood test variables comparing patients with and without upper GI bleeding. Logistic regression analysis was applied to detect the association of blood test parameters with upper GI bleeding, and receiver-operator characteristics were applied to establish threshold values. White blood cell count (WBC), platelet (Plt) count, and blood urea nitrogen (BUN) levels were higher, and hemoglobin (Hb) and albumin (Alb) levels were lower in patients with upper GI bleeding. Logistic regression analysis showed that low Hb was significantly associated with upper GI bleeding and a Hb value of 10.8 g/dl was established as the threshold for the diagnosis. In patients with upper GI bleeding, WBC, Plt count, and BUN levels were higher and Hb and Alb levels were reduced. Hb at 10.8 g/dl was established as a threshold value to detect upper GI bleeding.

Peptic ulcer bleeding can be fatal. Non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids and immunosuppressive agents are administered for long-term usage. The present study assessed the association between peptic ulcer bleeding and administration of NSAIDs, corticosteroids and immunosuppressive agents. Furthermore, the efficacy of lowering the risk of peptic ulcer bleeding with proton pump inhibitors (PPI) and histamine 2 receptor antagonists (H2RA) was evaluated. Medical records were retrospectively analyzed for patients subjected to an upper gastrointestinal (GI) endoscopy performed at the National Hospital Organization Shimoshizu Hospital (Yotsukaido, Japan) from October 2014 to September 2015. During this period, a total of 1,023 patients underwent an upper GI endoscopy. A total of 1,023 patients, including 431 males (age, 68.1±12.9 years) and 592 females (age, 66.4±12.3 years), who had been administered NSAIDs, corticosteroids, immunosuppressive agents, PPIs and H2RAs, were respectively enrolled. Endoscopic findings of the patients were reviewed and their data were statistically analyzed. Logistic regression analysis was used to determine the odds ratio of peptic ulcer bleeding for each medication; immunosuppressive agents had an odds ratio of 5.83, which was larger than that for NSAIDs (4.77). The Wald test was applied to confirm the correlation between immunosuppressive agents and peptic ulcer bleeding. Furthermore, χ2 tests were applied to the correlation between peptic ulcer bleeding and administration of PPIs or H2RAs. Immunosuppressive agents had the largest χ2, and the P-value was 0.03. Administration of PPIs was significantly correlated with non-peptic ulcer bleeding (P=0.02); furthermore, a tendency toward non-peptic ulcer bleeding with administration of H2RA was indicated, but it was not statistically significant (P=0.12). In conclusion, immunosuppressive agents were correlated with peptic ulcer bleeding and PPIs were effective at lowering the risk of peptic ulcer bleeding.

Prompt and accurate diagnosis is critical in the treatment of acute cholecystitis. Diffusion-weighted whole-body magnetic resonance imaging with background body signal suppression/T2 image fusion (DWIBS/T2) identifies areas with high signal intensity, corresponding to inflammation. In the present study, the records and images of patients with acute cholecystitis who underwent DWIBS/T2 between January 2013 and March 2014 were retrospectively analyzed. A total of 11 patients with acute cholecystitis were enrolled. In one patient, DWIBS/T2 identified a thickened wall and high signal intensity, with high signal intensity in the pericholecystic space that suggested localized peritonitis. Positive DWIBS/T2 results indicating acute cholecystitis were obtained in 10/11 patients, with a sensitivity of 90.9%. In addition, wall thickening and high signal intensity were absent in DWIBS/T2 images when wall thickening was not detected by computed tomography. Wall thickening and high signal intensity was attenuated when patients with acute cholecystitis were clinically treated. These data suggest that a thickened gallbladder wall and high signal intensity are indicative of acute cholecystitis and that DWIBS/T2 may be a useful technique in evaluating the severity of acute cholecystitis.

