MRI and PET Imaging in Predicting Treatment Response in Patients With Stage IB-IVA Cervical Cancer

ClinicalTrials.gov

2018-06-18

Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Cervical Undifferentiated Carcinoma; Recurrent Cervical Carcinoma; Stage IB2 Cervical Cancer; Stage II Cervical Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Cervical Cancer; Stage IIIA Cervical Cancer; Stage IIIB Cervical Cancer; Stage IVA Cervical Cancer

Prognostic factors of pathologic stage IB non-small cell lung cancer.

PubMed

Yano, Motoki; Sasaki, Hidefumi; Moriyama, Satoru; Kawano, Osamu; Hikosaka, Yu; Fujii, Yoshitaka

2011-01-01

In pathologic IB (pIB) non-small cell lung cancer, especially in adenocarcinoma, adjuvant chemotherapy with uracil-tegafur is widely recognized as being effective. The aim of this study was to determine the prognostic factors of pIB disease. Sixty patients who were diagnosed with pIB disease between 2004 and 2007 were retrospectively analyzed. Of 60 patients, 22 (36.7%) opted for surgery plus adjuvant chemotherapy with uracil-tegafur, whereas 38 (63.3%) opted for surgery only. The oral administration dose of uracil-tegafur was 400 mg/body. Compliance of adjuvant chemotherapy with uracil-tegafur was 65.5% in 12 months, 57.3% in 24 months. Adjuvant chemotherapy was interrupted in 11 patients because of the recurrence of disease in 3 patients and adverse reaction in 8 patients. Anorexia was the most common adverse reaction. The larger tumor diameter (5 cm<) and p2 pleural invasion were the worse prognostic factors in disease free survival in a univariate analysis and a multivariate analysis (hazard ratio = 0.26 and 0.25; p = 0.028 and 0.032, respectively). The prognosis of the patients with pleural invasion and a tumor diameter >5 cm was poor, and these, partly support the forthcoming classification.

Cisplatin and Radiation Therapy Followed by Paclitaxel and Carboplatin in Treating Patients With Stage IB-IVA Cervical Cancer

ClinicalTrials.gov

2017-05-03

Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Stage IB Cervical Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage IIIA Cervical Cancer; Stage IIIB Cervical Cancer; Stage IVA Cervical Cancer

Prognostic value of the new International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification in stage IB lung adenocarcinoma.

PubMed

Xu, C-h; Wang, W; Wei, Y; Hu, H-d; Zou, J; Yan, J; Yu, L-k; Yang, R-s; Wang, Y

2015-10-01

Patients with pathological stage IB lung adenocarcinoma have a variable prognosis, even if received the same treatment. This study investigated the prognostic value of the new International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society (IASLC/ATS/ERS) lung adenocarcinoma classification in resected stage IB lung adenocarcinoma. We identified 276 patients with pathological stage IB adenocarcinoma who had undergone surgical resection at the Nanjing Chest Hospital between 2005 and 2010. The histological subtypes of all patients were classified according to the 2011 IASLC/ATS/ERS international multidisciplinary lung adenocarcinoma classification. Kaplan-Meier and Cox regression analyses were used to analyze the correlation between the IASLC/ATS/ERS classification and patients' prognosis. Two hundred and seventy-six patients with pathological stage IB adenocarcinoma had an 86.2% 5-year overall survival (OS) and 80.4% 5-year disease-free survival (DFS). Patients with micropapillary and solid predominant tumors had a significantly worse OS and DFS as compared to those with other subtypes predominant tumors (p = 0.003 and 0.001). Multivariate analysis revealed that the new classification was an independent prognostic factor for both OS and DFS of pathological stage IB adenocarcinoma (p = 0.009 and 0.003). Our study revealed that the new IASLC/ATS/ERS classification was an independent prognostic factor of pathological stage IB adenocarcinoma. This new classification is valuable of screening out high risk patients to receive postoperative adjuvant therapy. Copyright © 2015. Published by Elsevier Ltd.

IBS simulation with different RF configurations in RHIC

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, C.; Fedotov, A.; Minty, M.

It is a crucial task to understand the beam emittance growth during RHIC cycle and the underlying causes. One would benefit not just for the current operation of RHIC, also for the design of eRHIC. This report focuses on the Intra-Beam Scattering (IBS) contribution to the emittance growth of the proton beam with two different configurations of RF system. The answers to these questions will be given in the end of the report; can IBS explain the emittance growth all alone? What’s the difference of IBS growth rates for different RF configurations?

Streptococcus sanguinis Class Ib Ribonucleotide Reductase

PubMed Central

Makhlynets, Olga; Boal, Amie K.; Rhodes, DeLacy V.; Kitten, Todd; Rosenzweig, Amy C.; Stubbe, JoAnne

2014-01-01

Streptococcus sanguinis is a causative agent of infective endocarditis. Deletion of SsaB, a manganese transporter, drastically reduces S. sanguinis virulence. Many pathogenic organisms require class Ib ribonucleotide reductase (RNR) to catalyze the conversion of nucleotides to deoxynucleotides under aerobic conditions, and recent studies demonstrate that this enzyme uses a dimanganese-tyrosyl radical (MnIII2-Y•) cofactor in vivo. The proteins required for S. sanguinis ribonucleotide reduction (NrdE and NrdF, α and β subunits of RNR; NrdH and TrxR, a glutaredoxin-like thioredoxin and a thioredoxin reductase; and NrdI, a flavodoxin essential for assembly of the RNR metallo-cofactor) have been identified and characterized. Apo-NrdF with FeII and O2 can self-assemble a diferric-tyrosyl radical (FeIII2-Y•) cofactor (1.2 Y•/β2) and with the help of NrdI can assemble a MnIII2-Y• cofactor (0.9 Y•/β2). The activity of RNR with its endogenous reductants, NrdH and TrxR, is 5,000 and 1,500 units/mg for the Mn- and Fe-NrdFs (Fe-loaded NrdF), respectively. X-ray structures of S. sanguinis NrdIox and MnII2-NrdF are reported and provide a possible rationale for the weak affinity (2.9 μm) between them. These streptococcal proteins form a structurally distinct subclass relative to other Ib proteins with unique features likely important in cluster assembly, including a long and negatively charged loop near the NrdI flavin and a bulky residue (Thr) at a constriction in the oxidant channel to the NrdI interface. These studies set the stage for identifying the active form of S. sanguinis class Ib RNR in an animal model for infective endocarditis and establishing whether the manganese requirement for pathogenesis is associated with RNR. PMID:24381172

Does a low FODMAP diet help IBS?

PubMed

2015-08-01

Irritable bowel syndrome (IBS) is a common condition that can have a significant impact on a person's quality of life. The cause of IBS is unknown but several mechanisms have been proposed including visceral hypersensitivity, central sensitisation, abnormal gut motility and altered gut microbiota. IBS is challenging to manage and many patients report insufficient symptomatic relief from treatment. Approximately 60% of patients identify food as a trigger for their symptoms, and there has been interest in exclusion diets for managing IBS. Dietary adaptation is a common self-management strategy for patients with IBS, with many self-diagnosing intolerance to specific foods. This may lead to patients adopting over-restrictive or inappropriate diets. In recent years, a diet low in poorly absorbed short-chain carbohydrates, known collectively as FODMAPs (fermentable oligosaccharides, disaccharides, monosaccharides and polyols), has been advocated for the treatment of IBS. Here, we discuss the background to the FODMAP diet and review the evidence supporting its use for people with IBS. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Down-regulation of the IbEXP1 gene enhanced storage root development in sweetpotato

PubMed Central

Bae, Jung Myung

2013-01-01

The role of an expansin gene (IbEXP1) in the formation of the storage root (SR) was investigated by expression pattern analysis and characterization of IbEXP1-antisense sweetpotato (Ipomoea batatas cv. Yulmi) plants in an attempt to elucidate the molecular mechanism underlying SR development in sweetpotato. The transcript level of IbEXP1 was high in the fibrous root (FR) and petiole at the FR stage, but decreased significantly at the young storage root (YSR) stage. IbEXP1-antisense plants cultured in vitro produced FRs which were both thicker and shorter than those of wild-type (WT) plants. Elongation growth of the epidermal cells was significantly reduced, and metaxylem and cambium cell proliferation was markedly enhanced in the FRs of IbEXP1-antisense plants, resulting in an earlier thickening growth in these plants relative to WT plants. There was a marked reduction in the lignification of the central stele of the FRs of the IbEXP1-antisense plants, suggesting that the FRs of the mutant plants possessed a higher potential than those of WT plants to develop into SRs. IbEXP1-antisense plants cultured in soil produced a larger number of SRs and, consequently, total SR weight per IbEXP1-antisense plant was greater than that per WT plant. These results demonstrate that SR development was accelerated in IbEXP1-antisense plants and suggest that IbEXP1 plays a negative role in the formation of SR by suppressing the proliferation of metaxylem and cambium cells to inhibit the initial thickening growth of SRs. IbEXP1 is the first sweetpotato gene whose role in SR development has been directly identified in soil-grown transgenic sweetpotato plants. PMID:22945944

Small intestinal permeability is increased in diarrhoea predominant IBS, while alterations in gastroduodenal permeability in all IBS subtypes are largely attributable to confounders.

PubMed

Mujagic, Z; Ludidi, S; Keszthelyi, D; Hesselink, M A M; Kruimel, J W; Lenaerts, K; Hanssen, N M J; Conchillo, J M; Jonkers, D M A E; Masclee, A A M

2014-08-01

Intestinal permeability has been studied in small groups of IBS patients with contrasting findings. To assess intestinal permeability at different sites of the GI tract in different subtypes of well-characterised IBS patients and healthy controls (HC), and to assess potential confounding factors. IBS patients and HC underwent a multi-sugar test to assess site-specific intestinal permeability. Sucrose excretion and lactulose/rhamnose ratio in 0-5 h urine indicated gastroduodenal and small intestinal permeability, respectively. Sucralose/erythritol ratio in 0-24 h and 5-24 h urine indicated whole gut and colonic permeability, respectively. Linear regression analysis was used to assess the association between IBS groups and intestinal permeability and to adjust for age, sex, BMI, anxiety or depression, smoking, alcohol intake and use of medication. Ninety-one IBS patients, i.e. 37% IBS-D, 23% IBS-C, 33% IBS-M and 7% IBS-U and 94 HC were enrolled. Urinary sucrose excretion was significantly increased in the total IBS group [μmol, median (Q1;Q3): 5.26 (1.82;11.03) vs. 2.44 (0.91;5.85), P < 0.05], as well as in IBS-C and IBS-D vs. HC. However, differences attenuated when adjusting for confounders. The lactulose/rhamnose ratio was increased in IBS-D vs. HC [0.023 (0.013;0.038) vs. 0.014 (0.008;0.025), P < 0.05], which remained significant after adjustment for confounders. No difference was found in 0-24 and 5-24 h sucralose/erythritol ratio between groups. Small intestinal permeability is increased in patients with IBS-D compared to healthy controls, irrespective of confounding factors. Adjustment for confounders is necessary when studying intestinal permeability, especially in a heterogeneous disorder such as IBS. © 2014 John Wiley & Sons Ltd.

Integrated Baseline System (IBS). Version 1.03, System Management Guide

DOE Office of Scientific and Technical Information (OSTI.GOV)

Williams, J.R.; Bailey, S.; Bower, J.C.

This IBS System Management Guide explains how to install or upgrade the Integrated Baseline System (IBS) software package. The IBS is an emergency management planning and analysis tool that was developed under the direction of the Federal Emergency Management Agency (FEMA). This guide includes detailed instructions for installing the IBS software package on a Digital Equipment Corporation (DEC) VAX computer from the IBS distribution tapes. The installation instructions include procedures for both first-time installations and upgrades to existing IBS installations. To ensure that the system manager has the background necessary for successful installation of the IBS package, this guide alsomore » includes information on IBS computer requirements, software organization, and the generation of IBS distribution tapes. When special utility programs are used during IBS installation and setups, this guide refers you to the IBS Utilities Guide for specific instructions. This guide also refers you to the IBS Data Management Guide for detailed descriptions of some IBS data files and structures. Any special requirements for installation are not documented here but should be included in a set of installation notes that come with the distribution tapes.« less

Exclusion of the GNAS locus in PHP-Ib patients with broad GNAS methylation changes: evidence for an autosomal recessive form of PHP-Ib?

PubMed

Fernández-Rebollo, Eduardo; Pérez de Nanclares, Guiomar; Lecumberri, Beatriz; Turan, Serap; Anda, Emma; Pérez-Nanclares, Gustavo; Feig, Denice; Nik-Zainal, Serena; Bastepe, Murat; Jüppner, Harald

2011-08-01

Most patients with autosomal dominant pseudohypoparathyroidism type Ib (AD-PHP-Ib) carry maternally inherited microdeletions upstream of GNAS that are associated with loss of methylation restricted to GNAS exon A/B. Only few AD-PHP-Ib patients carry microdeletions within GNAS that are associated with loss of all maternal methylation imprints. These epigenetic changes are often indistinguishable from those observed in patients affected by an apparently sporadic PHP-Ib form that has not yet been defined genetically. We have now investigated six female patients affected by PHP-Ib (four unrelated and two sisters) with complete or almost complete loss of GNAS methylation, whose healthy children (11 in total) showed no epigenetic changes at this locus. Analysis of several microsatellite markers throughout the 20q13 region made it unlikely that PHP-Ib is caused in these patients by large deletions involving GNAS or by paternal uniparental isodisomy or heterodisomy of chromosome 20 (patUPD20). Microsatellite and single-nucleotide variation (SNV) data revealed that the two affected sisters share their maternally inherited GNAS alleles with unaffected relatives that lack evidence for abnormal GNAS methylation, thus excluding linkage to this locus. Consistent with these findings, healthy children of two unrelated sporadic PHP-Ib patients had inherited different maternal GNAS alleles, also arguing against linkage to this locus. Based on our data, it appears plausible that some forms of PHP-Ib are caused by homozygous or compound heterozygous mutation(s) in an unknown gene involved in establishing or maintaining GNAS methylation. Copyright © 2011 American Society for Bone and Mineral Research.

Exclusion of the GNAS Locus in PHP-Ib Patients With Broad GNAS Methylation Changes: Evidence for an Autosomal Recessive Form of PHP-Ib?

PubMed Central

Fernández-Rebollo, Eduardo; de Nanclares, Guiomar Pérez; Lecumberri, Beatriz; Turan, Serap; Anda, Emma; Pérez-Nanclares, Gustavo; Feig, Denice; Nik-Zainal, Serena; Bastepe, Murat; Jüppner, Harald

2013-01-01

Most patients with autosomal dominant pseudohypoparathyroidism type Ib (AD-PHP-Ib) carry maternally inherited microdeletions upstream of GNAS that are associated with loss of methylation restricted to GNAS exon A/B. Only few AD-PHP-Ib patients carry microdeletions within GNAS that are associated with loss of all maternal methylation imprints. These epigenetic changes are often indistinguishable from those observed in patients affected by an apparently sporadic PHP-Ib form that has not yet been defined genetically. We have now investigated six female patients affected by PHP-Ib (four unrelated and two sisters) with complete or almost complete loss of GNAS methylation, whose healthy children (11 in total) showed no epigenetic changes at this locus. Analysis of several microsatellite markers throughout the 20q13 region made it unlikely that PHP-Ib is caused in these patients by large deletions involving GNAS or by paternal uniparental isodisomy or heterodisomy of chromosome 20 (patUPD20). Microsatellite and single-nucleotide variation (SNV) data revealed that the two affected sisters share their maternally inherited GNAS alleles with unaffected relatives that lack evidence for abnormal GNAS methylation, thus excluding linkage to this locus. Consistent with these findings, healthy children of two unrelated sporadic PHP-Ib patients had inherited different maternal GNAS alleles, also arguing against linkage to this locus. Based on our data, it appears plausible that some forms of PHP-Ib are caused by homozygous or compound heterozygous mutation(s) in an unknown gene involved in establishing or maintaining GNAS methylation. PMID:21523828

Endocannabinoid and cannabinoid-like fatty acid amide levels correlate with pain-related symptoms in patients with IBS-D and IBS-C: a pilot study.

PubMed

Fichna, Jakub; Wood, Jodianne T; Papanastasiou, Malvina; Vadivel, Subramanian K; Oprocha, Piotr; Sałaga, Maciej; Sobczak, Marta; Mokrowiecka, Anna; Cygankiewicz, Adam I; Zakrzewski, Piotr K; Małecka-Panas, Ewa; Krajewska, Wanda M; Kościelniak, Piotr; Makriyannis, Alexandros; Storr, Martin A

2013-01-01

Irritable bowel syndrome (IBS) is a functional gastrointestinal (GI) disorder, associated with alterations of bowel function, abdominal pain and other symptoms related to the GI tract. Recently the endogenous cannabinoid system (ECS) was shown to be involved in the physiological and pathophysiological control of the GI function. The aim of this pilot study was to investigate whether IBS defining symptoms correlate with changes in endocannabinoids or cannabinoid like fatty acid levels in IBS patients. AEA, 2-AG, OEA and PEA plasma levels were determined in diarrhoea-predominant (IBS-D) and constipation-predominant (IBS-C) patients and were compared to healthy subjects, following the establishment of correlations between biolipid contents and disease symptoms. FAAH mRNA levels were evaluated in colonic biopsies from IBS-D and IBS-C patients and matched controls. Patients with IBS-D had higher levels of 2AG and lower levels of OEA and PEA. In contrast, patients with IBS-C had higher levels of OEA. Multivariate analysis found that lower PEA levels are associated with cramping abdominal pain. FAAH mRNA levels were lower in patients with IBS-C. IBS subtypes and their symptoms show distinct alterations of endocannabinoid and endocannabinoid-like fatty acid levels. These changes may partially result from reduced FAAH expression. The here reported changes support the notion that the ECS is involved in the pathophysiology of IBS and the development of IBS symptoms.

TSH elevations as the first laboratory evidence for pseudohypoparathyroidism type Ib (PHP-Ib).

PubMed

Molinaro, Angelo; Tiosano, Dov; Takatani, Rieko; Chrysis, Dionisios; Russell, William; Koscielniak, Nikolas; Kottler, Marie-Laure; Agretti, Patrizia; De Marco, Giuseppina; Ahtiainen, Petteri; Christov, Marta; Mäkitie, Outi; Tonacchera, Massimo; Jüppner, Harald

2015-05-01

Hypocalcemia and hyperphosphatemia because of resistance toward parathyroid hormone (PTH) in the proximal renal tubules are the most prominent abnormalities in patients affected by pseudohypoparathyroidism type Ib (PHP-Ib). In this rare disorder, which is caused by GNAS methylation changes, resistance can occur toward other hormones, such as thyroid-stimulating hormone (TSH), that mediate their actions through G protein-coupled receptors. However, these additional laboratory abnormalities are usually not recognized until PTH-resistant hypocalcemia becomes clinically apparent. We now describe four pediatric patients, first diagnosed with subclinical or overt hypothyroidism between the ages of 0.2 and 15 years, who developed overt PTH-resistance 3 to 20 years later. Although anti-thyroperoxidase (anti-TPO) antibodies provided a plausible explanation for hypothyroidism in one of these patients, this and two other patients revealed broad epigenetic GNAS abnormalities, which included loss of methylation (LOM) at exons AS, XL, and A/B, and gain of methylation at exon NESP55; ie, findings consistent with PHP-Ib. LOM at GNAS exon A/B alone led in the fourth patient to the identification of a maternally inherited 3-kb STX16 deletion, a well-established cause of autosomal dominant PHP-Ib. Although GNAS methylation changes were not detected in additional pediatric and adult patients with subclinical hypothyroidism (23 pediatric and 39 adult cases), hypothyroidism can obviously be the initial finding in PHP-Ib patients. One should therefore consider measuring PTH, along with calcium and phosphate, in patients with unexplained hypothyroidism for extended periods of time to avoid hypocalcemia and associated clinical complications. © 2014 American Society for Bone and Mineral Research.

Pediatric IBS: an overview on pathophysiology, diagnosis and treatment.

PubMed

Chogle, Ashish; Mintjens, Stijn; Saps, Miguel

2014-04-01

Irritable bowel syndrome (IBS) is a common disorder in children and adults. The pathogenesis and pathophysiology of IBS remains incompletely understood. The biopsychosocial model, which conceptualizes chronic pain as a dysregulation of the gut-brain-homeostasis with peripheral and central factors mutually influencing each other, is the most accepted framework to explain IBS. Twin and family aggregation studies suggest a genetic component that does not exclusively explain the higher prevalence of IBS in certain families. Social learning (environmental factors) and maladaptive coping predispose children to develop IBS with greater disability and more frequent medical consultations. Early-life events constitute an additional risk factor for the development of IBS and other functional gastrointestinal disorders (FGIDs). Children with a history of cow's milk protein hypersensitivity or abdominal surgeries have a higher prevalence of IBS and other FGIDs years later. IBS frequently follows an episode of acute gastrointestinal inflammation (infectious or non-infectious). This article discusses the importance, known pathophysiological mechanisms, clinical approach, and evidence-based therapeutic options for the management of IBS in children and adolescents. Copyright 2014, SLACK Incorporated.

IBS suppression lattice in RHIC: theory and experimental verification

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fedotov,A.V.; Bai, M.; Bruno, D.

Intra-beam scattering (IBS) is the limiting factor of the luminosity lifetime for Relativistic Heavy Ion Collider (RHIC) operation with heavy ions. Over the last few years the process of IBS was carefully studied in RHIC with dedicated IBS measurements and their comparison with the theoretical models. A new lattice was recently designed and implemented in RHIC to suppress transverse IBS growth, which lowered the average arc dispersion by about 20% [1]. This lattice became operational during RHIC Run-8. We review the IBS suppression mechanism, IBS measurements before and after the lattice change, and comparisons with predictions.

Characterization of the complete sequences and stability of plasmids carrying the genes aac(6')-Ib-cr or qnrS in Shigella flexneri in the Hangzhou area of China.

PubMed

Pu, Xiao-Ying; Gu, Yaming; Li, Jun; Song, Shu-Juan; Lu, Zhe

2018-05-18

The aim of this study was to explore the fluoroquinolone resistance mechanism of aac (6')-Ib-cr and qnrS gene by comparing complete sequences and stability of the aac(6')-Ib-cr- and qnrS-positive plasmids from Shigella isolates in the Hangzhou area of China. The complete sequences of four newly acquired plasmids carrying aac(6')-Ib-cr or qnrS were compared with those of two plasmids obtained previously and two similar reference Escherichia coli plasmids. The results showed that the length, antibiotic resistance genes and genetic environment were different among the plasmids. Moreover, the plasmid stability of three wild-type isolates and five plasmid transformants carrying aac(6')-Ib-cr and/or qnrS was measured in vitro, and all eight isolates were found to have lost their aac(6')-Ib-cr- or qnrS-positive plasmids to a different extent at different stages. When the plasmids were electroporated into Shigella flexneri or they lost positive plasmids, the MICs of ciprofloxacin increased or decreased two- to eightfold for aac(6')-Ib-cr-positive plasmids and 16- to 32-fold for qnrS-positive plasmids. To our knowledge, this is the first report comparing the complete sequences and describing stability for the aac(6')-Ib-cr- and qnrS-positive plasmids from Shigella isolates.

Paternal uniparental isodisomy of the entire chromosome 20 as a molecular cause of pseudohypoparathyroidism type Ib (PHP-Ib).

PubMed

Bastepe, Murat; Altug-Teber, Ozge; Agarwal, Chhavi; Oberfield, Sharon E; Bonin, Michael; Jüppner, Harald

2011-03-01

Pseudohypoparathyoridism type Ib (PHP-Ib) typically defines the presence of end-organ resistance to parathyroid hormone in the absence of Albright's hereditary osteodystrophy. Patients affected by this disorder present with imprinting defects in the complex GNAS locus. Microdeletions within STX16 or GNAS have been identified in familial cases with PHP-Ib, but the molecular cause of the GNAS imprinting defects in sporadic PHP-Ib cases remains poorly defined. We now report a case with sporadic PHP-Ib for whom a SNPlex analysis revealed loss of the maternal GNAS allele. Further analysis of the entire genome with a 100K SNP chip identified a paternal uniparental isodisomy affecting the entire chromosome 20 without evidence for another chromosomal abnormality. Our findings explain the observed GNAS methylation changes and the patient's hormone resistance, and furthermore suggest that chromosome 20 harbors, besides GNAS, no additional imprinted region that contributes to the clinical and laboratory phenotype. Copyright © 2010 Elsevier Inc. All rights reserved.

TSH elevations as the first laboratory evidence for pseudohypoparathyroidism type Ib (PHP-Ib)†

PubMed Central

Molinaro, Angelo; Tiosano, Dov; Takatani, Rieko; Chrysis, Dionisios; Russell, William; Koscielniak, Nikolas; Kottler, Marie-Laure; Agretti, Patrizia; De Marco, Giuseppina; Ahtiainen, Petteri; Christov, Marta; Mäkitie, Outi; Tonacchera, Massimo; Jüppner, Harald

2014-01-01

Hypocalcemia and hyperphosphatemia because of resistance towards parathyroid hormone (PTH) in the proximal renal tubules are the most prominent abnormalities in patients affected by pseudohypoparathyroidism type Ib (PHP-Ib). In this rare disorder that is caused by GNAS methylation changes, resistance can occur towards other hormones, such as thyroid-stimulating hormone (TSH), that mediate their actions through G protein-coupled receptors. However, these additional laboratory abnormalities are usually not recognized until PTH-resistant hypocalcemia becomes clinically apparent. We now describe four pediatric patients, first diagnosed with subclinical or overt hypothyroidism between the ages of 0.2 and 15 years, who developed overt PTH-resistance 3-20 years later. Although anti-TPO antibodies provided a plausible explanation for hypothyroidism in one of these patients, this and two other patients revealed broad epigenetic GNAS abnormalities, which included loss of methylation (LOM) at exons AS, XL and A/B, and gain of methylation at exon NESP55, i.e. findings consistent with PHP-Ib. LOM at GNAS exon A/B alone led in the fourth patient to the identification of a maternally inherited 3-kb STX16 deletion, a well-established cause of autosomal dominant PHP-Ib. Although GNAS methylation changes were not detected in additional pediatric and adult patients with subclinical hypothyroidism (23 pediatric and 39 adult cases), hypothyroidism can obviously be the initial finding in PHP-Ib patients. One should therefore consider measuring PTH, along with calcium and phosphate, in patients with unexplained hypothyroidism for extended periods of time to avoid hypocalcemia and associated clinical complications. PMID:25403028

Lessons Learnt from Post-Infectious IBS

PubMed Central

Sarna, Sushil K.

2011-01-01

The development of IBS symptoms – altered bowel function and abdominal cramping in a subset of adult subjects exposed to severe enteric infections opened up an unprecedented opportunity to understand the etiology of this poorly understood disorder. Perhaps, for the reasons that these symptoms follow a severe enteric infection, and mucosal biopsy tissues are readily available, the focus of most studies thus far has been to show that mild/low-grade mucosal inflammation persisting after the initial infection has subsided causes the IBS symptoms. Parallel studies in non-infectious IBS patients, who did not have prior enteritis, showed similar mild mucosal inflammation. Together, these studies examined the mucosal infiltration of specific immune cells, increase of select inflammatory mediators, mast cell and enterochromaffin cell hyperplasia, and epithelial permeability. In spite of the fact that the data on these topics were not consistent among different studies and clinical trials with prednisone, fluoxetine, and ketotifen failed to provide relief of IBS symptoms, the predominant conclusions were that mild mucosal inflammation is the cause of IBS symptoms. However, the circular smooth muscle cells, and myenteric neurons are the primary regulators of gut motility function, while primary afferent neurons and CNS play essential roles in induction of visceral hypersensitivity – no explanation was provided as to how mild mucosal inflammation causes dysfunction in cells far removed. Accumulating evidence shows that mild mucosal inflammation in IBS patients is in physiological range. It has little deleterious effects on cells within its own environment and therefore it is unlikely to affect cells in the muscularis externa. This review discusses the disconnect between the focus on mild/low-grade mucosal inflammation and the potential mechanisms and molecular dysfunctions in smooth muscle cells, myenteric neurons, and primary afferent neurons that may underlie IBS

Molecular Characterization and Growth Association of Two Apolipoprotein A-Ib Genes in Common Carp (Cyprinus carpio)

PubMed Central

Wang, Xinhua; Yu, Xiaomu; Tong, Jingou

2016-01-01

Apolipoprotein A-I (ApoA-I) is functionally involved in the transportation and metabolism of lipids in vertebrates. In this study, two isoforms of apoA-Ib in common carp (Cyprinus carpio L.) were characterized. Sequence comparison and phylogenetic analysis showed that C. carpio ApoA-Ib is relatively conserved within cyprinid fishes. During embryonic development, C. carpio apoA-Ib was first expressed at the stage of multi-cells, and the highest mRNA level was observed at the stage of optic vesicle. A ubiquitous expression pattern was detected in various tissues with extreme predominance in the liver. Significantly different expression levels were observed between light and heavy body weight groups and also in the compensatory growth test. Seventeen and eight single-nucleotide polymorphisms (SNPs) were identified in matured mRNA of the C. carpio apoA-Ib.1 and apoA-Ib.2, respectively. Two of these SNPs (apoA-Ib.2-g.183A>T and apoA-Ib.2-g.1753C>T) were significantly associated with body weight and body length in two populations of common carp. These results indicate that apoA-Ib may play an important role in the modulation of growth and development in common carp. PMID:27649163

Molecular Characterization and Growth Association of Two Apolipoprotein A-Ib Genes in Common Carp (Cyprinus carpio).

PubMed

Wang, Xinhua; Yu, Xiaomu; Tong, Jingou

2016-09-16

Apolipoprotein A-I (ApoA-I) is functionally involved in the transportation and metabolism of lipids in vertebrates. In this study, two isoforms of apoA-Ib in common carp (Cyprinus carpio L.) were characterized. Sequence comparison and phylogenetic analysis showed that C. carpio ApoA-Ib is relatively conserved within cyprinid fishes. During embryonic development, C. carpio apoA-Ib was first expressed at the stage of multi-cells, and the highest mRNA level was observed at the stage of optic vesicle. A ubiquitous expression pattern was detected in various tissues with extreme predominance in the liver. Significantly different expression levels were observed between light and heavy body weight groups and also in the compensatory growth test. Seventeen and eight single-nucleotide polymorphisms (SNPs) were identified in matured mRNA of the C. carpio apoA-Ib.1 and apoA-Ib.2, respectively. Two of these SNPs (apoA-Ib.2-g.183A>T and apoA-Ib.2-g.1753C>T) were significantly associated with body weight and body length in two populations of common carp. These results indicate that apoA-Ib may play an important role in the modulation of growth and development in common carp.

The IB Diploma and UK University Degree Qualifications

ERIC Educational Resources Information Center

Frank-Gemmill, Gerda

2013-01-01

In recent years the International Baccalaureate (IB) Diploma has become widely accepted as a university-entry qualification in the UK, but there has been little quantitative research into the achievements of IB students at degree level. This study investigates IB students from one selective independent school who entered UK universities between…

Implications of Pharmacogenomics to the Management of IBS.

PubMed

Camilleri, Michael

2018-04-27

The objectives are to review the role of pharmacogenomics in drug metabolism of medications typically used in patients with irritable bowel syndrome (IBS) focusing predominantly on cytochrome P450 metabolism. Other aims are to provide examples of genetic variation of receptors or intermediary pathways that are targets for IBS drugs and to critically appraise the situations where precision medicine is impacting health in IBS. Pharmacogenomics impacts both pharmacokinetics and pharmacodynamics. Although large clinical trials have not incorporated testing for genetic variations that could impact the efficacy of medications in IBS, there are therapeutic advantages to inclusion of pharmacogenomics testing for individual patients, as has been demonstrated particularly in the treatment with central neuromodulators in psychiatry practice. Clinical practice in IBS is moving in the same direction with the aid of commercially available tests focused on drug metabolism. Specific mechanisms leading to pathophysiology of IBS are still poorly characterized, relative to diseases such as cancer and inflammatory bowel disease, and, therefore, pharmacogenomics related to drug pharmacodynamics is still in its infancy and requires extensive future research. With increased attention to pharmacogenomics affecting drug metabolism, it is anticipated that pharmacogenomics will impact care of IBS. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

Non-absorbed Antibiotics for IBS

DTIC Science & Technology

2012-03-16

absorbed antibiotic rifaximin for nonconstipated irritable bowel syndrome (IBS). This effort adds to the body of literature from other, smaller studies that...have demonstrated clinical efficacy for IBS with rifaximin . Non-absorbed antibiotics have been endorsed by the American College of Gastroenterology... rifaximin 400 mg three times daily for 10 days or placebo. During the initial 2 weeks of therapy and the subsequent 10 weeks of follow-up rifaximin

Advances in IBS 2016: A Review of Current and Emerging Data.

PubMed

Schoenfeld, Philip S

2016-08-01

Irritable bowel syndrome (IBS) is characterized by chronic intermittent abdominal pain and associated diarrhea (IBS-D), constipation (IBS-C), or both. IBS can significantly impact patient function and quality of life. The diagnosis of IBS is based on the presence of characteristic symptoms, the exclusion of concerning features, and selected tests to exclude organic diseases that can mimic IBS. The pathophysiology of IBS remains incompletely understood, and new contributing factors have been identified over the past decade. Altered gut immune activation, intestinal permeability, and the intestinal and colonic microbiome may be important factors. Poorly absorbed carbohydrates have been implicated in triggering IBS symptoms. Increasing evidence supports the benefit of a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs). Although there are several randomized controlled trials of probiotics in IBS, they are typically poorly designed and have not consistently demonstrated efficacy. Until recently, there were few effective treatments for IBS-D. Data from recent clinical trials support the use of rifaximin, eluxadoline, and peppermint oil. Options for the treatment of IBS-C include lubiprostone and linaclotide.

Advances in IBS 2016: A Review of Current and Emerging Data

PubMed Central

Schoenfeld, Philip S.

2016-01-01

Irritable bowel syndrome (IBS) is characterized by chronic intermittent abdominal pain and associated diarrhea (IBS-D), constipation (IBS-C), or both. IBS can significantly impact patient function and quality of life. The diagnosis of IBS is based on the presence of characteristic symptoms, the exclusion of concerning features, and selected tests to exclude organic diseases that can mimic IBS. The pathophysiology of IBS remains incompletely understood, and new contributing factors have been identified over the past decade. Altered gut immune activation, intestinal permeability, and the intestinal and colonic microbiome may be important factors. Poorly absorbed carbohydrates have been implicated in triggering IBS symptoms. Increasing evidence supports the benefit of a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs). Although there are several randomized controlled trials of probiotics in IBS, they are typically poorly designed and have not consistently demonstrated efficacy. Until recently, there were few effective treatments for IBS-D. Data from recent clinical trials support the use of rifaximin, eluxadoline, and peppermint oil. Options for the treatment of IBS-C include lubiprostone and linaclotide. PMID:28070176

Diagnosis of IBS: symptoms, symptom-based criteria, biomarkers or 'psychomarkers'?

PubMed

Sood, Ruchit; Law, Graham R; Ford, Alexander C

2014-11-01

IBS is estimated to have a prevalence of up to 20% in Western populations and results in substantial costs to health-care services worldwide, estimated to be US$1 billion per year in the USA. IBS remains difficult to diagnose due to its multifactorial aetiology, heterogeneous nature and overlap of symptoms with organic pathologies, such as coeliac disease and IBD. As a result, IBS often continues to be a diagnosis of exclusion, resulting in unnecessary investigations. Available methods for the diagnosis of IBS-including the current gold standard, the Rome III criteria-perform only moderately well. Visceral hypersensitivity and altered pain perception do not discriminate between IBS and other functional gastrointestinal diseases or health with any great accuracy. Attention has now turned to developing novel biomarkers and using psychological markers (so-called psychomarkers) to aid the diagnosis of IBS. This Review describes how useful symptoms, symptom-based criteria, biomarkers and psychomarkers, and indeed combinations of all these approaches, are in the diagnosis of IBS. Future directions in diagnosing IBS could include combining demographic data, gastrointestinal symptoms, biomarkers and psychomarkers using statistical methods. Latent class analysis to distinguish between IBS and non-IBS symptom profiles might also represent a promising avenue for future research.

Sensitivity to wheat, gluten and FODMAPs in IBS: facts or fiction?

PubMed

De Giorgio, Roberto; Volta, Umberto; Gibson, Peter R

2016-01-01

IBS is one of the most common types of functional bowel disorder. Increasing attention has been paid to the causative role of food in IBS. Food ingestion precipitates or exacerbates symptoms, such as abdominal pain and bloating in patients with IBS through different hypothesised mechanisms including immune and mast cell activation, mechanoreceptor stimulation and chemosensory activation. Wheat is regarded as one of the most relevant IBS triggers, although which component(s) of this cereal is/are involved remain(s) unknown. Gluten, other wheat proteins, for example, amylase-trypsin inhibitors, and fructans (the latter belonging to fermentable oligo-di-mono-saccharides and polyols (FODMAPs)), have been identified as possible factors for symptom generation/exacerbation. This uncertainty on the true culprit(s) opened a scenario of semantic definitions favoured by the discordant results of double-blind placebo-controlled trials, which have generated various terms ranging from non-coeliac gluten sensitivity to the broader one of non-coeliac wheat or wheat protein sensitivity or, even, FODMAP sensitivity. The role of FODMAPs in eliciting the clinical picture of IBS goes further since these short-chain carbohydrates are found in many other dietary components, including vegetables and fruits. In this review, we assessed current literature in order to unravel whether gluten/wheat/FODMAP sensitivity represent 'facts' and not 'fiction' in IBS symptoms. This knowledge is expected to promote standardisation in dietary strategies (gluten/wheat-free and low FODMAP) as effective measures for the management of IBS symptoms. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

A mechanistic multicentre, parallel group, randomised placebo-controlled trial of mesalazine for the treatment of IBS with diarrhoea (IBS-D).

PubMed

Lam, Ching; Tan, Wei; Leighton, Matthew; Hastings, Margaret; Lingaya, Melanie; Falcone, Yirga; Zhou, Xiaoying; Xu, Luting; Whorwell, Peter; Walls, Andrew F; Zaitoun, Abed; Montgomery, Alan; Spiller, Robin

2016-01-01

Immune activation has been reported in the mucosa of IBS patients with diarrhoea (IBS-D), and some small studies have suggested that mesalazine may reduce symptoms. We performed a double-blind, randomised placebo-controlled trial of 2 g mesalazine twice daily versus placebo for 3 months in patients with Rome III criteria IBS-D. Primary outcome was daily average stool frequency during weeks 11-12; secondary outcomes were abdominal pain, stool consistency, urgency and satisfactory relief of IBS symptoms. Participants were randomised after a 2-week baseline stool diary. All participants completed a 12-week stool diary and at the end of each week recorded the presence of 'satisfactory relief of IBS symptoms'. 136 patients with IBS-D (82 women, 54 men) were randomised, 10 patients withdrew from each group. Analysis by intention to treat showed the daily average stool frequency during weeks 11 and 12 were mean (SD), 2.8 (1.2) in mesalazine and 2.7 (1.9) in the placebo group with no significant group difference, (95% CI) 0.1 (-0.33 to 0.53), p=0.66. Mesalazine did not improve abdominal pain, stool consistency nor percentage with satisfactory relief compared with placebo during the last two-weeks follow-up. This study does not support any clinically meaningful benefit or harm of mesalazine compared with placebo in unselected patients with IBS-D. More precise subtyping based on underlying disease mechanisms is needed to allow more effective targeting of treatment in IBS. NCT01316718. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

A Comparison of FLT to FDG PET/CT in the Early Assessment of Chemotherapy Response in Stage IB-IIIA Resectable NSCLC

ClinicalTrials.gov

2017-01-27

Recurrent Non-Small Cell Lung Carcinoma; Stage IB Non-Small Cell Lung Carcinoma; Stage IIA Non-Small Cell Lung Carcinoma; Stage IIB Non-Small Cell Lung Carcinoma; Stage IIIA Non-Small Cell Lung Cancer; Stage IV Non-Small Cell Lung Cancer

Intestinal Microbiota And Diet in IBS: Causes, Consequences, or Epiphenomena?

PubMed Central

Rajilić-Stojanović, Mirjana; Jonkers, Daisy M; Salonen, Anne; Hanevik, Kurt; Raes, Jeroen; Jalanka, Jonna; de Vos, Willem M; Manichanh, Chaysavanh; Golic, Natasa; Enck, Paul; Philippou, Elena; Iraqi, Fuad A; Clarke, Gerard; Spiller, Robin C; Penders, John

2015-01-01

Irritable bowel syndrome (IBS) is a heterogeneous functional disorder with a multifactorial etiology that involves the interplay of both host and environmental factors. Among environmental factors relevant for IBS etiology, the diet stands out given that the majority of IBS patients report their symptoms to be triggered by meals or specific foods. The diet provides substrates for microbial fermentation, and, as the composition of the intestinal microbiota is disturbed in IBS patients, the link between diet, microbiota composition, and microbial fermentation products might have an essential role in IBS etiology. In this review, we summarize current evidence regarding the impact of diet and the intestinal microbiota on IBS symptoms, as well as the reported interactions between diet and the microbiota composition. On the basis of the existing data, we suggest pathways (mechanisms) by which diet components, via the microbial fermentation, could trigger IBS symptoms. Finally, this review provides recommendations for future studies that would enable elucidation of the role of diet and microbiota and how these factors may be (inter)related in the pathophysiology of IBS. PMID:25623659

Intestinal microbiota and diet in IBS: causes, consequences, or epiphenomena?

PubMed

Rajilić-Stojanović, Mirjana; Jonkers, Daisy M; Salonen, Anne; Hanevik, Kurt; Raes, Jeroen; Jalanka, Jonna; de Vos, Willem M; Manichanh, Chaysavanh; Golic, Natasa; Enck, Paul; Philippou, Elena; Iraqi, Fuad A; Clarke, Gerard; Spiller, Robin C; Penders, John

2015-02-01

Irritable bowel syndrome (IBS) is a heterogeneous functional disorder with a multifactorial etiology that involves the interplay of both host and environmental factors. Among environmental factors relevant for IBS etiology, the diet stands out given that the majority of IBS patients report their symptoms to be triggered by meals or specific foods. The diet provides substrates for microbial fermentation, and, as the composition of the intestinal microbiota is disturbed in IBS patients, the link between diet, microbiota composition, and microbial fermentation products might have an essential role in IBS etiology. In this review, we summarize current evidence regarding the impact of diet and the intestinal microbiota on IBS symptoms, as well as the reported interactions between diet and the microbiota composition. On the basis of the existing data, we suggest pathways (mechanisms) by which diet components, via the microbial fermentation, could trigger IBS symptoms. Finally, this review provides recommendations for future studies that would enable elucidation of the role of diet and microbiota and how these factors may be (inter)related in the pathophysiology of IBS.

Experience with IBS-suppression lattice in RHIC

DOE Office of Scientific and Technical Information (OSTI.GOV)

Litvinenko,V.N.; Luo, Y.; Ptitsyn, V.

An intra-beam scattering (IBS) is the limiting factor of the luminosity lifetime for RHIC operating with heavy ions. In order to suppress the IBS we designed and implemented new lattice with higher betatron tunes. This lattice had been developed during last three years and had been used for gold ions in yellow ring of the RHIC during d-Au part of the RHIC Run-8. The use of this lattice allowed both significant increases in the luminosity lifetime and the luminosity levels via reduction of beta-stars in the IPS. In this paper we report on the development, the tests and the performancemore » of IBS-suppression lattice in RHIC, including the resulting increases in the peak and the average luminosity. We also report on our plans for future steps with the IBS suppression.« less

Platelet Glycoprotein Ib-IX and Malignancy

DTIC Science & Technology

2010-09-01

provide a unique microenvironment supporting the accumulation of more platelets and the elaboration of a fibrin - rich network produced by coagulation...process and can initiate the formation of a platelet - rich thrombus by tethering the platelet to a thrombogenic surface. Several ligands binding to GP Ib... Platelet Glycoprotein Ib-IX and Malignancy PRINCIPAL INVESTIGATOR: Jerry Ware, Ph.D

Widening Participation to an IB Education

ERIC Educational Resources Information Center

Finkel, Ed

2012-01-01

The global economy demands globally educated workers and citizens. About 1,300 schools in the United States--and a total of about 3,200 in 141 countries worldwide--have turned to the International Baccalaureate (IB) curriculum as their ticket to educating students who are worldly-wise. But only 25 or 30 percent of students in IB World Schools are…

More negative self-esteem and inferior coping strategies among patients diagnosed with IBS compared with patients without IBS--a case-control study in primary care.

PubMed

Grodzinsky, Ewa; Walter, Susanna; Viktorsson, Lisa; Carlsson, Ann-Kristin; Jones, Michael P; Faresjö, Åshild

2015-01-28

Irritable Bowel Syndrome (IBS) is a chronic, relapsing gastrointestinal disorder, that affects approximately 10% of the general population and the majority are diagnosed in primary care. IBS has been reported to be associated with altered psychological and cognitive functioning such as mood disturbances, somatization, catastrophizing or altered visceral interoception by negative emotions and stress. The aim was to investigate the psychosocial constructs of self-esteem and sense of coherence among IBS patients compared to non-IBS patients in primary care. A case-control study in primary care setting among IBS patients meeting the ROME III criteria (n = 140) compared to controls i.e. non-IBS patients (n = 213) without any present or previous gastrointestinal complaints. The data were collected through self-reported questionnaires of psychosocial factors. IBS-patients reported significantly more negative self-esteem (p < 0.001), lower scores for positive self-esteem (p < 0.001), and lower sense of coherence (p < 0.001) than the controls. The IBS-cases were also less likely to report 'good' health status (p < 0.001) and less likely to report a positive belief in the future (p < 0.001). After controlling for relevant confounding factors in multiple regressions, the elevation in negative self-esteem among IBS patients remained statistically significant (p = 0.02), as did the lower scores for sense of coherence among IBS cases (p = 0.04). The more frequently reported negative self-esteem and inferior coping strategies among IBS patients found in this study suggest the possibility that psychological therapies might be helpful for these patients. However these data do not indicate the causal direction of the observed associations. More research is therefore warranted to determine whether these psychosocial constructs are more frequent in IBS patients.

Total costs of IBS: employer and managed care perspective.

PubMed

Cash, Brooks; Sullivan, Sean; Barghout, Victoria

2005-04-01

Irritable bowel syndrome (IBS) is a common gastrointestinal motility disorder that typically affects persons of working age and is costly to employers. The financial burden attributable to the direct (use of healthcare resources) and indirect (missed days from work [absenteeism] and loss of productivity while at work [presenteeism]) costs of IBS is similar to that of other common long-term medical disorders, such as asthma, migraine, hypertension, and congestive heart failure. The symptoms of IBS are significantly bothersome and place a substantial burden on the personal and working lives of patients. As with other long-term medical conditions that have a significant impact on productivity, directed efforts by employers can address IBS in the workplace and thereby potentially decrease its impact. In this article, the symptoms of IBS and its impact on patients and on society as a whole are discussed; options are outlined by which employers can help reduce the total costs of IBS, including lost productivity (both absenteeism and presenteeism), in the workplace.

