Early life stress has been implicated as a risk factor for irritable bowel syndrome (IBS). We studied the effect of neonatal maternal separation on the visceromotor response and the expression of ...c-fos, 5-HT, and its receptors/transporters along the brain-gut axis in an animal model of IBS. Male neonatal Sprague-Dawley rats were randomly assigned to a 3-h daily maternal separation (MS) or nonhandling (NH) on postnatal days 2-21. Colorectal balloon distention (CRD) was performed for assessment of abdominal withdrawal reflex as a surrogate marker of visceral pain. Tissues from dorsal raphe nucleus in midbrain, lumbar-sacral cord, and distal colon were harvested for semiquantitative analysis of c-fos and 5-HT. The expression of 5-HT expression, 5-HT3 receptors, and 5-HT transporter were analyzed by RT-PCR. Pain threshold was significantly lower in MS than NH rats. The abdominal withdrawal reflex score in response to CRD in MS rats was significantly higher with distension pressures of 40, 60, and 80 mmHg. In MS rats, the number of c-fos-like immunoreactive nuclei at dorsal horn of lumbar-sacral spinal cord increased significantly after CRD. 5-HT content in the spinal cord of MS rats was significant higher. In the colon, both 5-HT-positive cell number and 5-HT content were comparable between MS and NH groups before CRD. Post-CRD only MS rats had significant increase in 5-HT content. Protein and mRNA expression levels of 5-HT3 receptors and 5-HT transporter were similar in MS and NH rats. Neonatal maternal separation stress predisposes rats to exaggerated neurochemical responses and visceral hyperalgesia in colon mimicking IBS.
The impact of a realistic representation of gate-oxide granularity on negative-capacitance (NC) FETs at sub-5nm node is studied by a newly developed thermodynamic energy model based on the first ...principle calculation (FPC). For the first time, the calculation fully couples the Landau-Khalatnikov (L-K) equation with grain-size effect equation in NC-FETs. It explains the experimental results in phase transition and reveals excellent immunity against depolarization in ferroelectric (FE) layer owing to dopant concentration and stress in thin films. A sub-5nm node (LG=10nm) NC-FET with thin FE layer (T FE ~2nm) is integrated to achieve low subthreshold slope (SS) of 52mV/dec via a 1.9GPa-tensor stressed interfacial layer (IL) and 12% Zr-doped HfO 2 .
To retrospectively analyze the thin-section computed tomographic (CT) features in patients with severe acute respiratory syndrome (SARS) at the authors' institution.
From March 11, 2003, to April 2, ...2003, 74 patients with symptoms and signs suggestive of SARS underwent CT of the thorax; all underwent thin-section CT except for one patient who underwent conventional CT. Group 1 (n = 23) patients had symptoms of SARS in keeping with criteria from the Centers for Disease Control and Prevention and a positive chest radiograph. Group 2 (n = 17) patients had a high clinical suspicion of SARS but a normal radiograph. Group 3 (n = 34) patients had minor symptoms and a normal chest radiograph. The thin-section CT images were analyzed for ground-glass opacification or consolidation, lesion size in each lung segment, peripheral or central location, interstitial thickening, and other abnormalities.
Thin-section CT scans were abnormal only for patients in groups 1 and 2. The patient with only conventional CT scans was in group 3; scans for group 3 patients were normal. Affected segments were predominantly in the lower lobes (91 of 149 affected segments). Common findings included ground-glass opacification, sometimes with consolidation, and interlobular septal and intralobular interstitial thickening. The size of each lesion and the total number of segments involved were smaller in group 2 patients. A majority of patients in group 1 (14 of 23) had mixed central and peripheral lesions. In group 2, however, peripheral lesions were more common (10 of 17). In both groups, a purely central lesion was uncommon (one of 23 in group 1 and two of 17 in group 2).
Common thin-section CT features of SARS are ground-glass opacification and lower lobe and peripheral distribution.
Air-Stable Polymer Electronic Devices Lee, K.; Kim, J. Y.; Park, S. H. ...
Advanced materials (Weinheim),
09/2007, Letnik:
19, Številka:
18
Journal Article
Recenzirano
By introducing a titanium oxide (TiOx) layer between the active layer and the aluminum cathode in polymer‐based electronic devices (see figure), devices with excellent air stability and with enhanced ...performance are demonstrated. The TiOx layer acts as a shielding and scavenging layer that prevents the intrusion of oxygen and humidity into the electronically active polymers, thereby improving the lifetime of unpackaged devices exposed to air by nearly two orders of magnitude.
Targeted screening for colorectal cancer in high-risk individuals Wong, Martin C.S., MBChB, MD, MPH, FRACGP; Wong, Sunny H., MBChB (Hons), DPhil; Ng, Siew C., MBBS, PhD ...