Diffusion-weighted whole-body imaging with background body signal suppression/T2 image fusion (DWIBS/T2) strongly contrasts cancerous tissue against background healthy tissues. Positron emission tomography/computed tomography (PET/CT) applies the uptake of 18-fluorodeoxyglucose in the diagnosis of cancer. Our aim was to compare DWIBS/T2 and PET/CT in patients with upper gastrointestinal cancers. Patient records, including imaging results from July 2012 to March 2015, were analyzed retrospectively. Four men (age, 72.5 ± 5.3 years) and ten women (age, 71.6 ± 4.0 years) were enrolled in this study. The numbers of patients with esophageal cancer, gastric cancer, gastrointestinal stromal tumor, and duodenal cancer were one, eight, three, and two, respectively. Six out of eight patients with gastric cancer had positive results on both DWIBS/T2 and PET/CT. The diameter and depth of invasion of gastric cancer was larger in patients with positive DWIBS/T2 and PET/CT findings than those with negative findings. These results suggested that patients with gastric cancer with larger pixel numbers might tend to show positive results with DWIBS/T2. DWIBS/T2 and PET/CT have similar sensitivity for the diagnosis of upper gastrointestinal cancer. The diameter and depth of invasion affected the detectability of gastric cancer.

Diffusion-weighted whole-body imaging with background body signal suppression/T2 image fusion (DWIBS/T2) is useful for the diagnosis of cancer as it presents a clear contrast between cancerous and non-cancerous tissue. The present study investigated the limitations and advantages of DWIBS/T2 with regards to the diagnosis of colorectal polyp (CP) or cancer (CRC). The current study included patients diagnosed with CP or CRC following colonoscopy, who were subjected to DWIBS/T2 between July 2012 and March 2015. Patient records were analyzed retrospectively. Patients were subjected to DWIBS/T2 when they presented with abdominal cancers or inflammation. Colonoscopy was performed as part of screening, or if patients had suspected colon cancer or inflammatory bowel disease. A total of 8 male and 7 female patients were enrolled in the present study. All patients, with the exception of one who had been diagnosed with CRC following colonoscopy, had positive results and all patients diagnosed with CP following a colonoscopy, with the exception of one, had negative results on DWIBS/T2. Thus, CRC was detected by DWIBS/T2, while CP was not (P=0.0028). The diameter of CRC lesions was significantly larger than that of CP (P

The aim of this study was to identify factors affecting the detection of colorectal cancer (CRC) and colon polyps (CPs) using abdominal ultrasonography (US).Patient records were analyzed retrospectively. Those diagnosed as having either CRC or CPs by colonoscopy performed after screening abdominal US were enrolled. The diagnostic criterion for CRC was an irregularly thickened wall or mass. CPs were diagnosed as spherical or ovoid hypoechoic lesions arising within the colonic lumen as seen on abdominal US.Sixteen patients had a total of 16 CRC lesions and 11 patients had a total of 17 CPs. All CRC lesions invaded deeper than the subserosa. Cancer cell invasion limited to the submucosa was noted in the two 1.5-cm CPs. Detection of these lesions was not associated with invasion to lymph or blood vessels. These results suggest that wall thickening might be the consequence of cancer cells invading below the subserosa, thereby resulting in the lesions becoming detectable on abdominal US.Detection of CRC and CPs on abdominal US was associated with lesion size and depth of invasion.

Phospholipase A2 (PLA2) is a family of enzymes playing diverse roles in lipid signaling in neurons and glia cells. In this study, we examined the expression of subtypes of PLA2 in the cerebellum using immunolabeling and in situ hybridization methods. Two Ca2+-dependent cytosolic subtypes (cPLA2alpha and cPLA2beta), one Ca2+-independent cytosolic subtype (iPLA2), and two secretory subtypes (sPLA2IIA and sPLA2V) were detected in the cerebellum. cPLA2alpha is present in somata and dendrites of Purkinje cells, while sPLA2IIA is associated with the endoplasmic reticulum in perinuclear regions of Purkinje cell somata. iPLA2 is present in granule cells, stellate cells and also in the nucleus of Purkinje cells. In addition, cPLA2beta is localized in granule cells, and sPLA2V in Bergmann glia cells. These results provide an important basis for identifying functional roles of PLA2s in the cerebellum.