Chemoradiation Therapy and Ipilimumab in Treating Patients With Stages IB2-IIB or IIIB-IVA Cervical Cancer

ClinicalTrials.gov

2018-05-24

Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Positive Para-Aortic Lymph Node; Positive Pelvic Lymph Node; Stage IB2 Cervical Cancer AJCC v6 and v7; Stage II Cervical Cancer AJCC v7; Stage IIA Cervical Cancer AJCC v7; Stage IIB Cervical Cancer AJCC v6 and v7; Stage IIIB Cervical Cancer AJCC v6 and v7; Stage IVA Cervical Cancer AJCC v6 and v7

Effects of Disturbed Sleep on Gastrointestinal and Somatic Pain Symptoms in IBS

PubMed Central

Patel, Ami; Hasak, Stephen; Cassell, Benjamin; Ciorba, Matthew A.; Vivio, Emily E.; Kumar, Mrudula; Gyawali, C. Prakash; Sayuk, Gregory S.

2016-01-01

Summary Background Sleep disturbances are common, and perhaps are even more prevalent in irritable bowel syndrome (IBS). Aim To determine the effect of measured sleep on: 1) IBS symptoms the following day, and IBS-specific quality of life (IBS-QOL), and 2) non-GI pain symptoms. Methods IBS patients’ sleep patterns were compared to healthy individuals via wrist-mounted actigraphy over 7 days. Daily bowel pain logs (severity, distress; 10-point Likert), stool pattern (Bristol scale) and supporting symptoms (e.g., bloating, urgency; 5-point Likert) were kept. Validated measures, including the GI Symptom Rating Scale-IBS, Visceral Sensitivity Index, Pittsburgh Sleep Quality Index and the IBS-Quality of Life were collected. Mediation analysis explored the relationship between sleep, mood, and bowel symptoms. Results 50 subjects (38.6±1.0years old, 44 female; 24 IBS and 26 healthy controls) completed sleep monitoring. IBS patients slept more hours per day (7.7±0.2 vs 7.1±0.1, p=0.008), but felt less well-rested. IBS patients demonstrated more waking episodes during sleep (waking episodes; 12.1 vs 9.3, p<0.001). Waking episodes predicted worse abdominal pain (p≤0.01) and GI distress (p<0.001), but not bowel pattern or accessory IBS symptoms (p>0.3 for each). Waking episodes negatively correlated with general- and IBS-specific QOL in IBS (r= −0.58 and −0.52, p<0.001 for each). Disturbed sleep effects on abdominal pain were partially explained by mood as an intermediate. Conclusion Sleep disturbances are more common in IBS, and correlate with IBS-related pain, distress, and poorer IBS-related QOL. Disturbed sleep effects extend beyond the bowel, leading to worse mood and greater somatic pain in IBS patients. PMID:27240555

The fundamental ribosomal RNA transcription initiation factor-IB (TIF-IB, SL1, factor D) binds to the rRNA core promoter primarily by minor groove contacts.

PubMed

Geiss, G K; Radebaugh, C A; Paule, M R

1997-11-14

Acanthamoeba castellanii transcription initiation factor-IB (TIF-IB) is the TATA-binding protein-containing transcription factor that binds the rRNA promoter to form the committed complex. Minor groove-specific drugs inhibit TIF-IB binding, with higher concentrations needed to disrupt preformed complexes because of drug exclusion by bound TIF-IB. TIF-IB/DNA interactions were mapped by hydroxyl radical and uranyl nitrate footprinting. TIF-IB contacts four minor grooves in its binding site. TIF-IB and DNA wrap around each other in a right-handed superhelix of high pitch, so the upstream and downstream contacts are on opposite faces of the helix. Dimethyl sulfate protection assays revealed limited contact with a few guanines in the major groove. This detailed analysis suggests significant DNA conformation dependence of the interaction.

IBS Treatment Options

MedlinePlus

... also consider... The use and benefits offered by cognitive-behavioral therapy Consulting with your doctor about the use of ... Medications Probiotics and Antibiotics Psychological Treatments Understanding Stress Cognitive Behavioral Therapy Relaxation Techniques for IBS Take Part in Online ...

IBS-like symptoms in patients with ulcerative colitis

PubMed Central

Gracie, David J; Ford, Alexander C

2015-01-01

Ulcerative colitis (UC) and irritable bowel syndrome (IBS) are chronic gastrointestinal disorders that, until recently, have been considered dichotomous conditions falling on either side of a functional-organic divide. However, persistent gastrointestinal symptoms, akin to those of IBS, are observed in up to one in three patients with quiescent UC. Whether these lower gastrointestinal symptoms are secondary to coexistent IBS or occult UC disease activity is uncertain, but when objective evidence of disease activity is lacking, escalation of conventional pharmacotherapy in such patients is often ineffective. The etiologies of both UC and IBS remain unclear, but dysregulation of the enteric nervous system, an altered microbiome, low-grade mucosal inflammation, and activation of the brain–gut axis is common to both; this suggests that some overlap between the two conditions is plausible. How best to investigate and manage IBS-type symptoms in UC patients remains unclear. Studies that have assessed patients with UC who meet criteria for IBS for subclinical inflammation have been conflicting in their results. Although evidence-based treatments for IBS exist, their efficacy in UC patients reporting these types of symptoms remains unclear. Given the disturbances in gut microbiota in UC, and the possible role of the brain–gut axis in the generation of such symptoms, treatments such as probiotics, fecal transfer, antidepressants, or psychological therapies would seem logical approaches to use in this group of patients. However, there are only limited data for all of these therapies; this suggests that randomized controlled trials to investigate their efficacy in this setting may be warranted. PMID:25733921

IBS-like symptoms in patients with ulcerative colitis.

PubMed

Gracie, David J; Ford, Alexander C

2015-01-01

Ulcerative colitis (UC) and irritable bowel syndrome (IBS) are chronic gastrointestinal disorders that, until recently, have been considered dichotomous conditions falling on either side of a functional-organic divide. However, persistent gastrointestinal symptoms, akin to those of IBS, are observed in up to one in three patients with quiescent UC. Whether these lower gastrointestinal symptoms are secondary to coexistent IBS or occult UC disease activity is uncertain, but when objective evidence of disease activity is lacking, escalation of conventional pharmacotherapy in such patients is often ineffective. The etiologies of both UC and IBS remain unclear, but dysregulation of the enteric nervous system, an altered microbiome, low-grade mucosal inflammation, and activation of the brain-gut axis is common to both; this suggests that some overlap between the two conditions is plausible. How best to investigate and manage IBS-type symptoms in UC patients remains unclear. Studies that have assessed patients with UC who meet criteria for IBS for subclinical inflammation have been conflicting in their results. Although evidence-based treatments for IBS exist, their efficacy in UC patients reporting these types of symptoms remains unclear. Given the disturbances in gut microbiota in UC, and the possible role of the brain-gut axis in the generation of such symptoms, treatments such as probiotics, fecal transfer, antidepressants, or psychological therapies would seem logical approaches to use in this group of patients. However, there are only limited data for all of these therapies; this suggests that randomized controlled trials to investigate their efficacy in this setting may be warranted.

A Swedish national adoption study of risk of irritable bowel syndrome (IBS).

PubMed

Waehrens, Rasmus; Zöller, Bengt; Sundquist, Jan; Sundquist, Kristina; Pirouzifard, MirNabi

2017-01-01

Irritable bowel syndrome (IBS) clusters in families, but the familial risk of IBS has not been determined in adoptees. Studying adoptees and their biological and adoptive parents is a strong study design for separating genetic from environmental causes of familial clustering. This nationwide study aimed to separate the biological (genetic) and familial environmental contribution to the familial transmission of IBS. We performed a family study for Swedish-born adoptees born from 1951 until 1995, and their biological and adoptive parents. The Swedish Multigeneration Register was linked to the Hospital Register (inpatients and outpatients) for the period 1964-2012 and the Swedish Outpatient Care Register for 2001-2012, and the Swedish Primary Healthcare register for 1989-2012. ORs for IBS were calculated for adoptees with an affected biological parent with IBS compared with adoptees without a biological parent with IBS. The OR for IBS was also determined in adoptees with an adoptive parent with IBS compared with adoptees without an adoptive parent with IBS. Heritability h 2 (±SE) was also determined. The ORs for IBS were 1.67 in adoptees (95% CI 1.06 to 2.62) of biological parents diagnosed with IBS. The ORs for IBS were 0.88 in adoptees (95% CI 0.48 to 1.63) of adoptive parents diagnosed with IBS. The heritability was 19.5%±8.5%. The present study indicates that biological (genetic) factors are important for the familial clustering of IBS. The heritability calculated is in the range from twin studies and suggests that heritability may be estimated in adoptees.

Integrals for IBS and beam cooling

DOE Office of Scientific and Technical Information (OSTI.GOV)

Burov, A.; /Fermilab

Simulation of beam cooling usually requires performing certain integral transformations every time step or so, which is a significant burden on the CPU. Examples are the dispersion integrals (Hilbert transforms) in the stochastic cooling, wake fields and IBS integrals. An original method is suggested for fast and sufficiently accurate computation of the integrals. This method is applied for the dispersion integral. Some methodical aspects of the IBS analysis are discussed.

Integrals for IBS and Beam Cooling

DOE Office of Scientific and Technical Information (OSTI.GOV)

Burov, A.

Simulation of beam cooling usually requires performing certain integral transformations every time step or so, which is a significant burden on the CPU. Examples are the dispersion integrals (Hilbert transforms) in the stochastic cooling, wake fields and IBS integrals. An original method is suggested for fast and sufficiently accurate computation of the integrals. This method is applied for the dispersion integral. Some methodical aspects of the IBS analysis are discussed.

A Swedish national adoption study of risk of irritable bowel syndrome (IBS)

PubMed Central

Waehrens, Rasmus; Sundquist, Jan; Sundquist, Kristina; Pirouzifard, MirNabi

2017-01-01

Objectives Irritable bowel syndrome (IBS) clusters in families, but the familial risk of IBS has not been determined in adoptees. Studying adoptees and their biological and adoptive parents is a strong study design for separating genetic from environmental causes of familial clustering. This nationwide study aimed to separate the biological (genetic) and familial environmental contribution to the familial transmission of IBS. Methods We performed a family study for Swedish-born adoptees born from 1951 until 1995, and their biological and adoptive parents. The Swedish Multigeneration Register was linked to the Hospital Register (inpatients and outpatients) for the period 1964–2012 and the Swedish Outpatient Care Register for 2001–2012, and the Swedish Primary Healthcare register for 1989–2012. ORs for IBS were calculated for adoptees with an affected biological parent with IBS compared with adoptees without a biological parent with IBS. The OR for IBS was also determined in adoptees with an adoptive parent with IBS compared with adoptees without an adoptive parent with IBS. Heritability h 2 (±SE) was also determined. Results The ORs for IBS were 1.67 in adoptees (95% CI 1.06 to 2.62) of biological parents diagnosed with IBS. The ORs for IBS were 0.88 in adoptees (95% CI 0.48 to 1.63) of adoptive parents diagnosed with IBS. The heritability was 19.5%±8.5%. Conclusions The present study indicates that biological (genetic) factors are important for the familial clustering of IBS. The heritability calculated is in the range from twin studies and suggests that heritability may be estimated in adoptees. PMID:29119001

Robust vascular invasion concurrent with intense EGFR immunostaining can predict recurrence in patients with stage IB node-negative gastric cancer.

PubMed

Araki, Ippeita; Washio, Marie; Yamashita, Keishi; Hosoda, Kei; Ema, Akira; Mieno, Hiroaki; Moriya, Hiromitsu; Katada, Natsuya; Kikuchi, Shiro; Watanabe, Masahiko

2018-05-01

The prognosis of most patients with stage IB node-negative gastric cancer is good without postoperative chemotherapy; however, about 10% suffer recurrence and inevitably die. We conducted this study to establish the optimal indications for postoperative adjuvant chemotherapy in patients at risk of recurrence. The subjects of this retrospective study were 124 patients with stage IB node-negative gastric cancer, who underwent gastrectomy at the Kitasato University East Hospital, between 2001 and 2010. We reviewed EGFR immunohistochemistry (IHC) as well as clinicopathological factors. Of the 124 patients, 47 (38%) showed intense EGFR IHC (2+ or 3+), with significantly less frequency than in stage II/III advanced gastric cancer (p < 0.001). According to univariate analysis, intense EGFR IHC was significantly associated with relapse-free survival (RFS) (p = 0.023) and associated with overall survival (OS) (p = 0.045) as well as vascular invasion (p = 0.031). On the multivariate Cox proportional hazards model, intense EGFR IHC(p = 0.016) was an independent prognostic predictor for RFS, and both vascular invasion (p = 0.033) and intense EGFR IHC (p = 0.031) were independent prognostic predictors for OS. The combination of both factors increased the risk of recurrence (p = 0.001). In stage IB node-negative gastric cancer, vascular invasion and intense EGFR IHC increase the likelihood of recurrence. We recommend adjuvant chemotherapy for such patients because of the high risk of metachronous recurrence.

Nivolumab After Surgery and Chemotherapy in Treating Patients With Stage IB-IIIA Non-small Cell Lung Cancer (An ALCHEMIST Treatment Trial)

ClinicalTrials.gov

2018-06-28

Stage IB Non-Small Cell Lung Carcinoma AJCC v7; Stage II Non-Small Cell Lung Cancer AJCC v7; Stage IIA Non-Small Cell Lung Carcinoma AJCC v7; Stage IIB Non-Small Cell Lung Carcinoma AJCC v7; Stage IIIA Non-Small Cell Lung Cancer AJCC v7

Gefitinib in Treating Patients With Stage IB, II, or IIIA Non-small Cell Lung Cancer That Was Completely Removed by Surgery

ClinicalTrials.gov

2014-12-19

Adenocarcinoma of the Lung; Adenosquamous Cell Lung Cancer; Bronchoalveolar Cell Lung Cancer; Large Cell Lung Cancer; Squamous Cell Lung Cancer; Stage IB Non-small Cell Lung Cancer; Stage IIA Non-small Cell Lung Cancer; Stage IIB Non-small Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer

Genetic Testing in Screening Patients With Stage IB-IIIA Non-Small Cell Lung Cancer That Has Been or Will Be Removed by Surgery (The ALCHEMIST Screening Trial)

ClinicalTrials.gov

2018-06-29

Large Cell Lung Carcinoma; Lung Adenocarcinoma; Stage IB Non-Small Cell Lung Carcinoma AJCC v7; Stage IB Squamous Cell Lung Carcinoma AJCC v7; Stage II Non-Small Cell Lung Cancer AJCC v7; Stage II Squamous Cell Lung Carcinoma AJCC v7; Stage IIA Non-Small Cell Lung Carcinoma AJCC v7; Stage IIA Squamous Cell Lung Carcinoma AJCC v7; Stage IIB Non-Small Cell Lung Carcinoma AJCC v7; Stage IIB Squamous Cell Lung Carcinoma AJCC v7; Stage IIIA Non-Small Cell Lung Cancer AJCC v7; Stage IIIA Squamous Cell Lung Carcinoma AJCC v7

Patient educational media preferences for information about irritable bowel syndrome (IBS).

PubMed

Halpert, Albena; Dalton, Christine B; Palsson, Olafur; Morris, Carolyn; Hu, Yuming; Bangdiwala, Shrikant; Hankins, Jane; Norton, Nancy; Drossman, Douglas A

2008-12-01

To identify the educational media preferences of patients with irritable bowel syndrome (IBS). The IBS-Patient Education Questionnaire (PEQ) was administered to a national sample of IBS patients. Frequencies of item endorsements were compared and meaningful clinical differences were used to identify differences among subgroups. 1,242 patients completed the survey, mean age 39.3 years, 85% female, IBS duration 6.9 years, 79% had seen an MD for IBS within 6 months, and 92.6% used the web for medical information. The most desired source of education was "my doctor" (68%), followed by Internet (62%) and brochure (45%). Notably, patients favored an increase in use of media in the future (past vs. future): doctor (43 vs. 68%); Internet (36 vs. 62%); and brochures (26 vs. 45%). IBS patients expect more education than they have received. Understanding IBS patients' learning preferences can be highly valuable in the development or implementation of educational interventions.

Blastocystis sp. in Irritable Bowel Syndrome (IBS)--Detection in Stool Aspirates during Colonoscopy.

PubMed

Ragavan, Nanthiney Devi; Kumar, Suresh; Chye, Tan Tian; Mahadeva, Sanjiv; Shiaw-Hooi, Ho

2015-01-01

Blastocystis is one of the most common gut parasites found in the intestinal tract of humans and animals. Its' association with IBS is controversial, possibly as a result of irregular shedding of parasites in stool and variation in stool detection. We aimed to screen for Blastocystis in colonic stool aspirate samples in adult patients with and without IBS undergoing colonoscopy for various indications and measure the interleukin levels (IL-8, IL-3 and IL-5). In addition to standard stool culture techniques, polymerase chain reaction (PCR) techniques were employed to detect and subtype Blastocystis. All the serum samples collected were subjected for ELISA studies to measure the interleukin levels (IL-8, IL-3 and IL-5). Among 109 (IBS n = 35 and non-IBS n = 74) adults, direct stool examination and culture of colonic aspirates were initially negative for Blastocystis. However, PCR analysis detected Blastocystis in 6 (17%) IBS and 4 (5.5%) non-IBS patients. In the six positive IBS patients by PCR method, subtype 3 was shown to be the most predominant (3/6: 50%) followed by subtype 4 (2/6; 33.3%) and subtype 5 (1/6; 16.6%). IL-8 levels were significantly elevated in the IBS Blasto group and IBS group (p<0.05) compared to non-IBS and non-IBS Blasto group. The level of IL-3 in were seen to be significantly higher in than IBS Blasto group and IBS group (p<0.05) compared to non-IBS. Meanwhile, the IL-5 levels were significantly higher in IBS Blasto group (p<0.05) compared to non-IBS and non-IBS Blasto group. This study implicates that detecting Blastosystis by PCR method using colonic aspirate samples during colonoscopy, suggests that this may be a better method for sample collection due to the parasite's irregular shedding in Blastocystis-infected stools. Patients with IBS infected with parasite showed an increase in the interleukin levels demonstrate that Blastocystis does have an effect in the immune system.

Effects of omitting elective neck irradiation to nodal Level IB in nasopharyngeal carcinoma patients with negative Level IB lymph nodes treated by intensity-modulated radiotherapy: a Phase 2 study.

PubMed

Li, Mei; Huang, Xiao-Guang; Yang, Zhi-Ning; Lu, Jia-Yang; Zhan, Yi-Zhou; Xie, Wen-Jia; Zhou, Dong-Jie; Wang, Li; Zhu, Di-Xia; Lin, Zhi-Xiong

2016-09-01

To investigate the need for elective neck irradiation (ENI) to nodal Level IB in patients with nasopharyngeal carcinoma (NPC) with negative Level IB lymph nodes (IB-negative) treated by intensity-modulated radiotherapy (IMRT). We conducted a Phase 2 prospective study in 123 newly diagnosed IB-negative patients with NPC treated by IMRT, who met at least 1 of the following criteria: (1) unilateral or bilateral Level II involvement with 1 of the following: Level IIA involvement or any Level II node ≥2 cm/with extracapsular spread; (2) ≥2 unilateral node-positive regions. Bilateral Level IB nodes were not contoured as part of the treatment target and treated electively. Level IB regional recurrence rate; pattern of treatment failure; 3-year overall survival (3y-OS), 3-year local control (3y-LC) and 3-year regional control (3y-RC) rates; toxicities; and dosimetric data for planning target volumes, organs at risk, Level IB and submandibular glands (SMGs) were evaluated. Two patients developed failures at Level IB (1.6%). The 3y-LC, 3y-RC and 3y-OS rates were 93.5%, 93.5% and 78.0%, respectively. Bilateral Level IB received unplanned high-dose irradiation with a mean dose (Dmean) ≥50 Gy in 60% of patients. The average Dmean of bilateral SMGs was approximately 53 Gy. ENI to Level IB may be unnecessary in IB-negative patients with NPC treated by IMRT. A further Phase 3 study is warranted. Based on the results of this first Phase 2 study, we suggest omitting ENI to Level IB in Ib-negative patients with NPC with extensive nodal disease treated by IMRT.

Motility response to colonic distention is increased in postinfectious irritable bowel syndrome (PI-IBS).

PubMed

Kanazawa, M; Palsson, O S; van Tilburg, M A L; Gangarosa, L M; Fukudo, S; Whitehead, W E

2014-05-01

Acute intestinal infection leads to persistent intestinal smooth muscle hypercontractility and pain hypersensitivity after resolution of the infection in animal models. We investigated whether postinfectious irritable bowel syndrome (PI-IBS) is associated with abnormalities in phasic contractions of the colon, smooth muscle tone, and pain sensitivity compared to non-PI-IBS (NI-IBS) or healthy controls (HC). Two hundred and eighteen Rome III-positive IBS patients and 43 HC participated. IBS patients were designated PI-IBS, if their IBS symptoms began following an episode of gastroenteritis characterized by two or more of: fever, vomiting, or diarrhea. Pain threshold to phasic distentions of the descending colon was assessed using a barostat. Colonic motility was assessed with the barostat bag minimally inflated to the individual operating pressure (IOP), at 20 mmHg above the IOP, and following a test meal. IBS symptom severity and psychological symptoms were assessed by the IBS Severity Scale (IBS-SS) and the Brief Symptom Inventory-18 (BSI-18). Twenty two (10.1%) met criteria for PI-IBS. Both IBS and HC groups showed a significant increase in motility index during intraluminal distention and following meals. The magnitude of the response to distention above (orad to) the balloon was significantly greater in PI-IBS compared with NI-IBS (p < 0.05) or HC (p < 0.01). Differences between PI-IBS and NI-IBS were not significant for IBS symptom severity, pain threshold, barostat bag volumes, or any psychological score on the BSI-18. Patients with PI-IBS have greater colonic hypercontractility than NI-IBS. We speculate that sustained mild mucosal inflammation may cause this colonic irritability. © 2014 John Wiley & Sons Ltd.

Pseudohypoparathyroidism type Ib associated with novel duplications in the GNAS locus.

PubMed

Perez-Nanclares, Gustavo; Velayos, Teresa; Vela, Amaya; Muñoz-Torres, Manuel; Castaño, Luis

2015-01-01

Pseudohypoparathyroidism type 1b (PHP-Ib) is characterized by renal resistance to PTH (and, sometimes, a mild resistance to TSH) and absence of any features of Albright's hereditary osteodystrophy. Patients with PHP-Ib suffer of defects in the methylation pattern of the complex GNAS locus. PHP-Ib can be either sporadic or inherited in an autosomal dominant pattern. Whereas familial PHP-Ib is well characterized at the molecular level, the genetic cause of sporadic PHP-Ib cases remains elusive, although some molecular mechanisms have been associated with this subtype. The aim of the study was to investigate the molecular and imprinting defects in the GNAS locus in two unrelated patients with PHP-Ib. We have analyzed the GNAS locus by direct sequencing, Methylation-Specific Multiplex Ligation-dependent Probe Amplification, microsatellites, Quantitative Multiplex PCR of Short Fluorescent fragments and array-Comparative Genomic Hybridization studies in order to characterize two unrelated families with clinical features of PHP-Ib. We identified two duplications in the GNAS region in two patients with PHP-Ib: one of them, comprising ∼ 320 kb, occurred 'de novo' in the patient, whereas the other one, of ∼ 179 kb in length, was inherited from the maternal allele. In both cases, no other known genetic cause was observed. In this article, we describe the to-our-knowledge biggest duplications reported so far in the GNAS region. Both are associated to PHP-Ib, one of them occurring 'de novo' and the other one being maternally inherited.

Post-infectious IBS, tropical sprue and small intestinal bacterial overgrowth: the missing link.

PubMed

Ghoshal, Uday C; Gwee, Kok-Ann

2017-07-01

Evidence is emerging that IBS, a hitherto enigmatic disorder thought to be predominantly related to psychological factors, has a microorganic basis in a subset of patients with the disease. Post-infectious IBS (PI-IBS), commonly of the diarrhoea-predominant subtype (defined as new development of IBS following acute infectious diarrhoea), is one such condition known to occur in up to 10-30% individuals after acute gastroenteritis. However, following acute infectious gastroenteritis, patients can also develop post-infectious malabsorption syndrome (PI-MAS), popularly known as tropical sprue. As no study on PI-IBS has rigorously excluded tropical sprue by appropriate investigations, including small intestinal biopsy, the frequency of tropical sprue among patients with PI-IBS is not known. Small intestinal bacterial overgrowth (SIBO) has been suggested to be associated with IBS in general, and in particular diarrhoea-predominant IBS, including PI-IBS. SIBO is also known to be associated with tropical sprue. As both IBS, particularly the subset probably associated with SIBO, and tropical sprue improve with antibiotic treatment, we provide evidence and an explanatory model to support a link among these disorders.

Integrated Baseline System (IBS), Version 1. 03. [Chemical Stockpile Emergency Preparedness Program

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bailey, B.M.; Burford, M.J.; Downing, T.R.

The Integrated Baseline System (IBS), operated by the Federal Emergency Management Agency (FEMA), is a system of computerized tools for emergency planing and analysis. This document is the user guide for the IBS and explains how to operate the IBS system. The fundamental function of the IBS is to provide tools that civilian emergency management personnel can use in developing emergency plans and in supporting emergency management activities to cope with a chemical-releasing event at a military chemical stockpile. Emergency management planners can evaluate concepts and ideas using the IBS system. The results of that experience can then be factoredmore » into refining requirements and plans. This document provides information for the general system user, and is the primary reference for the system features of the IBS. It is designed for persons who are familiar with general emergency management concepts, operations, and vocabulary. Although the IBS manual set covers basic and advanced operations, it is not a complete reference document set. Emergency situation modeling software in the IBS is supported by additional technical documents. Some of the other LBS software is commercial software for which more complete documentation is available. The IBS manuals reference such documentation where necessary. IBS is a dynamic system. Its capabilities are in a state of continuing expansion and enhancement.« less

IBS FOR ION DISTRIBUTION UNDER ELECTRON COOLING.

DOE Office of Scientific and Technical Information (OSTI.GOV)

FEDOTOV,A.V.; BEN-ZVI,I.; EIDELMAN, YU.

Standard models of the intra-beam scattering (IBS) are based on the growth of the rms beam parameters for a Gaussian distribution. As a result of electron cooling, the core of beam distribution is cooled much faster than the tails, producing a denser core. In this paper, we compare various approaches to IBS treatment for such distribution. Its impact on the luminosity is also discussed.

New insights into visceral hypersensitivity —clinical implications in IBS

PubMed Central

Zhou, QiQi; Verne, G. Nicholas

2012-01-01

A subset of patients with IBS have visceral hypersensitivity and/or somatic hypersensitivity. Visceral hypersensitivity might have use as a clinical marker of IBS and could account for symptoms of urgency for bowel movements, bloating and abdominal pain. The mechanisms that lead to chronic visceral hypersensitivity in patients who have IBS are unclear. However, several working models may be considered, including: nociceptive input from the colon that leads to hypersensitivity; increased intestinal permeability that induces a visceral nociceptive drive; and alterations in the expression of microRNAs in gastrointestinal tissue that might be delivered via blood microvesicles to other target organs, such as the peripheral and/or central nervous system. As such, the chronic visceral hypersensitivity that is present in a subset of patients with IBS might be maintained by both peripheral and central phenomena. The theories underlying the development of chronic visceral hypersensitivity in patients with IBS are supported by findings from new animal models in which hypersensitivity follows transient inflammation of the colon. The presence of somatic hypersensitivity and an alteration in the neuroendocrine system in some patients who have IBS suggests that multisystemic factors are involved in the overall disorder. Thus, IBS is similar to other chronic pain disorders, such as fibromyalgia, chronic regional pain disorder and temporomandibular joint disorder, as chronic nociceptive mechanisms are activated in all of these disorders. PMID:21643039

Emerging treatments in neurogastroenterology: eluxadoline - a new therapeutic option for diarrhea-predominant IBS.

PubMed

Lacy, B E

2016-01-01

Irritable bowel syndrome (IBS) is the most common functional gastrointestinal disorder worldwide. The global prevalence of IBS is estimated to be as high as 15%. For many patients, IBS is a chronic disorder which can significantly reduce quality of life. Just as important as the effects on any one individual, IBS also places a significant impact on the population as a whole with its negative effects on the health care system. Irritable bowel syndrome is categorized into one of three main categories: IBS with diarrhea, IBS with constipation, and IBS with mixed bowel habits. Patients with diarrhea-predominant IBS (IBS-D) comprise a substantial proportion of the overall IBS population. A number of therapeutic options exist to treat the symptoms of abdominal pain, bloating, diarrhea, and fecal urgency, including non-pharmacologic therapies such as dietary changes and probiotics, or pharmacologic therapies such as loperamide and alosetron. However, many patients have persistent symptoms despite these therapies. This unmet need led to the development of eluxadoline, a mu-opioid receptor agonist/delta-opioid receptor antagonist/kappa-receptor agonist. Approved by the FDA in May 2015, this medication shows promise in the treatment of diarrhea-predominant IBS for both men and women. This monograph will briefly review the impact of IBS, discuss current treatments for IBS-D, and then focus on the pharmacology, clinical efficacy and safety of eluxadoline. Potential mechanisms related to rare events of acute pancreatitis or elevated liver tests will be discussed. © 2015 John Wiley & Sons Ltd.

Quality of life in patients with Irritable Bowel Syndrome (IBS), assessed using the IBS-Quality of Life (IBS-QOL) measure after 4 and 8 weeks of treatment with mebeverine hydrochloride or pinaverium bromide: results of an international prospective observational cohort study in Poland, Egypt, Mexico and China.

PubMed

Hou, Xiaohua; Chen, Shengliang; Zhang, Yali; Sha, Weihong; Yu, Xiaofeng; Elsawah, Hesham; Afifi, Afifi Fahmy; El-Khayat, Hisham Raafat; Nouh, Alaa; Hassan, Mohamed Fathalla; Fatah, Ayman Abdel; Rucker Joerg, Isabel; Sánchez Núñez, Juan Manuel; Osthoff Rueda, Rodolfo; Jurkowska, Grazyna; Walczak, Michal; Malecka-Panas, Ewa; Linke, Krzysztof; Hartleb, Marek; Janssen-van Solingen, Gwendolyn

2014-11-01

Irritable Bowel Syndrome (IBS) has a substantial impact on health-related quality of life (HR-QoL) but high-quality data pre- and post-treatment using the IBS-Quality of Life (IBS-QOL) measure are limited. The objective of this study was to evaluate the changes from baseline of the IBS-QOL scores, symptom scores and health economic data in IBS patients, after 4 and 8 weeks of treatment with mebeverine hydrochloride or pinaverium bromide. This was a prospective observational cohort study in patients with IBS, diagnosed using the Rome III criteria in four countries (Poland, Egypt, Mexico and China). A total of 607 patients were enrolled. At baseline, the IBS-QOL total scores were 52.0 in Poland, 48.9 in Egypt, 51.9 in Mexico, 76.4 in China and 56.4 overall. Increases in IBS-QOL total score were statistically significant at Weeks 4 and 8 overall and in each country (overall: 11.8 at Week 4, 24.3 at Week 8; p < 0.001). Improvements were shown in all IBS-QOL subscales and scores. Symptoms and health economic outcomes were improved. Furthermore, the favourable safety profile of these treatments was confirmed in this study. This study demonstrated that IBS patients have a substantially reduced HR-QoL and that treatment with mebeverine hydrochloride or pinaverium bromide improved HR-QoL.

Randomised controlled trial of mesalazine in IBS

PubMed Central

Barbara, Giovanni; Cremon, Cesare; Annese, Vito; Basilisco, Guido; Bazzoli, Franco; Bellini, Massimo; Benedetti, Antonio; Benini, Luigi; Bossa, Fabrizio; Buldrini, Paola; Cicala, Michele; Cuomo, Rosario; Germanà, Bastianello; Molteni, Paola; Neri, Matteo; Rodi, Marcello; Saggioro, Alfredo; Scribano, Maria Lia; Vecchi, Maurizio; Zoli, Giorgio; Corinaldesi, Roberto; Stanghellini, Vincenzo

2016-01-01

Objective Low-grade intestinal inflammation plays a role in the pathophysiology of IBS. In this trial, we aimed at evaluating the efficacy and safety of mesalazine in patients with IBS. Design We conducted a phase 3, multicentre, tertiary setting, randomised, double-blind, placebo-controlled trial in patients with Rome III confirmed IBS. Patients were randomly assigned to either mesalazine, 800 mg, or placebo, three times daily for 12 weeks, and were followed for additional 12 weeks. The primary efficacy endpoint was satisfactory relief of abdominal pain/discomfort for at least half of the weeks of the treatment period. The key secondary endpoint was satisfactory relief of overall IBS symptoms. Supportive analyses were also performed classifying as responders patients with a percentage of affirmative answers of at least 75% or >75% of time. Results A total of 185 patients with IBS were enrolled from 21 centres. For the primary endpoint, the responder patients were 68.6% in the mesalazine group versus 67.4% in the placebo group (p=0.870; 95% CI −12.8 to 15.1). In explorative analyses, with the 75% rule or >75% rule, the percentage of responders was greater in the mesalazine group with a difference over placebo of 11.6% (p=0.115; 95% CI −2.7% to 26.0%) and 5.9% (p=0.404; 95% CI −7.8% to 19.4%), respectively, although these differences were not significant. For the key secondary endpoint, overall symptoms improved in the mesalazine group and reached a significant difference of 15.1% versus placebo (p=0.032; 95% CI 1.5% to 28.7%) with the >75% rule. Conclusions Mesalazine treatment was not superior than placebo on the study primary endpoint. However, a subgroup of patients with IBS showed a sustained therapy response and benefits from a mesalazine therapy. Trial registration number ClincialTrials.gov number, NCT00626288. PMID:25533646

Glycoprotein and Glycan in Tissue and Blood Samples of Patients With Stage IB-IVA Cervical Cancer Undergoing Surgery to Remove Pelvic and Abdominal Lymph Nodes

ClinicalTrials.gov

2017-08-23

Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Small Cell Carcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Stage IB Cervical Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Cervical Cancer; Stage IVA Cervical Cancer

Integrated Baseline System (IBS) Version 2.0: Utilities Guide

DOE Office of Scientific and Technical Information (OSTI.GOV)

Burford, M.J.; Downing, T.R.; Williams, J.R.

1994-03-01

The Integrated Baseline System (IBS) is an emergency management planning and analysis tool being developed under the direction of the US Army Nuclear and Chemical Agency. This Utilities Guide explains how you can use the IBS utility programs to manage and manipulate various kinds of IBS data. These programs include utilities for creating, editing, and displaying maps and other data that are referenced to geographic location. The intended audience for this document are chiefly data managers but also system managers and some emergency management planners and analysts.

Motility Response to Colonic Distention is Increased in Post-infectious Irritable Bowel Syndrome (PI-IBS)

PubMed Central

Kanazawa, Motoyori; Palsson, Olafur S.; van Tilburg, Miranda A.L.; Gangarosa, Lisa M.; Fukudo, Shin; Whitehead., William E.

2015-01-01

Background Acute intestinal infection leads to persistent intestinal smooth muscle hypercontractility and pain hypersensitivity after resolution of the infection in animal models. We investigated whether post-infectious irritable bowel syndrome (PI-IBS) is associated with abnormalities in phasic contractions of the colon, smooth muscle tone and pain sensitivity compared to non-PI-IBS (NI-IBS) or healthy controls (HC). Methods 218 Rome III positive IBS patients and 43 healthy controls participated. IBS patients were designated PI-IBS if their IBS symptoms began following an episode of gastroenteritis characterized by 2 or more of: fever, vomiting, or diarrhea. Pain threshold to phasic distentions of the descending colon was assessed using a barostat. Colonic motility was assessed with the barostat bag minimally inflated to the individual operating pressure (IOP), at 20 mmHg above the IOP, and following a test meal. IBS symptom severity and psychological symptoms were assessed by the IBS Severity Scale (IBS-SS) and the Brief Symptom Inventory-18 (BSI-18). Key Results Twenty-two (10.1%) met criteria for PI-IBS. Both IBS and HC groups showed a significant increase in motility index during intraluminal distention and following meals. The magnitude of the response to distention above (orad to) the balloon was significantly greater in PI-IBS compared with NI-IBS (p<0.05) or HC (p<0.01). Differences between PI-IBS and NI-IBS were not significant for IBS symptom severity, pain threshold, barostat bag volumes, or any psychological score on the BSI-18. Conclusions & Inferences Patients with PI-IBS have greater colonic hypercontractility than NI-IBS. We speculate that sustained mild mucosal inflammation may cause this colonic irritability. PMID:24602083

How Accessible Is IB Schooling? Evidence from Australia

ERIC Educational Resources Information Center

Dickson, Anisah; Perry, Laura B.; Ledger, Susan

2017-01-01

This study examines access to International Baccalaureate schools in Australia. It is important to examine whether, as a highly regarded form of rigorous academic education, IB programmes are available to a wide range of students. We examine the location of schools in Australia that offer one or more of the IB Primary Years Programme, Middle Years…

2-Alkynoic fatty acids inhibit topoisomerase IB from Leishmania donovani.

PubMed

Carballeira, Néstor M; Cartagena, Michelle; Sanabria, David; Tasdemir, Deniz; Prada, Christopher F; Reguera, Rosa M; Balaña-Fouce, Rafael

2012-10-01

2-Alkynoic fatty acids display antimycobacterial, antifungal, and pesticidal activities but their antiprotozoal activity has received little attention. In this work we synthesized the 2-octadecynoic acid (2-ODA), 2-hexadecynoic acid (2-HDA), and 2-tetradecynoic acid (2-TDA) and show that 2-ODA is the best inhibitor of the Leishmania donovani DNA topoisomerase IB enzyme (LdTopIB) with an EC(50)=5.3±0.7μM. The potency of LdTopIB inhibition follows the trend 2-ODA>2-HDA>2-TDA, indicating that the effectiveness of inhibition depends on the fatty acid carbon chain length. All of the studied 2-alkynoic fatty acids were less potent inhibitors of the human topoisomerase IB enzyme (hTopIB) as compared to LdTopIB. 2-ODA also displayed in vitro activity against Leishmania donovani (IC(50)=11.0μM), but it was less effective against other protozoa, Trypanosoma cruzi (IC(50)=48.1μM) and Trypanosoma brucei rhodesiense (IC(50)=64.5μM). The antiprotozoal activity of the 2-alkynoic fatty acids, in general, followed the trend 2-ODA>2-HDA>2-TDA. The experimental information gathered so far indicates that 2-ODA is a promising antileishmanial compound. Copyright © 2012 Elsevier Ltd. All rights reserved.

Low fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) diet improves symptoms in adults suffering from irritable bowel syndrome (IBS) compared to standard IBS diet: A meta-analysis of clinical studies.

PubMed

Varjú, Péter; Farkas, Nelli; Hegyi, Péter; Garami, András; Szabó, Imre; Illés, Anita; Solymár, Margit; Vincze, Áron; Balaskó, Márta; Pár, Gabriella; Bajor, Judit; Szűcs, Ákos; Huszár, Orsolya; Pécsi, Dániel; Czimmer, József

2017-01-01

Irritable bowel syndrome (IBS) and functional digestive tract disorders, e.g. functional bloating, carbohydrate maldigestion and intolerances, are very common disorders frequently causing significant symptoms that challenge health care systems. A low Fermentable Oligosaccharides, Disaccharides, Monosaccharides and Polyols (FODMAP) diet is one of the possible therapeutic approaches for decreasing abdominal symptoms and improving quality of life. We aimed to meta-analyze data on the therapeutic effect of a low-FODMAP diet on symptoms of IBS and quality of life and compare its effectiveness to a regular, standard IBS diet with high FODMAP content, using a common scoring system, the IBS Symptom Severity Score (IBS-SSS). A systematic literature search was conducted in PubMed, EMBASE and the Cochrane Library as well as in the references in a recent meta-analysis. Adult patients diagnosed with IBS according to the Rome II, Rome III, Rome IV or NICE criteria were included in the analysis. Mean differences with 95% confidence intervals were calculated from studies that contained means, standard deviation (SD) or mean differences and SD of differences and p-values. A random effect model was used because of the heterogeneity (Q test (χ2) and I2 indicator). A p-value of less than 0.05 was chosen to indicate a significant difference. The literature search yielded 902 publications, but only 10 were eligible for our meta-analysis. Both regular and low-FODMAP diets proved to be effective in IBS, but post-diet IBS-SSS values were significantly lower (p = 0.002) in the low-FODMAP group. The low-FODMAP diet showed a correlation with the improvement of general symptoms (by IBS-SSS) in patients with IBS. This meta-analysis provides high-grade evidence of an improved general symptom score among patients with irritable bowel syndrome who have maintained a low-FODMAP diet compared to those on a traditional IBS diet, therefore showing its superiority to regular IBS dietary therapy. These

HLA class Ib in pregnancy and pregnancy-related disorders.

PubMed

Persson, Gry; Melsted, Wenna Nascimento; Nilsson, Line Lynge; Hviid, Thomas Vauvert F

2017-08-01

The HLA class Ib genes, HLA-E, HLA-F, and HLA-G, were discovered long after the classical HLA class Ia genes. The elucidation of their functions had a modest beginning. However, their basic functions and involvement in pathophysiology and a range of diseases are now emerging. Although results from a range of studies support the functional roles for the HLA class Ib molecules in adult life, especially HLA-G and HLA-F have most intensively been, and were also primarily, studied in relation to reproduction and pregnancy. The expression of HLA class Ib proteins at the feto-maternal interface in the placenta seems to be important for the maternal acceptance of the semi-allogenic fetus. In contrast to the functions of HLA class Ia, HLA-G possesses immune-modulatory and tolerogenic functions. Here, we review an accumulating amount of data describing the functions of HLA class Ib molecules in relation to fertility, reproduction, and pregnancy, and a possible role for these molecules in certain pregnancy complications, such as implantation failure, recurrent spontaneous abortions, and pre-eclampsia. The results from different kinds of studies point toward a role for HLA class Ib, especially HLA-G, throughout the reproductive cycle from conception to the birth weight of the child.

Interaction between preprandial and postprandial rectal sensory and motor abnormalities in IBS.

PubMed

Törnblom, Hans; Van Oudenhove, Lukas; Tack, Jan; Simrén, Magnus

2014-09-01

Rectal sensory and motor interactions in patients with IBS have not been studied in detail. The aim of this study was to evaluate fasting and postprandial rectal sensorimotor characteristics and their interactions in IBS compared with healthy controls. We included 274 patients with IBS and 34 controls. All subjects underwent a rectal barostat study before and 60 min after a standardised liquid meal (800 kcal; 60% fat). Sensory thresholds, intensity of sensations, viscerosomatic referral and compliance were measured. During 15 min before the first distension sequence and until 50 min after meal intake, rectal balloon volumes were registered in 5 min intervals at operating pressure to quantify rectal tone. Mixed models were used to analyse the rectal tone response over time. Rectal sensory thresholds and compliance were decreased and viscerosomatic referral areas increased in patients with IBS compared with controls. Meal intake increased rectal sensitivity, compliance and referral areas in patients and controls and the same proportions of patients were hypersensitive to distension before and after meal intake. There was a higher basal rectal tone in IBS and a significantly different rectal tone response after meal intake in patients with IBS compared with controls and, interestingly, also in IBS with rectal hypersensitivity (defined in the preprandial state), compared with normosensitive patients. Meal intake affects rectal sensorimotor function in IBS and health. Importantly, the rectal tone responses to a high-caloric meal are different between patients with IBS and controls, as well as between hypersensitive and normosensitive patients with IBS. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Low fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) diet improves symptoms in adults suffering from irritable bowel syndrome (IBS) compared to standard IBS diet: A meta-analysis of clinical studies

PubMed Central

Varjú, Péter; Farkas, Nelli; Hegyi, Péter; Garami, András; Szabó, Imre; Illés, Anita; Solymár, Margit; Vincze, Áron; Balaskó, Márta; Pár, Gabriella; Bajor, Judit; Szűcs, Ákos; Huszár, Orsolya; Pécsi, Dániel

2017-01-01

Background Irritable bowel syndrome (IBS) and functional digestive tract disorders, e.g. functional bloating, carbohydrate maldigestion and intolerances, are very common disorders frequently causing significant symptoms that challenge health care systems. A low Fermentable Oligosaccharides, Disaccharides, Monosaccharides and Polyols (FODMAP) diet is one of the possible therapeutic approaches for decreasing abdominal symptoms and improving quality of life. Objectives We aimed to meta-analyze data on the therapeutic effect of a low-FODMAP diet on symptoms of IBS and quality of life and compare its effectiveness to a regular, standard IBS diet with high FODMAP content, using a common scoring system, the IBS Symptom Severity Score (IBS-SSS). Methods A systematic literature search was conducted in PubMed, EMBASE and the Cochrane Library as well as in the references in a recent meta-analysis. Adult patients diagnosed with IBS according to the Rome II, Rome III, Rome IV or NICE criteria were included in the analysis. Statistical methods Mean differences with 95% confidence intervals were calculated from studies that contained means, standard deviation (SD) or mean differences and SD of differences and p-values. A random effect model was used because of the heterogeneity (Q test (χ2) and I2 indicator). A p-value of less than 0.05 was chosen to indicate a significant difference. Results The literature search yielded 902 publications, but only 10 were eligible for our meta-analysis. Both regular and low-FODMAP diets proved to be effective in IBS, but post-diet IBS-SSS values were significantly lower (p = 0.002) in the low-FODMAP group. The low-FODMAP diet showed a correlation with the improvement of general symptoms (by IBS-SSS) in patients with IBS. Conclusions This meta-analysis provides high-grade evidence of an improved general symptom score among patients with irritable bowel syndrome who have maintained a low-FODMAP diet compared to those on a traditional IBS diet

Evaluation of the Irritable Bowel Syndrome Quality of Life (IBS-QOL) questionnaire in diarrheal-predominant irritable bowel syndrome patients

PubMed Central

2013-01-01

Background Diarrhea-predominant irritable bowel syndrome (IBS-d) significantly diminishes the health-related quality of life (HRQOL) of patients. Psychological and social impacts are common with many IBS-d patients reporting comorbid depression, anxiety, decreased intimacy, and lost working days. The Irritable Bowel Syndrome Quality of Life (IBS-QOL) questionnaire is a 34-item instrument developed and validated for measurement of HRQOL in non-subtyped IBS patients. The current paper assesses this previously-validated instrument employing data collected from 754 patients who participated in a randomized clinical trial of a novel treatment, eluxadoline, for IBS-d. Methods Psychometric methods common to HRQOL research were employed to evaluate the IBS-QOL. Many of the historical analyses of the IBS-QOL validations were used. Other techniques that extended the original methods were applied where more appropriate for the current dataset. In IBS-d patients, we analyzed the items and substructure of the IBS-QOL via item reduction, factor structure, internal consistency, reproducibility, construct validity, and ability to detect change. Results This study supports the IBS-QOL as a psychometrically valid measure. Factor analyses suggested that IBS-specific QOL as measured by the IBS-QOL is a unidimensional construct. Construct validity was further buttressed by significant correlations between IBS-QOL total scores and related measures of IBS-d severity including the historically-relevant Irritable Bowel Syndrome Adequate Relief (IBS-AR) item and the FDA’s Clinical Responder definition. The IBS-QOL also showed a significant ability to detect change as evidenced by analysis of treatment effects. A minority of the items, unrelated to the IBS-d, performed less well by the standards set by the original authors. Conclusions We established that the IBS-QOL total score is a psychometrically valid measure of HRQOL in IBS-d patients enrolled in this study. Our analyses suggest that

Less versus more radical surgery in stage IB1 cervical cancer: A population-based study of long-term survival.