Baillière's best practice & research. Clinical gastroenterology,
12/2015, Letnik:
29, Številka:
6
Journal Article
Recenzirano
Abstract The idea of targeted screening for colorectal cancer based on risk profiles originates from its benefits to improve detection yield and optimize screening efficiency. Clinically, it allows ...individuals to be more aware of their own risk and make informed decisions on screening choice. From a public health perspective, the implementation of risk stratification strategies may better justify utilization of colonoscopic resources, and facilitate resource-planning in the formulation of population-based screening programmes. There are several at-risk groups who should receive earlier screening, and colonoscopy is more preferred. This review summarizes the currently recommended CRC screening strategies among subjects with different risk factors, and introduces existing risk scoring systems. Additional genetic, epidemiological, and clinical parameters may be needed to enhance their performance to risk-stratify screening participants. Future research studies should refine these scoring systems, and explore the adaptability, feasibility, acceptability, and user-friendliness of their use in clinical practice among different population groups.
This study aimed to clarify the relationship between TRPV1 activation-induced visceral pain and the serotonin pathway in the colon of rats. The effects of
para-chlorophenylalanine (
pCPA) on visceral ...pain threshold pressure were assessed in capsaicin -induced visceral pain of rats. The expression of TRPV1 in the colon was examined by immunohistochemistry and Western blot analysis, and TRPV1 excitability in dorsal root ganglion (DRG) neurons was examined by whole-cell patch-clamp recording in
pCPA-treated rats. Calcineurin and Ca
2+-calmodulin-dependent kinase II (CaMKII), the important proteins in maintaining TRPV1 function in the colon, were also tested by Western blot analysis and immunofluorescence staining. Results showed that
pCPA significantly increased the capsaicin-induced visceral pain threshold by 2.3-fold, and the enhanced visceral pain threshold corresponded with decreased 5-HT content (58% depleted) and enterochromaffin cell number (80% reduced). The reduced excitability of TRPV1 in DRG neurons, instead of changed TRPV1 expression, is responsible for the enhanced visceral pain threshold in 5-HT-depleted rats, and the mechanism may be related to the decreased expression of
pCaMKII. These results indicate that visceral hypersensitivity induced by TRPV1 activation is modulated through 5-HT pathways and the attenuated function of TRPV1 and decreased protein expression of
pCaMKII may play an important role in capsaicin-induced TRPV1 desensitization under 5-HT-depleted condition. The important role of TRPV1 and 5-HT in generating and maintaining visceral hypersensitivity may provide insights for the treatment of visceral hypersensitivity.
A disintegrins and metalloproteinases with thrombospondin motifs (ADAMTS) family members have been reported dysregulated in various cancers. Through refining a loss of heterozygosity locus at 11q25 ...by array-CGH, we identified ADAMTS8 as a novel candidate tumor suppressor gene. Although ADAMTS8 downregulation has been reported in several tumors, its biologic function and underlying mechanism remain largely unknown. Here, we found that ADAMTS8 is broadly expressed in normal tissues but frequently downregulated or silenced by promoter methylation in common carcinoma cell lines, including nasopharyngeal, esophageal squamous cell, gastric, and colorectal carcinomas. Pharmacologic or genetic demethylation restored ADAMTS8 expression, indicating that promoter methylation mediates its silencing. Aberrant methylation of ADAMTS8 was also detected in several types of primary tumors but rarely in normal tissues. Further functional studies showed that restoring ADAMTS8 expression suppressed tumor cell clonogenicity through inducing apoptosis. ADAMTS8 as a secreted protease inhibited epidermal growth factor receptor (EGFR) signaling along with decreased levels of phosphorylated MEK and ERK. We further found that ADAMTS8 disrupted actin stress fiber organization and inhibited tumor cell motility. Thus, our data demonstrate that ADAMTS8 metalloprotease acts as a functional tumor suppressor through antagonizing EGFR-MEK-ERK signaling, in addition to its previously reported anti-angiogenesis function, and is frequently methylated in common tumors.
This study uncovers the tumor suppressive function of ADAMTS8, one of the ADAMTS family members, and its frequent methylation in certain tumors could be developed as a potential biomarker.
Background and Aim: The prevalence and incidence of inflammatory bowel disease (IBD) differs worldwide. While the prevalence of IBD has stabilized in Europe, the USA and Japan, an increasing trend ...has been observed in Asia. However, there are no data on the current clinical practice for the management of IBD in the region. The present study aims to investigate the number of existing and new cases of IBD and to understand the current practice of diagnosis and treatment of IBD in different Asian countries.
Methods: A self‐administered questionnaire, designed according to European and US guidelines, was distributed to IBD specialists throughout Asia. The questionnaire estimated the annual incidence of existing and new IBD cases in physicians' clinical practices and evaluated their procedures of diagnosis and preference for therapeutic treatment and maintenance treatment.
Results: Eighty‐seven questionnaires were received out of the 107 distributed. In the clinical practices of these 87 respondents, there were 502 existing and 73 new cases per year for ulcerative colitis (UC) and 202 existing and 32 new cases per year for Crohn's disease (CD). Colonoscopy and histology were the most commonly used methods for the diagnosis of UC and CD, but clinical practice regarding the diagnosis of IBD varied. The treatment of choice for mild‐to‐moderate UC and CD was 5‐aminosalicylic acid (5‐ASA), which is also the preferred choice for the maintenance treatment of UC and CD.
Conclusion: Clinical practice with regards to IBD diagnosis and management varies within Asia.5‐ASA is the preferred treatment and maintenance therapy for mild‐to‐moderate IBD.
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