Colon diverticula cause bleeding and acute diverticulitis. The present study analyzed laboratory test variables, aiming to predict the presence of diverticula. Patient records from between April 2011 and March 2014 were analyzed retrospectively (1,520 patients) and a one-way analysis of variance was performed to analyze the association between the presence of diverticula and each variable. A χ2 test was then used to assess the correlation between the prevalence of diverticula and the percentage of patients with uric acid (UA) levels ≥5.1 mg/dl. A receiver operating characteristic (ROC) analysis was performed to determine the threshold values required to predict the presence of diverticula. Hemoglobin (Hb) levels were lower in patients with diverticula than in those without diverticula (P=0.0027), and compared with patients without diverticula, UA and triglyceride (TG) levels were higher in patients with diverticula (P=0.0066 and P=0.0136, respectively). The patients were divided into two groups, as follows: Patients with UA levels ≥5.1 mg/dl (the median value) and those with UA levels

Gastric cancer is occasionally diagnosed using transabdominal ultrasonography (US) during screening or investigation of patients with abdominal symptoms. Therefore, the present study analyzed the association of the tumor diameter, pathological T (pT) staging and depth of invasion with the detection of gastric cancer using US. Patient records were analyzed retrospectively and 13 patients were enrolled, who underwent US screening prior to endoscopic mucosal resection, endoscopic submucosal dissection or surgery. In total, 5 patients were diagnosed with gastric cancer using US (positive detection group), while US was unable to detect the gastric cancer in 8 patients (negative detection group). The tumor diameter and depth of invasion were determined by pathologists. One-way analysis of variance or the χ2 test was performed. Wall thickness in gastric cancer cases ranged between 7 and 20 mm (mean, 12.2±5.9 mm), as measured using abdominal US. The hemoglobin level was significantly lower in the positive detection patients compared with the negative detection patients (P=0.0455). In addition, the diameters of the gastric wall in the negative and positive detection patients were 24.5±16.4 and 54.4±26.2 mm, respectively (P=0.0266). These results indicate that gastric cancer in the positive detection patients were at a more advanced-stage compared with that in the negative detection patients. Furthermore, gastric cancer with a stage over pT2 was diagnosed using abdominal US (P=0.0242), whereas stage pT1a gastric cancer was not detected by abdominal US. Gastric tumors invading deeper than the submucosa were diagnosed using US (P=0.0242). However, the gastric cancer cases limited to the mucosa remained undetected. In conclusion, the detection of gastric cancer correlated well with the tumor diameter, pT staging and depth of invasion.

It has generally been thought that protein synthesis is required for relatively slow cellular processes such as synaptogenesis and synaptic plasticity. In this study on rat cerebellar slices, we found that metabotropic glutamate receptor-mediated synaptic transmission to cerebellar Purkinje cells was quickly and persistently depressed by brief (5 min) applications of translational inhibitors, which were confirmed to induce quick and persistent depression of protein synthesis in cerebellar tissues. Brief applications of transcriptional inhibitors also depressed metabotropic synaptic transmission, but progressively over 1 h, presumably due to depletion of mRNAs in the dendrites. Results of this study indicate the presence of a unique protein(s) that is dynamically involved in metabotropic synaptic transmission.

A case of endometriosis with a giant tumor in the pelvic cavity presenting with intestinal obstruction is described. A 48-year-old woman was referred to the hospital after colostomy for intenstinal obstruction at another hospital, where she consulted about severe abdominal distention and was diagnosed as having a rectal tumor causing intestinal obstruction. On admission abdominal CT scans and MR images revealed a large tumor occupying the pelvic cavity. The tumor filled the lumen of the rectum to cause complete obstruction and extended to the uterus, sacrum, and left piriformis muscle. It was unable to make a diagnosis by endoscopic bioposies, but CT-guided biopsy successfully provided the definite diagnosis of endometriosis for us. Medication for the disease was started thereafter. It is suggested that we have to make the diagnosis for large tumors in the pelvic cavity causing intestinal obstruction by entertaining not only malignancies such as rectal or ovarian cancer but also endometriosis as possible different diagnosis. If the definitive diagnosis is unable to be made by endoscopic biopsy, CT-guided biopsy is recommended.