PubMed

Tseng, Jill H; Aloisi, Alessia; Sonoda, Yukio; Gardner, Ginger J; Zivanovic, Oliver; Abu-Rustum, Nadeem R; Leitao, Mario M

2018-05-15

Standard surgical treatment for women with stage IB1 cervical cancer consists of radical hysterectomy. This study assesses survival outcomes of those treated with less radical surgery (LRS; conization, trachelectomy, simple hysterectomy) compared to more radical surgery (MRS; modified radical, radical hysterectomy). Using the Surveillance, Epidemiology and End Results database, we identified women <45 years with FIGO stage IB1 cervical cancer diagnosed from 1/1998 to 12/2012. Only those who underwent lymph node (LN) assessment were analyzed. Disease-specific survivals (DSSs) of LRS were compared with those of MRS. Of 2571 patients, 807 underwent LRS and 1764 underwent MRS, all with LN assessment. For LRS vs. MRS, 28% vs. 23% were diagnosed with adenocarcinoma (p = 0.024), 31% vs. 39% had G3 disease (p < 0.001), 40% vs. 45% had tumor size >2 cm (p < 0.001), and 27% vs. 29% received adjuvant radiation therapy (p = 0.005). Median follow-up was 79 months (range, 0-179). Ten-year DSS for LRS vs. MRS was 93.5% vs. 92.3% (p = 0.511). There was no difference in 10-year DSS when stratified by tumor size ≤2 cm (LRS 95.1% vs. MRS 95.6%, p = 0.80) or > 2 cm (LRS 90.1% vs. MRS 88.2%, p = 0.48). Factors independently associated with increased risk of death included adenosquamous histology (HR 2.37), G3 disease (HR 2.86), tumors >2 cm (HR 1.82), and LN positivity (HR 2.42). Compared to MRS, LRS was not associated with a higher risk of death. In a select group of young women with stage IB1 cervical cancer, LRS compared to MRS does not appear to compromise DSS. Copyright © 2018 Elsevier Inc. All rights reserved.

Risk strata-based therapy and outcome in stage Ib-IIa carcinoma cervix: single-centre ten-year experience.

PubMed

Kundargi, Rajshekar S; Guruprasad, B; Rathod, Praveen Shankar; Shakuntala, Pn; Shobha, K; Pallavi, Vr; Uma Devi, K; Bafna, Ud

2013-01-01

To review the outcome of stage (Ib, IIa), cervical cancer patients were primarily treated with radical hysterectomy and risk-based postoperative therapy. Between January 2001 and December 2011, 601 cases underwent surgery followed by tailored therapy. Patients were classified into low risk (pelvic lymph node negative, tumour less than 4 cm, no evidence of lympho-vascular invasion, less than one-third of thickness of surgical stoma involved), intermediate risk (positive lympho-vascular space invasion, tumour size more than 4 cm, and deep invasion of cervical stroma), and high risk (pelvic lymph node involved, positive parametrial, or vaginal margins) groups. Postoperative adju-vant therapy in the form of radiotherapy alone to those with intermediate risk and chemo-radiotherapy to those with high risk was given to patients. The median follow-up was 60 months. The majority of patients had intermediate risk. The overall event-free survival (EFS) at five years was 74.37%, with EFS of 86.5% in those from the low-risk group, 73% in those from the intermediate-risk group, and 64% in those from the high-risk group. In conclusion, risk strata-based adjuvant postoperative therapy is able to provide a favourable outcome in patients with stage Ib-IIa cervical cancer with a nearly 11% improvement in survival compared with historical control.

Critical Success Factors for Lean Thinking in the Application of Industrialised Building System (IBS)

NASA Astrophysics Data System (ADS)

Yunus, Riduan; Noor, Siti Rahimah Mohd; Halid Abdullah, Abd; Nagapan, Sasitharan; Hamid, Abdul Rahim Abdul; Tajudin, Saiful Azhar Ahmad; Rohani Mat Jusof, Siti

2017-08-01

Productivity in the manufacturing process of building components can be increased by optimising each advantage that is available in each activity. Identification of critical success factors (CSFs) for lean thinking in the Industrialised Building System (IBS) will be able to minimise cost and reduce time needed to complete a project. The focus of lean thinking in construction is on the production process and the client’s requirement. In developing countries such as Malaysia, the integration of lean thinking in IBS applications is still low and there is a shortage of comprehensive strategies to integrate lean thinking. As key stakeholders, feedback from contractors, manufacturers, developers and the local authority will be able to help the identification of CSFs in integrating lean thinking in IBS applications. The data was collected through a questionnaire survey and analysed quantitatively. There are 31 CSFs for lean thinking in IBS which have been identified in this study. A conceptual model was developed to assist researchers in investigating the influences of CSFs for lean thinking in IBS applications. This study will assist construction players to improvise their manufacturing process in the implementation of IBS to eliminate unnecessary activities and focus instead on significant processes without generating physical and non-physical waste.

The severity of inflammation at onset of ulcerative colitis is not associated with IBS-like symptoms during clinical remission.

PubMed

Jonefjäll, Börje; Simrén, Magnus; Öhman, Lena; Lasson, Anders; Svedlund, Jan; Strid, Hans

2015-09-01

Symptoms compatible with irritable bowel syndrome (IBS) are common in patients with ulcerative colitis (UC) in clinical remission. It has been suggested that these symptoms might arise due to post-inflammatory changes comparable with post-infectious IBS. The aim was to study factors at new onset of UC that predict development of IBS-like symptoms during clinical remission. In total, 98 patients with new onset of UC were followed prospectively for 3 years with yearly follow-up visits. Data from the first visit at the onset of UC were compared between a group of patients who fulfilled the criteria for IBS while in remission (UCR+IBS) during follow-up and a group who did not (UCR-IBS). Among the UC patients, 87 met the criteria for clinical remission and 25 (29%) of these reported IBS-like symptoms in remission during follow-up. There was no difference in inflammatory disease activity at the initial flare or in the prevalence of previous IBS symptoms when comparing UCR+IBS and UCR-IBS patients. The UCR+IBS patients reported more severe gastrointestinal symptoms, including abdominal pain, during their primary flare. The severity and extent of inflammation at onset of UC do not seem to affect the development of IBS-like symptoms in UC patients during clinical remission. The high prevalence of IBS-like symptoms is not explained by pre-existing IBS. UCR+IBS patients reported more severe gastrointestinal symptoms at disease onset, which might indicate a more sensitive gastrointestinal tract in this category of patients. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Comparison of the Rome IV and Rome III criteria for IBS diagnosis: A cross-sectional survey.

PubMed

Bai, Tao; Xia, Jing; Jiang, Yudong; Cao, Huan; Zhao, Yong; Zhang, Lei; Wang, Huan; Song, Jun; Hou, Xiaohua

2017-05-01

The aims of this study were to investigate the proportion of clinical irritable bowel syndrome (IBS) at a tertiary hospital in China, to compare the Rome III and Rome IV criteria with regard to IBS diagnosis, to describe the agreement between the Rome III and Rome IV criteria, and to identify differences between Rome IV-positive and -negative IBS patients. A cross-sectional survey was performed among outpatients in the gastrointestinal (GI) department of a tertiary hospital. The patients were categorized as having IBS using Rome III and Rome IV criteria. In total, 1,376 (91.7%) patients completed a GI symptom questionnaire. Among them, 352 were suspected of having IBS and 175 were diagnosed with IBS using the Rome III or Rome IV criteria. In particular, 170 (12.4%) patients were diagnosed with IBS using the Rome III criteria, and 84 (6.1%) patients were diagnosed using the Rome IV criteria. Rome IV IBS patients experienced more pain symptoms (P<0.01) and showed higher IBS severity scores. In contrast, no significant differences were noted for demographic characteristics, stool frequency, IBS subtype, disease course, operation history or GI infection history between Rome IV IBS patients and IBS patients not diagnosed with the Rome IV criteria. Rome IV-positive IBS patients represented approximately half of Rome III-positive IBS patients at a tertiary hospital in China. More specifically, Rome IV-positive IBS was mainly a subgroup of Rome III-positive IBS with more serious symptoms. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Integrated Baseline System (IBS), Version 1.03. User guide: Chemical Stockpile Emergency Preparedness Program

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bailey, B.M.; Burford, M.J.; Downing, T.R.

The Integrated Baseline System (IBS), operated by the Federal Emergency Management Agency (FEMA), is a system of computerized tools for emergency planing and analysis. This document is the user guide for the IBS and explains how to operate the IBS system. The fundamental function of the IBS is to provide tools that civilian emergency management personnel can use in developing emergency plans and in supporting emergency management activities to cope with a chemical-releasing event at a military chemical stockpile. Emergency management planners can evaluate concepts and ideas using the IBS system. The results of that experience can then be factoredmore » into refining requirements and plans. This document provides information for the general system user, and is the primary reference for the system features of the IBS. It is designed for persons who are familiar with general emergency management concepts, operations, and vocabulary. Although the IBS manual set covers basic and advanced operations, it is not a complete reference document set. Emergency situation modeling software in the IBS is supported by additional technical documents. Some of the other LBS software is commercial software for which more complete documentation is available. The IBS manuals reference such documentation where necessary. IBS is a dynamic system. Its capabilities are in a state of continuing expansion and enhancement.« less

Psychometric assessment of the IBS-D Daily Symptom Diary and Symptom Event Log.

PubMed

Rosa, Kathleen; Delgado-Herrera, Leticia; Zeiher, Bernie; Banderas, Benjamin; Arbuckle, Rob; Spears, Glen; Hudgens, Stacie

2016-12-01

Diarrhea-predominant irritable bowel syndrome (IBS-D) can considerably impact patients' lives. Patient-reported symptoms are crucial in understanding the diagnosis and progression of IBS-D. This study psychometrically evaluates the newly developed IBS-D Daily Symptom Diary and Symptom Event Log (hereafter, "Event Log") according to US regulatory recommendations. A US-based observational field study was conducted to understand cross-sectional psychometric properties of the IBS-D Daily Symptom Diary and Event Log. Analyses included item descriptive statistics, item-to-item correlations, reliability, and construct validity. The IBS-D Daily Symptom Diary and Event Log had no items with excessive missing data. With the exception of two items ("frequency of gas" and "accidents"), moderate to high inter-item correlations were observed among all items of the IBS-D Daily Symptom Diary and Event Log (day 1 range 0.67-0.90). Item scores demonstrated reliability, with the exception of the "frequency of gas" and "accidents" items of the Diary and "incomplete evacuation" item of the Event Log. The pattern of correlations of the IBS-D Daily Symptom Diary and Event Log item scores with generic and disease-specific measures was as expected, moderate for similar constructs and low for dissimilar constructs, supporting construct validity. Known-groups methods showed statistically significant differences and monotonic trends in each of the IBS-D Daily Symptom Diary item scores among groups defined by patients' IBS-D severity ratings ("none"/"mild," "moderate," or "severe"/"very severe"), supporting construct validity. Initial psychometric results support the reliability and validity of the items of the IBS-D Daily Symptom Diary and Event Log.

New insights in IBS-like disorders: Pandora's box has been opened; a review.

PubMed

Borghini, Raffaele; Donato, Giuseppe; Alvaro, Domenico; Picarelli, Antonio

2017-01-01

The most complained gastrointestinal symptoms are chronic diarrhea, bloating and abdominal pain. Once malignancies and inflammatory bowel diseases are excluded, irritable bowel syndrome (IBS) and the so called "IBS-like disorders" should be taken into account. The relationship between IBS as defined by Rome IV criteria and these clinical conditions is sometimes obscure, since many IBS patients identify food as a possible trigger for their symptoms. Here, we discuss IBS and the most common IBS-like disorders (celiac disease, non-celiac gluten sensitivity, fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs), lactose intolerance, small intestinal bacterial overgrowth (SIBO), α-amylase/trypsin inhibitor (ATIs), nickel allergic contact mucositis), focusing on epidemiologic, clinical, diagnostic and therapeutic aspects. Given the lack of specificity of symptoms, clinical investigation will be facilitated by awareness of these disorders as well as new specific diagnostic tools.

Identification of a small molecule inhibitor of the aminoglycoside 6'-N-acetyltransferase type Ib [AAC(6')-Ib] using mixture-based combinatorial libraries.

PubMed

Tran, Tung; Chiem, Kevin; Jani, Saumya; Arivett, Brock A; Lin, David L; Lad, Rupali; Jimenez, Verónica; Farone, Mary B; Debevec, Ginamarie; Santos, Radleigh; Giulianotti, Marc; Pinilla, Clemencia; Tolmasky, Marcelo E

2018-05-01

The aminoglycoside, 6'-N-acetyltransferase type Ib [AAC(6')-Ib] is the most widely distributed enzyme among AAC(6')-I-producing Gram-negative pathogens and confers resistance to clinically relevant aminoglycosides, including amikacin. This enzyme is therefore an ideal target for enzymatic inhibitors that could overcome resistance to aminoglycosides. The search for inhibitors was carried out using mixture-based combinatorial libraries, the scaffold ranking approach, and the positional scanning strategy. A library with high inhibitory activity had pyrrolidine pentamine scaffold and was selected for further analysis. This library contained 738,192 compounds with functionalities derived from 26 different amino acids (R1, R2 and R3) and 42 different carboxylic acids (R4) in four R-group functionalities. The most active compounds all contained S-phenyl (R1 and R3) and S-hydromethyl (R2) functionalities at three locations and differed at the R4 position. The compound containing 3-phenylbutyl at R4 (compound 206) was a robust enzymatic inhibitor in vitro, in combination with amikacin it potentiated the inhibition of growth of three resistant bacteria in culture, and it improved survival when used as treatment of Galleria mellonella infected with aac(6')-Ib-harboring Klebsiella pneumoniae and Acinetobacter baumannii strains. Copyright © 2018 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

Triapine With Chemotherapy and Radiation Therapy in Treating Patients With IB2-IVA Cervical or Vulvar Cancer

ClinicalTrials.gov

2018-04-25

Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Stage IB Vulvar Cancer AJCC v7; Stage IB2 Cervical Cancer AJCC v6 and v7; Stage II Vulvar Cancer AJCC v7; Stage IIA1 Cervical Cancer AJCC v7; Stage IIA2 Cervical Cancer AJCC v7; Stage IIB Cervical Cancer AJCC v6 and v7; Stage IIIA Cervical Cancer AJCC v6 and v7; Stage IIIA Vulvar Cancer AJCC v7; Stage IIIB Cervical Cancer AJCC v6 and v7; Stage IIIB Vulvar Cancer AJCC v7; Stage IIIC Vulvar Cancer AJCC v7; Stage IVA Cervical Cancer AJCC v6 and v7; Stage IVA Vulvar Cancer AJCC v7; Vulvar Adenocarcinoma; Vulvar Squamous Cell Carcinoma

Therapeutic Potential of Zataria multiflora Boiss in Treatment of Irritable Bowel Syndrome (IBS).

PubMed

Mahboubi, Mohaddese

2018-01-15

Irritable Bowel syndrome (IBS), the most common chronic functional gastrointestinal disorder, is categorized as IBS-C and IBS-D, which are equivalent to Ghoolenj Rihi and Maghs Rihi in Iranian traditional medicine. One of the main applications of Zataria multiflora Boiss in traditional medicine is its efficacy in the gastrointestinal tract with symptoms such as IBS. The aim of this study was to evaluate the efficacy of Zataria multiflora essential oil in management of IBS. We used all the accessible references (electronic and published books, theses, and reports) to write this article. The results of our investigation show that the majority of gas chromatography-mass spectrometry (GC-MS) analyses exhibited carvacrol and thymol as the main components of Zataria multiflora essential oil, and 60 drops oral daily dose of Z. multiflora essential oil (2%) can relieve the symptoms of IBS without any adverse effects. The pharmacological studies confirmed the analgesic, anti-inflammatory, antispasm and antiulcer effects of Z. multiflora essential oils and main components. According to the results of studies, oral Z. multiflora essential oil (2%) is a good candidate for management of IBS, but more studies are required to better understand its efficacies.

Serum Tryptophan Metabolite Levels During Sleep in Patients With and Without Irritable Bowel Syndrome (IBS).

PubMed

Heitkemper, Margaret M; Han, Claire Jungyoun; Jarrett, Monica E; Gu, Haiwei; Djukovic, Danijel; Shulman, Robert J; Raftery, Daniel; Henderson, Wendy A; Cain, Kevin C

2016-03-01

Poor sleep and stress are more frequently reported by women with irritable bowel syndrome (IBS) than by healthy control (HC) women. The pathophysiology linking poor sleep and stress to gastrointestinal symptoms remains poorly understood. We used a metabolomic approach to determine whether tryptophan (TRP) metabolites differ between women with and without IBS and whether the levels are associated with sleep indices and serum cortisol levels. This study sample included 38 women with IBS and 21 HCs. The women were studied in a sleep laboratory for three consecutive nights. On the third night of the study, a social stressor was introduced, then blood samples were drawn every 20 min and sleep indices were measured. Metabolites were determined by targeted liquid chromatography tandem mass spectrometry in a sample collected 1 hr after the onset of sleep. The ratios of each metabolite to TRP were used for analyses. Correlations were controlled for age and oral contraceptive use. Melatonin/TRP levels were lower (p = .005) in the IBS-diarrhea group versus the IBS-constipation and HC groups, and kynurenine/TRP ratios tended to be lower (p = .067) in the total IBS and IBS-diarrhea groups compared to HCs. Associations within the HC group included melatonin/TRP with polysomnography-sleep efficiency (r = .61, p = .006) and weaker positive correlations with the other ratios for either sleep efficiency or percentage time in rapid eye movement sleep (r > .40, p = .025-.091). This study suggests that reductions in early nighttime melatonin/TRP levels may be related to altered sleep quality in IBS, particularly those with diarrhea. © The Author(s) 2015.

Anxiety and depression comorbidities in irritable bowel syndrome (IBS): a systematic review and meta-analysis.

PubMed

Fond, Guillaume; Loundou, Anderson; Hamdani, Nora; Boukouaci, Wahid; Dargel, Aroldo; Oliveira, José; Roger, Matthieu; Tamouza, Ryad; Leboyer, Marion; Boyer, Laurent

2014-12-01

Irritable bowel syndrome (IBS) has been associated with high prevalence of psychological disorders. However, it remains unclear whether IBS and each of its subtypes (predominant diarrhea IBS-D, constipation IBS-C, mixed IBS-M) are associated with higher anxiety and depressive symptoms levels. This study aimed to determine the associations of IBS and each of its subtypes with anxiety and/or depression. We conducted a systematic review and meta-analysis using five electronic databases (PubMed, PsychINFO, BIOSIS, Science Direct, and Cochrane CENTRAL). We selected case-control studies comparing anxiety and depression levels of patients with IBS to healthy controls, using standardized rating scales. Outcomes were measured as random pooled standardized mean differences (SMD). Ten studies were included in our analysis (885 patients and 1,384 healthy controls). Patients with IBS had significant higher anxiety and depression levels than controls (respectively, SMD = 0.76, 95 % CI 0.47; 0.69, p < 0.01, I2 = 81.7 % and SMD = 0.80, 95 % CI 0.42; 1.19, p < 0.01, I2 = 90.7 %). This significant difference was confirmed for patients with IBS-C and -D subtypes for anxiety, and only in IBS-D patients for depression. However, other IBS subtypes had a statistical trend to be associated with both anxiety and depressive symptomatology, which suggests a lack of power due to the small number of studies included. Patients with IBS had significantly higher levels of anxiety and depression than healthy controls. Anxiety and depression symptomatology should be systematically checked and treated in IBS patients, as psychological factors are important moderators of symptom severity, symptom persistence, decisions to seek treatment, and response to treatment.

Clostridium perfringens Iota-Toxin: Mapping of Receptor Binding and Ia Docking Domains on Ib

PubMed Central

Marvaud, Jean-Christophe; Smith, Theresa; Hale, Martha L.; Popoff, Michel R.; Smith, Leonard A.; Stiles, Bradley G.

2001-01-01

Clostridium perfringens iota-toxin is a binary toxin consisting of iota a (Ia), an ADP-ribosyltransferase that modifies actin, and iota b (Ib), which binds to a cell surface protein and translocates Ia into a target cell. Fusion proteins of recombinant Ib and truncated variants were tested for binding to Vero cells and docking with Ia via fluorescence-activated cytometry and cytotoxicity experiments. C-terminal residues (656 to 665) of Ib were critical for cell surface binding, and truncated Ib variants containing ≥200 amino acids of the C terminus were effective Ib competitors and prevented iota cytotoxicity. The N-terminal domain (residues 1 to 106) of Ib was important for Ia docking, yet this region was not an effective competitor of iota cytotoxicity. Further studies showed that Ib lacking just the N-terminal 27 residues did not facilitate Ia entry into a target cell and subsequent cytotoxicity. Five monoclonal antibodies against Ib were also tested with each truncated Ib variant for epitope and structural mapping by surface plasmon resonance and an enzyme-linked immunosorbent assay. Each antibody bound to a linear epitope within the N terminus (residues 28 to 66) or the C terminus (residues 632 to 655). Antibodies that target the C terminus neutralized in vitro cytotoxicity and delayed the lethal effects of iota-toxin in mice. PMID:11254604

The effect of PDIA3 gene knockout on the mucosal immune function in IBS rats.

PubMed

Zhuang, Zhao-Meng; Wang, Xiao-Teng; Zhang, Lu; Tao, Li-Yuan; Lv, Bin

2015-01-01

To observe the changes of intestinal inflammation on PDIA3 gene knockout IBS rats and its effect on immune function. 36 SD rats were randomly divided into four groups: the control group (n = 8); IBS- empty virus group (IBS-GFP, which); IBS-PDIA3 knockout group (n = 12); IBS- the control group (n = 12). After modeling, colon and ileocecal tissue pathology in each group were observed separately. Changes of immune and inflammatory markers were measured. At the same time, ultrastructural changes in each group were observed by electron microscopy. Compared with the IBS control group, inflammation was reduced significantly in IBS-PDIA3 knockout group. IgE, IL-4 and IL-9 and the level of intestinal trypsin type were decreased significantly. Furthermore, mast cell degranulation and PAR 2 receptor reduced significantly. PDIA3 may play an important role in the development of IBS by mediating through immune responses of mucosal abnormalities. However, the mechanism needs to be confirmed in further study.

MLCK-mediated intestinal permeability promotes immune activation and visceral hypersensitivity in PI-IBS mice.

PubMed

Long, Y; Du, L; Kim, J J; Chen, B; Zhu, Y; Zhang, Y; Yao, S; He, H; Zheng, X; Huang, Z; Dai, N

2018-04-11

Alterations in intestinal permeability regulated by tight junctions (TJs) are associated with immune activation and visceral hypersensitivity in irritable bowel syndrome (IBS). Myosin light chain kinase (MLCK) is an important mediator of epithelial TJ. The aim of this study is to investigate the role of MLCK in the pathogenesis of IBS using a post infectious IBS (PI-IBS) mouse model. Trichinella spiralis-infected PI-IBS mouse model was used. Urine lactulose/mannitol ratio was measured to assess intestinal epithelial permeability. Western blotting was used to evaluate intestinal TJ protein (zonula occludens-1) and MLCK-associated protein expressions. Immune profile was assessed by measuring Th (T helper) 1/Th2 cytokine expression. Visceral sensitivity was determined by abdominal withdrawal reflex in response to colorectal distension. Eight weeks after inoculation with T. spiralis, PI-IBS mice developed decreased pain and volume thresholds during colorectal distention, increased urine lactulose/mannitol ratio, elevated colonic Th1/Th2 cytokine ratio, and decreased zonula occludens-1 expression compared to the control mice. MLCK expression was dramatically elevated in the colonic mucosa of PI-IBS mice compared to the control mice, alongside increased pMLC/MLC and decreased MLCP expression. Administration of MLCK inhibitor and TJ blocker both reversed the increased intestinal permeability, visceral hypersensitivity, and Th1-dominant immune profile in PI-IBS mice. MLCK is a pivotal step in inducing increased intestinal permeability promoting low-grade intestinal immune activation and visceral hypersensitivity in PI-IBS mice. MLCK inhibitor may provide a potential therapeutic option in the treatment of IBS. © 2018 John Wiley & Sons Ltd.

Key factors of successful JIT integration with IBS - An overview

NASA Astrophysics Data System (ADS)

Asri, Mohammad Azwanie Naim Mohammad; Nawi, Mohd Nasrun Mohd; Nadarajan, Santhirasegaran

2016-08-01

The Just-In-Time (JIT) philosophy has been used for many decades to increase productivity through waste elimination process. The purpose of this paper is to contribute to the knowledge by addressing the transportation and material delivery activities in Industrialized Building System (IBS) and integrating JIT to improve the performance of those activities. The literature review has been conducted through relevant database. It was found that there is a need for more holistic approach to be adopted to integrate JIT in IBS project. This paper discusses the key success factors for effective integration between JIT and IBS in the context of transportation and material delivery activities.

IBS and FAPS in children: a comparison of psychological and clinical characteristics.

PubMed

Rutten, Juliette M T M; Benninga, Marc A; Vlieger, Arine M

2014-10-01

It has been suggested that different subcategories of childhood abdominal pain-related functional gastrointestinal disorders (AP-FGIDs) are not separate clinical entities, but represent variable expressions of the same FGID. The aim of the present study was to compare clinical and psychological characteristics of children with irritable bowel syndrome (IBS), functional abdominal pain (FAP), and functional abdominal pain syndrome (FAPS). A total of 259 children, ages 8 to 18 years, fulfilling Rome III criteria for IBS or FAPS were included in a randomized controlled trial evaluating the effect of hypnotherapy. At inclusion, questionnaires assessed demographics, clinical features, abdominal pain frequency and intensity, depression and anxiety, somatization, health-related quality of life, pain beliefs, and coping strategies. No differences were found between children with IBS and those with FAPS with respect to the main outcomes: frequency and intensity of abdominal pain, symptoms of depression and anxiety, somatization, health-related quality of life, pain beliefs, and coping strategies. A significantly higher percentage of patients with IBS had a positive family history for AP-FGIDs (56.8% vs 37.8%; P = 0.00). Characteristics of patients with IBS subtypes did not differ. Patients with FAP or FAPS differed only with respect to problem-focused coping strategy (2.21 ± 0.61 vs 2.52 ± 0.49; P = 0.00). Pediatric patients with IBS and those with FAPS have similar psychosocial profiles. These results may explain why treatment response of psychological therapies in these AP-FGIDs is similar. These results may indicate that pediatric IBS and FAPS are different expressions of 1 underlying functional disorder, but similarities in psychosocial characteristics do not exclude the possibility that these disorders are different entities, because these similarities can exist between disorders of various causes. Therefore, future research is required on the role of other

Phenotyping of subjects for large scale studies on patients with IBS.

PubMed

Boeckxstaens, G E; Drug, V; Dumitrascu, D; Farmer, A D; Hammer, J; Hausken, T; Niesler, B; Pohl, D; Pojskic, L; Polster, A; Simren, M; Goebel-Stengel, M; Van Oudenhove, L; Vassallo, M; Wensaas, K-A; Aziz, Q; Houghton, L A

2016-08-01

Irritable bowel syndrome (IBS) is a complex condition with multiple factors contributing to its aetiology and pathophysiology. Aetiologically these include genetics, life-time events and environment, and physiologically, changes in motility, central processing, visceral sensitivity, immunity, epithelial permeability and gastrointestinal microflora. Such complexity means there is currently no specific reliable biomarker for IBS, and thus IBS continues to be diagnosed and classified according to symptom based criteria, the Rome Criteria. Carefully phenotyping and characterisation of a 'large' pool of IBS patients across Europe and even the world however, might help identify sub-populations with accuracy and consistency. This will not only aid future research but improve tailoring of treatment and health care of IBS patients. The aim of this position paper is to discuss the requirements necessary to standardize the process of selecting and phenotyping IBS patients and how to organise the collection and storage of patient information/samples in such a large multi-centre pan European/global study. We include information on general demographics, gastrointestinal symptom assessment, psychological factors, quality of life, physiological evaluation, genetic/epigenetic and microbiota analysis, biopsy/blood sampling, together with discussion on the organisational, ethical and language issues associated with implementing such a study. The proposed approach and documents selected to be used in such a study was the result of a thoughtful and thorough four-year dialogue amongst experts associated with the European COST action BM1106 GENIEUR (www.GENIEUR.eu). © 2016 John Wiley & Sons Ltd.

The enhancement of stress-related memory by glucocorticoids depends on synapsin-Ia/Ib

PubMed Central

Revest, J-M; Kaouane, N; Mondin, M; Le Roux, A; Rougé-Pont, F; Vallée, M; Barik, J; Tronche, F; Desmedt, A; Piazza, P V

2010-01-01

The activation of glucocorticoid receptors (GR) by glucocorticoids increases stress-related memory through the activation of the MAPK signaling pathway and the downstream transcription factor Egr-1. Here, using converging in vitro and in vivo approaches, respectively, GR-expressing cell lines, culture of hippocampal neurons, and GR genetically modified mice (GRNesCre), we identified synapsin-Ia/Ib as one of the effectors of the glucocorticoid signaling cascade. Stress and glucocorticoid-induced activation of the GR modulate synapsin-Ia/Ib through two complementary mechanisms. First, glucocorticoids driving Egr-1 expression increase the expression of synapsin-Ia/Ib, and second, glucocorticoids driving MAPK activation increase its phosphorylation. Finally, we showed that blocking fucosylation of synapsin-Ia/Ib in the hippocampus inhibits its expression and prevents the glucocorticoid-mediated increase in stress-related memory. In conclusion, our data provide a complete molecular pathway (GR/Egr-1/MAPK/Syn-Ia/Ib) through which stress and glucocorticoids enhance the memory of stress-related events and highlight the function of synapsin-Ia/Ib as molecular effector of the behavioral effects of stress. PMID:20368707

The impact of irritable bowel syndrome on daily functioning: Characterizing and understanding daily consequences of IBS.

PubMed

Ballou, S; Keefer, L

2017-04-01

Despite the well-documented economic and psychosocial burden of irritable bowel syndrome (IBS), few studies have focused on the impact of IBS on daily activities. This study aims to quantitate impairment in daily activities among IBS patients and to evaluate the relationship between impairment, IBS, quality of life, and psychiatric symptoms. A total of 179 participants meeting ROME-III criteria for IBS completed an online research survey evaluating the following variables: (i) the impact of IBS on daily activities, (ii) comorbid psychiatric diagnoses, (iii) symptom severity, (iv) quality of life, and (v) symptom-specific cognitive affective factors related to IBS. This sample reported a high degree of impairment due to IBS, with 76% of the sample reporting some degree of IBS-related impairment in at least five different domains of daily life. Rates of impairment were significantly higher for participants who met criteria for anxiety, depression, and/or panic disorder. This study contributes to existing literature by demonstrating a high level of daily impairment among patients with IBS, particularly those who meet criteria for anxiety, depression, and panic disorder. These findings support the importance of integrated psychosocial and medical care for IBS patients, and highlight the utility of evaluation and intervention for behavioral avoidance/impairment especially among those who exhibit signs or symptoms of psychiatric diagnoses. © 2016 John Wiley & Sons Ltd.

FODMAPs alter symptoms and the metabolome of patients with IBS: a randomised controlled trial.

PubMed

McIntosh, Keith; Reed, David E; Schneider, Theresa; Dang, Frances; Keshteli, Ammar H; De Palma, Giada; Madsen, Karen; Bercik, Premysl; Vanner, Stephen

2017-07-01

To gain mechanistic insights, we compared effects of low fermentable oligosaccharides, disaccharides and monosaccharides and polyols (FODMAP) and high FODMAP diets on symptoms, the metabolome and the microbiome of patients with IBS. We performed a controlled, single blind study of patients with IBS (Rome III criteria) randomised to a low (n=20) or high (n=20) FODMAP diet for 3 weeks. Symptoms were assessed using the IBS symptom severity scoring (IBS-SSS). The metabolome was evaluated using the lactulose breath test (LBT) and metabolic profiling in urine using mass spectrometry. Stool microbiota composition was analysed by 16S rRNA gene profiling. Thirty-seven patients (19 low FODMAP; 18 high FODMAP) completed the 3-week diet. The IBS-SSS was reduced in the low FODMAP diet group (p<0.001) but not the high FODMAP group. LBTs showed a minor decrease in H 2 production in the low FODMAP compared with the high FODMAP group. Metabolic profiling of urine showed groups of patients with IBS differed significantly after the diet (p<0.01), with three metabolites (histamine, p-hydroxybenzoic acid, azelaic acid) being primarily responsible for discrimination between the two groups. Histamine, a measure of immune activation, was reduced eightfold in the low FODMAP group (p<0.05). Low FODMAP diet increased Actinobacteria richness and diversity, and high FODMAP diet decreased the relative abundance of bacteria involved in gas consumption. IBS symptoms are linked to FODMAP content and associated with alterations in the metabolome. In subsets of patients, FODMAPs modulate histamine levels and the microbiota, both of which could alter symptoms. NCT01829932. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Increased colonic bile acid exposure: a relevant factor for symptoms and treatment in IBS.

PubMed

Bajor, Antal; Törnblom, Hans; Rudling, Mats; Ung, Kjell-Arne; Simrén, Magnus

2015-01-01

Bile acids may play a role in the pathogenesis of IBS. We investigated the potential effects of bile acids entering the colon and its role in the symptom pattern in IBS. We measured 75Se-labelled homocholic acid-taurine (75SeHCAT) retention, and serum levels of 7α-hydroxy-4-cholesten-3-one (C4) and fibroblast growth factor (FGF) 19 in patients with IBS (n=141) and control subjects (75SeHCAT n=29; C4 and FGF19 n=435). In patients with IBS stool frequency and form, as well as GI symptom severity were registered, and in a proportion of patients colonic transit time and rectal sensitivity were measured (n=66). An 8-week open-label treatment with colestipol was offered to patients with 75SeHCAT <20%, and the effect of treatment was evaluated with IBS severity scoring system and adequate relief of IBS symptoms. Compared with controls, patients with IBS had lower 75SeHCAT values (p=0.005), higher C4c levels (C4 corrected for cholesterol) (p<0.001), but similar FGF19 levels. Abnormal 75SeHCAT retention (<10%) was seen in 18% of patients, whereas 23% had elevated C4c levels. Patients with IBS with 75SeHCAT retention <10% had more frequent stools, accelerated colonic transit time, rectal hyposensitivity, a higher body mass index, higher C4c and lower FGF19 levels. Colestipol treatment improved IBS symptoms (IBS severity scoring system 220±109 vs. 277±106; p<0.01), and 15/27 patients fulfilled criteria for treatment response (adequate relief ≥50% of weeks 5-8). Increased colonic bile acid exposure influences bowel habit and colonic transit time in patients with IBS. A high response rate to open label treatment with colestipol supports this, but placebo-controlled studies are warranted. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

BmprIa is required in mesenchymal tissue and has limited redundant function with BmprIb in tooth and palate development

PubMed Central

Li, Lu; Lin, Minkui; Wang, Ying; Cserjesi, Peter; Chen, Zhi; Chen, YiPing

2010-01-01

The BMP signaling plays a pivotal role in the development of craniofacial organs, including the tooth and palate. BmprIa and BmprIb encode two type I BMP receptors that are primarily responsible for BMP signaling transduction. We investigated mesenchymal tissue-specific requirement of BmprIa and its functional redundancy with BmprIb during the development of mouse tooth and palate. BmprIa and BmprIb exhibit partially overlapping and distinct expression patterns in the developing tooth and palatal shelf. Neural crest specific inactivation of BmprIa leads to formation of an unusual type of anterior clefting of the secondary palate, an arrest of tooth development at the bud/early cap stages, and severe hypoplasia of the mandible. Defective tooth and palate development is accompanied by the down-regulation of BMP responsive genes and reduced cell proliferation levels in the palatal and dental mesenchyme. To determine if BmprIb could substitute for BmprIa during tooth and palate development, we expressed a constitutively active form of BmprIb (caBmprIb) in the neural crest cells in which BmprIa was simultaneously inactivated. We found that substitution of BmprIa by caBmprIb in neural rest cells rescues the development of molars and maxillary incisor, but the rescued teeth exhibit a delayed odontoblast and ameloblast differentiation. In contrast, caBmprIb fails to rescue the palatal and mandibular defects including the lack of lower incisors. Our results demonstrate an essential role for BmprIa in the mesenchymal component and a limited functional redundancy between BmprIa and BmprIb in a tissue specific manner during tooth and palate development. PMID:21034733

EXPERIMENTAL STUDIES OF IBS (INTRA-BEAM SCATTERING) IN RHIC AND COMPARISON WITH THEORY.

DOE Office of Scientific and Technical Information (OSTI.GOV)

FEDOTOV, A.V.; FISCHER, W.; TEPIKIAN, S.

A high-energy electron cooling system is presently being developed to overcome emittance growth due to Intra-beam Scattering (IBS) in RHIC. A critical item for choosing appropriate parameters of the cooler is an accurate description of the IBS. The analytic models were verified vs dedicated IBS measurements. Analysis of the 2004 data with the Au ions showed very good agreement for the longitudinal growth rates but significant disagreement with exact IBS models for the transverse growth rates. Experimental measurements were improved for the 2005 run with the Cu ions. Here, we present comparison of the 2005 data with theoretical models.

Nerve growth factor and diarrhea-predominant irritable bowel syndrome (IBS-D): a potential therapeutic target?

PubMed

Xu, Xiao-juan; Liu, Liang; Yao, Shu-kun

2016-01-01

Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder characterized by recurrent abdominal pain or discomfort associated with abnormal bowel habits. Diarrhea-predominant IBS (IBS-D) is a major subtype of IBS, the predominant manifestations of which are abdominal pain and diarrhea. The pathogenesis of IBS-D remained unknown until recently. The effects of psychosocial stress, central hypervigilance, neuroendocrine abnormality, disturbed gastrointestinal motility, mucosal immune activation, intestinal barrier dysfunction, visceral hypersensitivity (VH), altered gut flora, and genetic susceptibility may be involved in its development. Recently, increased attention has been placed on the neural-immune-endocrine network mechanism in IBS-D, especially the role of various neuroendocrine mediators. As a member of the neurotrophin family, nerve growth factor (NGF) has diverse biological effects, and participates in the pathogenesis of many diseases. Basic studies have demonstrated that NGF is associated with inflammatory- and stress-related VH, as well as stress-related intestinal barrier dysfunction. The aim of this study is to summarize recent literature and discuss the role of NGF in the pathophysiology of IBS-D, especially in VH and intestinal barrier dysfunction, as well as its potential as a therapeutic target in IBS-D.

Chronic Constipation and Constipation-Predominant IBS: Separate and Distinct Disorders or a Spectrum of Disease?

PubMed

Siah, Kewin T H; Wong, Reuben K; Whitehead, William E

2016-03-01

Rome III diagnostic criteria separate patients with idiopathic chronic constipation into mutually exclusive categories of constipation-predominant irritable bowel syndrome (IBS-C) or functional constipation (FC). However, several experts think that these conditions are not different disorders, but parts of a continuum. To shed light on this issue, we examined studies that compared IBS-C with FC with respect to symptoms, pathophysiologic mechanisms, and treatment response. When the Rome III requirement that patients meeting criteria for IBS cannot also be given a diagnosis of FC is suspended, most patients meet criteria for both, and, contrary to expectation, IBS-C patients have more symptoms of constipation than patients with FC. No symptoms reliably separate IBS-C from FC. Physiologic tests are not reliably associated with diagnosis, but visceral pain hypersensitivity tends to be more strongly associated with IBS-C than with FC, and delayed colonic transit tends to be more common in FC. Although some treatments are effective for both IBS-C and FC, such as prosecretory agents, other treatments are specific to IBS-C (eg, antidepressants, antispasmodics, cognitive behavior therapy) or FC (eg, prucalopride, biofeedback). Future studies should permit IBS-C and FC diagnoses to overlap. Physiologic tests comparing these disorders should include visceral pain sensitivity, colonic transit time, time to evacuate a water-filled balloon, and anal pressures or electromyographic activity from the anal canal. To date, differential responses to treatment provide the strongest evidence that IBS-C and FC may be different disorders, rather than parts of a spectrum.

Chronic Constipation and Constipation-Predominant IBS: Separate and Distinct Disorders or a Spectrum of Disease?

PubMed Central

Siah, Kewin T. H.; Wong, Reuben K.

2016-01-01

Rome III diagnostic criteria separate patients with idiopathic chronic constipation into mutually exclusive categories of constipation-predominant irritable bowel syndrome (IBS-C) or functional constipation (FC). However, several experts think that these conditions are not different disorders, but parts of a continuum. To shed light on this issue, we examined studies that compared IBS-C with FC with respect to symptoms, pathophysiologic mechanisms, and treatment response. When the Rome III requirement that patients meeting criteria for IBS cannot also be given a diagnosis of FC is suspended, most patients meet criteria for both, and, contrary to expectation, IBS-C patients have more symptoms of constipation than patients with FC. No symptoms reliably separate IBS-C from FC. Physiologic tests are not reliably associated with diagnosis, but visceral pain hypersensitivity tends to be more strongly associated with IBS-C than with FC, and delayed colonic transit tends to be more common in FC. Although some treatments are effective for both IBS-C and FC, such as prosecretory agents, other treatments are specific to IBS-C (eg, antidepressants, antispasmodics, cognitive behavior therapy) or FC (eg, prucalopride, biofeedback). Future studies should permit IBS-C and FC diagnoses to overlap. Physiologic tests comparing these disorders should include visceral pain sensitivity, colonic transit time, time to evacuate a water-filled balloon, and anal pressures or electromyographic activity from the anal canal. To date, differential responses to treatment provide the strongest evidence that IBS-C and FC may be different disorders, rather than parts of a spectrum. PMID:27231446

IB Offering Certificate for Careers

ERIC Educational Resources Information Center

Robelen, Erik W.

2012-01-01

The International Baccalaureate (IB) organization, best known in the United States for its prestigious two-year diploma program for juniors and seniors, will enter new terrain this fall as it formally rolls out an initiative centered on a variety of career pathways that includes engineering, culinary arts, and automotive technology. The move comes…

IBS: an illustrator for the presentation and visualization of biological sequences.

PubMed

Liu, Wenzhong; Xie, Yubin; Ma, Jiyong; Luo, Xiaotong; Nie, Peng; Zuo, Zhixiang; Lahrmann, Urs; Zhao, Qi; Zheng, Yueyuan; Zhao, Yong; Xue, Yu; Ren, Jian

2015-10-15

Biological sequence diagrams are fundamental for visualizing various functional elements in protein or nucleotide sequences that enable a summarization and presentation of existing information as well as means of intuitive new discoveries. Here, we present a software package called illustrator of biological sequences (IBS) that can be used for representing the organization of either protein or nucleotide sequences in a convenient, efficient and precise manner. Multiple options are provided in IBS, and biological sequences can be manipulated, recolored or rescaled in a user-defined mode. Also, the final representational artwork can be directly exported into a publication-quality figure. The standalone package of IBS was implemented in JAVA, while the online service was implemented in HTML5 and JavaScript. Both the standalone package and online service are freely available at http://ibs.biocuckoo.org. renjian.sysu@gmail.com or xueyu@hust.edu.cn Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press.

IBS: an illustrator for the presentation and visualization of biological sequences

PubMed Central

Liu, Wenzhong; Xie, Yubin; Ma, Jiyong; Luo, Xiaotong; Nie, Peng; Zuo, Zhixiang; Lahrmann, Urs; Zhao, Qi; Zheng, Yueyuan; Zhao, Yong; Xue, Yu; Ren, Jian

2015-01-01

Summary: Biological sequence diagrams are fundamental for visualizing various functional elements in protein or nucleotide sequences that enable a summarization and presentation of existing information as well as means of intuitive new discoveries. Here, we present a software package called illustrator of biological sequences (IBS) that can be used for representing the organization of either protein or nucleotide sequences in a convenient, efficient and precise manner. Multiple options are provided in IBS, and biological sequences can be manipulated, recolored or rescaled in a user-defined mode. Also, the final representational artwork can be directly exported into a publication-quality figure. Availability and implementation: The standalone package of IBS was implemented in JAVA, while the online service was implemented in HTML5 and JavaScript. Both the standalone package and online service are freely available at http://ibs.biocuckoo.org. Contact: renjian.sysu@gmail.com or xueyu@hust.edu.cn Supplementary information: Supplementary data are available at Bioinformatics online. PMID:26069263

Tight junctions and IBS--the link between epithelial permeability, low-grade inflammation, and symptom generation?

PubMed

Piche, T

2014-03-01

In this issue of Neurogastroenterology and Motility, Dr Ewa Wilcz-Villega and colleagues report low expression of E-cadherin, a tight junction protein involved in the regulation of paracellular permeability, in the colonic mucosa of patients with the irritable bowel syndrome (IBS) with predominance of diarrhea (IBS-D) or alternating symptoms (IBS-A). These findings constitute an improvement in our knowledge of epithelial barrier disruption associated with IBS. There is mounting evidence to indicate that a compromised epithelial barrier is associated with low-grade immune activation and intestinal dysfunction in at least a proportion of IBS patients. During the last 10 years of research, much interest has focused on the increase in the number of different types of immune cells in the gut mucosa of IBS patients including: mast cells, T lymphocytes, and other local cells such as enteroendocrine cells. The inflammatory mediators released by these cells or other luminal factors could be at the origin of altered epithelial barrier functions and enteric nervous system signaling, which lead to gut hypersensitivity. A current conceptual framework states that clinical symptoms of IBS could be associated with structural and functional abnormalities of the mucosal barrier, highlighting the crucial importance of elucidating the contributory role of epithelial barrier defects in the pathogenesis of IBS. More importantly, disruption of the epithelial barrier could also participate in the generation of persistent abdominal pain and discomfort mimicking IBS in patients with inflammatory bowel diseases considered in remission. This mini review gives a brief summary of clinical and experimental evidence concerning the mechanisms underlying epithelial barrier defects in IBS. © 2014 John Wiley & Sons Ltd.

Erlotinib Hydrochloride in Treating Patients With Stage IB-IIIA Non-small Cell Lung Cancer That Has Been Completely Removed by Surgery (An ALCHEMIST Treatment Trial)

ClinicalTrials.gov

2018-06-29

ALK Gene Rearrangement; EGFR Exon 19 Deletion Mutation; EGFR NP_005219.2:p.L858R; Stage IB Non-Small Cell Lung Carcinoma AJCC v7; Stage II Non-Small Cell Lung Cancer AJCC v7; Stage IIA Non-Small Cell Lung Carcinoma AJCC v7; Stage IIB Non-Small Cell Lung Carcinoma AJCC v7; Stage IIIA Non-Small Cell Lung Cancer AJCC v7

Fecal incontinence in irritable bowel syndrome (IBS): Prevalence and associated factors in Swedish and American patients

PubMed Central

Simrén, Magnus; Palsson, Olafur S.; Heymen, Steve; Bajor, Antal; Törnblom, Hans; Whitehead, William E.

2016-01-01

Background Fecal incontinence (FI) is a prevalent but poorly recognized problem in the general population with profound negative effects on daily life. The prevalence of FI in IBS and its association with clinical, demographic and pathophysiological factors are largely unknown. Methods One US (n=304) and one Swedish (n=168) patient cohort fulfilling Rome III criteria for IBS completed Rome III diagnostic questions on FI and IBS symptoms, and questionnaires on IBS symptom severity, quality of life, anxiety and depression, and work productivity impairment. The patients also underwent assessments of colorectal sensitivity and motility. Key Results FI ≥ one day per month was reported by 19.7% (USA) and 13.7% (Sweden) of IBS patients. These proportions rose to 43.4% and 29.8% if patients with less frequent FI were included. FI prevalence was higher in older age groups, with a clear increase above age 40. IBS patients with FI reported greater overall IBS symptom severity, more frequent and loose stools, and greater urgency. Negative effects of FI on quality of life, psychological distress, and work productivity were demonstrated. No associations were found between colorectal physiology and FI. Conclusions & Inferences FI is common in IBS patients, and similar to previous general population reports, the major risk factors for FI in IBS are older age, rectal urgency, and loose, frequent stools. When IBS patients have comorbid FI, the impact on quality of life, psychological symptoms, and work impairment appears greater. PMID:27581702

A review on the current issues and barriers of Industrialised Building System (IBS) adoption in Malaysia’s construction industry

NASA Astrophysics Data System (ADS)

Amin, M. A. Mohd; Abas, N. H.; Shahidan, S.; Rahmat, M. H.; Suhaini, N. A.; Nagapan, S.; Rahim, R. Abdul

2017-11-01

Malaysia considers the construction industry as one of the main contributors to its Gross Domestic Product (GDP). However, there are some unresolved issues arising from the ongoing and widespread adoption of the conventional method of construction such as the resultant fragmentation of the industry itself; delays in production and delivery time of unnecessary wastages and lack of sustainability practice. Malaysian Government has been continuously encouraging the industry to use, partly or if not wholly, the Industrialized Building System (IBS), which is considered to be an important part of sustainable construction initiative. IBS was introduced to Malaysia as the solution to issues related to dependencies of foreign workers, raising demand for affordable accommodations and improving image, quality and productivity of construction industry. However, the IBS adoption in Malaysia remains low. This paper presents the review of the current issues and barriers of IBS adoption in Malaysian construction industry.

Growth hormone deficiency in monozygotic twins with autosomal dominant pseudohypoparathyroidism type Ib.

PubMed

Sano, Shinichiro; Iwata, Hiromi; Matsubara, Keiko; Fukami, Maki; Kagami, Masayo; Ogata, Tsutomu

2015-01-01

Pseudohypoparathyroidism (PHP) is associated with compromised signal transductions via PTH receptor (PTH-R) and other G-protein-coupled receptors including GHRH-R. To date, while GH deficiency (GHD) has been reported in multiple patients with PHP-Ia caused by mutations on the maternally expressed GNAS coding regions and in two patients with sporadic form of PHP-Ib accompanied by broad methylation defects of maternally derived GNAS differentially methylated regions (DMRs), it has not been identified in a patient with an autosomal dominant form of PHP-Ib (AD-PHP-Ib) accompanied by an STX16 microdeletion and an isolated loss of methylation (LOM) at exon A/B-DMR. We studied 5 4/12-year-old monozygotic twins with short stature (both -3.4 SD) and GHD (peak GH values, <6.0 μg/L after arginine and clonidine stimulations). Molecular studies revealed maternally derived STX16 microdeletions and isolated LOMs at exon A/B-DMR in the twins, confirming the diagnosis of AD-PHP-Ib. GNAS mutation was not identified, and neither mutation nor copy number variation was detected in GH1, POU1F1, PROP1, GHRHR, LHX3, LHX4, and HESX1 in the twins. The results, in conjunction with the previous finding that GNAS shows maternal expression in the pituitary, suggest that GHD of the twins is primarily ascribed to compromised GHRH-R signaling caused by AD-PTH-Ib. Thus, resistance to multiple hormones including GHRH should be considered in AD-PHP-Ib.

Pembrolizumab and Interferon Gamma-1b in Treating Patients With Stage IB-IVB Relapsed or Refractory Mycosis Fungoides and Sezary Syndrome

ClinicalTrials.gov

2018-06-08

Recurrent Mycosis Fungoides and Sezary Syndrome; Refractory Mycosis Fungoides; Stage IB Mycosis Fungoides and Sezary Syndrome AJCC v7; Stage II Mycosis Fungoides and Sezary Syndrome AJCC v7; Stage IIA Mycosis Fungoides and Sezary Syndrome AJCC v7; Stage IIB Mycosis Fungoides and Sezary Syndrome AJCC v7; Stage III Mycosis Fungoides and Sezary Syndrome AJCC v7; Stage IIIA Mycosis Fungoides and Sezary Syndrome AJCC v7; Stage IIIB Mycosis Fungoides and Sezary Syndrome AJCC v7; Stage IV Mycosis Fungoides and Sezary Syndrome AJCC v7; Stage IVA Mycosis Fungoides and Sezary Syndrome AJCC v7; Stage IVB Mycosis Fungoides and Sezary Syndrome AJCC v7

Characterization of IBS-like symptoms in patients with ulcerative colitis in clinical remission.

PubMed

Jonefjäll, B; Strid, H; Ohman, L; Svedlund, J; Bergstedt, A; Simren, M

2013-09-01

Gastrointestinal symptoms compatible with Irritable Bowel Syndrome (IBS) are common in patients with inflammatory bowel disease. It has been suggested that these symptoms are a reflection of occult inflammation rather than coexisting IBS. The aim of this study was to characterize IBS-like symptoms in patients with Ulcerative Colitis (UC) in clinical remission by assessing inflammatory markers, psychological symptoms, and quality of life. Ninety-four patients with new onset of UC were followed prospectively during 3 years with yearly follow-up visits. The patients completed self-administrated questionnaires. Fecal calprotectin was used as an inflammatory biomarker. Remission was defined as a total Mayo-score ≤2 and an endoscopic subscore ≤1, with no relapse during the 3-month period prior to visit. The prevalence of patients that fulfilled Rome II criteria for IBS among UC patients in remission was 11% at visit 1, 23% at visit 2, and 17% at visit 3. When comparing UC patients in remission with and without IBS-like symptom, patients with IBS-like symptoms had more severe gastrointestinal symptoms, tendencies toward more severe psychological symptoms and reduced levels of quality of life, but the calprotectin levels did not differ between the two groups. IBS-like symptoms are common in patients with UC in clinical remission and these fluctuate over time. The symptoms are associated with poor psychological well-being and reduced quality of life, and do not seem to be a reflection of low-grade inflammatory activity. © 2013 John Wiley & Sons Ltd.

An Evidence-Based Look at Misconceptions in the Treatment of Patients with IBS-D

PubMed Central

Lacy, Brian E.; Chey, William D.; Chang, Lin

2013-01-01

Irritable bowel syndrome (IBS) is the most common functional gastrointestinal disorder and affects up to 12% to 15% of adults in the United States, with a higher prevalence among women and those younger than 50 years. IBS adversely impacts quality of life and medical expenditures, with significant costs arising from healthcare visits and reduced workplace productivity. Recent studies have shown that the adverse effects of IBS are so significant that many patients are willing to accept risks of adverse events from effective treatment to gain symptom relief. Alosetron is a 5-HT3 receptor antagonist approved by the US Food and Drug Administration (FDA) for women with severe diarrhea-predominant IBS that has not responded to traditional therapies. Alosetron yields overall improvements in IBS symptoms in 51% of patients vs 36% treated with placebo, with efficacy continuing undiminished over the course of a 48-week randomized, controlled trial. In real-world clinical practice, patients receiving alosetron had significant improvements in multiple IBS-related clinical parameters, including the new FDA IBS-diarrhea composite endpoint, lower gastrointestinal symptoms, fecal incontinence, and quality of life. Ischemic colitis and complications of constipation have been rare in occurrence. After nearly a decade of alosetron use under the risk management plan, adjudication of ischemic colitis and complications of constipation cases indicate that their incidence rates have remained low and stable. PMID:24872792

Increased production of BDNF in colonic epithelial cells induced by fecal supernatants from diarrheic IBS patients.

PubMed

Wang, Peng; Chen, Fei-Xue; Du, Chao; Li, Chang-Qing; Yu, Yan-Bo; Zuo, Xiu-Li; Li, Yan-Qing

2015-05-22

Colonic brain-derived neurotrophic factor (BDNF) plays an essential role in pathogenesis of abdominal pain in diarrhea-predominant irritable bowel syndrome (IBS-D), but regulation on its expression remains unclear. We investigated the role of fecal supernatants (FSN) from IBS-D patients on regulating BDNF expression in colonic epithelial cells of human and mice. Using human Caco-2 cells, we found that IBS-D FSN significantly increased BDNF mRNA and protein levels compared to control FSN, which were remarkably suppressed by the serine protease inhibitor. To further explore the potential mechanisms, we investigated the impact of protease-activated receptor-2 (PAR-2) on BDNF expression. We found a significant increase in PAR-2 expression in Caco-2 after IBS-D FSN stimulation. Knockdown of PAR-2 significantly inhibited IBS-D FSN-induced upregulation of BDNF. Moreover, we found that phosphorylation of p38 MAPK, not NF-κB p65, contributed to PAR-2-mediated BDNF overexpression. To confirm these results, we intracolonically infused IBS-D or control FSN in mice and found that IBS-D FSN significantly elevated colonic BDNF and visceral hypersensitivity in mice, which were both suppressed by the inhibitor of serine protease or antagonist of PAR-2. Together, our data indicate that activation of PAR-2 signaling by IBS-D FSN promotes expression of colonic BDNF, thereby contributing to IBS-like visceral hypersensitivity.

Eluxadoline Efficacy in IBS-D Patients Who Report Prior Loperamide Use.

PubMed

Lacy, Brian E; Chey, William D; Cash, Brooks D; Lembo, Anthony J; Dove, Leonard S; Covington, Paul S

2017-06-01

Irritable bowel syndrome with diarrhea (IBS-D) is often managed with over-the-counter therapies such as loperamide, though with limited success. This analysis evaluated the efficacy of eluxadoline in patients previously treated with loperamide in two phase 3 studies. Adults with IBS-D (Rome III criteria) were enrolled and randomized to placebo or eluxadoline (75 or 100 mg) twice daily for 26 (IBS-3002) or 52 (IBS-3001) weeks. Patients reported loperamide use over the previous year and recorded their rescue loperamide use during the studies. The primary efficacy end point was the proportion of patients with a composite response of simultaneous improvement in abdominal pain and reduction in diarrhea. A total of 2,428 patients were enrolled; 36.0% reported prior loperamide use, of whom 61.8% reported prior inadequate IBS-D symptom control with loperamide. Among patients with prior loperamide use, a greater proportion treated with eluxadoline (75 and 100 mg) were composite responders vs. those treated with placebo with inadequate prior symptom control, over weeks 1-12 (26.3% (P=0.001) and 27.0% (P<0.001) vs. 12.7%, respectively); similar results were observed over weeks 1-26. When daily rescue loperamide use was imputed as a nonresponse day, the composite responder rate was still higher in patients receiving eluxadoline (75 and 100 mg) vs. placebo over weeks 1-12 (P<0.001) and weeks 1-26 (P<0.001). Adverse events included nausea and abdominal pain. Eluxadoline effectively and safely treats IBS-D symptoms of abdominal pain and diarrhea in patients who self-report either adequate or inadequate control of their symptoms with prior loperamide treatment, with comparable efficacy and safety irrespective of the use of loperamide as a rescue medication during eluxadoline treatment.

Crizotinib in Treating Patients With Stage IB-IIIA Non-small Cell Lung Cancer That Has Been Removed by Surgery and ALK Fusion Mutations (An ALCHEMIST Treatment Trial)

ClinicalTrials.gov

2017-12-07

ALK Gene Rearrangement; ALK Gene Translocation; ALK Positive; Stage IB Non-Small Cell Lung Carcinoma AJCC v7; Stage II Non-Small Cell Lung Cancer AJCC v7; Stage IIA Non-Small Cell Lung Carcinoma AJCC v7; Stage IIB Non-Small Cell Lung Carcinoma AJCC v7; Stage IIIA Non-Small Cell Lung Cancer AJCC v7

Neuroimmune interactions at different intestinal sites are related to abdominal pain symptoms in children with IBS.

PubMed

Di Nardo, G; Barbara, G; Cucchiara, S; Cremon, C; Shulman, R J; Isoldi, S; Zecchi, L; Drago, L; Oliva, S; Saulle, R; Barbaro, M R; Stronati, L

2014-02-01

Neuroimmune interactions and inflammation have been proposed as factors involved in sensory-motor dysfunction and symptom generation in adult irritable bowel syndrome (IBS) patients. In children with IBS and healthy controls, we measured ileocolonic mast cell infiltration and fecal calprotectin and evaluated the relationships between these parameters and abdominal pain symptoms and stooling pattern. Irritable bowel syndrome patients diagnosed according to Pediatric Rome III criteria and healthy controls kept a 2-week pain/stooling diary. Ileocolonic mucosal mast cells (MC) and MC in close proximity to nerve fibers (MC-NF) were identified immunohistochemically and quantified. Fecal calprotectin concentration was measured. 21 IBS patients and 10 controls were enrolled. The MC-NF count was significantly higher in the ileum (p = 0.01), right colon (p = 0.04), and left colon (p < 0.001) of IBS patients compared with controls. No differences in fecal calprotectin concentration were noted. Abdominal pain intensity score correlated with ileal MC count (r(s) = 0.47, p = 0.030) and right colon MC-NF count (r(s) = 0.52, p = 0.015). In addition, children with IBS with >3 abdominal pain episodes/week had greater ileal (p = 0.002) and right colonic (p = 0.01) MC counts and greater ileal (p = 0.05) and right colonic (p = 0.016) MC-NF counts than children with less frequent pain. No relationship was found between MC and MC-NF and fecal calprotectin or stooling pattern. Mast cells-nerve fibers counts are increased in the ileocolonic mucosa of children with IBS. Mast cells and MC-NF counts are related to the intensity and frequency of abdominal pain. © 2013 John Wiley & Sons Ltd.

Immersed boundary peridynamics (IB/PD) method to simulate aortic dissection

NASA Astrophysics Data System (ADS)

Bhalla, Amneet Pal Singh; Griffith, Boyce

2016-11-01

Aortic dissection occurs when an intimal tear in the aortic wall propagates into the media to form a false lumen within the vessel wall. Rupture of the false lumen and collapse of the true lumen both carry a high risk of morbidity and mortality. Surgical treatment consists of either replacement of a portion of the aorta, or stent implantation to cover the affected segment. Both approaches carry significant risks: open surgical intervention is highly invasive, whereas stents can be challenging to implant and offer unclear long-term patient outcomes. It is also difficult to time optimally the intervention to ensure that the benefits of treatment outweigh its risks. In this work we develop innovative fluid-structure interaction (FSI) model combining elements from immersed boundary (IB) and peridynamics (PD) methods to simulate tears in membranes. The new approach is termed as IB/PD method. We use non-ordinary state based PD to represent material hyperelasticity. Several test problems are taken to validate peridynamics approach to model structural dynamics, with and without accounting for failure in the structures. FSI simulations using IB/PD method are compared with immersed finite element method (IB/FE) to validate the new hybrid approach. NIH Award R01HL117163 NSF Award ACI 1450327.

Detection of the High-Level Aminoglycoside Resistance Gene aph(2")-Ib in Enterococcus faecium

PubMed Central

Kao, Susan J.; You, Il; Clewell, Don B.; Donabedian, Susan M.; Zervos, Marcus J.; Petrin, Joanne; Shaw, Karen J.; Chow, Joseph W.

2000-01-01

A new high-level gentamicin resistance gene, designated aph(2")-Ib, was cloned from Enterococcus faecium SF11770. The deduced amino acid sequence of the 897-bp open reading frame of aph(2")-Ib shares homology with the aminoglycoside-modifying enzymes AAC(6′)-APH(2"), APH(2")-Ic, and APH(2")-Id. The observed phosphotransferase activity is designated APH(2")-Ib. PMID:10991878

IbMADS1 (Ipomoea batatas MADS-box 1 gene) is Involved in Tuberous Root Initiation in Sweet Potato (Ipomoea batatas)

PubMed Central

Ku, Amy Tsu; Huang, Yi-Shiuan; Wang, Yu-Shu; Ma, Daifu; Yeh, Kai-Wun

2008-01-01

Background and Aims The tuberization mechanism of sweet potato (Ipomoea batatas) has long been studied using various approaches. Morphological data have revealed that the tuberizing events result from the activation of the cambium, followed by cell proliferation. However, uncertainties still remain regarding the regulators participating in this signal-transduction pathway. An attempt was made to characterize the role of one MADS-box transcription factor, which was preferentially expressed in sweet potato roots at the early tuberization stage. Methods A differential expression level of IbMADS1 (Ipomoea batatas MADS-box 1) was detected temporally and spatially in sweet potato tissues. IbMADS1 responses to tuberization-related hormones were assessed. In order to identify the evolutionary significance, the expression pattern of IbMADS1 was surveyed in two tuber-deficient Ipomoea relatives, I. leucantha and I. trifida, and compared with sweet potato. In functional analyses, potato (Solanum tuberosum) was employed as a heterologous model. The resulting tuber morphogenesis was examined anatomically in order to address the physiological function of IbMADS1, which should act similarly in sweet potato. Key Results IbMADS1 was preferentially expressed as tuberous root development proceeded. Its expression was inducible by tuberization-related hormones, such as jasmonic acid and cytokinins. In situ hybridization data showed that IbMADS1 transcripts were specifically distributed around immature meristematic cells within the stele and lateral root primordia. Inter-species examination indicated that IbMADS1 expression was relatively active in sweet potato roots, but undetectable in tuber-deficient Ipomoea species. IbMADS1-transformed potatoes exhibited tuber morphogenesis in the fibrous roots. The partial swellings along fibrous roots were mainly due to anomalous proliferation and differentiation in the xylem. Conclusions Based on this study, it is proposed that IbMADS1 is an

Epidemiology of Dyspepsia and Irritable Bowel Syndrome (IBS) in Medical Students of Northern India.

PubMed

Basandra, Sumeena; Bajaj, Divyansh

2014-12-01

Dyspepsia and Irritable Bowel Syndrome (IBS) are perhaps one of the most common gastrointestinal diseases universally. The prevalence of dyspepsia ranges from 7-40% while the prevalence of IBS ranges between 3-22% in population based studies worldwide. This study was conducted to estimate the prevalence, socio-demographic and lifestyle associated risk factors of Dyspepsia and IBS among medical college students of urban Delhi, Northern India. It is a cross-sectional study and was carried out from January to March 2014 at Maulana Azad Medical College, New Delhi, India. A total of 210 students from a Medical College were asked to complete a semi-structured questionnaire based on identification and socio-demographic data, questions pertaining to lifestyle and Rome III criteria. Of the valid 200 subjects, 90(45%) were males and 110(55%) were females, with a mean age of 20.43± 1.05 y. Majority of the subjects (diagnosed with uninvestigated dyspepsia and IBS) were in the age group of 18-20 y with female gender having higher odds for both. The prevalence of dyspepsia was 18% while that of IBS was 16.5%.Consumption of fatty food, cigarettes and low physical activity were observed as most significant correlates. Rome III criteria enables symptom based diagnosis of dyspepsia and IBS.The prevalence of dyspepsia and IBS in college students from Delhi is observed to be higher. Association with lifestyle related factors highlights the importance of modifications in their prevention.

6 Tips: IBS and Complementary Health Practices

MedlinePlus

... as anxiety, depression, disability, and quality of life. Probiotics . Probiotics such as Bifidobacterium and Lactobacillus are live microorganisms ... There is some preliminary evidence that suggests some probiotics may improve symptoms of IBS, such as abdominal ...

International Education, Values and Attitudes: A Critical Analysis of the International Baccalaureate (IB) Learner Profile

ERIC Educational Resources Information Center

Wells, John

2011-01-01

This article provides a critical review of the way that the International Baccalaureate (IB) promotes international education and international mindedness through the IB Learner Profile. While discussing theories of values and attitudes, and the teaching of values and theories of value acquisition, the paucity of such topics in IB texts is noted.…

Measuring IBS patient reported outcomes with an abdominal pain numeric rating scale: results from the proof cohort

PubMed Central

SPIEGEL, B.; BOLUS, R.; HARRIS, L. A.; LUCAK, S.; NALIBOFF, B.; ESRAILIAN, E.; CHEY, W. D.; LEMBO, A.; KARSAN, H.; TILLISCH, K.; TALLEY, J.; MAYER, E.; CHANG, L.

2009-01-01

Background Controversy exists about how to effectively measure patient reported outcomes in IBS clinical trials. Pain numeric rating scales (NRS) are widely used in the non-IBS pain literature. The FDA has proposed using the NRS in IBS. Aim To test the psychometrics of an abdominal pain NRS in IBS. Methods We analyzed data from a longitudinal cohort of Rome III IBS subjects. At entry, subjects completed a 10-point NRS, bowel symptoms, IBS severity measurements (IBSSS, FBDSI), health related quality of life indices (IBS-QOL, EQ5D), and the worker productivity activity index (WPAI). We repeated assessments at 3 months along with a response scale to calculate the minimal clinically important difference (MCID). Results There were 277 subjects (82% women; age=42±15) at baseline and 90 at 3 months. The NRS correlated cross-sectionally with IBSSS (r=0.60; p<0.0011), FBDSI (r=0.49; p<0.0001), IBS-QOL (r=0.43; p<0.0001), EQ5D (r=0.48; p<0.0001), presenteeism (r=0.39; p<0.0001), absenteeism (r=0.17; p=0.04), and distension (r=0.46; p<0.0001), but not stool frequency or form. The MCID was 2.2 points, correlating with a 29.5% reduction over time. Conclusions An abdominal pain NRS exhibits excellent validity and can be readily interpreted with an MCID in patients with IBS. These data support the use of the NRS in IBS clinical trials. PMID:19751360

Politics and Pedagogy: Discursive Constructions in the IB "Theory of Knowledge--Guide"

ERIC Educational Resources Information Center

Smith, Nigel V.; Morgan, Mandy

2010-01-01

The International Baccalaureate (IB) curriculum is increasingly popular in both national and international secondary education settings. The "Theory of knowledge" (TOK) course is cast as the prime example of the international globalised values the IB Diploma represents. This article argues that such a positioning is contested within the TOK…

Reduced E-cadherin expression is associated with abdominal pain and symptom duration in a study of alternating and diarrhea predominant IBS.

PubMed

Wilcz-Villega, E; McClean, S; O'Sullivan, M

2014-03-01

Increased intestinal permeability and altered expression of tight junction (TJ) proteins may be implicated in the pathogenesis of irritable bowel syndrome (IBS). This study aimed to investigate the expression of adherens junction (AJ) protein E-cadherin and TJ proteins zonula occludens (ZO)-1 and claudin (CLD)-1 and associations with IBS symptoms. Junctional proteins were immunostained in cecal biopsy tissue of Rome II IBS patients (n = 34) comprising both alternating (IBS-A) and diarrhea predominant (IBS-D) subtypes, and controls (n = 12). IBS symptom duration, abdominal pain severity and stool frequency were assessed for IBS patients. Protein expression was determined by immunofluorescence. E-cadherin and ZO-1 protein expression was significantly lower (p = 0.03 and p = 0.016, respectively) in the cecal surface epithelium of the IBS group comprising both IBS-A and IBS-D subtypes. CLD-1 expression was not significantly altered compared with controls. On subtype analysis, ZO-1 expression was significantly reduced in both IBS-A and IBS-D compared with controls, whereas E-cadherin was reduced only in IBS-A. Lower E-cadherin expression was associated with longer symptoms duration specifically in IBS-A patients (rs = -0.76, p = 0.004). Reduced E-cadherin associated with abdominal pain severity in the overall IBS group (rs = -0.36, p = 0.041), but this association was unrelated to IBS subtype. E-cadherin protein expression in the cecum was significantly lower in IBS-A compared with controls and associated with longstanding symptoms. E-cadherin was further associated with abdominal pain severity in the IBS group overall, but unrelated to IBS subtype. Altered E-cadherin expression may provide novel insights into mechanisms underlying intestinal barrier dysfunction in IBS. © 2013 John Wiley & Sons Ltd.

The clinical potential of ramosetron in the treatment of irritable bowel syndrome with diarrhea (IBS-D).

PubMed

Min, Yang Won; Rhee, Poong-Lyul

2015-05-01

Irritable bowel syndrome (IBS) is a highly prevalent functional bowel disorder. Serotonin (5-HT) is known to play a physiological and pathophysiological role in the regulation of gastrointestinal function. In experimental studies, 5-HT3 receptor antagonists have been reported to slow colon transit, to blunt gastrocolonic reflex, and to reduce rectal sensitivity. Alosetron and cilansetron, potent and selective 5-HT3 receptor antagonists, have proven efficacy in the treatment of IBS with diarrhea (IBS-D). However, alosetron was voluntarily withdrawn due to postmarketing reports of ischemic colitis and complications of constipation, and cilansetron was never marketed. Currently alosetron is available under a risk management program for women with severe IBS-D. Ramosetron is another potent and selective 5-HT3 receptor antagonist, which has been marketed in Japan, South Korea, and Taiwan. In animal studies, ramosetron reduced defecation induced by corticotrophin-releasing hormone and had inhibitory effects on colonic nociception. In two randomized controlled studies including 957 patients with IBS-D, ramosetron increased monthly responder rates of patient-reported global assessment of IBS symptom relief compared with placebo. Ramosetron was also as effective as mebeverine in male patients with IBS-D. In a recent randomized controlled trial with 343 male patients with IBS-D, ramosetron has proved effective in improving stool consistency, relieving abdominal pain/discomfort, and improving health-related quality of life. Regarding safety, ramosetron is associated with a lower incidence of constipation compared with other 5-HT3 receptor antagonists and has not been associated with ischemic colitis. Although further large prospective studies are needed to assess whether ramosetron is effective for female patients with IBS-D and to evaluate its long-term safety, ramosetron appears to be one of the most promising agents for patients with IBS-D.

The communication in industrialised building system (IBS) construction project: Virtual environment

NASA Astrophysics Data System (ADS)

Pozin, Mohd Affendi Ahmad; Nawi, Mohd Nasrun Mohd

2017-10-01

Large portion of numbers team organization in the IBS construction sector is known are being fragmented. That is contributed from a segregation of construction activity thus create team working in virtually. Virtual team are the nature when teams are working in distributed area, across culture and time. Therefore, teams can be respond to the task without relocating to the site project and settle down a problem through information and communication technology (ICT). The emergence of virtual team are carry out by advancements in communication technologies as a medium to improve project team communication in project delivery process on IBS construction. Based on literature review from previous study and data collected from interviewing, this paper aim to identified communication challenges among project team members according to current project development practices in IBS construction project. Hence, in attempt to develop effective communication through the advantages of virtual team approach for IBS construction project. In order to ensure the data is gathered comprehensively and accurately, the data was collected from project managers by using semi structured interview method. It was found that virtual team approach could be enable competitive challenges on complexity in the construction project management process.

Development and pilot testing of an integrated, web-based self-management program for irritable bowel syndrome (IBS).

PubMed

Dorn, S D; Palsson, O S; Woldeghebriel, M; Fowler, B; McCoy, R; Weinberger, M; Drossman, D A

2015-01-01

Although essential, many medical practices are unable to adequately support irritable bowel syndrome (IBS) patient self-management. Web-based programs can help overcome these barriers. We developed, assessed, and refined an integrated IBS self-management program (IBS Self-care). We then conducted a 12-week pilot test to assess program utilization, evaluate its association with patients' self-efficacy and quality of life, and collect qualitative feedback to improve the program. 40 subjects with generally mild IBS were recruited via the Internet to participate in a 12-week pilot study. Subjects found the website easy to use (93%) and personally relevant (95%), and 90% would recommend it to a friend. Self-rated IBS knowledge increased from an average of 47.1 on a 100-point VAS scale (SD 22.1) at baseline to 77.4 (SD: 12.4) at week 12 (p < 0.0001). There were no significant changes in patient self-efficacy (Patient Activation Measure) or quality of life (IBS -Quality of Life Scale). The IBS Self-Care program was well received by users who after 12 weeks reported improved knowledge about IBS, but no significant changes in self-efficacy or quality of life. If applied to the right population, this low cost solution can overcome some of the deficiencies of medical care and empower individuals to better manage their own IBS. © 2014 John Wiley & Sons Ltd.

A TBP-containing multiprotein complex (TIF-IB) mediates transcription specificity of murine RNA polymerase I.

PubMed

Eberhard, D; Tora, L; Egly, J M; Grummt, I

1993-09-11

TIF-IB is a transcription factor which interacts with the mouse ribosomal gene promoter and nucleates the formation of an initiation complex containing RNA polymerase I (Pol I). We have purified this factor to near homogeneity and demonstrate that TIF-IB is a large complex (< 200 kDa) which contains several polypeptides. One of the subunits present in this protein complex is the TATA-binding protein (TBP) as revealed by copurification of TIF-IB activity and TBP over different chromatographic steps including immunoaffinity purification. In addition to TBP, three tightly associated proteins (TAFs-I) with apparent molecular weights of 95, 68, and 48 kDa are contained in this multimeric complex. This subunit composition is similar--but not identical--to the analogous human factor SL1. Depletion of TBP from TIF-IB-containing fractions by immunoprecipitation eliminates TIF-IB activity. Neither TBP alone nor fractions containing other TBP complexes are capable of substituting for TIF-IB activity. Therefore, TIF-IB is a unique complex with Pol I-specific TAFs distinct from other TBP-containing complexes. The identification of TBP as an integral part of the murine rDNA promoter-specific transcription initiation factor extends the previously noted similarity of transcriptional initiation by the three nuclear RNA polymerases and underscores the importance of TAFs in determining promoter specificity.

A TBP-containing multiprotein complex (TIF-IB) mediates transcription specificity of murine RNA polymerase I.

PubMed Central

Eberhard, D; Tora, L; Egly, J M; Grummt, I

1993-01-01

TIF-IB is a transcription factor which interacts with the mouse ribosomal gene promoter and nucleates the formation of an initiation complex containing RNA polymerase I (Pol I). We have purified this factor to near homogeneity and demonstrate that TIF-IB is a large complex (< 200 kDa) which contains several polypeptides. One of the subunits present in this protein complex is the TATA-binding protein (TBP) as revealed by copurification of TIF-IB activity and TBP over different chromatographic steps including immunoaffinity purification. In addition to TBP, three tightly associated proteins (TAFs-I) with apparent molecular weights of 95, 68, and 48 kDa are contained in this multimeric complex. This subunit composition is similar--but not identical--to the analogous human factor SL1. Depletion of TBP from TIF-IB-containing fractions by immunoprecipitation eliminates TIF-IB activity. Neither TBP alone nor fractions containing other TBP complexes are capable of substituting for TIF-IB activity. Therefore, TIF-IB is a unique complex with Pol I-specific TAFs distinct from other TBP-containing complexes. The identification of TBP as an integral part of the murine rDNA promoter-specific transcription initiation factor extends the previously noted similarity of transcriptional initiation by the three nuclear RNA polymerases and underscores the importance of TAFs in determining promoter specificity. Images PMID:8414971

Tegaserod in the treatment of irritable bowel syndrome (IBS) with constipation as the prime symptom

PubMed Central

Layer, Peter; Keller, Jutta; Loeffler, Helena; Kreiss, Andreas

2007-01-01

Irritable bowel syndrome with constipation (IBS-C) as the predominant bowel symptom is a prevalent disorder, characterized by recurring abdominal pain/discomfort, bloating, and constipation, and imposes a significant socio-economic burden. Traditional treatments generally address just one of the multiple IBS symptoms. The efficacy and safety profile of tegaserod, a serotonin 5-HT4 receptor agonist, has been demonstrated in several randomized, placebo-controlled, and open-label trials. This review discusses the major clinical trials of tegaserod, which have involved 8948 IBS patients. Overall, data reveal that tegaserod is an effective treatment for IBS-C, providing statistically significant relief of overall and multiple individual IBS-C symptoms (abdominal pain/discomfort, bloating, and constipation) in both placebo-controlled and “real-life” open-label settings. Repeat treatments with tegaserod were also shown to be effective, which is noteworthy given the chronic and episodic nature of IBS. Moreover, tegaserod was associated with improvements in patients’ quality of life and work productivity. Data also indicate that tegaserod is well tolerated over the short-term (4 weeks), long-term (12 months), and repeated treatments. Diarrhea is the only adverse event consistently associated with tegaserod and was generally mild and transient. Overall, tegaserod has been demonstrated to offer effective and well-tolerated treatment of IBS-C, providing patients with meaningful symptom relief. PMID:18360619

Purification, crystallization and preliminary X-ray analysis of Enterococcus faecium aminoglycoside-2′′-phosphotransferase-Ib [APH(2′′)-Ib

DOE Office of Scientific and Technical Information (OSTI.GOV)

Walanj, Rupa; Young, Paul; Baker, Heather M.

2005-04-01

APH(2′′)-Ib is an enzyme responsible for high-level gentamicin resistance in E. faecium isolates. Native crystals of this enzyme have been prepared and preliminary X-ray diffraction experiments have been undertaken. Bacterial resistance to the aminoglycoside antibiotics is primarily the result of deactivation of the drugs. Three families of enzymes are responsible for this activity, with one such family being the aminoglycoside phosphotransferases (APHs). The gene encoding one of these enzymes, APH(2′′)-Ib, has been cloned and the protein (comprising 299 amino-acid residues) expressed in Escherichia coli, purified and crystallized in the presence of 16%(w/v) PEG 3350 and gentamicin. The crystals belong tomore » the monoclinic space group P2{sub 1}, with approximate unit-cell parameters a = 79.7, b = 58.8, c = 81.4 Å, β = 98.4°, and preliminary X-ray diffraction analysis is consistent with the presence of two molecules in the asymmetric unit. Synchrotron diffraction data to approximately 2.65 Å resolution were collected from a native APH(2′′)-Ib crystal at beamline BL9-2 at SSRL (Stanford, CA, USA). Selenium-substituted crystals have also been produced and structure determination is proceeding.« less

Supply Chain Management on IBS Implementation in Klang Valley Construction Industry: Challenges and Issues

NASA Astrophysics Data System (ADS)

Azrizal Fauzi, Mohd; Hasim, Sulaiman; Awang, Anizah; Ridzuan, Ahmad Ruslan Mohd; Nur Yunus, Juzailah

2017-12-01

Industrialized Building System (IBS) is a system where the components of the building are manufactured in a factory and it will be transported to the site to form the structures. The supply chain management (SCM) is a system where the delivery flows of the IBS products from manufacturers to the site. The aim of this research is to identify the major challenges and to analyze the issues on IBS implementation in SCM in Klang Valley from the manufacturers perspective. The methodology used in this paper is based on primary data through questionnaire and interview. Questionnaires were sent to the Manufacturers. It can be concluded that this paper attempts to present more on the challenges and issues that those companies of manufacturers faced during their success journey in finding integration in their supply chain. The main contributions of this paper are integrating all the supply chain integration challenges and issues on IBS. Therefore, these contributions will be helpful for the organization of manufacturers and IBS players that establish the integration in their SCM.

Improved platelet survival after cold storage by prevention of glycoprotein Ibα clustering in lipid rafts

PubMed Central

Gitz, Eelo; Koekman, Cornelis A; van den Heuvel, Dave J.; Deckmyn, Hans; Akkerman, Jan W.; Gerritsen, Hans C.; Urbanus, Rolf T.

2012-01-01

Background Storing platelets for transfusion at room temperature increases the risk of microbial infection and decreases platelet functionality, leading to out-date discard rates of up to 20%. Cold storage may be a better alternative, but this treatment leads to rapid platelet clearance after transfusion, initiated by changes in glycoprotein Ibα, the receptor for von Willebrand factor. Design and Methods: We examined the change in glycoprotein Ibα distribution using Förster resonance energy transfer by time-gated fluorescence lifetime imaging microscopy. Results Cold storage induced deglycosylation of glycoprotein Ibα ectodomain, exposing N-acetyl-Dglucosamine residues, which sequestered with GM1 gangliosides in lipid rafts. Raft-associated glycoprotein Ibα formed clusters upon binding of 14-3-3ζ adaptor proteins to its cytoplasmic tail, a process accompanied by mitochondrial injury and phosphatidyl serine exposure. Cold storage left glycoprotein Ibα surface expression unchanged and although glycoprotein V decreased, the fall did not affect glycoprotein Ibα clustering. Prevention of glycoprotein Ibα clustering by blockade of deglycosylation and 14-3-3ζ translocation increased the survival of cold-stored platelets to above the levels of platelets stored at room temperature without compromising hemostatic functions. Conclusions We conclude that glycoprotein Ibα translocates to lipid rafts upon cold-induced deglycosylation and forms clusters by associating with 14-3-3ζ. Interference with these steps provides a means to enable cold storage of platelet concentrates in the near future. PMID:22733027

A prospective study of the psychobehavioral factors responsible for a change from non-patient irritable bowel syndrome to IBS patient status

PubMed Central

Fujii, Yasushi; Nomura, Shinobu

2008-01-01

Background To investigate non-patient irritable bowel syndrome (IBS) change to IBS and to determine factors predictive of the onset of IBS, individual biological factors, psychological factors, behavioral factors, and environmental factors were examined. Methods The subjects were 105 non-patient IBS (male = 59, female = 46, average age:21.49 ± 2.37), including 68 of the diarrhea-predominant type and 37 of the constipation-predominant type selected from 1,409 university and technical college students by use of a questionnaire based on the Rome II diagnostic criteria. The subjects were followed for three years, and various characteristics and IBS symptoms were serially observed (12 times). The IBS incidence rate was calculated. Results During the three years, 37 non-patient IBS (35.24%) changed to IBS: 28 diarrhea-predominant type and 9 constipation-predominant type. All IBS symptoms disappeared in 26 non-patient IBS subjects (24.76%). According to quantification method II (discriminant analysis), seven factors (stressor, two kinds of stress coping styles, cognitive appraisal, eating habits, sleeping time, and psychologically abuse) were adopted as a predictive model for IBS incidence and were confirmed as predictive of IBS. Conclusion The results of this research show that non-patient IBS is a changeable state that can change into IBS or persons without symptoms. Most of the non-patient IBS subjects who became asymptomatic had had symptoms for six months or less. Furthermore, the longer a non-patient IBS subject had symptoms, the higher the risk of a change to IBS became. The findings suggest the usefulness of identifying and approaching non-patient IBS as early as possible to prevent the onset of IBS. It must be noted that the persons surveyed in the present study had only the diarrhea-predominant and constipation-predominant types. Therefore, the findings of the present study are limited only these two types. Further study including the mixed type is needed. PMID

MiR-144 Increases Intestinal Permeability in IBS-D Rats by Targeting OCLN and ZO1.

PubMed

Hou, Qiuke; Huang, Yongquan; Zhu, Shuilian; Li, Peiwu; Chen, Xinlin; Hou, Zhengkun; Liu, Fengbin

2017-01-01

targets of miR-144. Additionally, intestinal hyperpermeability was enhanced by miR-144 up-regulation and attenuated by miR-144 down-regulation in IBS-D rat colonic epithelial cells. Moreover, rescue experiments showed that overexpression of OCLN and ZO1 significantly eliminated the inhibitory effect of miR-144, which showed a stronger effect on the attenuation of intestinal hyperpermeability. Up-regulation of miR-144 could promote intestinal hyperpermeability and impair the protective effect of the epithelial barrier by directly targeting OCLN and ZO1. miR-144 is likely a key regulator of intestinal hyperpermeability and could be a potential therapeutic target for IBS-D. © 2017 The Author(s). Published by S. Karger AG, Basel.

Stimulation of ANP secretion by 2-Cl-IB-MECA through A(3) receptor and CaMKII.

PubMed

Yuan, Kuichang; Bai, Guang Yi; Park, Woo Hyun; Kim, Sung Zoo; Kim, Suhn Hee

2008-12-01

Adenosine is a potent mediator of myocardial protection against hypertrophy via A(1) or A(3) receptors that may be partly related to atrial natriuretic peptide (ANP) release. However, little is known about the possible involvement of the A(3) receptor on ANP release. We studied the effects of the A(3) receptor on atrial functions and its modification in hypertrophied atria. A selective A(3) receptor agonist, 2-chloro-N(6)-(3-iodobenzyl) adenosine-5'-N-methyluronamide (2-CI-IB-MECA), was perfused into isolated, beating rat atria with and without receptor modifiers. 2-CI-IB-MECA dose-dependently increased the ANP secretion, which was blocked by the A(3) receptor antagonist, but the increased atrial contractility and decreased cAMP levels induced by 30muM 2-CI-IB-MECA were not affected. The 100muM 2-(1-hexylnyl)-N-methyladenosine (HEMADO) and N(6)-(3-iodobenzyl) adenosine-5'-N-methyluronamide (IB-MECA), A(3) receptor agonist, also stimulated the ANP secretion without positive inotropy. The potency for the stimulation of ANP secretion was 2-CI-IB-MECA>IB-MECA=HEMADO. The inhibition of the ryanodine receptor or calcium/calmodulin-dependent kinase II (CaMKII) attenuated 2-CI-IB-MECA-induced ANP release, positive inotropy, and translocation of extracellular fluid. However, the inhibition of L-type Ca(2+) channels, sarcoplasmic reticulum Ca(2+)-reuptake, phospholipase C or inositol 1,4,5-triphosphate receptors did not affect these parameters. 2-CI-IB-MECA decreased cAMP level, which was blocked only with an inhibitor of CaMKII or adenylyl cyclase. These results suggest that 2-CI-IB-MECA increases the ANP secretion mainly via A(3) receptor activation and positive inotropy by intracellular Ca(2+) regulation via the ryanodine receptor and CaMKII.

Randomized clinical trial on the effect of a multispecies probiotic on visceroperception in hypersensitive IBS patients.

PubMed

Ludidi, S; Jonkers, D M; Koning, C J; Kruimel, J W; Mulder, L; van der Vaart, I B; Conchillo, J M; Masclee, A A M

2014-05-01

Irritable bowel syndrome (IBS) is characterized by heterogeneous pathophysiology and low response to treatment. Up to 60% of IBS patients suffers from visceral hypersensitivity, which is associated with symptom severity and underlying pathophysiological mechanisms. Recently, positive effects of probiotics in IBS have been reported, but overall the response was modest. We performed a study in IBS patients, characterized by visceral hypersensitivity measured with the rectal barostat, aiming to assess the effect of 6 weeks of multispecies probiotic mix on visceral pain perception. We conducted a randomized, placebo-controlled, double-blind trial in forty Rome III IBS patients with visceral hypersensitivity. Prior to intake, patients kept a 2-week symptom diary and underwent a rectal barostat measurement. When hypersensitivity was confirmed, participation was allowed and patients received a multispecies probiotic with in vitro proven potential beneficial effects on mechanisms contributing to visceral hypersensitivity (six different probiotic strains; 10(9)  cfu/g), or a placebo product of one sachet (5 g) per day for 6 weeks. At the end of the intervention period, visceroperception and symptoms were reassessed. Thirty-five patients completed the trial. The percentage of patients with visceral hypersensitivity decreased significantly in the probiotic and placebo group (76.5% and 71.4%, respectively; N.S. between groups). Improvement in pain scores and mean symptom score did not differ between the probiotic and placebo group. In this placebo-controlled trial in IBS patients with visceral hypersensitivity, no significant effect of a multispecies probiotic on viscerperception was observed. The study has been registered in the US National Library of Medicine (http://www.clinicaltrials.gov, NCT00702026). © 2014 John Wiley & Sons Ltd.

A purified transcription factor (TIF-IB) binds to essential sequences of the mouse rDNA promoter.

PubMed Central

Clos, J; Buttgereit, D; Grummt, I

1986-01-01

A transcription factor that is specific for mouse rDNA has been partially purified from Ehrlich ascites cells. This factor [designated transcription initiation factor (TIF)-IB] is required for accurate in vitro synthesis of mouse rRNA in addition to RNA polymerase I and another regulatory factor, TIF-IA. TIF-IB activity is present in extracts both from growing and nongrowing cells in comparable amounts. Prebinding competition experiments with wild-type and mutant templates suggest that TIF-IB interacts with the core control element of the rDNA promoter, which is located immediately upstream of the initiation site. The specific binding of TIF-IB to the RNA polymerase I promoter is demonstrated by exonuclease III protection experiments. The 3' border of the sequences protected by TIF-IB is shown to be on the coding strand at position -21 and on the noncoding strand at position -7. The results suggest that direct binding of TIF-IB to sequences in the core promoter element is the mechanism by which this factor imparts promoter selectivity to RNA polymerase I. Images PMID:3456157

SYMPOSIUM REPORT: An Evidence-Based Approach to IBS and CIC: Applying New Advances to Daily Practice

PubMed Central

Chey, William D.

2017-01-01

Many nonpharmacologic and pharmacologic therapies are available to manage irritable bowel syndrome (IBS) and chronic idiopathic constipation (CIC). The American College of Gastroenterology (ACG) regularly publishes reviews on IBS and CIC therapies. The most recent of these reviews was published by the ACG Task Force on the Management of Functional Bowel Disorders in 2014. The key objective of this review was to evaluate the efficacy of therapies for IBS or CIC compared with placebo or no treatment in randomized controlled trials. Evidence-based approaches to managing diarrhea-predominant IBS include dietary measures, such as a diet low in gluten and fermentable oligo-, di-, and monosaccharides and polyols (FODMAPs); loperamide; antispasmodics; peppermint oil; probiotics; tricyclic antidepressants; alosetron; eluxadoline, and rifaximin. Evidence-based approaches to managing constipation-predominant IBS and CIC include fiber, stimulant laxatives, polyethylene glycol, selective serotonin reuptake inhibitors, lubiprostone, and guanylate cyclase agonists. With the growing evidence base for IBS and CIC therapies, it has become increasingly important for clinicians to assess the quality of evidence and understand how to apply it to the care of individual patients. PMID:28729815

Lactulose Breath Test Gas Production in Childhood IBS Is Associated With Intestinal Transit and Bowel Movement Frequency.

PubMed

Chumpitazi, Bruno P; Weidler, Erica M; Shulman, Robert J

2017-04-01

In adults with irritable bowel syndrome (IBS), bacterial gas production (colonic fermentation) is related to both symptom generation and intestinal transit. Whether gas production affects symptom generation, psychosocial distress, or intestinal transit in childhood IBS is unknown. Children (ages 7-17 years) with pediatric Rome III IBS completed validated psychosocial questionnaires and a 2-week daily diary capturing pain and stooling characteristics. Stool form determined IBS subtype. Subjects then completed a 3-hour lactulose breath test for measurement of total breath hydrogen and methane production. Carmine red was used to determine whole intestinal transit time. A total of 87 children (mean age 13 ± 2.6 [standard deviation] years) were enrolled, of whom 50 (57.5%) were girls. All children produced hydrogen and 51 (58.6%) produced methane. Hydrogen and methane production did not correlate with either abdominal pain frequency/severity or psychosocial distress. Hydrogen and methane production did not differ significantly by IBS subtype. Methane production correlated positively with whole intestinal transit time (r = 0.31, P < 0.005) and inversely with bowel movement frequency (r = -0.245, P < 0.05). Methane production (threshold 3 ppm) as a marker for identifying IBS-C had a sensitivity of 60% and specificity of 42.9%. Lactulose breath test total methane production may serve as a biomarker of whole intestinal transit time and bowel movement frequency in children with IBS. In children with IBS, lactulose breath test hydrogen and methane production did not, however, correlate with abdominal pain, IBS subtype, or psychosocial distress.

39. VIEW OF CHRYSLER WORKERS LOADING A SATURN IB BOOSTER ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

39. VIEW OF CHRYSLER WORKERS LOADING A SATURN IB BOOSTER INTO THE EAST POSITION ON THE STATIC TEST TOWER. AS THE MAIN CONTRACTOR OF THE SATURN IB BOOSTER, CHRYSLER TOOK OVER OPERATIONS OF THE EAST POSITION OF THE STATIC TEST TOWER IN 1963. THAT SAME YEAR, THE WEST POSITION OF THE TEST TOWER WAS MODIFIED (AS SEEN IN THE PHOTO) FOR RESEARCH AND DEVELOPMENT TESTS OF THE SATURN V BOOSTER'S ENGINE, THE F-1. MARCH 1963, MSFC PHOTO LAB. - Marshall Space Flight Center, Saturn Propulsion & Structural Test Facility, East Test Area, Huntsville, Madison County, AL

The ties that bind: perceived social support, stress, and IBS in severely affected patients.

PubMed

Lackner, J M; Brasel, A M; Quigley, B M; Keefer, L; Krasner, S S; Powell, C; Katz, L A; Sitrin, M D

2010-08-01

This study assessed the association between social support and the severity of irritable bowel syndrome (IBS) symptoms in a sample of severely affected IBS patients recruited to an NIH-funded clinical trial. In addition, we examined if the effects of social support on IBS pain are mediated through the effects on stress. Subjects were 105 Rome II diagnosed IBS patients (F = 85%) who completed seven questionnaires which were collected as part of a pretreatment baseline assessment. Partial correlations were conducted to clarify the relationships between social support and clinically relevant variables with baseline levels of psychopathology, holding constant number of comorbid medical diseases, age, gender, marital status, ethnicity, and education. Analyses indicated that social support was inversely related to IBS symptom severity. Social support was positively related with less severe pain. A similar pattern of data was found for perceived stress but not quality of life impairment. Regression analyses examined if the effects of social support on pain are mediated by stress. The effects of social support on bodily pain were mediated by stress such that the greater the social support the less stress and the less pain. This effect did not hold for symptom severity, quality of life, or psychological distress. This study links the perceived adequacy of social support to the global severity of symptoms of IBS and its cardinal symptom (pain). It also suggests that the mechanism by which social support alleviates pain is through a reduction in stress levels.

Critical ICT-Inhibiting Factors on IBS Production Management Processes in the Malaysia Construction Industry

NASA Astrophysics Data System (ADS)

Ern, Peniel Ang Soon; Kasim, Narimah; Hamid, Zuhairi Abd; Chen, Goh Kai

2017-10-01

Industrialized Building System (IBS) is one of the approaches that had been introduced as an alternative to conventional building method where it becomes the new strategy of enhancing the sustainable construction in current industries while spearheading a huge advancement of benefits with green constructions into the existing industries. The IBS approach is actively promoted through several strategies and incentives as an alternative to conventional building methods. Extensive uptakes of modern Information Communication Technology (ICT) applications are able to support the different IBS processes for effective production. However, it is argued that ICT uptake at the organisational level is still in its infancy. This raises the importance to identify critical inhibitors which are inhibing the effective uptake of ICT in the IBS production management process. Critical inhibitors to ICT uptake were identified through questionnaire survey with the IBS industry stakeholders. The mean index and critical t-values are generated with the use of the quantitative tool, Statistical Package for Social Sciences (SPSS). The top ten priority ranked inhibitors reflect the Cost, People and Process elements to ICT uptake. High costs in acquiring the technologies and resistance to change were some main concerns from the findings.

Radiation Therapy and Cisplatin With or Without Triapine in Treating Patients With Newly Diagnosed Stage IB2, II, or IIIB-IVA Cervical Cancer or Stage II-IVA Vaginal Cancer

ClinicalTrials.gov

2018-06-20

Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Stage IB2 Cervical Cancer AJCC v6 and v7; Stage II Cervical Cancer AJCC v7; Stage II Vaginal Cancer AJCC v6 and v7; Stage IIA Cervical Cancer AJCC v7; Stage IIB Cervical Cancer AJCC v6 and v7; Stage III Vaginal Cancer AJCC v6 and v7; Stage IIIB Cervical Cancer AJCC v6 and v7; Stage IVA Cervical Cancer AJCC v6 and v7; Stage IVA Vaginal Cancer AJCC v6 and v7; Vaginal Adenocarcinoma; Vaginal Adenosquamous Carcinoma; Vaginal Squamous Cell Carcinoma, Not Otherwise Specified

Foreign Language Training in U.S. Undergraduate IB Programs: Are We Providing Students What They Need to Be Successful?

ERIC Educational Resources Information Center

Johnson, Jim

2017-01-01

A growing number of U.S. business schools now offer an undergraduate degree in international business (IB), for which training in a foreign language is a requirement. However, there appears to be considerable variance in the minimum requirements for foreign language training across U.S. business schools, including the provision of…

Antibodies to CBir1 are Associated with Glycogen Storage Disease Type Ib

PubMed Central

Davis, Michael K.; Valentine, John F.; Weinstein, David A.; Polyak, Steven

2009-01-01

Objectives Glycogen storage disease (GSD) type Ib is a congenital disorder of glycogen metabolism that is associated with neutropenia, neutrophil and monocyte dysfunction, and an inflammatory bowel disease (IBD) that mimics a Crohn's disease phenotype. The enteric microflora is implicated in the pathogenesis of IBD; however, its role in the development of GSD-associated IBD is unknown. Antibody reactivity to Saccharomyces cerevisiae antibodies (ASCA), Escherichia coli outer membrane porin C (anti-OmpC) and bacterial flagellin (anti-CBir1) have been associated with Crohn's disease in the general population, but they have an undetermined association in children and adults with GSD-Ib. Our goal was to examine the association of ASCA, anti-OmpC and anti-CBir1 with the clinical features of GSD-Ib enterocolitis. Methods A retrospective review identified 19 GSD-Ib patients with or without a known diagnosis of enterocolitis. Radiographic, endoscopic and serologic data were collected and assays for ASCA, anti-OmpC, and anti-CBir1 obtained. Results Seven patients had combined radiographic, endoscopic, and histological evidence of intestinal inflammation; the majority had ileocolonic involvement. Seventeen of 19 (89%) patients had elevated anti-CBir1 levels (6/7 in the IBD group and 11/12 in the no clinical evidence of IBD group). Thirteen of 19 (68%) had elevated anti-OmpC levels (5/7 in the IBD group and 8/12 in the no clinical evidence of IBD group). Eleven of 19 (58%) patients had elevated ASCA IgA levels (4/7 in the IBD group and 7/12 in the no clinical evidence of IBD group). Conclusion Nearly all of the GSD type Ib patients had elevated anti-CBir1 levels. The antibody did not differentiate those with and without a diagnosis of GSD-Ib-associated IBD. Seroreactivity to flagellin may represent immune dysfunction rather than active enterocolitis in this patient population. Long-term follow-up of the group without known IBD is required to determine if these antibodies can

How the Change in IBS Criteria From Rome III to Rome IV Impacts on Clinical Characteristics and Key Pathophysiological Factors.

PubMed

Aziz, Imran; Törnblom, Hans; Palsson, Olafur S; Whitehead, William E; Simrén, Magnus

2018-06-08

The diagnostic criteria for irritable bowel syndrome (IBS) have recently been updated from Rome III to Rome IV. Whereas in Rome III a diagnosis of IBS entailed chronic abdominal pain or discomfort at least 3 days per month, in Rome IV the term discomfort has been removed and the frequency of abdominal pain increased to at least 1 day per week. We examined how this change in IBS criteria impacts on clinical characteristics and pathophysiological factors. A total of 542 Swedish subjects with Rome III IBS completed a baseline questionnaire enquiring for the number of abdominal pain days in the last 10 days; this was subsequently used as a surrogate marker to identify Rome IV IBS, in that (a) those with 0 or 1 day of pain were classed as Rome IV-negative, and (b) those with ≥2 days of pain were classed as Rome IV-positive. Comparisons were made between Rome IV-positive and -negative IBS groups for demographics, IBS subtype, gastrointestinal and psychological symptoms, somatisation, fatigue, disease-specific quality of life, rectal sensitivity, and oro-anal transit time. Overall, 85% of Rome III IBS patients fulfilled the Rome IV criteria for IBS, but 15% did not. Rome IV-positive subjects were significantly more likely to be female, have poorer quality of life, greater pain severity, bloating, somatisation, fatigue, and rectal sensitivity than Rome IV-negative subjects. There were no differences in severity of anxiety or depression, IBS subtypes, bowel habit dissatisfaction, or oro-anal transit time. Finally, increasing number of pain days correlated positively with symptoms and visceral hypersensitivity. Most Rome III-positive IBS patients seeking healthcare fulfil the Rome IV IBS criteria. They constitute a more severe group than those who lose their IBS diagnosis.

The International Baccalaureate (IB) Programme: An International Gateway to Higher Education and Beyond

ERIC Educational Resources Information Center

Hill, Ian; Saxton, Susan

2014-01-01

The aim of this article is to present the International Baccalaureate (IB) Programme and briefly outline its core components, followed by a review of what authoritative reports identify as skills for the future, esteemed by universities and the job market. There is a striking match between these skills and IB outcomes; thus, DP graduates perform…

The ties that bind: perceived social support, stress, and IBS in severely affected patients

PubMed Central

LACKNER, J. M.; BRASEL, A. M.; QUIGLEY, B M.; KEEFER, L.; KRASNER, S. S.; POWELL, C.; KATZ, L. A.; SITRIN, M. D.

2016-01-01

Background This study assessed the association between social support and the severity of irritable bowel syndrome (IBS) symptoms in a sample of severely affected IBS patients recruited to an NIH-funded clinical trial. In addition, we examined if the effects of social support on IBS pain are mediated through the effects on stress. Methods Subjects were 105 Rome II diagnosed IBS patients (F = 85%) who completed seven questionnaires which were collected as part of a pretreatment baseline assessment. Key Results Partial correlations were conducted to clarify the relationships between social support and clinically relevant variables with baseline levels of psychopathology, holding constant number of comorbid medical diseases, age, gender, marital status, ethnicity, and education. Analyses indicated that social support was inversely related to IBS symptom severity. Social support was positively related with less severe pain. A similar pattern of data was found for perceived stress but not quality of life impairment. Regression analyses examined if the effects of social support on pain are mediated by stress. The effects of social support on bodily pain were mediated by stress such that the greater the social support the less stress and the less pain. This effect did not hold for symptom severity, quality of life, or psychological distress. Conclusions & Inferences This study links the perceived adequacy of social support to the global severity of symptoms of IBS and its cardinal symptom (pain). It also suggests that the mechanism by which social support alleviates pain is through a reduction in stress levels. PMID:20465594

With World Growing Smaller, IB Gets Big

ERIC Educational Resources Information Center

Cech, Scott J.

2007-01-01

The perception that the Geneva, Switzerland-based International Baccalaureate Organization's academic programs offer just what American students need in today's more globally competitive environment seems to be catching on. After decades of obscurity and slow expansion, the pace of growth in IB--including courses of study for the primary and…

Characterization of Tn6238 with a New Allele of aac(6′)-Ib-cr

PubMed Central

Quiroga, María P.; Orman, Betina; Errecalde, Laura; Kaufman, Sara

2015-01-01

Here, we report that the genetic structure of Tn1331 remained conserved in Argentina from 1989 to 2013 (72 of 73 isolates), with the exception being the plasmid-borne Tn1331-like transposon Tn6238 containing a new aac(6′)-Ib-cr allele recovered from a colistin-resistant Klebsiella pneumoniae clinical isolate. A bioinformatic analysis of aac(6′)-Ib-like gene cassettes suggests that this new aac(6′)-Ib-cr allele emerged through mutation or homologous recombination in the Tn1331 genetic platform. Tn6238 is a novel platform for the dissemination of aminoglycoside and fluoroquinolone resistance determinants. PMID:25691640

Gastrointestinal permeability (GIPerm) is increased in family members of children with functional abdominal pain (FAP) and irritable bowel syndrome (IBS)

USDA-ARS?s Scientific Manuscript database

Increased GIPerm has been described in children with FAP/IBS and adults with IBS. We sought to determine if baseline GIPerm is increased and if ibuprofen induces a greater increase in GIPerm in parents and siblings of children with FAP/IBS vs. control families without children with FAP/IBS. Site spe...

Possible Involvement of Avoidant Attachment Style in the Relations Between Adult IBS and Reported Separation Anxiety in Childhood.

PubMed

Ben-Israel, Yuval; Shadach, Eran; Levy, Sigal; Sperber, Ami; Aizenberg, Dov; Niv, Yaron; Dickman, Ram

2016-12-01

Irritable bowel syndrome (IBS) in adults as well as separation anxiety disorder (SAD) and recurrent abdominal pain (RAP) in childhood are associated with anxiety and somatization. Our aim was to examine possible associations between IBS in adulthood and SAD in childhood. Patients with IBS and healthy subjects completed a demographic questionnaire, the Separation Anxiety Symptom Inventory (SASI), the Somatization Subscale of Symptom Checklist-90-R (SCL-90-R), the Attachment Style Questionnaire, and a retrospective self-report questionnaire regarding RAP. Compared with controls, patients with IBS were characterized by an avoidant attachment style and scored higher on the SCL-90-R scale regarding the tendency to somatization (25.35 ± 7.47 versus16.50 ± 4.40, p < 0.001). More patients with IBS (25% versus 7.5%) reported RAP in childhood, but contrary to prediction, also had significantly lower SASI scores. Adults with IBS were characterized by somatization, insecure attachment style and recalled higher rates of RAP and surprisingly less symptoms of SAD in childhood. Based on these results, an etiological model for IBS is suggested, in which an avoidant attachment style and a tendency to somatization play an important role in the development of IBS. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Neoadjuvant chemotherapy followed by surgery has no therapeutic advantages over concurrent chemoradiotherapy in International Federation of Gynecology and Obstetrics stage IB-IIB cervical cancer.

PubMed

Lee, Jeongshim; Kim, Tae Hyung; Kim, Gwi Eon; Keum, Ki Chang; Kim, Yong Bae

2016-09-01

We aimed to assess the efficacy of neoadjuvant chemotherapy followed by surgery (NACT+S), and compared the clinical outcome with that of concurrent chemoradiotherapy (CCRT) in patients with International Federation of Gynecology and Obstetrics (FIGO) IB-IIB cervical cancer. We reviewed 85 patients with FIGO IB-IIB cervical cancer who received NACT+S between 1989 and 2012, and compared them to 358 control patients who received CCRT. The clinical application of NACT was classified based on the following possible therapeutic benefits: increasing resectability after NACT by reducing tumor size or negative conversion of node metastasis; downstaging adenocarcinoma regarded as relatively radioresistant; and preservation of fertility through limited surgery after NACT. Of 85 patients in the NACT+S group, the pathologic downstaging and complete response rates were 68.2% and 22.6%, respectively. Only two young patients underwent limited surgery for preservation of fertility. Patients of the NACT+S group were younger, less likely to have node metastasis, and demonstrated a higher proportion of FIGO IB cases than those of the CCRT group (p≤0.001). The 5-year locoregional control, progression-free survival, and overall survival rates in the NACT+S group were 89.7%, 75.6%, and 92.1%, respectively, which were not significantly different from the rates of 92.5%, 74%, and 84.9% observed in the CCRT group, respectively (p>0.05). NACT+S has no therapeutic advantages over CCRT, the standard treatment. Therefore, NACT+S should be considered only in selected patients through multidisciplinary discussion or clinical trial setting.

[Effect of Tongxie Yaofang on endogenous metabolites in serum of IBS model rats].

PubMed

Li, Kai; Kuang, Hai-Xue; Yin, Yue; Zhang, Jie-Yu; Wang, Zhi; Zhang, Qiu-Yue; Wang, Jian-Wei

2017-03-01

To evaluate the effect of Tongxie Yaofang on cardiac endogenous metabolism in irritable bowel syndrome(IBS) rats by using metabolomics method, find its potential biomarkers, analyze the metabolic pathways, and explore the pharmacological effects, mechanisms of action and syndrome essence of syndrome model. Forty Wistar rats were used to establish IBS models, and then randomly divided into four groups： model control group and Tongxie Yaofang treatment groups (high, medium, low dose). Another 10 rats were used as normal group. The rats in Tongxie Yaofang-treated(low, medium and high dose) groups were orally administrated with Tongxie Yaofang extracts once a day for 2 weeks, respondingly with the doses of 0.203,0.406,0.812 g•mL⁻¹. The rats in normal group and model control group were given with equal volume of saline once a day for 2 weeks. On the 0 and 15th days, serum was collected and each sample extract was analyzed by UPLC-Q-TOF-MS. Eight potential biomarkers were identified and 8 major metabolic pathways were found to be related with IBS diseases neurotransmitter metabolism, inflammatory immunity, brain function and energy metabolism, etc. Tongxie Yaofang had certain pharmacological effects on IBS, and its mechanism may be related to serotonergic synapse, tryptophan metabolism, cysteine and methionine metabolism, glycerophospholipid metabolism, nicotinate and nicotinamide metabolism and so on, which might be the biological basis of IBS liver-spleen deficiency syndrome. Copyright© by the Chinese Pharmaceutical Association.

The Futility of Propensity Score Methods in a Statewide Study of International Baccalaureate (IB)

ERIC Educational Resources Information Center

May, Henry; Rodriguez, Awilda; Sirinides, Philip M.; Perna, Laura W.; Yee, April; Ransom, Tafaya

2014-01-01

With the goal of increasing students' academic readiness for college, high schools in the United States are increasingly offering "credit-based transition programs," including International Baccalaureate (IB), Advanced Placement (AP), and dual enrollment. Existing research points to the promise of IB, AP, and other credit-based…

Travel Tips Help IBS Sufferers Enjoy Their Vacations

MedlinePlus

... can feel more in control when traveling." IFFGD's travel tips include: Allow enough time in the morning to get to the airport ... Heartache 2004-0929 Norton Honored 2004-0525 IBS Travel Tips ... Real World 2001-1119 Heartburn or Heart Attack Commentary ...

Comparison of medical costs generated by IBS patients in primary and secondary care in the Netherlands.

PubMed

Flik, Carla E; Laan, Wijnand; Smout, André J P M; Weusten, Bas L A M; de Wit, Niek J

2015-11-26

Irritable Bowel Syndrome (IBS) is a functional somatic syndrome characterized by patterns of persistent bodily complaints for which a thorough diagnostic workup does not reveal adequate explanatory structural pathology. Detailed insight into disease-specific health-care costs is critical because it co-determines the societal impact of the disease, enables the assessment of cost-effectiveness of existing and new treatments, and facilitates choices in treatment policy. In the present study the aim was, to compare the costs and magnitude of healthcare consumption for patients diagnosed with Irritable Bowel Syndrome (IBS) in primary and secondary care, compare these costs with the average health care expenditure for patients without IBS and describe these costs in further detail. Reimbursement data for patients diagnosed with IBS by a general practitioner (GP) or specialist between 2006 and 2009 were extracted from a healthcare insurance company and compared to an age and gender matched control group of patients without IBS. Using a case-control design, direct medical costs for GP consultations, specialist care and medication prescriptions were calculated. Data of 326 primary care and 9274 secondary care IBS patients were included in the analysis. For primary care patients, the mean total annual health care costs for the three years after diagnosis compared to the three years before diagnosis, increased with 486 Euro after IBS was diagnosed, whereas for secondary care patients, these costs increased with 2328 Euro. Total health care costs remained higher in the three years after the initial diagnosis when the patient is treated in secondary care, compared to primary care. This increase was significant for hospital specialist costs and medications, but not for GP contacts. For controls, there was no significant difference in mean total annual health costs in the three years before and the three years after the diagnosis and also no significant difference in cost

Streptococcus agalactiae serotype Ib as an agent of meningitis in two adult nonpregnant women.

PubMed

Martins, E R; Florindo, C; Martins, F; Aldir, I; Borrego, M J; Brum, L; Ramirez, M; Melo-Cristino, J

2007-11-01

Two temporally and geographically clustered cases of meningitis caused by Streptococcus agalactiae expressing the infrequent Ib serotype are reported. Characterization by pulsed-field gel electrophoresis and multilocus sequence typing revealed that the isolates were identical and represented the widely distributed ST10/ST8 lineage associated with serotype Ib.

IBS Patients Show Frequent Fluctuations between Loose/Watery and Hard/Lumpy Stools: Implications for Treatment

PubMed Central

Palsson, Olafur S.; Baggish, Jeffrey S.; Turner, Marsha J.; Whitehead, William E.

2013-01-01

Aims To determine how variable stool consistency is in patients with irritable bowel (IBS) and assess the relationship between stool consistency and gastrointestinal symptoms. Methods Individuals with a physician diagnosis of IBS were recruited by advertisement. Enrollment questionnaires included the Rome III Diagnostic Questionnaire and IBS Symptom Severity Scale. Then 185 patients meeting Rome criteria for IBS rated the consistency (using the Bristol Stool Scale) of each bowel movement (BM) for 90 days and whether the BM was accompanied by pain, urgency, or soiling. Each night they transferred BM ratings from a paper diary to an internet form and also reported the average daily intensity of abdominal pain, bloating, bowel habit dissatisfaction, and life interference of bowel symptoms. Only the longest sequence of consecutive days of diary data was used in analysis (average of 73 days). Results Patients were 89% female with average age 36.6 years. 78% had both loose/watery and hard/lumpy stools; the average was 3 fluctuations between these extremes per month. The proportion of loose/watery stools correlated r=.78 between the first and second months and the proportion of hard/lumpy stools correlated r=.85 between months. Loose/watery stools were associated with more BM-related pain, urgency, and soiling than hard/lumpy or normal stools; however, IBS-C patients had significantly more BM-unrelated abdominal pain, bloating, dissatisfaction with bowel habits, and life interference than IBS-D. Questionnaires overestimated the frequency of abnormal stool consistency and gastrointestinal symptoms compared to diaries. Conclusions Stool consistency varies greatly within individuals. However, stool patterns are stable within an individual from month to month. The paradoxical findings of greater symptom severity after individual loose/watery BMs vs. greater overall symptom severity in IBS-C implies different physiological mechanisms for symptoms in constipation compared to

Does Education Have Any Influence on Symptom Score of IBS Patients: A Randomized Controlled Study.

PubMed

Sarkar, S K; Tarafder, A J; Chowdhury, M; Alam, M S; Mohsin, M

2016-04-01

Despite much research, the pathophysiology of IBS remains poorly understood. So it is very difficult to treat. There is no standard treatment for IBS. Because IBS symptoms can be elicited or exacerbated by diet and stress, this suggests that patient education regarding his or her illness might be beneficial to patients in managing their symptoms. This study was done to see the short term effects of outpatient education in relation to change of symptom score in IBS patients. This is a prospective randomized comparative study. In this study a total of 80 patients were included. Forty patients were given only pharmacological management with Mebevarine hydrochloride 135mg thrice daily half an hour before meal and Amitryptline 10mg at night for six months and another forty were given education in addition to the same pharmacological treatment. In both the study group [medical management only versus medical management with education] changes of symptoms and quality of life of patients of IBS were assessed by using previously used, specially designed symptoms scoring system and a validated IBS-QOL instrument. There was no significant difference in severity of symptoms between only drug treatment group (118.973) and education plus drug treatment group (119.57) before treatment. The difference of improvement between the education group and without education group was not statistically significant (P>0.05), though the subsidence of pain in both the group before and after treatment was statistically significant (P<0.01).

Preinduced intestinal HSP70 improves visceral hypersensitivity and abnormal intestinal motility in PI-IBS mouse model.

PubMed

Lan, Cheng; Sun, Xiao-Ning; Zhou, Xu-Chun; Yang, Bo; Huang, Bai-Li; Deng, Tao-Zhi; He, Zhou-Tao; Han, Xiang-Yang

2016-03-01

To investigate the impact of the preinduced intestinal heat shock protein 70 (HSP70) on the visceral hypersensitivity and abnormal intestinal motility in a post-infectious irritable bowel syndrome (PI-IBS) mouse model. Eighty-four female C57BL/6 mice were randomly assigned to four groups: control group (n = 21) and induction + PI-IBS group (n = 21), PI-IBS group (n = 21) and induction group (n = 21). The mice in PI-IBS group were infected in vivo with Trichinella spiralis by oral administration. The visceral hypersensitivity and intestinal motility were evaluated respectively with abdominal withdrawal reflex and colon transportation test. The intestinal HSP70 protein and mRNA level was measured by Western blot and real-time PCR. Meanwhile, the intestinal proinflammatory cytokines IL-10 and TNF-α level was detected by ELISA. Compared with their counterparts in PI-IBS group, the animals in the Induction + PI-IBS group show significantly increased intestinal level of HSP70 and obviously ameliorative clinical figures, including abdominal withdrawal reflex score, intestine transportation time and Bristol scores (P < 0.05). Meanwhile, the intestinal post-inflammatory cytokines remarkably changed, including increased IL-10 level and decreased TNF-α level (P < 0.05). Intestinal HSP70 may play a potential protective role through improving the imbalance between the intestinal post-inflammatory and anti-inflammatory cytokines in PI-IBS. Copyright © 2016 Hainan Medical College. Production and hosting by Elsevier B.V. All rights reserved.

Fear of GI symptoms has an important impact on quality of life in patients with moderate-to-severe IBS.

PubMed

Lackner, Jeffrey M; Gudleski, Gregory D; Ma, Chang-Xing; Dewanwala, Akriti; Naliboff, Bruce

2014-11-01

Because irritable bowel syndrome (IBS) is a functional medical condition for which there is no curative therapy, treatment goals emphasize relieving gastrointestinal (GI) symptoms and optimizing the quality of life (QOL). This study sought to characterize the magnitude of the associations between QOL impairment, fear of IBS symptoms, and confounding variables. Subjects included 234 Rome III-diagnosed IBS patients (mean age, 41 years, 79%, female) without comorbid organic GI disease who were referred to two specialty care clinics of an National Institutes of Health trial for IBS. Subjects completed a testing battery that included the IBS-specific QOL (IBS-QOL), SF-12 (generic QOL), the UCLA GI Symptom Severity Scale, the Visceral Sensitivity Index, Trait Anxiety Inventory, and Brief Symptom Inventory. Multiple linear regression was used to develop a model for predicting QOL. Data supported an overall model that included sociodemographic, clinical (e.g., current severity of GI symptoms), and psychosocial (e.g., fear of GI symptoms, distress, neuroticism) variables, accounting for 48.7% of the variance in IBS-QOL (F=15.1, P <0.01). GI symptom fear was the most robust predictor of IBS-QOL (β=-0.45 P <0.01), accounting for 14.4% of the total variance. Patients' fear that GI symptoms have aversive consequences, is a predictor of QOL impairment that cannot be fully explained by the severity of their GI symptoms, overall emotional well-being, neurotic personality style, or other clinical features of IBS. An understanding of the unique impact that GI symptom fears have on QOL can inform treatment planning and help gastroenterologists to better manage more severe IBS patients seen in tertiary care clinics.

Pharmacokinetic properties of IB1001, an investigational recombinant factor IX, in patients with haemophilia B: repeat pharmacokinetic evaluation and sialylation analysis.

PubMed

Martinowitz, U; Shapiro, A; Quon, D V; Escobar, M; Kempton, C; Collins, P W; Chowdary, P; Makris, M; Mannucci, P M; Morfini, M; Valentino, L A; Gomperts, E; Lee, M

2012-11-01

IB1001 trenacog alfa is an investigational recombinant factor IX (FIX) for the treatment and prevention of bleeding in individuals with haemophilia B. To compare the pharmacokinetics (PK) of IB1001 with nonacog alfa in individuals with haemophilia B and to assess the relationship between sialylation and PK of IB1001 (NCT00768287). A randomized, double-blind, non-inferiority, cross-over study conducted in participants aged ≥ 12 years weighing ≥ 40 kg, with severe or moderately severe haemophilia B (FIX activity ≤ 2 IU dL (-1) ). PK parameters were derived using observed FIX concentration levels and actual PK sampling times, and repeated in a subset of participants who had received IB1001 prophylaxis for 4-18 months. A retrospective analysis was conducted in subgroups according to the sialylation levels of IB1001 (50.8, 57.8-59.0%, or 71.7%). In the 32 adolescent and adult males evaluated, there were no clinically meaningful differences in PK parameters between those receiving IB1001 75 IU kg(-1) or nonacog alfa. The lower limit of the one-sided 95% confidence interval for the ratio of AUC(0-t) and AUC(0-∞) (IB1001/nonacog alfa) was 0.90, establishing non-inferiority. Terminal phase half-lives were similar (29.7 ± 18.2 h for IB1001 and 33.4 ± 21.2 h for nonacog alfa). The PK results were stable for up to 18 months of IB1001 exposure; the impact of sialylation levels was not clinically meaningful. There were no clinically meaningful PK differences between IB1001 and nonacog alfa. IB1001 was well tolerated and without safety concerns. The non-inferiority of IB1001 to nonacog alfa supports IB1001 becoming a useful alternative recombinant agent for the management of haemophilia B. © 2012 Blackwell Publishing Ltd.

Blastocystis specific serum immunoglobulin in patients with irritable bowel syndrome (IBS) versus healthy controls.

PubMed

Nagel, Robyn; Traub, Rebecca J; Kwan, Marcella M S; Bielefeldt-Ohmann, Helle

2015-09-15

Blastocystis species are common enteric human parasites and carriage has been linked to Irritable Bowel Syndrome (IBS), particularly diarrhoea-predominant IBS. The spectrum of immune reactivity to Blastocystis proteins has been reported previously in symptomatic patients. We investigated differences in serum immunoglobulin profiles between patients with IBS, both positive and negative for Blastocystis carriage, and healthy controls (HC). Forty diarrhoea-predominant IBS patients (26 patients positive for Blastocystis sp., 14 negative patients) and forty HC (24 positive, 16 Blastocystis-negative) were enrolled. Age, gender, ethnicity and serum immunoglobulin A (IgA) levels were recorded and faecal specimens were analysed using smear, culture and polymerase chain reaction amplification of ribosomal DNA. Sera were tested in Western blots and the reactivities compared to known targets using monoclonal antibodies Blastofluor® (Blastocystis specific antibody), MAb1D5 (cytopathicto Blastocystis cells), anti-promatrix metalloprotease-9 (anti-MMP-9) and SDS-PAGE zymograms. Levels of serum IgA were significantly lower in Blastocystis carriers (p < 0.001) but had no relationship to symptoms. Western blots demonstrated serum IgG antibodies specific for Blastocystis proteins of 17,27,37,50,60-65, 75-90, 95-105 and 150 kDa MW. Reactivity to the 27, 50 and 75-95 kDa proteins were found more frequently in the IBS group compared to the HC's (p < 0.001) and correlation was greater for Blastocystis-positive IBS patients (p < 0.001) than for negative IBS patients (p < 0.05). MAb1D5 reacted with proteins of 27 and 100 kDa, and anti-MMP-9 with 27, 50 and 75-100 kDa proteins. Bands were seen in zymograms around 100 kDa. Low serum IgA levels are associated with Blastocystis carriage. All IBS patients were more likely to demonstrate reactivity with Blastocystis proteins of 27 kDa (likely a cysteine protease), 50 and 75-95 kDa MW compared to HC. The presence of

Long-term clincopathological characteristics of alpacas naturally infected with bovine viral diarrhea virus type Ib

USDA-ARS?s Scientific Manuscript database

Background: Substantial bovine viral diarrhea virus (BVDV)-related production losses in North American alpaca herds have been associated with BVDV type Ib infection. Objectives: To classify and differentiate the long-term clinicopathological characteristics of BVDV type Ib infection of alpaca crias,...

Streptococcus sanguinis class Ib ribonucleotide reductase: high activity with both iron and manganese cofactors and structural insights.

PubMed

Makhlynets, Olga; Boal, Amie K; Rhodes, Delacy V; Kitten, Todd; Rosenzweig, Amy C; Stubbe, JoAnne

2014-02-28

Streptococcus sanguinis is a causative agent of infective endocarditis. Deletion of SsaB, a manganese transporter, drastically reduces S. sanguinis virulence. Many pathogenic organisms require class Ib ribonucleotide reductase (RNR) to catalyze the conversion of nucleotides to deoxynucleotides under aerobic conditions, and recent studies demonstrate that this enzyme uses a dimanganese-tyrosyl radical (Mn(III)2-Y(•)) cofactor in vivo. The proteins required for S. sanguinis ribonucleotide reduction (NrdE and NrdF, α and β subunits of RNR; NrdH and TrxR, a glutaredoxin-like thioredoxin and a thioredoxin reductase; and NrdI, a flavodoxin essential for assembly of the RNR metallo-cofactor) have been identified and characterized. Apo-NrdF with Fe(II) and O2 can self-assemble a diferric-tyrosyl radical (Fe(III)2-Y(•)) cofactor (1.2 Y(•)/β2) and with the help of NrdI can assemble a Mn(III)2-Y(•) cofactor (0.9 Y(•)/β2). The activity of RNR with its endogenous reductants, NrdH and TrxR, is 5,000 and 1,500 units/mg for the Mn- and Fe-NrdFs (Fe-loaded NrdF), respectively. X-ray structures of S. sanguinis NrdIox and Mn(II)2-NrdF are reported and provide a possible rationale for the weak affinity (2.9 μM) between them. These streptococcal proteins form a structurally distinct subclass relative to other Ib proteins with unique features likely important in cluster assembly, including a long and negatively charged loop near the NrdI flavin and a bulky residue (Thr) at a constriction in the oxidant channel to the NrdI interface. These studies set the stage for identifying the active form of S. sanguinis class Ib RNR in an animal model for infective endocarditis and establishing whether the manganese requirement for pathogenesis is associated with RNR.

Responders vs clinical response: a critical analysis of data from linaclotide phase 3 clinical trials in IBS-C.

PubMed

Lacy, B E; Lembo, A J; Macdougall, J E; Shiff, S J; Kurtz, C B; Currie, M G; Johnston, J M

2014-03-01

US Food and Drug Administration (FDA) set a rigorous standard for defining patient responders in irritable bowel syndrome-C (IBS-C; i.e., FDA's Responder Endpoint) for regulatory approval. However, this endpoint's utility for health-care practitioners to assess clinical response has not been determined. We analyzed pooled IBS-C linaclotide trial data to evaluate clinically significant responses in linaclotide-treated patients who did not meet the FDA responder definition. Percentages of FDA non-responders reporting improvement in abdominal pain, bowel function and/or global relief measures were determined using pooled data from two linaclotide Phase 3 IBS-C trials. 1602 IBS-C patients enrolled; 34% of linaclotide-treated and 17% of placebo-treated patients met the FDA Responder Endpoint (p < 0.0001). Among FDA non-responders at week 12, 63% of linaclotide-treated patients reported their abdominal pain was at least somewhat relieved, compared with 48% of placebo-treated patients. For stool frequency, 62% of linaclotide-treated patients reported that they were at least somewhat improved at week 12, compared with 46% of placebo-treated patients. For global IBS symptoms, 65% of linaclotide-treated patients reported at least some IBS-symptom relief, 43% reported adequate relief of IBS symptoms, and 57% reported being satisfied with linaclotide treatment, vs placebo rates of 48%, 34%, and 41% respectively. Most linaclotide-treated IBS-C patients who were FDA non-responders reported some improvement in abdominal pain and stool frequency, and global relief/satisfaction. In addition to the FDA Responder Endpoint, differing response thresholds and symptom-specific change from baseline should be considered by clinicians for a complete understanding of clinical response to linaclotide and other IBS-C therapies. © 2013 Ironwood Pharmaceuticals. Neurogastroenterology & Motility published by John Wiley & Sons Ltd.

The impact of physical complaints, social environment, and psychological functioning on IBS patients' health perceptions: looking beyond GI symptom severity.

PubMed

Lackner, Jeffrey M; Gudleski, Gregory D; Thakur, Elyse R; Stewart, Travis J; Iacobucci, Gary J; Spiegel, Brennan Mr

2014-02-01

In the absence of a reliable biomarker, clinical decisions for a functional gastrointestinal (GI) disorder like irritable bowel syndrome (IBS) depend on asking patients to appraise and communicate their health status. Self-ratings of health (SRH) have proven a powerful and consistent predictor of health outcomes, but little is known about how they relate to those relevant to IBS (e.g., quality of life (QOL), IBS symptom severity). This study examined what psychosocial factors, if any, predict SRH among a cohort of more severe IBS patients. Subjects included 234 Rome III-positive IBS patients (mean age=41 years, female=78%) without comorbid organic GI disease. Subjects were administered a test battery that included the IBS Symptom Severity Scale, Screening for Somatoform Symptoms, IBS Medical Comorbidity Inventory, SF-12 Vitality Scale, Perceived Stress Scale, Beck Depression Inventory, Trait Anxiety Inventory, and Negative Interactions Scale. Partial correlations identified somatization, depression, fatigue, stress, anxiety, and medical comorbidities as variables with the strongest correlations with SRH (r values=0.36-0.41, P values <0.05). IBS symptom severity was weakly associated with SRH (r=0.18, P<0.05). The final regression model explained 41.3% of the variance in SRH scores (F=8.49, P<0.001) with significant predictors including fatigue, medical comorbidities, somatization, and negative social interactions. SRH are associated with psychological (anxiety, stress, depression), social (negative interactions), and extraintestinal somatic factors (fatigue, somatization, medical comorbidities). The severity of IBS symptoms appears to have a relatively modest role in how IBS patients describe their health in general.

Localization and characterization of an alpha-thrombin-binding site on platelet glycoprotein Ib alpha.

PubMed

De Marco, L; Mazzucato, M; Masotti, A; Ruggeri, Z M

1994-03-04

Glycoprotein (GP) Ib alpha is required for expression of the highest affinity alpha-thrombin-binding site on platelets, possibly contributing to platelet activation through a pathway involving cleavage of a specific receptor. This function may be important for the initiation of hemostasis and may also play a role in the development of pathological vascular occlusion. We have now identified a discrete sequence in the extracytoplasmic domain of GP Ib alpha, including residues 271-284 of the mature protein, which appears to be part of the high affinity alpha-thrombin-binding site. Synthetic peptidyl mimetics of this sequence inhibit alpha-thrombin binding to GP Ib as well as platelet activation and aggregation induced by subnanomolar concentrations of the agonist; they also inhibit alpha-thrombin binding to purified glycocalicin, the isolated extracytoplasmic portion of GP Ib alpha. The inhibitory peptides interfere with the clotting of fibrinogen by alpha-thrombin but not with the amidolytic activity of the enzyme on a small synthetic substrate, a finding compatible with the concept that the identified GP Ib alpha sequence interacts with the anion-binding exosite of alpha-thrombin but not with its active proteolytic site. The crucial structural elements of this sequence necessary for thrombin binding appear to be a cluster of negatively charged residues as well as three tyrosine residues that, in the native protein, may be sulfated. GP Ib alpha has no significant overall sequence homology with the thrombin inhibitor, hirudin, nor with the specific thrombin receptor on platelets; all three molecules, however, possess a distinct region rich in negatively charged residues that appear to be involved in thrombin binding. This may represent a case of convergent evolution of unrelated proteins for high affinity interaction with the same ligand.

An exploratory review on critical factors of IBS formwork implementation for Malaysian construction stakeholders

NASA Astrophysics Data System (ADS)

Baharuddin, Mohd Nurfaisal; Bahardin, Nur Fadhilah; Zaidi, Mohd Azian; Lokman, Ikhwan; Nawi, Mohd Nasrun Mohd

2016-08-01

The goals of this paper is to analysed the critical factors of driving or hindering the used of Industrialised Building System (IBS) formwork system in the Malaysian construction industry. Based on the reviews of a previous research and related literature, this paper was identified four (4) critical factor that classified as a difficulties to the success of IBS formwork system application; The issues related to the lack of knowledge and awareness, high cost and financial barriers, lack of incentive and promotion and lack of enforcement for government policy were highlight as a key dimension for the uses of IBS formwork system to success. The objective of this paper is to determine the importance factors in implementing IBS formwork in Malaysia. A preliminary survey which qualitative research approach has been adopted for this study as to validate the factors which found in the literature study. Based on the result analysis, it can be confirmed that the entire factors in literature review are strongly related with challenges in construction industry.

Effect of linaclotide in irritable bowel syndrome with constipation (IBS-C): a systematic review and meta-analysis.

PubMed

Atluri, D K; Chandar, A K; Bharucha, A E; Falck-Ytter, Y

2014-04-01

Treatment options for constipation-predominant irritable bowel syndrome (IBS-C) are limited. While linaclotide improved IBS-C symptoms in randomized controlled trials (RCTs), results vary among studies and the magnitude of benefit is unclear. Two investigators independently extracted data on study participants, methods and outcomes (i.e., symptoms, quality of life, and adverse events) from eligible articles i.e., RCTs comparing linaclotide with placebo in adult patients with IBS-C with a follow-up of 12 weeks or longer. The grading of recommendations assessment, development and evaluation (GRADE) methodology was used to rate the quality of evidence. Of 182 identified citations, three RCTs enrolling 1773 patients met the inclusion criteria. Compared with placebo, fewer patients on linaclotide failed to achieve responses i.e., FDA endpoint (1604 patients, risk ratio [RR] = 0.80; 95%CI 0.76-0.85), adequate IBS symptom relief (1773 patients, RR = 0.73; 95%CI 0.65-0.82), and clinically meaningful improvement in IBS-QOL (1659 patients, RR = 0.78; 95%CI 0.72-0.86). The incidence of diarrhea leading to discontinuation of treatment was higher for linaclotide (1773 patients, RR = 14.75; 95%CI 4.04-53.81). The quality of evidence was rated as moderate for FDA endpoint and adequate relief response, high for diarrhea, and low for IBS-QOL. Generalizability may be limited by the study population (i.e., predominantly white female patients), lack of data regarding prior therapy, and availability of few RCTs. The number of patients is insufficient to identify rare adverse events. Linaclotide is moderately effective in improving symptoms of IBS-C with diarrhea being the major side effect. Further studies are needed to evaluate the long-term efficacy and safety of linaclotide for IBS-C. © 2013 John Wiley & Sons Ltd.

Probiotic Fermented Milk Containing Dietary Fiber Has Additive Effects in IBS with Constipation Compared to Plain Probiotic Fermented Milk.

PubMed

Choi, Sung Chul; Kim, Beom Jin; Rhee, Poong-Lyul; Chang, Dong Kyung; Son, Hee Jung; Kim, Jae J; Rhee, Jong Chul; Kim, Soon Im; Han, Young Sil; Sim, Ki Hyeon; Park, Seok Nam

2011-03-01

Although controversial, probiotics and dietary fiber are commonly used for patients with irritable bowel syndrome (IBS). We evaluated the effects of multistrain probiotics on the symptoms of IBS to determine whether the addition of dietary fi ber had an additive effect on constipation-predominant IBS. A total of 142 participants who met the Rome III criteria were recruited and randomized into a control group or a test group. Participants in the control group received multistrain probiotic fermented milk with Streptococcus thermophilus, Lactobacillus acidophilus and Bifidobacterium infantis; the participants in the test group received the same probiotic fermented milk mixed with dietary fi ber such as sea tangle extracts, radish extracts and glasswort extracts. The patients were treated for four weeks. Most of the symptoms of IBS, with the exception of fl atulence, stool consistency, and frequency of defecation, signifi cantly improved in both groups. In the analysis of IBS subtypes, especially constipation-predominant IBS, the frequency and duration of defecation and straining at stool were improved more in the test group than in the control group. Dietary fiber had additive benefits for the symptoms of constipation, especially in constipation-predominant IBS.

Decreased TESK1-mediated cofilin 1 phosphorylation in the jejunum of IBS-D patients may explain increased female predisposition to epithelial dysfunction.

PubMed

Rodiño-Janeiro, Bruno K; Martínez, Cristina; Fortea, Marina; Lobo, Beatriz; Pigrau, Marc; Nieto, Adoración; González-Castro, Ana María; Salvo-Romero, Eloísa; Guagnozzi, Danila; Pardo-Camacho, Cristina; Iribarren, Cristina; Azpiroz, Fernando; Alonso-Cotoner, Carmen; Santos, Javier; Vicario, Maria

2018-02-02

Disturbed intestinal epithelial barrier and mucosal micro-inflammation characterize irritable bowel syndrome (IBS). Despite intensive research demonstrating ovarian hormones modulation of IBS severity, there is still limited knowledge on the mechanisms underlying female predominance in this disorder. Our aim was to identify molecular pathways involved in epithelial barrier dysfunction and female predominance in diarrhea-predominant IBS (IBS-D) patients. Total RNA and protein were obtained from jejunal mucosal biopsies from healthy controls and IBS-D patients meeting the Rome III criteria. IBS severity was recorded based on validated questionnaires. Gene and protein expression profiles were obtained and data integrated to explore biological and molecular functions. Results were validated by western blot. Tight junction signaling, mitochondrial dysfunction, regulation of actin-based motility by Rho, and cytoskeleton signaling were differentially expressed in IBS-D. Decreased TESK1-dependent cofilin 1 phosphorylation (pCFL1) was confirmed in IBS-D, which negatively correlated with bowel movements only in female participants. In conclusion, deregulation of cytoskeleton dynamics through TESK1/CFL1 pathway underlies epithelial intestinal dysfunction in the small bowel mucosa of IBS-D, particularly in female patients. Further understanding of the mechanisms involving sex-mediated regulation of mucosal epithelial integrity may have significant preventive, diagnostic, and therapeutic implications for IBS.

Abdominal bloating is the most bothersome symptom in irritable bowel syndrome with constipation (IBS-C): a large population-based Internet survey in Japan.

PubMed

Kanazawa, Motoyori; Miwa, Hiroto; Nakagawa, Ayako; Kosako, Masanori; Akiho, Hiraku; Fukudo, Shin

2016-01-01

Abdominal bloating is a common symptom in patients with irritable bowel syndrome with constipation (IBS-C). However, it is not included among the required items in the Rome III diagnostic criteria for IBS. Little is known about an impact of abdominal bloating seen in patients with IBS-C. Using a large population-based sample, the aim of the present study was to investigate what is the most bothersome symptom in subjects with IBS-C. An Internet survey of 30,000 adults drawn from the general public throughout Japan was conducted to identify subtypes of IBS using the Rome III diagnostic questionnaire. Consecutively, the screened subjects with IBS-C and the same number of age- and sex-matched non-IBS subjects who were randomly selected as controls were asked to answer a questionnaire on the degree of anxiety they experienced in their daily lives, thoughts about bowel habit, and their dominant gastrointestinal symptoms together with exacerbation factors (for IBS-C only). The screening survey showed that the prevalence of overall IBS was 16.5 % (female 17.4 %, male 15.5 %) and that 2.8 % met the criteria for IBS-C, 4.5 % for IBS with diarrhea (IBS-D) and 8.2 % for mixed IBS (IBS-M). Seven hundred and fifty-nine of 835 (90.9 %) subjects with IBS-C and 746 of 830 (89.9 %) control subjects completed the consecutive questionnaire. IBS-C subjects felt a higher degree of anxiety in their daily lives (p < 0.01) and considered bowel habit to be an indicator of health (p < 0.01) to a greater extent than control subjects. In IBS-C, the degree of anxiety was significantly associated with abdominal discomfort (p < 0.01), pain (p < 0.01) and bloating (p = 0.02), but not with the frequency of bowel habit (p > 0.1). Abdominal bloating was the most bothersome symptom (27.5 %), which was more likely to occur after a meal (52.2 %), at work/school (29.2 %) and during times of stress (26.8 %). Only 4.5 % of IBS-C subjects reported abdominal pain as the

Genetic recombination and Cryptosporidium hominis virulent subtype IbA10G2.

PubMed

Li, Na; Xiao, Lihua; Cama, Vitaliano A; Ortega, Ynes; Gilman, Robert H; Guo, Meijin; Feng, Yaoyu

2013-10-01

Little is known about the emergence and spread of virulent subtypes of Cryptosporidium hominis, the predominant species responsible for human cryptosporidiosis. We conducted sequence analyses of 32 genetic loci of 53 C. hominis specimens isolated from a longitudinally followed cohort of children living in a small community. We identified by linkage disequilibrium and recombination analyses only limited genetic recombination, which occurred exclusively within the 60-kDa glycoprotein gene subtype IbA10G2, a predominant subtype for outbreaks in industrialized nations and a virulent subtype in the study community. Intensive transmission of virulent subtype IbA10G2 in the study area might have resulted in genetic recombination with other subtypes. Moreover, we identified selection for IbA10G2 at a 129-kb region around the 60-kDa glycoprotein gene in chromosome 6. These findings improve our understanding of the origin and evolution of C. hominis subtypes and the spread of virulent subtypes.

Reduced Responses of Submucous Neurons from Irritable Bowel Syndrome Patients to a Cocktail Containing Histamine, Serotonin, TNFα, and Tryptase (IBS-Cocktail).

PubMed

Ostertag, Daniela; Buhner, Sabine; Michel, Klaus; Pehl, Christian; Kurjak, Manfred; Götzberger, Manuela; Schulte-Frohlinde, Ewert; Frieling, Thomas; Enck, Paul; Phillip, Josef; Schemann, Michael

2015-01-01

Malfunctions of enteric neurons are believed to play an important role in the pathophysiology of irritable bowel syndrome (IBS). Our aim was to investigate whether neuronal activity in biopsies from IBS patients is altered in comparison to healthy controls (HC). Activity of human submucous neurons in response to electrical nerve stimulation and local application of nicotine or a mixture of histamine, serotonin, tryptase, and TNF-α (IBS-cocktail) was recorded in biopsies from 17 HC and 35 IBS patients with the calcium-sensitive-dye Fluo-4 AM. The concentrations of the mediators resembeled those found in biopsy supernatants or blood. Neuronal activity in guinea-pig submucous neurons was studied with the voltage-sensitive-dye di-8-ANEPPS. Activity in submucous ganglia in response to nicotine or electrical nerve stimulation was not different between HC and IBS patients (P = 0.097 or P = 0.448). However, the neuronal response after application of the IBS-cocktail was significantly decreased (P = 0.039) independent of whether diarrhea (n = 12), constipation (n = 5) or bloating (n = 5) was the predominant symptom. In agreement with this we found that responses of submucous ganglia conditioned by overnight incubation with IBS mucosal biopsy supernatant to spritz application of this supernatant was significantly reduced (P = 0.019) when compared to incubation with HC supernatant. We demonstrated for the first time reduced neuronal responses in mucosal IBS biopsies to an IBS mediator cocktail. While excitability to classical stimuli of enteric neurons was comparable to HC, the activation by the IBS-cocktail was decreased. This was very likely due to desensitization to mediators constantly released by mucosal and immune cells in the gut wall of IBS patients.

The Impact of AP and IB Programs on High Stakes College Admissions

ERIC Educational Resources Information Center

Chodl, Joseph

2012-01-01

The purpose of this study was to examine the impact on undergraduate college admissions decisions at selective U.S. colleges and universities of student enrolment in the Advanced Placement (AP) or International Baccalaureate (IB) programs of international schools. A total of 30 interviews were conducted by the researcher with admissions personnel…

Psychological comorbidity increases the risk for postinfectious IBS partly by enhanced susceptibility to develop infectious gastroenteritis.

PubMed

Wouters, Mira M; Van Wanrooy, Sander; Nguyen, Anh; Dooley, James; Aguilera-Lizarraga, Javier; Van Brabant, Winde; Garcia-Perez, Josselyn E; Van Oudenhove, Lukas; Van Ranst, Marc; Verhaegen, Jan; Liston, Adrian; Boeckxstaens, Guy

2016-08-01

Psychological factors increase the risk to develop postinfectious IBS (PI-IBS), but the mechanisms involved are unclear. As stress affects the immune system, we investigated the potential interaction between psychological factors, the immune response against infectious gastroenteritis (IGE) and the development of IGE and PI-IBS in a large cohort exposed to contaminated drinking water. 18 620 people exposed to contaminated drinking water (norovirus, Giardia lamblia, Campylobacter jejuni) were invited to participate in a prospective controlled cohort study. They were asked to complete questionnaires assessing demographic, psychological and clinical data during the outbreak and 1 year later. At both time points, in-depth immune function (peripheral blood and rectal biopsies) was studied in a subgroup of subjects. 1379 subjects completed the questionnaires during the outbreak, of which 271 developed IGE. Risk factors for IGE included younger age, pre-existing dyspepsia-like symptoms, anxiety and drinking contaminated tap water. Anxiety scores before the outbreak inversely correlated with interleukin-2-expressing CD4+ T cells (r=0.6, p=0.01, n=23). At follow-up, 34 of 172 (20%) IGE subjects developed IBS compared with 24/366 exposed participants (7%, p<0.0001, χ(2) test). A Th2 cytokine phenotype at time of infection was associated with increased risk for PI-IBS 1 year later. Except for increased B cell numbers, no evidence for systemic or rectal mucosal immune activation in PI-IBS was demonstrated at follow-up. Our study shows that the increased risk of patients with psychological comorbidity to develop PI-IBS may partly result from an increased susceptibility to develop IGE, possibly resulting from a Th2-immune bias. (ClinicalTrials.gov NCT01497847). Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

TRPA1 Is Functionally Expressed Primarily by IB4-Binding, Non-Peptidergic Mouse and Rat Sensory Neurons

PubMed Central

Stucky, Cheryl L.

2012-01-01

Subpopulations of somatosensory neurons are characterized by functional properties and expression of receptor proteins and surface markers. CGRP expression and IB4-binding are commonly used to define peptidergic and non-peptidergic subpopulations. TRPA1 is a polymodal, plasma membrane ion channel that contributes to mechanical and cold hypersensitivity during tissue injury, making it a key target for pain therapeutics. Some studies have shown that TRPA1 is predominantly expressed by peptidergic sensory neurons, but others indicate that TRPA1 is expressed extensively within non-peptidergic, IB4-binding neurons. We used FURA-2 calcium imaging to define the functional distribution of TRPA1 among peptidergic and non-peptidergic adult mouse (C57BL/6J) DRG neurons. Approximately 80% of all small-diameter (<27 µm) neurons from lumbar 1–6 DRGs that responded to TRPA1 agonists allyl isothiocyanate (AITC; 79%) or cinnamaldehyde (84%) were IB4-positive. Retrograde labeling via plantar hind paw injection of WGA-Alexafluor594 showed similarly that most (81%) cutaneous neurons responding to TRPA1 agonists were IB4-positive. Additionally, we cultured DRG neurons from a novel CGRP-GFP mouse where GFP expression is driven by the CGRPα promoter, enabling identification of CGRP-expressing live neurons. Interestingly, 78% of TRPA1-responsive neurons were CGRP-negative. Co-labeling with IB4 revealed that the majority (66%) of TRPA1 agonist responders were IB4-positive but CGRP-negative. Among TRPA1-null DRGs, few small neurons (2–4%) responded to either TRPA1 agonist, indicating that both cinnamaldehyde and AITC specifically target TRPA1. Additionally, few large neurons (≥27 µm diameter) responded to AITC (6%) or cinnamaldehyde (4%), confirming that most large-diameter somata lack functional TRPA1. Comparison of mouse and rat DRGs showed that the majority of TRPA1-responsive neurons in both species were IB4-positive. Together, these data demonstrate that TRPA1 is functionally

Learning Negotiation Policies Using IB3 and Bayesian Networks

NASA Astrophysics Data System (ADS)

Nalepa, Gislaine M.; Ávila, Bráulio C.; Enembreck, Fabrício; Scalabrin, Edson E.

This paper presents an intelligent offer policy in a negotiation environment, in which each agent involved learns the preferences of its opponent in order to improve its own performance. Each agent must also be able to detect drifts in the opponent's preferences so as to quickly adjust itself to their new offer policy. For this purpose, two simple learning techniques were first evaluated: (i) based on instances (IB3) and (ii) based on Bayesian Networks. Additionally, as its known that in theory group learning produces better results than individual/single learning, the efficiency of IB3 and Bayesian classifier groups were also analyzed. Finally, each decision model was evaluated in moments of concept drift, being the drift gradual, moderate or abrupt. Results showed that both groups of classifiers were able to effectively detect drifts in the opponent's preferences.

Neuroimmune interactions at different intestinal sites are related to abdominal pain symptoms in children with IBS

USDA-ARS?s Scientific Manuscript database

Neuroimmune interactions and inflammation have been proposed as factors involved in sensory-motor dysfunction and symptom generation in adult irritable bowel syndrome (IBS) patients. In children with IBS and healthy controls, we measured ileocolonic mast cell infiltration and fecal calprotectin and ...

Effect of acupuncture and its influence on visceral hypersensitivity in IBS-D patients: Study protocol for a randomized controlled trial.

PubMed

Pei, Lixia; Chen, Hao; Guo, Jing; Chen, Lu; Wu, Xiaoliang; Xu, Wanli; Weng, Shengjie; Yang, EunMee; Hammer, Trine; Sun, Jianhua

2018-05-01

Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder associated with visceral hypersensitivity. Increased expression of colonic TRPV1 and decreased expression of microRNA-199 are implicated in the pathogenesis of visceral hypersensitivity in IBS-D patients. Acupuncture is one of the frequently used complementary and alternative therapies for the treatment of IBS. The existing clinical studies mostly use IBS-SSS or other subjective scales, so there is a lack of objective biochemical evidence regarding the effect of acupuncture on IBS. Therefore, we designed this study to investigate whether acupuncture alleviate visceral hypersensitivity by influencing the expression of TRPV1 and microRNA-199. This study is a randomized, sham-controlled trial involving 40 patients and 10 healthy volunteers. A total of 40 eligible patients with IBS-D will be randomly assigned to a traditional acupuncture group or sham acupuncture group in a 1:1 ratio. Patients will receive 3 acupuncture treatment sessions per week for 12 consecutive weeks, for a total of 36 sessions during the study. The primary outcome measure is the IBS-Symptom Severity Score (IBS-SSS). Secondary outcomes are Visceral Pain Scale and levels of TRPV1 and microRNA-199 in colonic tissues. Healthy volunteers will not receive any clinical intervention. The safety of interventions will be assessed at every visit. The purpose of this trial is to evaluate the efficacy of acupuncture for IBS-D through IBS-SSS and Visceral Pain Scale. Furthermore, we want to explore the intervention mechanism of acupuncture in improving visceral hypersensitivity by analyzing the colonic TRPV1 and microRNA-199. This trial is registered with Chinese Clinical Trials Register, ChiCTR-IOR- 17010860(http://www.chictr.org.cn/showproj.aspx?proj=18445).

Multivariate modelling of faecal bacterial profiles of patients with IBS predicts responsiveness to a diet low in FODMAPs.

PubMed

Bennet, Sean M P; Böhn, Lena; Störsrud, Stine; Liljebo, Therese; Collin, Lena; Lindfors, Perjohan; Törnblom, Hans; Öhman, Lena; Simrén, Magnus

2018-05-01

The effects of dietary interventions on gut bacteria are ambiguous. Following a previous intervention study, we aimed to determine how differing diets impact gut bacteria and if bacterial profiles predict intervention response. Sixty-seven patients with IBS were randomised to traditional IBS (n=34) or low fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs) (n=33) diets for 4 weeks. Food intake was recorded for 4 days during screening and intervention. Faecal samples and IBS Symptom Severity Score (IBS-SSS) reports were collected before (baseline) and after intervention. A faecal microbiota dysbiosis test (GA-map Dysbiosis Test) evaluated bacterial composition. Per protocol analysis was performed on 61 patients from whom microbiome data were available. Responders (reduced IBS-SSS by ≥50) to low FODMAP, but not traditional, dietary intervention were discriminated from non-responders before and after intervention based on faecal bacterial profiles. Bacterial abundance tended to be higher in non-responders to a low FODMAP diet compared with responders before and after intervention. A low FODMAP intervention was associated with an increase in Dysbiosis Index (DI) scores in 42% of patients; while decreased DI scores were recorded in 33% of patients following a traditional IBS diet. Non-responders to a low FODMAP diet, but not a traditional IBS diet had higher DI scores than responders at baseline. Finally, while a traditional IBS diet was not associated with significant reduction of investigated bacteria, a low FODMAP diet was associated with reduced Bifidobacterium and Actinobacteria in patients, correlating with lactose consumption. A low FODMAP, but not a traditional IBS diet may have significant impact on faecal bacteria. Responsiveness to a low FODMAP diet intervention may be predicted by faecal bacterial profiles. NCT02107625. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a

Reduced Responses of Submucous Neurons from Irritable Bowel Syndrome Patients to a Cocktail Containing Histamine, Serotonin, TNFα, and Tryptase (IBS-Cocktail)

PubMed Central

Ostertag, Daniela; Buhner, Sabine; Michel, Klaus; Pehl, Christian; Kurjak, Manfred; Götzberger, Manuela; Schulte-Frohlinde, Ewert; Frieling, Thomas; Enck, Paul; Phillip, Josef; Schemann, Michael

2015-01-01

Background and Aims: Malfunctions of enteric neurons are believed to play an important role in the pathophysiology of irritable bowel syndrome (IBS). Our aim was to investigate whether neuronal activity in biopsies from IBS patients is altered in comparison to healthy controls (HC). Methods: Activity of human submucous neurons in response to electrical nerve stimulation and local application of nicotine or a mixture of histamine, serotonin, tryptase, and TNF-α (IBS-cocktail) was recorded in biopsies from 17 HC and 35 IBS patients with the calcium-sensitive-dye Fluo-4 AM. The concentrations of the mediators resembeled those found in biopsy supernatants or blood. Neuronal activity in guinea-pig submucous neurons was studied with the voltage-sensitive-dye di-8-ANEPPS. Results: Activity in submucous ganglia in response to nicotine or electrical nerve stimulation was not different between HC and IBS patients (P = 0.097 or P = 0.448). However, the neuronal response after application of the IBS-cocktail was significantly decreased (P = 0.039) independent of whether diarrhea (n = 12), constipation (n = 5) or bloating (n = 5) was the predominant symptom. In agreement with this we found that responses of submucous ganglia conditioned by overnight incubation with IBS mucosal biopsy supernatant to spritz application of this supernatant was significantly reduced (P = 0.019) when compared to incubation with HC supernatant. Conclusion: We demonstrated for the first time reduced neuronal responses in mucosal IBS biopsies to an IBS mediator cocktail. While excitability to classical stimuli of enteric neurons was comparable to HC, the activation by the IBS-cocktail was decreased. This was very likely due to desensitization to mediators constantly released by mucosal and immune cells in the gut wall of IBS patients. PMID:26733780

A new method using insert-based systems (IBS) to improve cell behavior study on flexible and rigid biomaterials.

PubMed

Grenade, Charlotte; Moniotte, Nicolas; Rompen, Eric; Vanheusden, Alain; Mainjot, Amélie; De Pauw-Gillet, Marie-Claire

2016-12-01

In vitro studies about biomaterials biological properties are essential screening tests. Yet cell cultures encounter difficulties related to cell retention on material surface or to the observation of both faces of permeable materials. The objective of the present study was to develop a reliable in vitro method to study cell behavior on rigid and flexible/permeable biomaterials elaborating two specific insert-based systems (IBS-R and IBS-F respectively). IBS-R was designed as a specific cylindrical polytetrafluoroethylene (PTFE) system to evaluate attachment, proliferation and morphology of human gingival fibroblasts (HGFs) on grade V titanium and lithium disilicate glass-ceramic discs characteristics of dental prostheses. The number of cells, their covering on discs and their morphology were determined from MTS assays and microscopic fluorescent images after 24, 48 and 72 h. IBS-F was developed as a two components system to study HGFs behavior on guided bone regeneration polyester membranes. The viability and the membrane barrier effect were evaluated by metabolic MTS assays and by scanning electron microscopy. IBS-R and IBS-F were shown to promote (1) easy and rapid handling; (2) cell retention on biomaterial surface; (3) accurate evaluation of the cellular proliferation, spreading and viability; (4) use of non-toxic material. Moreover IBS-F allowed the study of the cell migration through degradable membranes, with an access to both faces of the biomaterial and to the bottom of culture wells for medium changing.

Effects of gut-directed hypnotherapy on IBS in different clinical settings-results from two randomized, controlled trials.

PubMed

Lindfors, Perjohan; Unge, Peter; Arvidsson, Patrik; Nyhlin, Henry; Björnsson, Einar; Abrahamsson, Hasse; Simrén, Magnus

2012-02-01

Gut-directed hypnotherapy has been found to be effective in irritable bowel syndrome (IBS). However, randomized, controlled studies are rare and few have been performed outside highly specialized research centers. The objective of this study was to study the effect of gut-directed hypnotherapy in IBS in different clinical settings outside the traditional research units. The study population included IBS patients refractory to standard management. In study 1, patients were randomized to receive gut-directed hypnotherapy (12 sessions, 1 h/week) in psychology private practices or supportive therapy, whereas patients were randomized to receive gut-directed hypnotherapy in a small county hospital or to serve as waiting list controls in study 2. Gastrointestinal symptom severity and quality of life were evaluated at baseline, at 3 months follow-up and after 1 year. We randomized 138 IBS patients refractory to standard management, 90 in study 1 and 48 in study 2. In both the studies, IBS-related symptoms were improved at 3 months in the gut-directed hypnotherapy groups (P<0.05), but not in the control groups (ns). In study 1, a significantly greater improvement of IBS-related symptom severity could be detected in the gut-directed hypnotherapy group than in the control group (P<0.05), and a trend in the same direction was seen in study 2 (P=0.17). The results seen at 3 months were sustained up to 1 year. Gut-directed hypnotherapy is an effective treatment alternative for patients with refractory IBS, but the effectiveness is lower when the therapy is given outside the highly specialized research centers.

Apples and Oranges: Comparing the Backgrounds and Academic Trajectories of International Baccalaureate (IB) Students to a Matched Comparison Group

ERIC Educational Resources Information Center

May, Henry; Rodriguez, Awilda; Sirinides, Philip M.; Perna, Laura W.; Yee, April; Ransom, Tafaya

2013-01-01

As a critical step in understanding the impacts of IB, the analyses presented in this report examined the selection mechanisms behind IB participation across Florida, the state with the second highest representation of IB programs in the nation. We use longitudinal student and school-level data from 1995 through 2009 from the Florida K-20…

Gastrointestinal (GI) permeability is associated with trait anxiety in children with functional abdominal pain (FAP) and Irritable Bowel Syndrome (IBS)

USDA-ARS?s Scientific Manuscript database

FAP and IBS affect 10-15% of school age children and bear many physiological similarities to irritable bowel syndrome (IBS) in adults (e.g., functional pain, visceral hyperalgesia). Animal models of IBS have suggested a relationship between neonatal stress and increased GI permeability later in life...

Reduced interstitial cells of Cajal and increased intraepithelial lymphocytes are associated with development of small intestinal bacterial overgrowth in post-infectious IBS mouse model.

PubMed

Chen, Binrui; Zhu, Shuwen; Du, Lijun; He, Huiqin; Kim, John J; Dai, Ning

2017-10-01

Intestinal dysmotility and immune activation are likely involved in the pathogenesis of small intestinal bacteria overgrowth (SIBO) in irritable bowel syndrome (IBS). We aimed at investigating the role of interstitial cells of Cajal (ICC) and intestinal inflammation in the development of SIBO using a post-infectious IBS (PI-IBS) mouse model. NIH mice were randomly infected with Trichinella spiralis. Visceral sensitivity and stool pattern were assessed at 8-weeks post-infection (PI). Intestinal bacteria counts from jejunum and ileum were measured by quantitative real-time PCR to evaluate the presence of SIBO. ICC density, intraepithelial lymphocytes (IELs) counts, and intestinal cytokine levels (IL1-β, IL-6, toll-like receptor-4 (TLR-4), IL-10) in the ileum were examined. PI-IBS mice demonstrated increased visceral sensitivity compared with the control group. One-third of the PI-IBS mice developed SIBO (SIBO+/PI-IBS) and was more likely to have abnormal stool form compared with SIBO negative PI-IBS (SIBO-/PI-IBS) mice but without difference in visceral sensitivity. SIBO+/PI-IBS mice had decreased ICC density and increased IELs counts in the ileum compared with SIBO-/PI-IBS mice. No difference in inflammatory cytokine expression levels were detected among the groups except for increased TLR-4 in PI-IBS mice compared with the control group. Development of SIBO in PI-IBS mice was associated with reduced ICC density and increased IELs counts in the ileum. Our findings support the role of intestinal dysmotility and inflammation in the pathogenesis of SIBO in IBS and may provide potential therapeutic targets.

Using "Competing Visions of Human Rights" in an International IB World School

ERIC Educational Resources Information Center

Tolley, William J.

2013-01-01

William Tolley, a teaching fellow with the Choices Program, is the Learning and Innovation Coach and head of history at the International School of Curitiba, Brazil (IB). He writes in this article that he has found that the "Competing Visions of Human Rights" teaching unit, developed by Brown University's Choices Program, provides a…

Clopidogrel IBS Patients Have Higher Incidence of Gastrointestinal Symptoms Influenced by Age and Gender.

PubMed

Soghomonyan, Suren; Abdel-Rasoul, Mahmoud; Zuleta-Alarcon, Alix; Grants, Iveta; Davila, Victor; Yu, Jeffrey; Zhang, Cheng; Whitaker, Emmett E; Bergese, Sergio D; Stoicea, Nicoleta; Arsenescu, Razvan; Christofi, Fievos L

2017-10-01

Clopidogrel is an irreversible antagonist of P2Y 12 receptors (P2Y 12 Rs) used as an antiplatelet drug to reduce risk of thrombosis. P2Y 12 Rs are expressed in gastrointestinal (GI) tract where they might regulate GI function. To evaluate if blockade of P2Y 12 Rs by clopidogrel is associated with higher incidence of GI symptoms in patients with irritable bowel syndrome (IBS). A retrospective analysis of our institutional database was conducted for a 13-year period. IBS patients were identified, and their demographics, GI symptoms and clopidogrel therapy were collected. Logistic regression models were used to characterize symptoms in clopidogrel versus no-clopidogrel IBS-groups, adjusting for Age and Sex differences. An additional study characterized the P2Y 12 R distribution in human gut. The search identified 7217 IBS patients (6761 no-clopidogrel/456 clopidogrel). There were a higher proportion of patients with GI symptoms on clopidogrel (68%) compared to controls (60%, p = 0.0011) that were Females (70 vs. 60%, p = 0.0003) not Males (61 vs. 60%; p = 0.8312). In Females, clopidogrel was associated with higher incidence of GI symptoms (Age adjusted; p < 0.0001) for pain, constipation, gastroparesis (p ≤ 0.0001) and psychogenic pain (p = 0.0006). Age or Sex (adjusted models) influenced one or more GI symptoms (i.e., pain, p < 0.0001; constipation, p < 0.0001/p = 0.008; diarrhea, flatulence, p = 0.01). P2Y 12 R immunoreactivity was abundant in human ENS; glial-to-neuron ratio of P2Y 12 Rs expressed in Females ≫ Males. Irreversible blockade of P2Y 12 R by clopidogrel is associated with higher incidence of GI symptoms in Female IBS patients, although Age or Sex alone contributes to symptomatology. Prospective studies can determine clinical implications of P2Y 12 Rs in IBS.

Molecular detection and genetic analysis of Akabane virus genogroup Ib in small ruminants in Turkey.

PubMed

Şevik, Murat

2017-09-01

Akabane disease is a viral disease transmitted by biting midges and can cause teratogenic malformations in cattle, sheep and goats. Abortion outbreaks associated with arthrogryposis and cerebellar hypoplasia in two epidemiologically independent flocks were reported in the Mediterranean region of Turkey in 2015. Phylogenetic analysis based on nucleocapsid (N) gene sequences showed that the field isolates presented here belong to the genogroup Ib. The akabane virus (AKAV) field isolates analysed in this study displayed 6 new amino acid substitutions in N and non-structural protein chains compared with those of AKAV strains belonging to genogroup Ib. To the best of our knowledge, this is the first report on the presence of the AKAV genogroup Ib in Turkey.

BDNF contributes to IBS-like colonic hypersensitivity via activating the enteroglia-nerve unit

PubMed Central

Wang, Peng; Du, Chao; Chen, Fei-Xue; Li, Chang-Qing; Yu, Yan-Bo; Han, Ting; Akhtar, Suhail; Zuo, Xiu-Li; Tan, Xiao-Di; Li, Yan-Qing

2016-01-01

The over-expressed colonic brain-derived neurotrophic factor (BDNF) has been reported to be associated with abdominal pain in patients with irritable bowel syndrome (IBS). However, the neuropathological mechanism is unclear. We here investigated the involvement of enteroglial cells (EGCs) and enteric nerves in IBS-like visceral hypersensitivity. We showed that glial fibrillary acidic protein (GFAP), tyrosine receptor kinase B (TrkB) and substance P (SP) were significantly increased in the colonic mucosa of IBS patients. The upregulation of those proteins was also observed in the colon of mice with visceral hypersensitivity, but not in the colon of BDNF+/− mice. Functionally, TrkB or EGC inhibitors, or BDNF knockdown significantly suppressed visceral hypersensitivity in mice. Using the EGC cell line, we found that recombinant human BDNF (r-HuBDNF) could directly activate EGCs via the TrkB-phospholipase Cγ1 pathway, thereby inducing a significant upregulation of SP. Moreover, supernatants from r-HuBDNF-activated EGC culture medium, rather than r-HuBDNF alone, triggered markedly augmented discharges in isolated intestinal mesenteric afferent nerves. r-HuBDNF alone could cause mesenteric afferent mechanical hypersensitivity independently, and this effect was synergistically enhanced by activated EGCs. We conclude that EGC-enteric nerve unit may be involved in IBS-like visceral hypersensitivity, and this process is likely initiated by BDNF-TrkB pathway activation. PMID:26837784

[Synthesis of exo-β-glucosaminidase BY FUNGUS Penicillium sp. IB-37-2].

PubMed

Aktuganov, G E; Galimzyanova, N F; Teregulova, G A; Melentjev, A I

2016-01-01

A new strain Penicillium sp. IB-37-2, which actively hydrolyzes chitosan (SD ∼80–85%) but possesses low activity against colloidal chitin, was isolated. The fungus was observed to have a high level chitosanase biosynthesis (1.5–3.0 U/mL) during submerged cultivation at 28°C, with a pH of 3.5–7.0 and 220 rpm in nutrient media containing chitosan or chitin from shells of crabs. Purification of the chitosanase enzyme complex from Penicillium sp. IB-37-2 by ultrafiltration and hydrophobic chromatography, followed by denaturing electrophoresis, revealed two predominant proteins with molecular weights of 89 and 41 kDa. The purified enzyme complex demonstrated maximal activity (maximal rate of hydrolysis of dissolved chitosan) and stability at 50–55°C and a pH of 3.5–4.0. The enzyme preparation also hydrolyzed laminarin, β-(1,3)-(1,4)-glycan, and colloidal chitin. Exohydrolysis of chitosan by the preparation isolated from Penicillium sp. IB-37-2 resulted in the formation of single product, D-glucosamine.

30 CFR 57.22217 - Seals and stoppings (I-A, I-B, and I-C mines).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Seals and stoppings (I-A, I-B, and I-C mines... NONMETAL MINES Safety Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22217 Seals and stoppings (I-A, I-B, and I-C mines). All seals, and those stoppings that separate main intake from main...

30 CFR 57.22217 - Seals and stoppings (I-A, I-B, and I-C mines).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Seals and stoppings (I-A, I-B, and I-C mines... NONMETAL MINES Safety Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22217 Seals and stoppings (I-A, I-B, and I-C mines). All seals, and those stoppings that separate main intake from main...

Isolation and functional characterization of TIF-IB, a factor that confers promoter specificity to mouse RNA polymerase I.

PubMed

Schnapp, A; Clos, J; Hädelt, W; Schreck, R; Cvekl, A; Grummt, I

1990-03-25

The murine ribosomal gene promoter contains two cis-acting control elements which operate in concert to promote efficient and accurate transcription initiation by RNA polymerase I. The start site proximal core element which is indispensable for promoter recognition by RNA polymerase I (pol I) encompasses sequences from position -39 to -1. An upstream control element (UCE) which is located between nucleotides -142 and -112 stimulates the efficiency of transcription initiation both in vivo and in vitro. Here we report the isolation and functional characterization of a specific rDNA binding protein, the transcription initiation factor TIF-IB, which specifically interacts with the core region of the mouse ribosomal RNA gene promoter. Highly purified TIF-IB complements transcriptional activity in the presence of two other essential initiation factors TIF-IA and TIF-IC. We demonstrate that the binding efficiency of purified TIF-IB to the core promoter is strongly enhanced by the presence in cis of the UCE. This positive effect of upstream sequences on TIF-IB binding is observed throughout the purification procedure suggesting that the synergistic action of the two distant promoter elements is not mediated by a protein different from TIF-IB. Increasing the distance between both control elements still facilitates stable factor binding but eliminates transcriptional activation. The results demonstrate that TIF-IB binding to the rDNA promoter is an essential early step in the assembly of a functional transcription initiation complex. The subsequent interaction of TIF-IB with other auxiliary transcription initiation factors, however, requires the correct spacing between the UCE and the core promoter element.

[Full Sibling Identification by IBS Scoring Method and Establishment of the Query Table of Its Critical Value].

PubMed

Li, R; Li, C T; Zhao, S M; Li, H X; Li, L; Wu, R G; Zhang, C C; Sun, H Y

2017-04-01

To establish a query table of IBS critical value and identification power for the detection systems with different numbers of STR loci under different false judgment standards. Samples of 267 pairs of full siblings and 360 pairs of unrelated individuals were collected and 19 autosomal STR loci were genotyped by Golden e ye™ 20A system. The full siblings were determined using IBS scoring method according to the 'Regulation for biological full sibling testing'. The critical values and identification power for the detection systems with different numbers of STR loci under different false judgment standards were calculated by theoretical methods. According to the formal IBS scoring criteria, the identification power of full siblings and unrelated individuals was 0.764 0 and the rate of false judgment was 0. The results of theoretical calculation were consistent with that of sample observation. The query table of IBS critical value for identification of full sibling detection systems with different numbers of STR loci was successfully established. The IBS scoring method defined by the regulation has high detection efficiency and low false judgment rate, which provides a relatively conservative result. The query table of IBS critical value for identification of full sibling detection systems with different numbers of STR loci provides an important reference data for the result judgment of full sibling testing and owns a considerable practical value. Copyright© by the Editorial Department of Journal of Forensic Medicine

BK polyomavirus genotypes Ia and Ib1 exhibit different biological properties in renal transplant recipients.

PubMed

Varella, Rafael B; Zalona, Ana Carolina J; Diaz, Nuria C; Zalis, Mariano G; Santoro-Lopes, Guilherme

2018-01-02

BK polyomavirus (BKV) is an opportunist agent associated with nephropathy (BKVAN) in 1-10% of kidney transplant recipients. BKV is classified into genotypes or subgroups according to minor nucleotidic variations with unknown biological implications. Studies assessing the possible association between genotypes and the risk of BKVAN in kidney transplant patients have presented conflicting results. In these studies, genotype Ia, which is highly prevalent in Brazil, was less frequently found and, thus, comparative data on the biological properties of this genotype are lacking. In this study, BKV Ia and Ib1 genotypes were compared according to their viral load, genetic evolution (VP1 and NCCR) - in a cohort of renal transplant recipients. The patients infected with Ia (13/23; 56.5%) genotype exhibited higher viral loads in urine [>1.4 log over Ib1 (10/23; 43.5%); p=0.025]. In addition, genotype Ia was associated with diverse mutations at VP1 loops and sites under positive selection outside loops, which were totally absent in Ib1. Although the number of viremic patients was similar, the three patients who had BK nephropathy (BKVAN) were infected with Ia genotype. NCCR architecture (ww or rr) were not distinctive between Ia and Ib1 genotypes. Ia genotype, which is rare in other published BKV cohorts, presented some diverse biological properties in transplanted recipients in comparison to Ib1. Copyright © 2017 Elsevier B.V. All rights reserved.

Finally, the Progenitor of the Type Ib iPTF13bvn

NASA Astrophysics Data System (ADS)

Van Dyk, Schulyer

2017-08-01

Supernovae (SNe) are among the most powerful events in the Universe and have a profound influence on galaxy evolution. Whereas we have been able to identify the luminous red supergiant progenitor stars of the most common core-collapse explosions, the hydrogen-rich Type II, the progenitors of hydrogen-poor Type Ib and Type Ic have been far more elusive. To strip away a SN Ib/c progenitor's outer layers, theoretical models with either (a) a highly-massive star with prodigious winds during the Wolf-Rayet phase or (b) a somewhat lower-mass star in a close, mass-exchange binary system have been proposed. One example exists so far of a progenitor identification, for the SN Ib iPTF13bvn in NGC 5806. Both models have been invoked to explain this event, although most evidence to date points toward the binary model. Our combined team observed this SN with WFC3 in Cycle 22, about 2 years after explosion, to investigate whether the progenitor had disappeared. As a result, we were able to report that indeed it had. We also attempted to better characterize the nature of the progenitor by subtracting our images from the pre-explosion HST data. Unfortunately, the old SN was apparently still conspicuously present. We therefore propose to reimage the SN site, when the SN should then be well below detectability, to produce high-quality templates of the host galaxy for subtraction. We can then finally fully reveal the progenitor and understand its true nature. iPTF13bvn is one of the most important historical SNe and will most probably be the best available case of a SN Ib progenitor for HST's remaining lifetime. It is imperative to understand the nature of this SN and its progenitor object.

OUTLINE OF MATHEMATICS - LEVELS I-A AND I-B FOR TALENT PRESERVATION CLASSES IN GRADE SEVEN.

ERIC Educational Resources Information Center

Houston Public Schools, TX.

LEVEL I-A UNIT AREAS COVER THE MEANING OF "NUMBER," ADDITION, MULTIPLICATION, SUBTRACTION, AND DIVISION. LEVEL I-B COVERS INTRODUCTION TO COMMON FRACTIONS, COMBINING FRACTION, FRACTIONAL PARTS, SEPARATING FRACTIONS, AND APPLICATIONS. EACH UNIT UNDER I-B HAS SUBDIVISIONS, WITH A PARAGRAPH OF TEACHING HINTS AND EXAMPLES. STRESS IS UPON…

Nonclassical MHC Ib-restricted CD8+ T Cells Recognize Mycobacterium tuberculosis-Derived Protein Antigens and Contribute to Protection Against Infection

PubMed Central

Shang, Shaobin; Siddiqui, Sarah; Bian, Yao; Zhao, Jie; Wang, Chyung-Ru

2016-01-01

MHC Ib-restricted CD8+ T cells have been implicated in host defense against Mycobacterium tuberculosis (Mtb) infection. However, the relative contribution of various MHC Ib-restricted T cell populations to anti-mycobacterial immunity remains elusive. In this study, we used mice that lack MHC Ia (Kb-/-Db-/-), MHC Ia/H2-M3 (Kb-/-Db-/-M3-/-), or β2m (β2m-/-) to study the role of M3-restricted and other MHC Ib-restricted T cells in immunity against Mtb. Unlike their dominant role in Listeria infection, we found that M3-restricted CD8+ T cells only represented a small proportion of the CD8+ T cells responding to Mtb infection. Non-M3, MHC Ib-restricted CD8+ T cells expanded preferentially in the lungs of Mtb-infected Kb-/-Db-/-M3-/- mice, exhibited polyfunctional capacities and conferred protection against Mtb. These MHC Ib-restricted CD8+ T cells recognized several Mtb-derived protein antigens at a higher frequency than MHC Ia-restricted CD8+ T cells. The presentation of Mtb antigens to MHC Ib-restricted CD8+ T cells was mostly β2m-dependent but TAP-independent. Interestingly, a large proportion of Mtb-specific MHC Ib-restricted CD8+ T cells in Kb-/-Db-/-M3-/- mice were Qa-2-restricted while no considerable numbers of MR1 or CD1-restricted Mtb-specific CD8+ T cells were detected. Our findings indicate that nonclassical CD8+ T cells other than the known M3, CD1, and MR1-restricted CD8+ T cells contribute to host immune responses against Mtb infection. Targeting these MHC Ib-restricted CD8+ T cells would facilitate the design of better Mtb vaccines with broader coverage across MHC haplotypes due to the limited polymorphism of MHC class Ib molecules. PMID:27272249

Lactulose breath test gas production in childhood IBS is associated with intestinal transit and bowel movement frequency

USDA-ARS?s Scientific Manuscript database

In adults with irritable bowel syndrome (IBS), bacterial gas production (colonic fermentation) is related to both symptom generation and intestinal transit. Whether gas production affects symptom generation, psychosocial distress, or intestinal transit in childhood IBS is unknown. Children (ages 7-1...

A novel one-step real-time multiplex PCR assay to detect Streptococcus agalactiae presence and serotypes Ia, Ib, and III.

PubMed

Furfaro, Lucy L; Chang, Barbara J; Payne, Matthew S

2017-09-01

Streptococcus agalactiae is the leading cause of early-onset neonatal sepsis. Culture-based screening methods lack the sensitivity of molecular assays and do not indicate serotype; a potentially important virulence marker. We aimed to develop a multiplex PCR to detect S. agalactiae while simultaneously identifying serotypes Ia, Ib, and III; commonly associated with infant disease. Primers were designed to target S. agalactiae serotype-specific cps genes and the dltS gene. The assay was validated with 512 vaginal specimens from pregnant women. 112 (21.9%) were dltS positive, with 14.3%, 0.9%, and 6.3% of these identified as cps Ia, Ib, and III, respectively. Our assay is a specific and sensitive method to simultaneously detect S. agalactiae and serotypes Ia, Ib, and III in a single step. It is of high significance for clinical diagnostic applications and also provides epidemiological data on serotype, information that may be important for vaccine development and other targeted non-antibiotic therapies. Copyright © 2017 Elsevier Inc. All rights reserved.

Clinical and Microbiological Effect of a Multispecies Probiotic Supplementation in Celiac Patients With Persistent IBS-type Symptoms: A Randomized, Double-Blind, Placebo-controlled, Multicenter Trial.

PubMed

Francavilla, Ruggiero; Piccolo, Maria; Francavilla, Antonio; Polimeno, Lorenzo; Semeraro, Francesco; Cristofori, Fernanda; Castellaneta, Stefania; Barone, Michele; Indrio, Flavia; Gobbetti, Marco; De Angelis, Maria

2018-04-23

The goals of this study were to evaluate the efficacy and safety of a probiotic mixture in patients with celiac disease (CD) with irritable bowel syndrome (IBS)-type symptoms despite a strict gluten-free diet (GFD). About 30% of patients with CD adherent to a GFD suffer from IBS-type symptoms; a possible cause resides in the imbalances of the intestinal microbiota in CD. Probiotics may represent a potential treatment. CD patients with IBS-type symptoms entered a prospective, double-blind, randomized placebo-controlled study. A 6-week treatment period was preceded by a 2-week run-in and followed by a 6-week follow-up phase. Clinical data were monitored throughout the study by validated questionnaires: IBS Severity Scoring System (IBS-SSS); Gastrointestinal Symptom Rating Scale (GSRS); Bristol Stool Form Scale (BSFS); and IBS Quality of Life Questionnaire (IBS-QOL). The fecal microbiota were assayed using plate counts and 16S rRNA gene-based analysis. In total, 109 patients were randomized to probiotics (n=54) or placebo (n=55). IBS-SSS and GSRS decreased significantly in probiotics, as compared with placebo [(-15.9%±14.8% vs. 8.2%±25.9%; P<0.001) and (-19.8%±16.6% vs. 12.9%±31.6%; P<0.001)], respectively. Treatment success was significantly higher in patients receiving probiotics, as compared with placebo (15.3% vs. 3.8%; P<0.04). Presumptive lactic acid bacteria, Staphylococcus and Bifidobacterium, increased in patients receiving probiotic treatment. No adverse events were reported. A 6-week probiotic treatment is effective in improving the severity of IBS-type symptoms, in CD patients on strict GFD, and is associated with a modification of gut microbiota, characterized by an increase of bifidobacteria.

Decreased miR-199 augments visceral pain in patients with IBS through translational upregulation of TRPV1.

PubMed

Zhou, QiQi; Yang, Liuqing; Larson, Scott; Basra, Sapreet; Merwat, Shehzad; Tan, Alai; Croce, Carlo; Verne, G Nicholas

2016-05-01

Many patients with irritable bowel syndrome IBS not only have abdominal pain but also may suffer from visceral hypersensitivity and heighted visceral nociception. Moreover, IBS has few effective therapeutic agents and mechanisms of disease are unclear. Our goals were to (i) identify microRNA (miRNA) expression, signalling and targets in human colon (controls; patients with IBS); (ii) verify in vitro, IBS-associated changes in miRNAs, especially miR-199, which is complementary to the transient receptor potential vanilloid type 1 (TRPV1) gene; and (iii) determine whether modulating the expression of miRNAs in vivo, especially miR-199, reverses associated changes and pathological hallmarks of visceral hypersensitivity via TRPV1 signalling. We evaluated 45 patients with diarrhoea-predominant IBS (IBS-D) and 40 controls with (1) visceral pain severity score and (2) colonoscopy with biopsies. miRNA expression was evaluated in human colon following miRNA array analysis. Luciferase assays were done to confirm relationships between miR-199 and TRPV1 expression. A rat model of visceral hypersensitivity was used to study miR-199 and its target gene (TRPV1) expression in dorsal root ganglion (DRG) and colon in vivo. Gut miR-199a/b expression in IBS-D was significantly decreased, which correlated directly with both increased visceral pain scores and TRPV1 expression. In vivo upregulation of miR-199a by intraperitoneal injection of lenti-miR-199a precursors decreased visceral hypersensitivity via diminished TRPV1 signalling. Decreased colonic miR-199a/b correlates with visceral pain in patients with IBS-D. Similarly, reduced miR-199a expression in rat DRG and colon tissue is associated with heightened visceral hypersensitivity. In vivo upregulation of miR-199a decreases visceral pain via inhibition of TRPV1 signalling. Thus, miR-199 precursors may be promising therapeutic candidates for the treatment in patients with visceral pain. Published by the BMJ Publishing Group Limited

Sham acupuncture is as efficacious as true acupuncture for the treatment of IBS: A randomized placebo controlled trial.

PubMed

Lowe, C; Aiken, A; Day, A G; Depew, W; Vanner, S J

2017-07-01

Irritable bowel syndrome (IBS) patients increasingly seek out acupuncture therapy to alleviate symptoms, but it is unclear whether the benefit is due to a treatment-specific effect or a placebo response. This study examined whether true acupuncture is superior to sham acupuncture in relieving IBS symptoms and whether benefits were linked to purported acupuncture mechanisms. A double blind sham controlled acupuncture study was conducted with Rome I IBS patients receiving twice weekly true acupuncture for 4 weeks (n=43) or sham acupuncture (n=36). Patients returned at 12 weeks for a follow-up review. The primary endpoint of success as determined by whether patients met or exceeded their established goal for percentage symptom improvement. Questionnaires were completed for symptom severity scores, SF-36 and IBS-36 QOL tools, McGill pain score, and Pittsburg Sleep Quality Index. A subset of patients underwent barostat measurements of rectal sensation at baseline and 4 weeks. A total of 53% in the true acupuncture group met their criteria for a successful treatment intervention, but this did not differ significantly from the sham group (42%). IBS symptom scores similarly improved in both groups. Scores also improved in the IBS-36, SF-36, and the Pittsburg Sleep Quality Index, but did not differ between groups. Rectal sensory thresholds were increased in both groups following treatment and pain scores decreased; however, these changes were similar between groups. The lack of differences in symptom outcomes between sham and true treatment acupuncture suggests that acupuncture does not have a specific treatment effect in IBS. © 2017 John Wiley & Sons Ltd.

Cytokine Response after Stimulation with Key Commensal Bacteria Differ in Post-Infectious Irritable Bowel Syndrome (PI-IBS) Patients Compared to Healthy Controls.

PubMed

Sundin, Johanna; Rangel, Ignacio; Repsilber, Dirk; Brummer, Robert-Jan

2015-01-01

Microbial dysbiosis and prolonged immune activation resulting in low-grade inflammation and intestinal barrier dysfunction have been suggested to be underlying causes of post-infectious irritable bowel syndrome (PI-IBS). The aim of this study was to evaluate the difference in cytokine response between mucosal specimens of PI-IBS patients and healthy controls (HC) after ex vivo stimulation with key anaerobic bacteria. Colonic biopsies from 11 PI-IBS patients and 10 HC were stimulated ex vivo with the commensal bacteria Bacteroides ovatus, Ruminococcus gnavus, Akkermansia muciniphila, Subdoligranulum variabile and Eubacterium limosum, respectively. The cytokine release (IL-1β, IL-2, IL-8, IL-10, IL-13, IL-17, TNF-α and IFN-γ) in stimulation supernatants was analyzed using the LUMINEX assay. Comparison of cytokine release between PI-IBS patients and healthy controls was performed taking both unstimulated and bacterially stimulated mucosal specimens into account. IL-13 release from mucosal specimens without bacterial stimulation was significantly lower in PI-IBS patients compared to HC (p < 0.05). After stimulation with Subdoligranulum variabile, IL-1β release from PI-IBS patients was significantly increased compared to HC (p < 0.05). Stimulation with Eubacterium limosum resulted in a significantly decreased IL-10 release in HC compared to PI-IBS patients (p < 0.05) and a tendency to decreased IL-13 release in HC compared to PI-IBS patients (p = 0.07). PI-IBS patients differ from HC with regard to cytokine release ex vivo after stimulation with selected commensal bacteria. Hence, our results support that the pathogenesis of PI-IBS comprises an altered immune response against commensal gut microbes.

Hexagonally ordered nanodots: Result of substrate rotation during oblique incidence low energy IBS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chowdhury, Debasree, E-mail: debasree.chowdhury@saha.ac.in; Ghose, Debabrata, E-mail: debasree.chowdhury@saha.ac.in

The anisotropic regular patterns are often results during oblique incidence ion beam sputtering (IBS). Simultaneous substrate rotation (SR) during IBS can suppress surface roughening and removes anisotropic nature of surface pattern. Here, the evolution of Si surface morphology as result of with and without SR is studied during oblique incidence low energy Ar{sup +} sputtering. Resultant topography shows smooth surface to hexagonally ordered nanodots at different rotating conditions. Interestingly, surface roughness exhibits non-monotonic dependence on rotation frequency. The underlying mechanism for dot formation can be described within the framework of isotropic DKS equation.

Changes in ciprofloxacin resistance levels in Enterobacter aerogenes isolates associated with variable expression of the aac(6')-Ib-cr gene.

PubMed

Ruiz, Elena; Ocampo-Sosa, Alain A; Alcoba-Flórez, Julia; Román, Elena; Arlet, Guillaume; Torres, Carmen; Martínez-Martínez, Luis

2012-02-01

Two closely related Enterobacter aerogenes isolates presented a new identical aac(6')-Ib-cr genetic environment, including IS26. One isolate showed lower MICs of ciprofloxacin, norfloxacin, tobramycin, and amikacin and decreased expression of aac(6')-Ib-cr, which might be related to a 12-bp deletion causing a displacement of the -10 box upstream of the aac(6')-Ib-cr gene.

A Randomized Controlled Trial Comparing the Low FODMAP Diet vs. Modified NICE Guidelines in US Adults with IBS-D.

PubMed

Eswaran, Shanti L; Chey, William D; Han-Markey, Theresa; Ball, Sarah; Jackson, Kenya

2016-12-01

There has been an increasing interest in the role of fermentable oligo-, di-, and monosaccharides and polyols (FODMAPs) in irritable bowel syndrome (IBS). We report results from the first randomized controlled trial of the low FODMAP diet in US adults with IBS and diarrhea (IBS-D). The objectives were to compare the efficacy of the low FODMAP diet vs. a diet based upon modified National Institute for Health and Care Excellence guidelines (mNICE) on overall and individual symptoms in IBS-D patients. This was a single-center, randomized-controlled trial of adult patients with IBS-D (Rome III) which compared 2 diet interventions. After a 2-week screening period, eligible patients were randomized to a low FODMAP or mNICE diet for 4 weeks. The primary end point was the proportion of patients reporting adequate relief of IBS-D symptoms ≥50% of intervention weeks 3-4. Secondary outcomes included a composite end point which required response in both abdominal pain (≥30% reduction in mean daily pain score compared with baseline) and stool consistency (decrease in mean daily Bristol Stool Form of ≥1 compared with baseline), abdominal pain and stool consistency responders, and other key individual IBS symptoms assessed using daily questionnaires. After screening, 92 subjects (65 women, median age 42.6 years) were randomized. Eighty-four patients completed the study (45 low FODMAP, 39 mNICE). Baseline demographics, symptom severity, and nutrient intake were similar between groups. Fifty-two percent of the low FODMAP vs. 41% of the mNICE group reported adequate relief of their IBS-D symptoms (P=0.31). Though there was no significant difference in the proportion of composite end point responders (P=0.13), the low FODMAP diet resulted in a higher proportion of abdominal pain responders compared with the mNICE group (51% vs. 23%, P=0.008). Compared with baseline scores, the low FODMAP diet led to greater reductions in average daily scores of abdominal pain, bloating

Co-occurrence of IBS and symptoms of anxiety or depression, among Norwegian twins, is influenced by both heredity and intrauterine growth.

PubMed

Bengtson, May-Bente; Aamodt, Geir; Vatn, Morten H; Harris, Jennifer R

2015-02-05

Environmental and genetic factors contribute to variation in irritable bowel syndrome (IBS), anxiety and depression. Comorbidity between these disorders is high. A previous investigation of our population-based twin cohort revealed that low birth weight increased the risk for development of IBS, with environmental influences in utero as the most relevant contributing factor. We hypothesise that both intrauterine and genetic factors influence the co-occurrence of IBS and symptoms of anxiety and depression. A postal questionnaire sent to 12700 Norwegian twins born between 1967 and 1979 comprised a checklist of 31 illnesses and symptoms, including IBS and symptoms of anxiety and depression. The influence of genetic factors and intrauterine growth on comorbidity between these disorders were analysed in the full sample and compared to those based on only monozygotic (MZ) twin pairs discordant for IBS (95 pairs) in birth weight group < 2500 g and ≥ 2500 g. In the co-twin analyses restricted growth (birth weight < 2500 g) was significantly associated with anxiety and depression (average birth weight difference of 181.0 g (p <0.0001) and 249.9 g (p < 0.0001), respectively). The analysis of the full sample revealed that IBS was significantly associated with symptoms of anxiety (adjusted OR = 2.5, 95% CI: 1.9, 3.3) and depression (adjusted OR = 2.3. 95% CI: 1.8, 3.0). Analyses of MZ pairs discordant for IBS indicated significant associations between IBS and symptoms of anxiety (OR = 3.7, 95% CI: 1.3, 10.5) and between IBS and symptoms of depression (OR = 4.2, 95% CI: 1.7, 9.9) only in the birth weight group below 2500 g. Our findings suggest that genetic factors partly explain the association between IBS and symptoms of anxiety and depression. In the low range of birth weight (<2500 g), restricted fetal growth seems to be a common contributing factor to the co-occurrence between these disorders.

Design and validation of a German version of the GSRS-IBS - an analysis of its psychometric quality and factorial structure.

PubMed

Schäfer, Sarah K; Weidner, Kathrin Julia; Hoppner, Jorge; Becker, Nicolas; Friedrich, Dana; Stokes, Caroline S; Lammert, Frank; Köllner, Volker

2017-12-04

Currently, a suitable questionnaire in German language is not available to monitor the progression and evaluate the severity of irritable bowel syndrome (IBS). Therefore, this study aimed to translate the Gastrointestinal Symptom Rating Scale for Irritable Bowel Syndrome (GSRS-IBS) into German and to evaluate its psychometric qualities and factorial structure. This study is based on a total sample of 372 participants [62.6% female, mean age = 41 years (SD = 17 years)]. 17.5% of the participants had a diagnosis of IBS, 19.9% were receiving treatment for chronic inflammatory bowel disease, 12.1% of the participants were recruited from a psychosomatic clinic, and 50.5% belonged to a control group. All participants completed the German version of GSRS-IBS (called Reizdarm-Fragebogen, RDF), as well as the Gießen Subjective Complaints List (GBB-24) and the Hospital Anxiety and Depression Scale - German version (HADS-D). The internal consistency of the RDF total scale was at least satisfactory in all subsamples (Cronbach's Alpha between .77 and .92), and for all subscales (Cronbach's Alpha between .79 and .91). The item difficulties (between .25 and .73) and the item-total correlations (between .48 and .83) were equally satisfactory. Principal axis analysis revealed a four-factorial structure of the RDF items, which mainly resembled the structure of the English original. Convergent validity was established based on substantial and significant correlations with the stomach-complaint scale of the GBB-24 (r = .71; p < .01) and the anxiety (r = .42; p < .01) and depression scales (r = .43; p < .01) of the HADS-D. The German version of the GSRS-IBS RDF proves to be an effective, reliable, and valid questionnaire for the assessment of symptom severity in IBS, which can be used in clinical practice as well as in clinical studies.

Myasthenia gravis in a patient affected by glycogen storage disease type Ib: a further manifestation of an increased risk for autoimmune disorders?

PubMed

Melis, D; Balivo, F; Della Casa, R; Romano, A; Taurisano, R; Capaldo, B; Riccardi, G; Monsurrò, M R; Parenti, G; Andria, G

2008-12-01

Glycogen storage disease type Ib (GSD Ib, OMIM 232220) is an inborn disorder of glucose metabolism, caused by mutations in the G6PT gene, encoding a glucose 6-phosphate transporter (G6PT). GSD Ib is mainly associated with fasting hypoglycaemia and hepatomegaly. Most GSD Ib patients also show neutropenia and neutrophil dysfunction and therefore are at risk of developing severe infections and inflammatory bowel disease (IBD). An increased risk for autoimmune disorders, such as thyroid autoimmunity and Crohn-like disease, has also been demonstrated, but no systematic study on the prevalence of autoimmune disorders in GSD Ib patients has ever been performed. We describe a 25-year-old patient affected by GSD Ib who developed 'seronegative' myasthenia gravis (MG), presenting with bilateral eyelid ptosis, diplopia, dysarthria, severe dysphagia, dyspnoea and fatigue. The repetitive stimulation of peripheral nerves test showed signs of exhaustion of neuromuscular transmission, particularly evident in the cranial area. Even in the absence of identifiable anti-acetylcholine receptor antibodies, seronegative MG is considered an autoimmune disorder and may be related to the disturbed immune function observed in GSD Ib patients.

Investigation of the feasibility of elective irradiation to neck level Ib using intensity-modulated radiotherapy for patients with nasopharyngeal carcinoma: a retrospective analysis.

PubMed

Zhang, Fan; Cheng, Yi-Kan; Li, Wen-Fei; Guo, Rui; Chen, Lei; Sun, Ying; Mao, Yan-Ping; Zhou, Guan-Qun; Liu, Xu; Liu, Li-Zhi; Lin, Ai-Hua; Tang, Ling-Long; Ma, Jun

2015-10-15

To assess the feasibility of elective neck irradiation to level Ib in nasopharyngeal carcinoma (NPC) using intensity-modulated radiation therapy (IMRT). We retrospectively analyzed 1438 patients with newly-diagnosed, non-metastatic and biopsy-proven NPC treated with IMRT. Greatest dimension of level IIa LNs (DLN-IIa) ≥ 20 mm and/or level IIa LNs with extracapsular spread (ES), oropharynx involvement and positive bilateral cervical lymph nodes (CLNs) were independently significantly associated with metastasis to level Ib LN at diagnosis. No recurrence at level Ib was observed in the 904 patients without these characteristics (median follow-up, 38.7 months; range, 1.3-57.8 months), these patients were classified as low risk. Level Ib irradiation was not an independent risk factor for locoregional failure-free survival, distant failure-free survival, failure-free survival or overall survival in low risk patients. The frequency of grade ≥ 2 subjective xerostomia at 12 months after radiotherapy was not significantly different between low risk patients who received level Ib-sparing, unilateral level Ib-covering or bilateral level Ib-covering IMRT. Level Ib-sparing IMRT should be safe and feasible for patients without a DLN-IIa ≥ 20 mm and/or level IIa LNs with ES, positive bilateral CLNs or oropharynx involvement at diagnosis. Further investigations based on specific criteria for dose constraints for the submandibular glands are warranted to confirm the benefit of elective level Ib irradiation.

The low FODMAP diet: recent advances in understanding its mechanisms and efficacy in IBS.

PubMed

Staudacher, Heidi M; Whelan, Kevin

2017-08-01

There is an intensifying interest in the interaction between diet and the functional GI symptoms experienced in IBS. Recent studies have used MRI to demonstrate that short-chain fermentable carbohydrates increase small intestinal water volume and colonic gas production that, in those with visceral hypersensitivity, induces functional GI symptoms. Dietary restriction of short-chain fermentable carbohydrates (the low fermentable oligosaccharide, disaccharide, monosaccharide and polyol (FODMAP) diet) is now increasingly used in the clinical setting. Initial research evaluating the efficacy of the low FODMAP diet was limited by retrospective study design and lack of comparator groups, but more recently well-designed clinical trials have been published. There are currently at least 10 randomised controlled trials or randomised comparative trials showing the low FODMAP diet leads to clinical response in 50%-80% of patients with IBS, in particular with improvements in bloating, flatulence, diarrhoea and global symptoms. However, in conjunction with the beneficial clinical impact, recent studies have also demonstrated that the low FODMAP diet leads to profound changes in the microbiota and metabolome, the duration and clinical relevance of which are as yet unknown. This review aims to present recent advances in the understanding of the mechanisms by which the low FODMAP diet impacts on symptoms in IBS, recent evidence for its efficacy, current findings regarding the consequences of the diet on the microbiome and recommendations for areas for future research. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Clinical and Molecular Epidemiology of Multidrug-Resistant P. aeruginosa Carrying aac(6')-Ib-cr, qnrS1 and blaSPM Genes in Brazil

PubMed Central

Araujo, Bruna Fuga; Ferreira, Melina Lorraine; de Campos, Paola Amaral; Royer, Sabrina; Batistão, Deivid William da Fonseca; Dantas, Raquel Cristina Cavalcanti; Gonçalves, Iara Rossi; Faria, Ana Luiza Souza; de Brito, Cristiane Silveira; Yokosawa, Jonny; Gontijo-Filho, Paulo Pinto; Ribas, Rosineide Marques

2016-01-01

We described a comprehensive analysis of the molecular epidemiology of multidrug-resistant (MDR) P. aeruginosa. Molecular analysis included typing by Pulsed Field Gel Electrophoresis, identification of genes of interest through PCR-based assays and sequencing of target genes. Case-control study was conducted to better understand the prognostic of patients and the impact of inappropriate therapy in patients with bacteremia, as well as the risk factors of MDR infections. We observed a high rate of MDR isolates (40.7%), and 51.0% of them was independently associated with inappropriate antibiotic therapy. Bacteremia was detected in 66.9% of patients, and prolonged hospital stay was expressive in those resistant to fluoroquinolone. Plasmid-mediated quinolone resistance genes (PMQR), qnrS1 and aac(6’)Ib-cr, were detected in two different nosocomial isolates (5.3%), and the aac(6’)-Ib7 variant was detected at a high frequency (87.5%) in those negative to PMQR. The presence of mutations in gyrA and parC genes was observed in 100% and 85% of selected isolates, respectively. Isolates harboring PMQR genes or mutations in gyrA and parC were not closely related, except in those containing SPM (São Paulo metallo-β-lactamase) clone. In addition, there is no study published in Brazil to date reporting the presence of Pseudomonas aeruginosa isolates harboring both qnrS1 and aac(6’)Ib-cr genes, with alarming frequency of patients with inappropriate therapy. PMID:27219003

The impact of abuse and mood on bowel symptoms and health-related quality of life in irritable bowel syndrome (IBS).

PubMed

Kanuri, N; Cassell, B; Bruce, S E; White, K S; Gott, B M; Gyawali, C P; Sayuk, G S

2016-10-01

Irritable bowel syndrome (IBS) is a common abdominal pain disorder without an organic explanation. Abuse histories (physical, sexual, emotional) are prevalent in IBS. While abuse relates to mood disorders (depression and anxiety) also common in IBS, the influence of abuse on gastrointestinal (GI) symptoms and health-related quality of life (HRQOL) and its independence from psychological symptom comorbidity has not been studied. Consecutive GI outpatients completed the ROME III Research Diagnostic Questionnaire and questionnaires on trauma (Life-Stress Questionnaire), mood (Beck Depression/Anxiety Inventories), somatic symptoms (PHQ-12), and HRQOL (SF-36). Current GI symptom severity and bother were assessed using 10-cm Visual Analog Scales. 272 ROME-defined IBS (47.6 ± 0.9 years, 81% female) and 246 non-FGID (51.6 ± 1.0 years, 65% female) subjects participated. IBS patients reported greater rates of physical, sexual, and emotional abuse (p < 0.006 each), and higher depression, anxiety, and somatic symptoms (p < 0.001). Greater bowel symptom bother (7.4 ± 0.2 vs 6.7 ± 0.2, p = 0.040), severity (7.7 ± 0.2 vs 6.5 ± 0.2, p < 0.001), recent symptomatic days (9.8 ± 0.4 vs 8.5 ± 0.3, p = 0.02), and poorer HRQOL (40.9 ± 2.3 vs 55.5 ± 1.7, p < 0.001) were noted in IBS with abuse. Abuse effects were additive, with greater IBS symptom severity and poorer HRQOL noted in cases with multiple forms of abuse. Mediation analyses suggested that abuse effects on GI symptoms and HRQOL were partially mediated by mood. Abuse experiences common among IBS sufferers are associated with reports of greater GI symptoms and poorer HRQOL, particularly in those with multiple forms of abuse; this relationship may be partially mediated by concomitant mood disturbances. © 2016 John Wiley & Sons Ltd.

A Measure of Suffering in relation to Anxiety and Quality of Life in IBS Patients: Preliminary Results.

PubMed

Pletikosić Tončić, Sanda; Tkalčić, Mladenka

2017-01-01

Irritable bowel syndrome (IBS) is a chronic gastrointestinal (GI) disorder with a severe impact on quality of life (QoL). We explored the relationship of a visual measure of suffering, the PRISM-RII, with quality of life (QoL) and anxiety measures in IBS patients. Participants were 44 IBS patients who completed several questionnaires and kept a symptom diary for two weeks. The measures used were PRISM-RII (self-illness separation (SIS); illness perception measure (IPM)); IBS-36 (IBS health related QoL); SF-36 (physical and mental health related QoL); State-Trait Anxiety Inventory (STAI-T); Visceral Sensitivity Index (VSI; GI-specific anxiety); and a symptom diary. SIS was negatively correlated to VSI, while IPM was negatively correlated to SIS and the physical component of SF-36 and positively to VSI and symptom severity. We found significant differences between participants who perceive their illness as small and those who perceive it as medium in SIS, symptom severity, VSI, and the mental component of SF-36. Participants, who perceived their illness as small, represented their illness as more distant, showed lower average symptom severity, and had lower GI-specific anxiety and higher QoL. The results indicate that IPM and SIS can be useful in discriminating patients with more prominent psychological difficulties and QoL impairment.

Stadium IB - IIA cervical cancer patient’s survival rate after receiving definitive radiation and radical operation therapy followed by adjuvant radiation therapy along with analysis of factors affecting the patient’s survival rate

NASA Astrophysics Data System (ADS)

Ruslim, S. K.; Purwoto, G.; Widyahening, I. S.; Ramli, I.

2017-08-01

To evaluate the characteristics and overall survival rates of early stage cervical cancer (FIGO IB-IIA) patients who receive definitive radiation therapy and those who are prescribed adjuvant postoperative radiation and to conduct a factors analysis of the variables that affect the overall survival rates in both groups of therapy. The medical records of 85 patients with cervical cancer FIGO stages IB-IIA who were treated at the Department of Radiotherapy of Cipto Mangunkusumo Hospital were reviewed and analyzed to determine their overall survival and the factors that affected it between a definitive radiation group and an adjuvant postoperative radiation group. There were 25 patients in the definitive radiation and 60 patients in the adjuvant radiation group. The overall survival rates in the adjuvant radiation group at years one, two, and three were 96.7%, 95%, and 93.3%, respectively. Negative lymph node metastasis had an average association with overall survival (p < 0.2). In the definitive radiation group, overall survival at years one, two, and three were 96%, 92%, and 92%, respectively. A hemoglobin (Hb) level >12 g/dl was a factor with an average association with the overall survival (p < 0.2). The differences between both groups of therapy were not statistically significant (92% vs. 93.3%; p = 0.138). This study did not show any statistically significant overall survival for cervical cancer FIGO stage IB-IIA patients who received definitive radiation or adjuvant postoperative radiation. Negative lymph node metastasis had an effect on the overall survival rate in the adjuvant postoperative radiation group, while a preradiation Hb level >12 g/dl tended to affect the overall survival in the definitive radiation group patients.

IBS and possible luminosity improvement for RHIC operation below transition energy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fedotov,A.V.

There is a strong interest in low-energy RHIC collisions in the energy range below present RHIC transition energy. These collisions win help to answer one of the key questions in the field of QCD about the existence and location of a critical point on the QCD phase diagram. For such low-energy RHIC operation, particle losses from the RF bucket are of particular concern since the longitudinal beam size is comparable to the existing RF bucket at low energies. In this paper, we explore an Intrabeam Scattering (IBS) feature below transition energy that drives the transverse and longitudinal beam temperatures towardsmore » equilibrium to see whether we can minimize longitudinal diffusion due to IBS and predict some luminosity improvement for the low-energy RHIC project.« less

Effective factor of virtual team: Resolving communication breakdown in IBS construction project

NASA Astrophysics Data System (ADS)

Pozin, Mohd Affendi Ahmad; Nawi, Mohd. Nasrun Mohd.

2016-08-01

Currently, rapid development of information technology has provided new opportunities to organisation toward increasing the effectiveness of collaboration and teamwork management. Thus the virtual team approach has been implemented in numerous of field. However, there is limited study of virtual team in construction project management. Currently IBS project is still based on traditional construction process which is isolation team working environment. Therefore this approach has been declared as a main barrier to ensure cooperative working relation in term of communication and information in between project stakeholders. Thus, this paper through literature review is attempted to present a discussion of the virtual team approach toward IBS project in developing effective team communication during construction project.

Reports of "satisfactory relief" by IBS patients receiving usual medical care are confounded by baseline symptom severity and do not accurately reflect symptom improvement.

PubMed

Whitehead, William E; Palsson, Olafur S; Levy, Rona L; Feld, Andrew D; VonKorff, Michael; Turner, Marsha

2006-05-01

Treatment trials for irritable bowel syndrome (IBS) usually define a responder as a patient who reports satisfactory relief or adequate relief of symptoms at the end of the trial. However, these measures have not been adequately validated. (1) Compare a binary satisfactory relief measure to alternative ways of defining a treatment responder. (2) Determine whether baseline IBS symptom severity or psychological distress influence the sensitivity of these outcome measures. A total of 350 patients (81% females, average age 50 yr) who had a medical diagnosis of IBS and satisfied Rome II criteria, were recruited from Group Health Cooperative of Puget Sound. At baseline the Irritable Bowel Severity Scale (IBSS) was used to assess symptom severity and to classify patients as mild, moderate, or severe. Psychological distress and IBS-specific quality of life (IBS-QOL) were also assessed. After 6 months treatment with standard medical care, IBSS and IBS-QOL were reassessed, and patients were asked whether they had experienced satisfactory relief and whether they were somewhat or markedly better. Initial severity of IBS significantly affected the proportion who reported satisfactory relief (mild, 72%; moderate, 53%; severe, 44%) and the proportion who were somewhat or markedly better (mild, 62%; moderate, 44%; severe, 38%), but did not affect the proportion with a 50% reduction in symptoms (mild, 26%; moderate, 25%; severe, 23%). Although mild patients were the most likely to report satisfactory relief, they showed no average decrease in symptom severity or improvement in IBS-QOL. Conversely, severe patients, who were the least likely to report satisfactory relief, had the largest reductions in IBS symptom severity and the largest improvements in IBS-QOL. Psychological distress had no significant effect on the responder rate after adjusting for IBS symptom severity. These data from a descriptive study suggest that satisfactory relief is confounded with initial IBS symptom

Virtual Screening for the Development of Dual-Inhibitors Targeting Topoisomerase IB and Tyrosyl-DNA Phosphodiesterase 1.

PubMed

Cardamone, Francesca; Pizzi, Simone; Iacovelli, Federico; Falconi, Mattia; Desideri, Alessandro

2017-01-01

Human topoisomerase IB is an important target in cancer therapy and drugs selectively stabilizing the topoisomerase IB-DNA covalent complex are in clinical use for several cancer types. Tyrosyl- DNA phosphodiesterase 1 is involved in the DNA repair resolving the topoisomerase IB-DNA covalent complex that is extremely dangerous for the survival of the cells since it produces an irreversible DNA damage. Given the close biological relationship between these two enzymes, the development of synergistic inhibitors, called dual-inhibitors, is an important challenge in cancer therapy and computer-aided drug design may help in the identification of the best compounds. In this review, an overview of the compounds inhibiting one of the two enzymes or acting as dual inhibitors is provided. Moreover, the general procedures of the virtual screening approach, providing a description of two widely used opensource programs, namely AutoDock4 and AutoDock Vina, are described. Finally, an application of the two programs on a selected number of dual inhibitors for tyrosyl-DNA phosphodiesterase 1 and topoisomerase IB and their performance is briefly discussed. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

A Novel RNA Polymerase I Transcription Initiation Factor, TIF-IE, Commits rRNA Genes by Interaction with TIF-IB, Not by DNA Binding

PubMed Central

Al-Khouri, Anna Maria; Paule, Marvin R.

2002-01-01

In the small, free-living amoeba Acanthamoeba castellanii, rRNA transcription requires, in addition to RNA polymerase I, a single DNA-binding factor, transcription initiation factor IB (TIF-IB). TIF-IB is a multimeric protein that contains TATA-binding protein (TBP) and four TBP-associated factors that are specific for polymerase I transcription. TIF-IB is required for accurate and promoter-specific initiation of rRNA transcription, recruiting and positioning the polymerase on the start site by protein-protein interaction. In A. castellanii, partially purified TIF-IB can form a persistent complex with the ribosomal DNA (rDNA) promoter while homogeneous TIF-IB cannot. An additional factor, TIF-IE, is required along with homogeneous TIF-IB for the formation of a stable complex on the rDNA core promoter. We show that TIF-IE by itself, however, does not bind to the rDNA promoter and thus differs in its mechanism from the upstream binding factor and upstream activating factor, which carry out similar complex-stabilizing functions in vertebrates and yeast, respectively. In addition to its presence in impure TIF-IB, TIF-IE is found in highly purified fractions of polymerase I, with which it associates. Renaturation of polypeptides excised from sodium dodecyl sulfate-polyacrylamide gels showed that a 141-kDa polypeptide possesses all the known activities of TIF-IE. PMID:11784852

A novel RNA polymerase I transcription initiation factor, TIF-IE, commits rRNA genes by interaction with TIF-IB, not by DNA binding.

PubMed

Al-Khouri, Anna Maria; Paule, Marvin R

2002-02-01

In the small, free-living amoeba Acanthamoeba castellanii, rRNA transcription requires, in addition to RNA polymerase I, a single DNA-binding factor, transcription initiation factor IB (TIF-IB). TIF-IB is a multimeric protein that contains TATA-binding protein (TBP) and four TBP-associated factors that are specific for polymerase I transcription. TIF-IB is required for accurate and promoter-specific initiation of rRNA transcription, recruiting and positioning the polymerase on the start site by protein-protein interaction. In A. castellanii, partially purified TIF-IB can form a persistent complex with the ribosomal DNA (rDNA) promoter while homogeneous TIF-IB cannot. An additional factor, TIF-IE, is required along with homogeneous TIF-IB for the formation of a stable complex on the rDNA core promoter. We show that TIF-IE by itself, however, does not bind to the rDNA promoter and thus differs in its mechanism from the upstream binding factor and upstream activating factor, which carry out similar complex-stabilizing functions in vertebrates and yeast, respectively. In addition to its presence in impure TIF-IB, TIF-IE is found in highly purified fractions of polymerase I, with which it associates. Renaturation of polypeptides excised from sodium dodecyl sulfate-polyacrylamide gels showed that a 141-kDa polypeptide possesses all the known activities of TIF-IE.

Towards a better understanding of the evolution of Wolf-Rayet stars and Type Ib/Ic supernova progenitors

NASA Astrophysics Data System (ADS)

Yoon, Sung-Chul

2017-10-01

Hydrogen-deficient Wolf-Rayet (WR) stars are potential candidates of Type Ib/Ic supernova (SN Ib/Ic) progenitors and their evolution is governed by mass-loss. Stellar evolution models with the most popular prescription for WR mass-loss rates given by Nugis & Lamers have difficulties in explaining the luminosity distribution of WR stars of WC and WO types and the SN Ic progenitor properties. Here, we suggest some improvements in the WR mass-loss rate prescription and discuss its implications for the evolution of WR stars and SN Ib/Ic progenitors. Recent studies on Galactic WR stars clearly indicate that the mass-loss rates of WC stars are systematically higher than those of WNE stars for a given luminosity. The luminosity and initial metallicity dependences of WNE mass-loss rates are also significantly different from those of WC stars. These factors have not been adequately considered together in previous stellar evolution models. We also find that an overall increase of WR mass-loss rates by about 60 per cent compared to the empirical values obtained with a clumping factor of 10 is needed to explain the most faint WC/WO stars. This moderate increase with our new WR mass-loss rate prescription results in SN Ib/Ic progenitor models more consistent with observations than those given by the Nugis & Lamers prescription. In particular, our new models predict that the properties of SN Ib and SN Ic progenitors are distinctively different, rather than they form a continuous sequence.

Descending pain modulation in irritable bowel syndrome (IBS): a systematic review and meta-analysis.

PubMed

Chakiath, Rosemary J; Siddall, Philip J; Kellow, John E; Hush, Julia M; Jones, Mike P; Marcuzzi, Anna; Wrigley, Paul J

2015-12-10

Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder. While abdominal pain is a dominant symptom of IBS, many sufferers also report widespread hypersensitivity and present with other chronic pain conditions. The presence of widespread hypersensitivity and extra-intestinal pain conditions suggests central nervous dysfunction. While central nervous system dysfunction may involve the spinal cord (central sensitisation) and brain, this review will focus on one brain mechanism, descending pain modulation. We will conduct a comprehensive search for the articles indexed in the databases Ovid MEDLINE, Ovid Embase, Ovid PsycINFO and Cochrane Central Register of Controlled Trial (CENTRAL) from their inception to August 2015, that report on any aspect of descending pain modulation in irritable bowel syndrome. Two independent reviewers will screen studies for eligibility, assess risk of bias and extract relevant data. Results will be tabulated and, if possible, a meta-analysis will be carried out. The systematic review outlined in this protocol aims to summarise current knowledge regarding descending pain modulation in IBS. PROSPERO CRD42015024284.

New therapeutic options for IBS: the role of the first in class mixed µ- opioid receptor agonist and δ-opioid receptor antagonist (mudelta) eluxadoline.

PubMed

Corsetti, Maura; Whorwell, Peter

2017-04-01

Irritable bowel syndrome (IBS) is a prevalent functional gastrointestinal disorder which represents a major cost to healthcare services. IBS-D patients represent about one-third of the IBS population and are currently treated with antispasmodics, loperamide, bile acid sequestrants and antidepressants. Alosetron and rifaximin are also available in USA, ramosetron in Japan, Korea and Thailand and ondansetron as an off-label treatment. Areas covered: This article focuses on eluxadoline, a novel pharmacological agent that has recently been approved by both the FDA and EMA for treatment of patients with IBS-D. Expert commentary: The efficacy and safety of eluxadoline in treating bowel habit alterations and pain, both in the short and long-term, make the drug a welcome addition to our therapeutic alternatives in IBS-D. Its positioning in any IBS algorithm will depend on the 'real world' prevalence of the small risk of sphincter of Oddi spasm and mild pancreatitis.

Glucose-6-phosphate transporter gene therapy corrects metabolic and myeloid abnormalities in glycogen storage disease type Ib mice

PubMed Central

Yiu, Wai Han; Pan, Chi-Jiunn; Allamarvdasht, Mohammad; Kim, So Youn; Chou, Janice Y.

2008-01-01

Glycogen storage disease type Ib (GSD-Ib) is caused by a deficiency in the glucose-6-phosphate transporter (G6PT), an endoplasmic reticulum-associated transmembrane protein that is ubiquitously expressed. GSD-Ib patients suffer from disturbed glucose homeostasis and myeloid dysfunctions. To evaluate the feasibility of gene replacement therapy for GSD-Ib, we have infused adenoviral (Ad) vector containing human G6PT (Ad-hG6PT) into G6PT-deficient (G6PT-/-) mice that manifest symptoms characteristics of the human disorder. Ad-hG6PT-infusion restores significant levels of G6PT mRNA expression in the liver, bone marrow, and spleen and corrects metabolic as well as myeloid abnormalities in G6PT-/- mice. The G6PT-/- mice receiving gene therapy exhibit improved growth; normalized serum profiles for glucose, cholesterol, triglyceride, uric acid, and lactic acid; and reduced hepatic glycogen deposition. The therapy also corrects neutropenia and lowers the elevated serum levels of granulocyte colony stimulating factor. The development of bone and spleen in the infused G6PT-/- mice is improved and accompanied by increased cellularity and normalized myeloid progenitor cell frequencies in both tissues. This effective use of gene therapy to correct metabolic imbalances and myeloid dysfunctions in GSD-Ib mice holds promise for the future of gene therapy in humans. PMID:17006547

In vitro activity and in vivo animal model efficacy of IB-367 alone and in combination with imipenem and colistin against Gram-negative bacteria.

PubMed

Simonetti, Oriana; Cirioni, Oscar; Ghiselli, Roberto; Orlando, Fiorenza; Silvestri, Carmela; Mazzocato, Susanna; Kamysz, Wojciech; Kamysz, Elzbieta; Provinciali, Mauro; Giacometti, Andrea; Guerrieri, Mario; Offidani, Annamaria

2014-05-01

The aim of our study was to evaluate the in vitro activity of IB-367 and its bactericidal effect for Pseudomonas aeruginosa and Escherichia coli, associated to a synergic study to test the antibiotic combinations between the peptide and colistin or imipenem. Minimum inhibitory concentrations (MICs), the minimum bactericidal concentrations (MBCs), the synergy test and killing study were carried out to evaluate the IB-367 activity. In the in vivo model, a wound was incised through the panniculus carnosus of BALB/c mice, and then inoculated with 5 × 107 colony-forming units of P. aeruginosa and E. coli. For each strain, the study included an infected or not infected group that did not receive any treatment, and five contaminated groups treated with local IB- 367, intraperitoneal imipenem, intraperitoneal colistin, topical IB-367 local plus intraperitoneal imipenem or intraperitoneal colistin. All isolates were inhibited by IB-367 at concentrations of 4-64 mg/l. Killing by IB-367 was shown to be very rapid: its activity on all Gram-negative bacteria was completed within a 40 min exposure period at a concentration of 2 × MIC/l. Synergy was demonstrated when IB-367 was combined with colistin or imipenem. In in vivo studies, the groups treated with topical IB-367 and intraperitoneal colistin showed the best results in terms of bacterial load inhibition either for Pseudomonas or for E. coli. The good in vitro activity and in vivo efficacy, as well as, the synergic interactions with antibiotics suggest that IB-367 is a promising candidate for potential application in the treatment of wound Gram-negative infections. Copyright © 2014 Elsevier Inc. All rights reserved.

IBS-like Symptoms in Patients with Ulcerative Colitis in Deep Remission Are Associated with Increased Levels of Serum Cytokines and Poor Psychological Well-being.

PubMed

Jonefjäll, Börje; Öhman, Lena; Simrén, Magnus; Strid, Hans

2016-11-01

Gastrointestinal symptoms (GI) compatible with irritable bowel syndrome (IBS) are common in patients with ulcerative colitis (UC) in remission. The causes of these symptoms remain to be clarified. Our aim was to investigate prevalence and factors associated with IBS-like symptoms in patients with UC in deep remission. We included 298 patients with UC and used Mayo score, sigmoidoscopy, and fecal calprotectin to define deep remission versus active disease. Presence of IBS-like symptoms according to the Rome III criteria, severity of GI, extraintestinal and psychological symptoms, stress levels, and quality of life were measured with validated questionnaires. Serum cytokines and high-sensitive C-reactive peptide were determined. The criteria for deep remission was fulfilled by 132 patients (44%) and 24 of these fulfilled the Rome III criteria for IBS (18%). Patients with UC in deep remission with IBS-like symptoms had comparable levels of GI symptoms, non-GI somatic symptoms, and quality of life as patients with active UC. The patients with UC in deep remission with IBS-like symptoms had similar levels of fecal calprotectin as patients in deep remission without IBS-like symptoms (18 versus 31 μg/g, P = 0.11), but higher levels of serum cytokines (interleukin [IL]-1β, IL-6, IL-13, IL-10 and IL-8, P < 0.05) and higher levels of anxiety (P < 0.001), depression (P = 0.02) and perceived stress (P = 0.03). IBS-like symptoms in patients with UC in deep remission are common, but not as prevalent as previously reported. Poor psychological well-being and increased serum cytokine levels, but not colonic low-grade inflammation, were associated with IBS-like symptoms.

A double-blind, placebo-controlled study to assess the effect of a probiotic mixture on symptoms and inflammatory markers in women with diarrhea-predominant IBS.

PubMed

Hod, K; Sperber, A D; Ron, Y; Boaz, M; Dickman, R; Berliner, S; Halpern, Z; Maharshak, N; Dekel, R

2017-07-01

Micro-inflammation is considered an element in the pathogenesis of irritable bowel syndrome (IBS). High-sensitivity C reactive protein (hs-CRP) was previously shown to be higher in IBS compared to healthy controls, albeit within the normal range. Since probiotics may suppress micro-inflammation in the gut, we tested if they reduce symptoms and inflammatory markers (hs-CRP and fecal calprotectin (FC) in diarrhea-predominant IBS (IBS-D). The aim of this study was to assess the clinical and laboratory effects of BIO-25, a multispecies probiotic, in women with IBS-D. A double-blind, placebo-controlled study. Following a 2-week run-in, eligible women were assigned at random to a probiotic capsule or an indistinguishable placebo, twice daily for 8 weeks. IBS symptoms and stool consistency were rated daily by Visual Analogue Scales (VAS) and the Bristol Stool Scale (BSS). High-sensitivity C reactive protein was tested at baseline, 4 and 8 weeks. FC was tested at baseline and 8 weeks. One hundred and seventy-two IBS-D patients were recruited and 107 eligible patients were allocated to the intervention (n=54) or placebo (n=53) group. All symptoms improved in both groups with no significant difference between them in symptom improvement, hs-CRP or FC levels. An 8-week treatment with BIO-25 improved symptoms in women with IBS-D, but was not superior to placebo. This rigorously designed and executed study supports the findings of other studies that did not demonstrate superiority of probiotics over placebo in IBS. High quality clinical studies are necessary to examine the efficacy of other specific probiotics in IBS-D patients since data are still conflicting. © 2017 John Wiley & Sons Ltd.

Disparities in Adherence to National Comprehensive Cancer Network Treatment Guidelines and Survival for Stage IB-IIA Cervical Cancer in California.

PubMed

Pfaendler, Krista S; Chang, Jenny; Ziogas, Argyrios; Bristow, Robert E; Penner, Kristine R

2018-05-01

To evaluate the association of sociodemographic and hospital characteristics with adherence to National Comprehensive Cancer Network treatment guidelines for stage IB-IIA cervical cancer and to analyze the relationship between adherent care and survival. This is a retrospective population-based cohort study of patients with stage IB-IIA invasive cervical cancer reported to the California Cancer Registry from January 1, 1995, through December 31, 2009. Adherence to National Comprehensive Cancer Network guideline care was defined by year- and stage-appropriate surgical procedures, radiation, and chemotherapy. Multivariate logistic regression, Kaplan-Meier estimate, and Cox proportional hazard models were used to examine associations between patient, tumor, and treatment characteristics and National Comprehensive Cancer Network guideline adherence and cervical cancer-specific 5-year survival. A total of 6,063 patients were identified. Forty-seven percent received National Comprehensive Cancer Network guideline-adherent care, and 18.8% were treated in high-volume centers (20 or more patients/year). On multivariate analysis, lowest socioeconomic status (adjusted odds ratio [OR] 0.69, 95% CI 0.57-0.84), low-middle socioeconomic status (adjusted OR 0.76, 95% CI 0.64-0.92), and Charlson-Deyo comorbidity score 1 or higher (adjusted OR 0.78, 95% CI 0.69-0.89) were patient characteristics associated with receipt of nonguideline care. Receiving adherent care was less common in low-volume centers (45.9%) than in high-volume centers (50.9%) (effect size 0.90, 95% CI 0.84-0.96). Death from cervical cancer was more common in the nonadherent group (13.3%) than in the adherent group (8.6%) (effect size 1.55, 95% CI 1.34-1.80). Black race (adjusted hazard ratio 1.56, 95% CI 1.08-2.27), Medicaid payer status (adjusted hazard ratio 1.47, 95% CI 1.15-1.87), and Charlson-Deyo comorbidity score 1 or higher (adjusted hazard ratio 2.07, 95% CI 1.68-2.56) were all associated with increased

Longitudinal impact of IBS-type symptoms on disease activity, healthcare utilization, psychological health, and quality of life in inflammatory bowel disease.

PubMed

Gracie, David J; Hamlin, P John; Ford, Alexander C

2018-05-01

The impact of irritable bowel syndrome (IBS)-type symptoms on the natural history of inflammatory bowel disease (IBD) is uncertain. We aimed to address this in a longitudinal study of secondary care patients. Longitudinal disease activity was defined by disease flare, escalation of medical therapy, hospitalization, or intestinal resection. The number of investigations performed and clinics attended determined healthcare utilization. Psychological well-being and quality of life were assessed using validated questionnaires. These outcomes were compared over a minimum period of 2 years between patients reporting IBS-type symptoms and patients with quiescent disease, occult inflammation, and active disease at baseline. In 360 IBD patients, there were no differences in longitudinal disease activity between patients with IBS-type symptoms and patients with quiescent disease or occult inflammation. Disease flare and escalation of medical therapy was more common in patients with active disease than in patients with IBS-type symptoms (hazard ratio (HR) = 3.16; 95% confidence interval (CI) 1.93-5.19 and HR = 3.24; 95% CI 1.98-5.31, respectively). A greater number of investigations were performed in patients with IBS-type symptoms than quiescent disease (P = 0.008), but not compared with patients with occult inflammation or active disease. Anxiety, depression, and somatization scores at follow up were higher, and quality-of-life scores lower, in patients with IBS-type symptoms when compared with patients with quiescent disease, but were similar to patients with active disease. IBS-type symptoms in IBD were associated with increased healthcare utilization, psychological comorbidity, reduced quality of life, but not adverse disease activity outcomes during extended follow-up.

Differential protective effects of immune lymphoid cells against transplanted line Ib leukemia and immune polioencephalomyelitis. [X radiation, mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Duffey, P.S.; Lukasewycz, O.A.; Olson, D.S.

1978-12-01

The capacity of immune cells obtained from the major lymphoid compartments to protect C58 mice from transplanted line Ib leukemia, and from an age-dependent autoimmune CNS disease (immune polioencephalomyelitis = IPE) elicited by immunizing old C58 mice with inactivated Ib cells was quantified. Cells used for comparative adoptive protection tests were harvested from the major lymphoid compartments 14 to 15 days after young C58 mice were immunized with inactivated Ib cell preparations. Regression curves were plotted from survival data and the log/sub 10/PD/sub 50/ values were determined. Immune spleen (ISC) and peritoneal cells (IPEC) were significantly more protective against transplantedmore » Ib cells than immune lymph node (ILNC), thymic (ITC), and marrow cells (IMC). In contrast, IPEC and IMC were not protective against IPE and ITC were only marginally protective. ILNC afforded significant protection to transplantable leukemia but were only marginally protective to IPE. When ISC were treated with anti-thy 1.2 serum and complement, protection against transplanted leukemia and IPE was reduced > 99%. When donors of immune lymphoid cells were treated with 12.5 mg of cortisone acetate daily for 2 days before lymphoid cells were harvested, protection against transplanted Ib cells by ISC was reduced by approximately 90% whereas protection against IPE was totally eliminated. Considered together, these results indicate that the protective mechanisms to transplantable leukemia and IPE differ significantly in the same indicator mouse strain.« less

[Using a multicomponent functional food in IBS patients with constipation a comparative controlled study].

PubMed

Pilipenko, V I; Teplyuk, D A; Shakhovskaya, A K; Isakov, V A; Vorobyova, V M; Vorobyova, I S; Sarkisyan, V A; Kochetkova, A A; Mikheeva, G A; Yudina, A V

2016-01-01

Irritable bowel syndrome (IBS) is highly prevalent functional gastrointestinal disorder associated with decrease in quality of life and a high social cost. Diet is one of several therapeutic options in IBS treatment; therefore the development and clinical evaluation of innovative functional food for IBS patients are actual. Instant drink containing 4 g inulin, 4 mg menthol and 2 mg of pyridoxine (in daily dose) has been evaluated. 49 patients 18-68 (41.5±16.5) years old fulfilling the Rome III criteria for IBS-C were randomly assigned into two groups: one received standard diet plus two drinks per day for 2 weeks and control group received standard diet. Response to therapy was recorded daily using Likert scale of abdominal pain, bloating and feeling of incomplete bowel emptying, frequency of bowel movement, Bristol stool scale, and quality of life was assessed by IBSQoL questionnaire before and after the treatment. The consumption of the drink with inulin and menthol contributed to a significant positive effect on the stool parameters (from 0.91±0.73 to 1.12±0.45 bowel movements per day in stool frequency, p=0.05, from 2.68±1.63 to 3.43±1.27 index Bristol scale, p=0.05), reduced the severity of abdominal pain (from 1.78±0.58 to 1.47?0.61 Likert scale points, p=0.05), bloating (from 2.22±0.83 to 1.53±0.71 points ofLikertscale,p= 0.01) and a sense of incomplete bowelemptying (from 2.22 ± 0.88 to 1.61± 0.81 points of Likert scale, p=0.001), as well as increased the quality of life (from 75.3± 12.0 to 83.3±6.7%, p=0.05), but a significant part of patients (10 of 25) complained the appearance of heartburn after the start of the treatment. In conclusion, the consumption of the functional drink containing inulin, menthol and pyridoxine is associated with improve in stool parameters, abdominal pain, Bristol scale index and increase in quality of life in patients with IBS-C, but produce noticeable heartburn. Changes in functional drink composition are needed to

Effects on gastrointestinal transit and antroduodenojejunal manometry after gut-directed hypnotherapy in irritable bowel syndrome (IBS).

PubMed

Lindfors, Perjohan; Törnblom, Hans; Sadik, Riadh; Björnsson, Einar S; Abrahamsson, Hasse; Simrén, Magnus

2012-12-01

Gut-directed hypnotherapy is an effective treatment in irritable bowel syndrome (IBS) but little is known about the mechanisms of action. In this study we aimed to investigate the effects on gastrointestinal motility when treating IBS with gut-directed hypnotherapy. We randomized 90 patients with IBS, refractory to standard management to receive gut-directed hypnotherapy 1 h/week for 12 weeks or supportive treatment for the same time period. Eighty-one subjects (40 hypnotherapy, 41 controls) could be evaluated by one or more of the following investigations, both before and after the intervention: gastric emptying time, small bowel transit time, colonic transit time, and antroduodenojejunal manometry. No significant differences in gastric emptying time, small bowel transit time, or colonic transit time was found when comparing the baseline and post-intervention measurements in the hypnotherapy group or in the control group. The same was true concerning the results of the antroduodenojejunal manometry. However, there was a numerical trend toward a higher number of migrating motor complexes at manometry and an accelerated gastric emptying time after hypnotherapy that did not reach statistical significance. In this study, we were not able to find evidence for long-standing effects on gastrointestinal motility as a mediator of the effects on IBS when treating the condition with gut-directed hypnotherapy. Further research to understand the mechanism of action is needed.

Intestinal recruiting and activation profiles in peripheral blood mononuclear cells in response to pathogen-associated molecular patterns stimulation in patients with IBS.

PubMed

Rodríguez-Fandiño, O; Hernández-Ruíz, J; López-Vidal, Y; Charúa, L; Bandeh-Moghaddam, H; Minzoni, A; Guzmán, C; Schmulson, M

2013-11-01

Immune activation, increased Toll-like Receptors (TLR) expression, and gut epithelial diffusion of bacterial molecules have been reported in irritable bowel syndrome (IBS). Thus, we sought to relate these factors by analyzing gut homing (integrin α4β7), intestinal recruiting (CCR5) and activation (CD28) phenotypes, and the cytokines and chemokines concentration in peripheral blood T-lymphocytes stimulated with TLR-ligands. Twenty-one IBS-Rome II (1 PI-IBS) patients and 19 controls were studied. Isolated peripheral blood mononuclear cells were cultured with and without Escherichia coli lipopolysaccharide (LPS), Staphylococcus aureus peptidoglycan (PGN), and unmethylated cytosine-phosphate-guanine motifs (CpG). Phenotypes were investigated by flow cytometry and supernatant cytokines and chemokines were also measured. After LPS, CCR5 expression in CD4⁺ α4β7⁺ cells remained unchanged in IBS, but decreased in controls (p = 0.002), to lower levels than in IBS (Mean fluorescence intensity [MFI]: 1590 ± 126.9 vs 2417 ± 88.4, p < 0.001). There were less CD8(+) α4β7⁺ CCR5⁺ cells (85.7 ± 1.5 vs 90.8 ± 0.9%, p = 0.006) after LPS and CD3⁺ α4β7⁺ CCR5⁺ (40.0 ± 1.7 vs 51.2 ± 4.3%, p = 0.006) after PGN in controls. Also, after LPS, CD28 decreased in CD4⁺ α4β7⁺ CCR5⁺ in IBS (MFI: 2337 ± 47.2 vs 1779 ± 179.2, p < 0.001), but not in controls. Cytokines and chemokines were similar, except for lower IL8/CXCL8 in the unstimulated condition in IBS (4.18, 95% CI: 3.94-4.42 vs 3.77, 3.59-3.95; p = 0.006). Pathogen-associated molecular patterns stimulation of peripheral blood T cells expressing gut homing marker in IBS compared with controls resulted in an unsuccessful down-regulation of the co-expression of intestinal recruiting/residence phenotype and a state of activation. These findings support an interaction between an innate immune predisposition and microbial triggers, which may unleash or exacerbate IBS. © 2013 John Wiley & Sons Ltd.

A Distributed Perspective on Instructional Leadership in International Baccalaureate (IB) Schools

ERIC Educational Resources Information Center

Lee, Moosung; Hallinger, Philip; Walker, Allan

2012-01-01

Purpose: The purpose of this study is to provide a better understanding of how instructional leadership responsibilities are distributed in International Baccalaureate (IB) schools in East Asia. Research Design: Case studies were conducted in five international schools located in Thailand, Vietnam, Hong Kong, and China. These schools were selected…

The Gut-Brain Axis and the Microbiome: Clues to Pathophysiology and Opportunities for Novel Management Strategies in Irritable Bowel Syndrome (IBS).

PubMed

Quigley, Eamonn M M

2018-01-03

Irritable bowel syndrome (IBS) is one of the most common of all medical disorders worldwide and, while for some it represents no more than a nuisance, for others it imposes significant negative impacts on daily life and activities. IBS is a heterogeneous disorder and may well have a number of causes which may lie anywhere from the external environment to the contents of the gut lumen and from the enteric neuromuscular apparatus and the gut immune system to the central nervous system. Consequently, the paradigm of the gut-brain axis, which includes the participation of these various factors, has proven a useful model to assist clinicians and patients alike in understanding the genesis of symptoms in IBS. Now, given the widespread interest in the gut microbiome in health and disease, in general, reports of disordered enteric bacterial communities in IBS, and experimental data to indicate that components of the gut microbiota can influence brain morphology and function, as well as behavior and cognition, this concept has been extended to encompass the microbiota-gut-brain axis. The implications of this novel concept to the assessment and management of IBS will be explored in this review.

Mutation analysis of the muscarinic cholinergic receptor genes in isolated growth hormone deficiency type IB.

PubMed

Mohamadi, Ali; Martari, Marco; Holladay, Cindy D; Phillips, John A; Mullis, Primus E; Salvatori, Roberto

2009-07-01

Isolated GH deficiency (IGHD) is familial in 5-30% of patients. The most frequent form (IGHD-IB) has autosomal recessive inheritance, and it is known that it can be caused by mutations in the GHRH receptor (GHRHR) gene or in the GH gene. However, most forms of IGHD-IB have an unknown genetic cause. In normal subjects, muscarinic cholinergic stimulation causes an increase in pituitary GH release, whereas its blockade has the opposite effect, suggesting that a muscarinic acetylcholine receptor (mAchR) is involved in stimulating GH secretion. Five types of mAchR (M(1)-M(5)) exist. A transgenic mouse in which the function of the M(3) receptor was selectively ablated in the central nervous system has isolated GH deficiency similar to animals with defective GHRH or GHRHR gene. We hypothesized that mAchR mutations may cause a subset of familial IGHD. After confirming the expression of M(1)-M(5) receptor mRNA in human hypothalamus, we analyzed the index cases of 39 families with IGHD-IB for mutations in the genes encoding for the five receptors. Coding sequences for each of the five mAchRs were subjected to direct sequencing. In one family, an affected member was homozygous for a M(3) change in codon 65 that replaces valine with isoleucine (V65I). The V65I receptor was expressed in CHO cells where it had normal ability to transmit methacholine signaling. mAchR mutations are absent or rare (less than 2.6%) in familial IGHD type IB.

Comparison of breath testing with fructose and high fructose corn syrups in health and IBS

PubMed Central

Skoog, S. M.; Bharucha, A. E.; Zinsmeister, A. R.

2008-01-01

Although incomplete fructose absorption has been implicated to cause gastrointestinal symptoms, foods containing high fructose corn syrup (HFCS) contain glucose. Glucose increases fructose absorption in healthy subjects. Our hypothesis was that fructose intolerance is less prevalent after HFCS consumption compared to fructose alone in healthy subjects and irritable bowel syndrome (IBS). Breath hydrogen levels and gastrointestinal symptoms were assessed after 40 g of fructose (12% solution) prepared either in water or as HFCS, administered in double-blind randomized order on 2 days in 20 healthy subjects and 30 patients with IBS. Gastrointestinal symptoms were recorded on 100-mm Visual Analogue Scales. Breath hydrogen excretion was more frequently abnormal (P < 0.01) after fructose (68%) than HFCS (26%) in controls and patients. Fructose intolerance (i.e. abnormal breath test and symptoms) was more prevalent after fructose than HFCS in healthy subjects (25% vs 0%, P = 0.002) and patients (40% vs 7%, P = 0.062). Scores for several symptoms (e.g. bloating r = 0.35) were correlated (P ≤ 0.01) to peak breath hydrogen excretion after fructose but not HFCS; in the fructose group, this association did not differ between healthy subjects and patients. Symptoms were not significantly different after fructose compared to HFCS. Fructose intolerance is more prevalent with fructose alone than with HFCS in health and in IBS. The prevalence of fructose intolerance is not significantly different between health and IBS. Current methods for identifying fructose intolerance should be modified to more closely reproduce fructose ingestion in daily life. PMID:18221251

Comparison of breath testing with fructose and high fructose corn syrups in health and IBS.

PubMed

Skoog, S M; Bharucha, A E; Zinsmeister, A R

2008-05-01

Although incomplete fructose absorption has been implicated to cause gastrointestinal symptoms, foods containing high fructose corn syrup (HFCS) contain glucose. Glucose increases fructose absorption in healthy subjects. Our hypothesis was that fructose intolerance is less prevalent after HFCS consumption compared to fructose alone in healthy subjects and irritable bowel syndrome (IBS). Breath hydrogen levels and gastrointestinal symptoms were assessed after 40 g of fructose (12% solution) prepared either in water or as HFCS, administered in double-blind randomized order on 2 days in 20 healthy subjects and 30 patients with IBS. Gastrointestinal symptoms were recorded on 100-mm Visual Analogue Scales. Breath hydrogen excretion was more frequently abnormal (P < 0.01) after fructose (68%) than HFCS (26%) in controls and patients. Fructose intolerance (i.e. abnormal breath test and symptoms) was more prevalent after fructose than HFCS in healthy subjects (25% vs. 0%, P = 0.002) and patients (40% vs. 7%, P = 0.062). Scores for several symptoms (e.g. bloating r = 0.35) were correlated (P < or = 0.01) to peak breath hydrogen excretion after fructose but not HFCS; in the fructose group, this association did not differ between healthy subjects and patients. Symptoms were not significantly different after fructose compared to HFCS. Fructose intolerance is more prevalent with fructose alone than with HFCS in health and in IBS. The prevalence of fructose intolerance is not significantly different between health and IBS. Current methods for identifying fructose intolerance should be modified to more closely reproduce fructose ingestion in daily life.

A novel transcription initiation factor (TIF), TIF-IE, is required for homogeneous Acanthamoeba castellanii TIF-IB (SL1) to form a committed complex.

PubMed

Radebaugh, C A; Kubaska, W M; Hoffman, L H; Stiffler, K; Paule, M R

1998-10-16

The fundamental transcription initiation factor (TIF) for ribosomal RNA expression by eukaryotic RNA polymerase I, TIF-IB, has been purified to near homogeneity from Acanthamoeba castellanii using standard techniques. The purified factor consists of the TATA-binding protein and four TATA-binding protein-associated factors with relative molecular weights of 145,000, 99,000, 96,000, and 91,000. This yields a calculated native molecular weight of 460, 000, which compares well with its mass determined by scanning transmission electron microscopy (493,000) and its sedimentation rate, which is close to RNA polymerase I (515,000). Both impure and nearly homogeneous TIF-IB exhibit an apparent equilibrium dissociation constant of 56 +/- 3 pM. However, although impure TIF-IB can form a promoter-DNA complex resistant to challenge by other promoter-containing DNAs, near homogeneous TIF-IB cannot do so. An additional transcription factor, dubbed TIF-IE, restores the ability of near homogeneous TIF-IB to sequester DNA into a committed complex.

Induction by TNF-α of IL-6 and IL-8 in cystic fibrosis bronchial IB3-1 epithelial cells encapsulated in alginate microbeads.

PubMed

Borgatti, Monica; Mazzitelli, Stefania; Breveglieri, Giulia; Gambari, Roberto; Nastruzzi, Claudio

2010-01-01

We have developed a microencapsulation procedure for the entrapment and manipulation of IB3-1 cystic fibrosis cells. The applied method is based on generation of monodisperse droplets by a vibrational nozzle. Different experimental parameters were analyzed, including frequency and amplitude of vibration, polymer pumping rate and distance between the nozzle and the gelling bath. We have found that the microencapsulation procedure does not alter the viability of the encapsulated IB3-1 cells. The encapsulated IB3-1 cells were characterized in term of secretomic profile, analyzing the culture medium by Bio-Plex strategy. The experiments demonstrated that most of the analyzed proteins, were secreted both by the free and encapsulated cells, even if in a different extent. In order to determine the biotechnological applications of this procedure, we determined whether encapsulated IB3-1 cells could be induced to pro-inflammatory responses, after treatment with TNF-α. In this experimental set-up, encapsulated and free IB3-1 cells were treated with TNF-α, thereafter the culture media from both cell populations were collected. As expected, TNF-α induced a sharp increase in the secretion of interleukins, chemokines and growth factors. Of great interest was the evidence that induction of interleukin-6 and interleukin-8 occurs also by encapsulated IB3-1 cells.

Long‐Term Monitoring of a Geosynthetic Reinforced Soil Integrated Bridge System (GRS‐IBS)

DOT National Transportation Integrated Search

2017-11-01

The geosynthetic reinforced soil integrated bridge system (GRS-IBS) is an innovative alternative to conventional bridge technology that utilizes closely spaced layers of geosynthetic reinforcement and compacted granular fill material to provide direc...

Lactobacillus acidophilus CL1285, Lactobacillus casei LBC80R and Lactobacillus rhamnosus CLR2 improve quality-of-life and IBS symptoms: a double-blind, randomised, placebo-controlled study.

PubMed

Preston, K; Krumian, R; Hattner, J; de Montigny, D; Stewart, M; Gaddam, S

2018-06-11

A combination of Lactobacillus acidophilus CL1285, Lactobacillus casei LBC80R and Lactobacillus rhamnosus CLR2 was compared to placebo for relief of symptoms of irritable bowel syndrome (IBS). A total of 113 subjects at 3 clinical sites were randomised in a 2:1 ratio and followed for 12 weeks. Subjects ingested either 2 capsules of active study product, containing 50×10 9 cfu of live organisms, or 2 placebo capsules daily. Endpoints included improvement in abdominal pain, days of pain, distention, stool consistency and frequency, quality of life (QOL), and adequate relief (AR) of IBS symptoms. IBS subtypes constipation (IBS-C), diarrhoea (IBS-D), and mixed (IBS-M) were evaluated separately; the effect of gender was also examined. For all efficacy endpoints improvement of 30% or more vs placebo was considered clinically significant. With the exception of pain intensity and AR, the endpoints demonstrated a therapeutic advantage of active over placebo for IBS symptoms in at least some subject subgroups. The IBS-D and female subgroups showed the largest and most consistent effects. Stool frequency and consistency were evaluated in the IBS-C and IBS-D subgroups, and improvement of active vs placebo was noted in both. QOL improvement was seen overall and in specific domains. Adverse events (AEs) were limited to 7 subjects; all were of mild or moderate intensity except one, severe cramping. Four AEs in the same subject in the placebo group were judged to be related to study product; these resolved by the end of study. There were no serious AEs.

[Abdominal spasms, meteorism, diarrhea: fructose intolerance, lactose intolerance or IBS?].

PubMed

Litschauer-Poursadrollah, Margaritha; El-Sayad, Sabine; Wantke, Felix; Fellinger, Christina; Jarisch, Reinhart

2012-12-01

Meteorism, abdominal spasms, diarrhea, casually obstipation, flatulence and nausea are symptoms of fructose malabsorption (FIT) and/or lactose intolerance (LIT), but are also symptoms of irritable bowel syndrome (IBS). Therefore these diseases should be considered primarily in patients with digestive complaints. For diagnosis an H(2)-breath test is used.In 1,935 patients (526 m, 1,409 f) a fructose intolerance test and in 1,739 patients (518 m,1,221 f) a lactose intolerance test was done.FIT is found more frequently than LIT (57 versus 52 % in adults (p < 0,02) and in children 90 versus 62 % (p < 0,001)) and is in polyintolerances most frequently correlated to histamine intolerance (HIT). Headache (ca. 10 %), fatigue (ca. 5 %) and dizziness (ca. 3 %) may occur after the test, irrespective whether the test was positive or negative.In more than 2/3 of patients a diet reduced in fructose or lactose may lead to improvement or remission of these metabolic disorders. IBS, which is often correlated with FIT (183/221 patients = 83 %), can be improved by relevant but also not relevant diets indicating that irritable bowel disease seems to be caused primarily by psychological disorders.

Adhesive properties of the isolated amino-terminal domain of platelet glycoprotein Ibα in a flow field

PubMed Central

Marchese, Patrizia; Saldívar, Enrique; Ware, Jerry; Ruggeri, Zaverio M.

1999-01-01

We have examined the interaction between the amino-terminal domain of platelet glycoprotein (GP) Ibα and immobilized von Willebrand Factor (vWF) under flow conditions in the absence of other components of the GP Ib–IX–V complex. Latex beads were coated with a recombinant fragment containing GP Ibα residues 1–302, either with normal sequence or with the single G233V substitution that causes enhanced affinity for plasma vWF in platelet-type pseudo-von-Willebrand disease. Beads coated with native fragment adhered to vWF in a manner comparable to platelets, showing surface translocation that reflected the transient nature of the bonds formed. Thus, the GP Ibα extracellular domain is necessary and sufficient for interacting with vWF under high shear stress. Beads coated with the mutated fragment became tethered to vWF in greater number and had lower velocity of translocation than beads coated with the normal counterpart, suggesting that the G233V mutation lowers the rate of bond dissociation. Our findings define an approach for studying the biomechanical properties of the GP Ibα–vWF bond and suggest that this interaction is tightly regulated to allow rapid binding at sites of vascular injury, while permitting the concurrent presence of receptor and ligand in the circulation. PMID:10393908

30 CFR 57.22238 - Actions at 2.0 percent methane (I-B, II-B, V-B, and VI mines).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Actions at 2.0 percent methane (I-B, II-B, V-B, and VI mines). 57.22238 Section 57.22238 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION... Actions at 2.0 percent methane (I-B, II-B, V-B, and VI mines). If methane reaches 2.0 percent in the mine...

30 CFR 57.22231 - Actions at 0.25 percent methane (I-B, II-B, V-B, and VI mines).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Actions at 0.25 percent methane (I-B, II-B, V-B, and VI mines). 57.22231 Section 57.22231 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION... Actions at 0.25 percent methane (I-B, II-B, V-B, and VI mines). If methane reaches 0.25 percent in the...

30 CFR 57.22238 - Actions at 2.0 percent methane (I-B, II-B, V-B, and VI mines).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Actions at 2.0 percent methane (I-B, II-B, V-B... AND NONMETAL MINES Safety Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22238 Actions at 2.0 percent methane (I-B, II-B, V-B, and VI mines). If methane reaches 2.0 percent in the mine...

30 CFR 57.22231 - Actions at 0.25 percent methane (I-B, II-B, V-B, and VI mines).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Actions at 0.25 percent methane (I-B, II-B, V-B... AND NONMETAL MINES Safety Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22231 Actions at 0.25 percent methane (I-B, II-B, V-B, and VI mines). If methane reaches 0.25 percent in the...

Better Understanding and Recognition of the Disconnects, Experiences, and Needs of Patients with Irritable Bowel Syndrome with Constipation (BURDEN IBS-C) Study: Results of an Online Questionnaire.

PubMed

Quigley, Eamonn M M; Horn, John; Kissous-Hunt, Michele; Crozier, Robert A; Harris, Lucinda A

2018-06-26

The BURDEN IBS-C study was conducted to better understand the experiences, attitudes, and unmet needs of sufferers of irritable bowel syndrome with constipation (IBS-C) in comparison to the perceptions and challenges of healthcare providers (HCPs) who treat IBS-C patients. This was an author-developed, online questionnaire using KnowledgePanel ® to survey individuals with IBS-C (N = 1311). HCPs participated in a complementary online questionnaire and were recruited separately (N = 331). The study was fielded from June 29, 2016, to January 30, 2017. Most patients had used (86%) and/or were using (76%) over-the-counter treatments for their IBS-C, with 12% currently on prescription therapy. At the time this study was conducted, 66% and 63% were not satisfied/completely satisfied with over-the-counter or prescription treatment, respectively, citing inadequate efficacy (55%) and side effects (39%), most commonly diarrhea, as common reasons for dissatisfaction. IBS-C respondents most commonly reported feeling frustrated (43%) and stressed (28%) regarding IBS-C, though 39% were accepting of IBS-C as part of daily life. HCPs were aligned with patients in thinking that patients were frustrated (76%) and stressed (65%) but HCPs were less likely to recognize that patients had become accepting of their IBS-C (13%). Most HCPs (79%) were not satisfied/completely satisfied with the prescription treatments available at the time this study was conducted. Inadequate response rates to current therapies (55%) and treatment adherence/compliance issues (58%) were the most frequent challenges encountered by HCPs. IBS-C respondents reported that their symptoms impacted productivity and personal activity, on average, 4 and 3 days/month, respectively. These results suggest that current management pathways may not be adequately addressing the symptoms and needs of individuals with IBS-C, most notably side effects and lack of efficacy. Patients and HCPs expressed dissatisfaction

A Systematic Review of the Effectiveness of Psychological Treatments for IBS in Gastroenterology Settings: Promising but in Need of Further Study.

PubMed

Thakur, Elyse R; Shapiro, Jordan; Chan, Johanna; Lumley, Mark A; Cully, Jeffrey A; Bradford, Andrea; El-Serag, Hashem B

2018-05-10

Psychological treatments are efficacious for irritable bowel syndrome (IBS) in clinical trials; however, their effectiveness when conducted in gastroenterology practice settings is unclear. To perform a systematic review of the types and effects of psychological treatments for IBS conducted in gastroenterology clinics. We searched PubMed, EMBASE, and Cochrane central register. Studies conducted in gastroenterology clinic settings with IBS patients who were clinically referred from gastroenterology were included. We identified 3078 citations, of which only eight studies were eligible. Seven studies compared psychological treatments (average n = 25.7; range 12-43) to controls (average n = 25.4 patients; range 12-47), whereas one study compared two active "bonafide" interventions. Psychological treatments varied (cognitive-behavioral therapy, guided affective imagery, mindfulness, hypnosis, biofeedback, emotional awareness training). However, across approaches, short-term benefits were seen. IBS symptoms improved significantly among patients in cognitive and behavioral therapies, mindfulness-based stress reduction, guided affective imagery, and emotional awareness training compared with controls; there was a similar trend for gut-directed hypnotherapy. Similarly, IBS symptoms improved in a study of two active biofeedback and hypnosis treatments. Evidence for the effectiveness of psychological treatment in gastroenterology practice is promising but limited. Study designs that involve a blending of efficacy and effectiveness components are needed.

A Novel Spirooxindole Derivative Inhibits the Growth of Leishmania donovani Parasites both In Vitro and In Vivo by Targeting Type IB Topoisomerase

PubMed Central

Saha, Sourav; Acharya, Chiranjit; Pal, Uttam; Chowdhury, Somenath Roy; Sarkar, Kahini; Maiti, Nakul C.

2016-01-01

Visceral leishmaniasis is a fatal parasitic disease, and there is an emergent need for development of effective drugs against this neglected tropical disease. We report here the development of a novel spirooxindole derivative, N-benzyl-2,2′α-3,3′,5′,6′,7′,7α,α′-octahydro-2methoxycarbonyl-spiro[indole-3,3′-pyrrolizidine]-2-one (compound 4c), which inhibits Leishmania donovani topoisomerase IB (LdTopIB) and kills the wild type as well as drug-resistant parasite strains. This compound inhibits catalytic activity of LdTopIB in a competitive manner. Unlike camptothecin (CPT), the compound does not stabilize the DNA-topoisomerase IB cleavage complex; rather, it hinders drug-DNA-enzyme covalent complex formation. Fluorescence studies show that the stoichiometry of this compound binding to LdTopIB is 2:1 (mole/mole), with a dissociation constant of 6.65 μM. Molecular docking with LdTopIB using the stereoisomers of compound 4c produced two probable hits for the binding site, one in the small subunit and the other in the hinge region of the large subunit of LdTopIB. This spirooxindole is highly cytotoxic to promastigotes of L. donovani and also induces apoptosis-like cell death in the parasite. Treatment with compound 4c causes depolarization of mitochondrial membrane potential, formation of reactive oxygen species inside parasites, and ultimately fragmentation of nuclear DNA. Compound 4c also effectively clears amastigote forms of wild-type and drug-resistant parasites from infected mouse peritoneal macrophages but has less of an effect on host macrophages. Moreover, compound 4c showed strong antileishmanial efficacies in the BALB/c mouse model of leishmaniasis. This compound potentially can be used as a lead for developing excellent antileishmanial agents against emerging drug-resistant strains of the parasite. PMID:27503653

Adipokine profile in celiac patients: differences in comparison with patients suffering from diarrhea-predominant IBS and healthy subjects.

PubMed

Russo, Francesco; Chimienti, Guglielmina; Clemente, Caterina; D'Attoma, Benedetta; Linsalata, Michele; Orlando, Antonella; De Carne, Massimo; Cariola, Filomena; Semeraro, Francesco P; Pepe, Gabriella; Riezzo, Giuseppe

2013-12-01

OBJECTIVE. The role of adipokines such as resistin, leptin, and adiponectin could be pivotal in the molecular crosstalk between the inflamed intestine and the surrounding mesenteric adipose tissue. Our aims were to a) evaluate their circulating concentrations in patients with active celiac disease (ACD) and compare them to those in patients with diarrhea-predominant irritable bowel syndrome (IBS-d) and healthy subjects; b) establish the impact of genetic variability in resistin; and c) evaluate whether a 1-year gluten-free diet (GFD) modifies circulating concentrations of resistin, leptin, and adiponectin in celiac patients. MATERIAL AND METHODS. The study included 34 ACD patients, 29 IBS-d patients, and 27 healthy controls. Circulating concentrations of resistin, leptin, adiponectin, IL-6, and IL-8 were evaluated at the time of enrollment. Resistin +299 G/A polymorphism was also analysed. In CD patients, biochemical measurements were repeated after a 1-year GFD. RESULTS. Along with higher IL-6 and IL-8 plasma levels, higher resistin and adiponectin concentrations were found in ACD and IBS-d patients compared with controls (p: 0.0351 and p: 0.0020, respectively). Resistin values proved to be predictable from a linear combination of IL-8 and +299 polymorphism. GFD affected resistin (p: 0.0009), but not leptin and adiponectin concentrations. CONCLUSIONS. Our data suggest that these adipokines are involved in modulating inflammatory processes in both CD and IBS-d patients. Alterations in the adipokine profile as well as the higher prevalence of the resistin +299 G/A SNP A allele compared to controls support the hypothesis that, at least in well-defined cases of IBS, a genetic component may also be supposed.

Efficacy of combination therapy with probiotics and mosapride in patients with IBS without diarrhea: a randomized, double-blind, placebo-controlled, multicenter, phase II trial.

PubMed

Choi, C H; Kwon, J G; Kim, S K; Myung, S-J; Park, K S; Sohn, C-I; Rhee, P-L; Lee, K J; Lee, O Y; Jung, H-K; Jee, S R; Jeen, Y T; Choi, M-G; Choi, S C; Huh, K C; Park, H

2015-05-01

Probiotics can be beneficial in irritable bowel syndrome (IBS). Mosapride citrate, a selective 5-HT4 receptor agonist, stimulates gastrointestinal motility. We investigated the efficacy of combination therapy with probiotics and mosapride for non-diarrheal-type IBS. Two hundred and eighty-five IBS patients were randomly assigned to either a combination of probiotics (Bacillus subtilis and Streptococcus faecium) and mosapride at one of four different doses or a placebo for 4 weeks. The primary outcome was the proportion of patients experiencing adequate relief (AR) of global IBS symptoms at week 4. The secondary outcomes included subject's global assessment (SGA) of IBS symptom relief, individual symptoms, stool parameters, and IBS-quality of life. The proportion of AR at week 4 was significantly higher in all treatment groups compared to the placebo group (53.7% in group 1, 55.0% in group 2, 55.2% in group 3, 53.6% in group 4 [the highest dose], and 35.1% in placebo group, respectively, p < 0.05). The proportion of patients reporting 'completely or considerably relieved' in the SGA was higher in the treatment groups than in the placebo group. The abdominal pain/discomfort score in the treatment group 4 was more prominently improved compared with that of the placebo group. In patients with constipation-predominant IBS, the improvements in stool frequency and consistency were significantly higher in the treatment groups 4 and 1, respectively, than those in the placebo group. Combination therapy with probiotics and mosapride is effective for relief of symptoms in patients with non-diarrheal-type IBS. The study has been registered in the US National Library of Medicine (http://www.clinicaltrials.gov, NCT01505777). © 2015 John Wiley & Sons Ltd.

Sparing bilateral neck level IB in oropharyngeal carcinoma and xerostomia outcomes.

PubMed

Tam, Moses; Riaz, Nadeem; Kannarunimit, Danita; Peña, Angela P; Schupak, Karen D; Gelblum, Daphna Y; Wolden, Suzanne L; Rao, Shyam; Lee, Nancy Y

2015-08-01

To assess whether sparing neck-level IB in target delineation of node-positive (N+) oropharyngeal carcinoma (OPC) can improve xerostomia outcomes without compromising locoregional control (LRC). A total of 125 N+ OPC patients with a median age of 57 years underwent chemoradiation between May 2010 and December 2011. A total of 74% of patients had T1-T2 disease, 26% T3-T4, 16% N1, 8% N2A, 48% N2B, 28% N2C; 53% base of tongue, 41% tonsil, and 6% other. Patients were divided into those who had target delineation sparing of bilateral level IB (the spared cohort) versus no sparing (the treated cohort). Sparing of contralateral high-level II nodes was also performed more consistently in the spared cohort. A prospective xerostomia questionnaire (patient reported) was given at each patient follow-up visit to this cohort of patients to assess late xerostomia. Clinical assessment (observer rated) at each patient follow-up visit was also recorded. The 2-year LRC for the spared and treated cohorts was 97.5% and 93.8%, respectively (median follow-up, 23.2 mo). No locoregional failures occurred outside of treatment fields. The spared cohort experienced significant benefits in patient-reported xerostomia summary scores (P=0.021) and observer-rated xerostomia scores (P=0.006). In addition, there were significant reductions in mean doses to the ipsilateral submandibular gland (63.9 vs. 70.5 Gy; P<0.001), contralateral submandibular gland (45.0 vs. 56.2 Gy; P<0.001), oral cavity (35.9 vs. 45.2 Gy; P<0.001), and contralateral parotid gland (20.0 vs. 24.4 Gy; P<0.001). Target delineation sparing of bilateral level IB nodes in N+ OPC reduced mean doses to salivary organs without compromising LRC. Patients with reduced target volumes had better patient-reported xerostomia outcomes.

IBS and Potential Luminosity Improvement for RHIC Operation Below Transition Energy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fedotov,A.

There is a strong interest in low-energy RHIC operations in the single-beam total energy range of 2.5-25 GeV/nucleon [1-3]. Collisions in this energy range, much of which is below nominal RHIC injection energy, will help to answer one of the key questions in the field of QeD about the existence and location of a critical point on the QCD phase diagram [4]. There have been several short test runs during 2006-2008 RHIC operations to evaluate RHIC operational challenges at these low energies [5]. Beam lifetimes observed during the test runs were limited by machine nonlinearities. This performance limit can bemore » improved with sufficient machine tuning. The next luminosity limitation comes from transverse and longitudinal Intra-beam Scattering (IBS), and ultimately from the space-charge limit. Detailed discussion of limiting beam dynamics effects and possible luminosity improvement with electron cooling can be found in Refs. [6-8]. For low-energy RHIC operation, particle losses from the RF bucket are of particular concern since the longitudinal beam size is comparable to the existing RF bucket at low energies. However, operation below transition energy allows us to exploit an Intra-beam Scattering (IBS) feature that drives the transverse and longitudinal beam temperatures towards equilibrium by minimizing the longitudinal diffusion rate using a high RF voltage. Simulation studies were performed with the goal to understand whether one can use this feature of IBS to improve luminosity of RHIC collider at low-energies. This Note presents results of simulations which show that additional luminosity improvement for low-energy RHIC project may be possible with high RF voltage from a 56 MHz superconducting RF cavity that is presently under development for RHIC.« less

A recombinant Bacillus anthracis strain producing the Clostridium perfringens Ib component induces protection against iota toxins.

PubMed

Sirard, J C; Weber, M; Duflot, E; Popoff, M R; Mock, M

1997-06-01

The Bacillus anthracis toxinogenic Sterne strain is currently used as a live veterinary vaccine against anthrax. The capacity of a toxin-deficient derivative strain to produce a heterologous antigen by using the strong inducible promoter of the B. anthracis pag gene was investigated. The expression of the foreign gene ibp, encoding the Ib component of iota toxin from Clostridium perfringens, was analyzed. A pag-ibp fusion was introduced by allelic exchange into a toxin-deficient Sterne strain, thereby replacing the wild-type pag gene. This recombinant strain, called BAIB, was stable and secreted large quantities of Ib protein in induced culture conditions. Mice given injections of live BAIB spores developed an antibody response specific to the Ib protein. The pag-ibp fusion was therefore functional both in vitro and in vivo. Moreover, the immunized animals were protected against a challenge with C. perfringens iota toxin or with the homologous Clostridium spiroforme toxin. The protective immunity was mediated by neutralizing antibodies. In conclusion, B. anthracis is promising for the development of live veterinary vaccines.

A recombinant Bacillus anthracis strain producing the Clostridium perfringens Ib component induces protection against iota toxins.

PubMed Central

Sirard, J C; Weber, M; Duflot, E; Popoff, M R; Mock, M

1997-01-01

The Bacillus anthracis toxinogenic Sterne strain is currently used as a live veterinary vaccine against anthrax. The capacity of a toxin-deficient derivative strain to produce a heterologous antigen by using the strong inducible promoter of the B. anthracis pag gene was investigated. The expression of the foreign gene ibp, encoding the Ib component of iota toxin from Clostridium perfringens, was analyzed. A pag-ibp fusion was introduced by allelic exchange into a toxin-deficient Sterne strain, thereby replacing the wild-type pag gene. This recombinant strain, called BAIB, was stable and secreted large quantities of Ib protein in induced culture conditions. Mice given injections of live BAIB spores developed an antibody response specific to the Ib protein. The pag-ibp fusion was therefore functional both in vitro and in vivo. Moreover, the immunized animals were protected against a challenge with C. perfringens iota toxin or with the homologous Clostridium spiroforme toxin. The protective immunity was mediated by neutralizing antibodies. In conclusion, B. anthracis is promising for the development of live veterinary vaccines. PMID:9169728

The Association of Myosin IB with Actin Waves in Dictyostelium Requires Both the Plasma Membrane-Binding Site and Actin-Binding Region in the Myosin Tail

PubMed Central

Brzeska, Hanna; Pridham, Kevin; Chery, Godefroy; Titus, Margaret A.; Korn, Edward D.

2014-01-01

F-actin structures and their distribution are important determinants of the dynamic shapes and functions of eukaryotic cells. Actin waves are F-actin formations that move along the ventral cell membrane driven by actin polymerization. Dictyostelium myosin IB is associated with actin waves but its role in the wave is unknown. Myosin IB is a monomeric, non-filamentous myosin with a globular head that binds to F-actin and has motor activity, and a non-helical tail comprising a basic region, a glycine-proline-glutamine-rich region and an SH3-domain. The basic region binds to acidic phospholipids in the plasma membrane through a short basic-hydrophobic site and the Gly-Pro-Gln region binds F-actin. In the current work we found that both the basic-hydrophobic site in the basic region and the Gly-Pro-Gln region of the tail are required for the association of myosin IB with actin waves. This is the first evidence that the Gly-Pro-Gln region is required for localization of myosin IB to a specific actin structure in situ. The head is not required for myosin IB association with actin waves but binding of the head to F-actin strengthens the association of myosin IB with waves and stabilizes waves. Neither the SH3-domain nor motor activity is required for association of myosin IB with actin waves. We conclude that myosin IB contributes to anchoring actin waves to the plasma membranes by binding of the basic-hydrophobic site to acidic phospholipids in the plasma membrane and binding of the Gly-Pro-Gln region to F-actin in the wave. PMID:24747353

A kinetic clutch governs uncoiling by type IB topoisomerases

NASA Astrophysics Data System (ADS)

Neuman, Keir

2013-03-01

Type IB topoisomerases (Top1B) are essential enzymes that relax excessive DNA supercoiling associated with replication and transcription and are important drug targets for cancer chemotherapy. The natural compound camptothecin (CPT) and the cancer chemotherapeutics derived from it, irinotecan and topotecan, are highly specific inhibitors of human nuclear Type IB topoisomerase (nTop1). We employed a magnetic-tweezers based single-molecule DNA supercoil relaxation assay to measure the torque dependence of human nuclear Top1 relaxation (nTop1) and inhibition by CPT. For comparison, we examined the human mitochondrial (Top1mt) topoisomerase and an N-terminal deletion mutant of nTop1 (Top68). Despite substantial sequence homology in their core domains, nTop1 and Top1mt exhibit dramatic differences in sensitivity to torque and CPT, with Top68 betraying intermediate characteristics. In particular, nTop1 displays nearly torque-independent religation probability, distinguishing it from other Top1B enzymes studied to date. Kinetic modeling reveals a hitherto unobserved torque-independent transition linking the DNA rotation and religation phases of the enzymatic cycle. The parameters of this transition determine the torque sensitivity of religation, and the efficiency of CPT binding. This ``kinetic clutch'' mechanism explains the molecular basis of CPT sensitivity and more generally provides a framework with which to interpret Top1B activity and inhibition.

Deformation-related spectroscopic features in natural Type Ib-IaA diamonds from Zimmi (West African craton)

NASA Astrophysics Data System (ADS)

Smit, Karen V.; D'Haenens-Johansson, Ulrika F. S.; Howell, Daniel; Loudin, Lorne C.; Wang, Wuyi

2018-06-01

Zimmi diamonds (Sierra Leone) have 500 million year mantle residency times whose origin is best explained by rapid tectonic exhumation to shallower depths in the mantle, associated with continental collision but prior to kimberlite eruption. Here we present spectroscopic data for a new suite of Zimmi sulphide-bearing diamonds that allow us to evaluate the link between their spectroscopic features and their unusual geological history. Cathodoluminesence (CL) imaging of these diamonds revealed irregular patterns with abundant deformation lamellae, associated with the diamonds' tectonic exhumation. Vacancies formed during deformation were subsequently naturally annealed to form vacancy clusters, NV0/- centres and H3 (NVN0). The brownish-yellow to greenish-yellow colours observed in Zimmi Ib-IaA diamonds result from visible absorption by a combination of isolated substitutional nitrogen ( {N}S^0 ) and deformation-related vacancy clusters. Colour-forming centres and other spectroscopic features can all be attributed to the unique geological history of Zimmi Ib-IaA diamonds and their rapid exhumation after formation.

HD139614: the Interferometric Case for a Group-Ib Pre-Transitional Young Disk

NASA Technical Reports Server (NTRS)

Labadie, Lucas; Matter, Alexis; Kreplin, Alexander; Lopez, Bruno; Wolf, Sebastian; Weigelt, Gerd; Ertel, Steve; Berger, Jean-Philippe; Pott, Jorg-Uwe; Danchi, William C.

2014-01-01

The Herbig Ae star HD139614 is a group-Ib object, which featureless SED indicates disk flaring and a possible pre-transitional evolutionary stage. We present mid- and near-IR interferometric results collected with MIDI, AMBER and PIONIER with the aim of constraining the spatial structure of the 0.1-10 AU disk region and assess its possible multi-component structure. A two-component disk model composed of an optically thin 2-AU wide inner disk and an outer temperature-gradient disk starting at 5.6 AU reproduces well the observations. This is an additional argument to the idea that group-I HAeBe inner disks could be already in the disk-clearing transient stage. HD139614 will become a prime target for mid-IR interferometric imaging with the second-generation instrument MATISSE of the VLTI.

A study of the methodological and clinical validity of the combined lactulose hydrogen breath test with scintigraphic oro-cecal transit test for diagnosing small intestinal bacterial overgrowth in IBS patients.

PubMed

Zhao, J; Zheng, X; Chu, H; Zhao, J; Cong, Y; Fried, M; Fox, M; Dai, N

2014-06-01

Small intestinal bacterial overgrowth (SIBO) may be a cause of irritable bowel syndrome (IBS); however, current investigations have important limitations. We aimed to identify clinically relevant diagnostic criteria for SIBO based on lactulose hydrogen breath test (LHBT) alone and combined with scintigraphic measurement of oro-cecal transit (SOCT). Results of LHBT/SOCT investigation from 89 IBS patients and 13 healthy volunteers were included in a systematic analysis of six published criteria for SIBO diagnosis. Clinical relevance of competing criteria was determined by assessing (i) prevalence of SIBO in IBS patients and healthy volunteers (ii) if SIBO diagnosis predicted improvement in IBS symptoms in a prospective, pilot therapeutic trial of a non-absorbable antibiotic (rifaximin 600 mg b.d.) in IBS patients. Reproducibility of SIBO diagnosis by combined LHBT/SOCT was near perfect. A ≥5 ppm H2 increase prior to appearance of cecal contrast was detected in more IBS patients than healthy volunteers (35/89 vs 1/13; p = 0.026), but not for other diagnostic criteria. IBS patients with SIBO, compared to those without SIBO, reported significantly greater improvement in abdominal symptoms following rifaximin therapy (p < 0.002 overall IBS symptom severity). This improvement was most marked in D-IBS patients in whom all symptoms improved, including stool frequency and consistency (all p < 0.004). Combined LHBT/SOCT testing using a H2 5 ppm cutoff may identify a subgroup of IBS patients with SIBO. Pilot data examining the clinical response to rifaximin suggest that this subset of IBS patients may benefit more than those with a normal test. © 2014 John Wiley & Sons Ltd.

Post-infectious irritable bowel syndrome (PI-IBS) after infection with Shiga-like toxin-producing Escherichia coli (STEC) O104:H4: A cohort study with prospective follow-up.

PubMed

Andresen, Viola; Löwe, Bernd; Broicher, Wiebke; Riegel, Björn; Fraedrich, Katharina; von Wulffen, Moritz; Gappmayer, Kerrin; Wegscheider, Karl; Treszl, András; Rose, Matthias; Layer, Peter; Lohse, Ansgar W

2016-02-01

In May/June 2011, the new Shiga-like toxin-producing Escherichia coli (STEC) strain O104:H4 caused the severest outbreak ever recorded of hemorrhagic enterocolitis in 3842 patients in Germany. As bacterial enterocolitis is an established risk factor of subsequent irritable bowel syndrome (IBS), we aimed to estimate prevalence and incidence of post-infectious (PI)-IBS after six and 12 months in a cohort of STEC O104:H4 patients and to prospectively identify associated somatic and psychometric risk factors. A total of 389 patients were studied prospectively at baseline and at six and 12 months after STEC infection using STEC disease-related questionnaires and validated instruments for IBS (Rome III) and psychological factors. Frequencies and logistic regression models using multiple imputations were applied to assess predictor variables. Prevalence of IBS increased from 9.8% prior to STEC infection to 23.6% at six and 25.3% at 12 months after STEC infection. In patients without IBS symptoms prior to STEC infection, incidence of new IBS was 16.9%. Logistic regression models indicated higher somatization and anxiety scores as risk factors for, and mesalazine treatment during, STEC infection as the only significant protective factor against IBS. No other factor analyzed, including disease severity, showed an association. PI-IBS rates following this unusually severe STEC outbreak were similar to what has been observed after other infectious gastroenteritis outbreaks. Our findings suggest that mesalazine may have reduced the risk of subsequent PI-IBS. As altered mucosal immune activity is a pivotal pathogenic factor in PI-IBS, our observation of a potential protective effect of mesalazine might be explained by its known modulatory action on mucosal immunity, and may warrant further investigation.

Post-infectious irritable bowel syndrome (PI-IBS) after infection with Shiga-like toxin-producing Escherichia coli (STEC) O104:H4: A cohort study with prospective follow-up

PubMed Central

Löwe, Bernd; Broicher, Wiebke; Riegel, Björn; Fraedrich, Katharina; von Wulffen, Moritz; Gappmayer, Kerrin; Wegscheider, Karl; Treszl, András; Rose, Matthias; Layer, Peter; Lohse, Ansgar W

2015-01-01

Background In May/June 2011, the new Shiga-like toxin-producing Escherichia coli (STEC) strain O104:H4 caused the severest outbreak ever recorded of hemorrhagic enterocolitis in 3842 patients in Germany. Objectives As bacterial enterocolitis is an established risk factor of subsequent irritable bowel syndrome (IBS), we aimed to estimate prevalence and incidence of post-infectious (PI)-IBS after six and 12 months in a cohort of STEC O104:H4 patients and to prospectively identify associated somatic and psychometric risk factors. Methods A total of 389 patients were studied prospectively at baseline and at six and 12 months after STEC infection using STEC disease-related questionnaires and validated instruments for IBS (Rome III) and psychological factors. Frequencies and logistic regression models using multiple imputations were applied to assess predictor variables. Results Prevalence of IBS increased from 9.8% prior to STEC infection to 23.6% at six and 25.3% at 12 months after STEC infection. In patients without IBS symptoms prior to STEC infection, incidence of new IBS was 16.9%. Logistic regression models indicated higher somatization and anxiety scores as risk factors for, and mesalazine treatment during, STEC infection as the only significant protective factor against IBS. No other factor analyzed, including disease severity, showed an association. Conclusions PI-IBS rates following this unusually severe STEC outbreak were similar to what has been observed after other infectious gastroenteritis outbreaks. Our findings suggest that mesalazine may have reduced the risk of subsequent PI-IBS. As altered mucosal immune activity is a pivotal pathogenic factor in PI-IBS, our observation of a potential protective effect of mesalazine might be explained by its known modulatory action on mucosal immunity, and may warrant further investigation. PMID:26966532

Activation of the endogenous nociceptin system by selective nociceptin receptor agonist SCH 221510 produces antitransit and antinociceptive effect: a novel strategy for treatment of diarrhea-predominant IBS.

PubMed

Fichna, J; Sobczak, M; Mokrowiecka, A; Cygankiewicz, A I; Zakrzewski, P K; Cenac, N; Sałaga, M; Timmermans, J-P; Vergnolle, N; Małecka-Panas, E; Krajewska, W M; Storr, M

2014-11-01

Diarrhea-predominant irritable bowel syndrome (IBS-D) is a functional gastrointestinal (GI) disorder, defined by the presence of loose stools and abdominal pain. In search for a novel anti-IBS-D therapy, here we investigated the nociceptin receptor (NOP)-dependent effects in the GI tract. A novel potent and selective NOP agonist SCH 221510 was used in the study. The effect of NOP activation on mouse intestinal motility was characterized in vitro and in vivo, in physiological conditions and in animal models of hypermotility and diarrhea. Well-established mouse models of visceral pain were used to characterize the antinociceptive effect of the NOP activation. To provide additional evidence that the endogenous nociceptin system is a relevant target for IBS, NOP expression and nociceptin levels were quantified in serum and colonic biopsies from IBS-D patients. SCH 221510 produced a potent NOP-mediated inhibitory effect on mouse intestinal motility in vitro and in vivo in physiological conditions. The NOP agonist displayed an antidiarrheal and analgesic action after oral administration in animal models mimicking the symptoms of IBS-D. Studies on human samples revealed a strong decrease in endogenous nociceptin system expression in IBS-D patients compared with healthy controls. Collectively, mouse and human data suggest that the endogenous nociceptin system is involved in IBS-D and may become a target for anti-IBS-D treatments using potent and selective synthetic NOP agonists. © 2014 John Wiley & Sons Ltd.

Key role of glycoprotein Ib/V/IX and von Willebrand factor in platelet activation-dependent fibrin formation at low shear flow

PubMed Central

Cosemans, Judith M. E. M.; Schols, Saskia E. M.; Stefanini, Lucia; de Witt, Susanne; Feijge, Marion A. H.; Hamulyák, Karly; Deckmyn, Hans; Bergmeier, Wolfgang

2011-01-01

A microscopic method was developed to study the role of platelets in fibrin formation. Perfusion of adhered platelets with plasma under coagulating conditions at a low shear rate (250−1) resulted in the assembly of a star-like fibrin network at the platelet surface. The focal fibrin formation on platelets was preceded by rises in cytosolic Ca2+, morphologic changes, and phosphatidylserine exposure. Fibrin formation was slightly affected by αIIbβ3 blockage, but it was greatly delayed and reduced by the following: inhibition of thrombin or platelet activation; interference in the binding of von Willebrand factor (VWF) to glycoprotein Ib/V/IX (GpIb-V-IX); plasma or blood from patients with type 1 von Willebrand disease; and plasma from mice deficient in VWF or the extracellular domain of GpIbα. In this process, the GpIb-binding A1 domain of VWF was similarly effective as full-length VWF. Prestimulation of platelets enhanced the formation of fibrin, which was abrogated by blockage of phosphatidylserine. Together, these results show that, in the presence of thrombin and low shear flow, VWF-induced activation of GpIb-V-IX triggers platelet procoagulant activity and anchorage of a star-like fibrin network. This process can be relevant in hemostasis and the manifestation of von Willebrand disease. PMID:21037087

Poor predictive value of breath hydrogen response for probiotic effects in IBS.

PubMed

Yao, Chu K; Barrett, Jacqueline S; Philpott, Hamish; Chung, Alvin R T; van Langenberg, Daniel; Garg, Mayur; Gibson, Peter R

2015-12-01

Previous observations suggested that an early rise in breath hydrogen after lactulose (ERBHAL) may identify patients with irritable bowel syndrome (IBS) likely to respond to probiotics. Therefore, we aimed to (i) investigate whether treatment with a probiotic changes breath hydrogen response in patients with ERBHAL and (ii) whether these changes identify patients who may benefit symptomatically from probiotics. In a randomized, double-blind, placebo-controlled trial, patients with IBS (Rome III) were randomized to either 65 mL/day fermented milk product containing probiotic (FMPP) or placebo for 6 weeks, followed by 6 weeks' open-label treatment and 6 weeks' withdrawal. Breath hydrogen responses to lactulose (15 g) and liquid-gastric emptying time were evaluated before and at the end of each treatment period. Symptoms were measured using a 100-mm visual analog scale. Loss of ERBHAL occurred in 36% of 23 patients receiving FMPP and 41% of 22 receiving placebo (P = 1.00). Amongst 40 patients who completed open-label FMPP treatment, ERBHAL was lost in a further 38%, continued in 25%, and regained in 10%. Similar variability occurred in the withdrawal phase. Variability was unrelated to changes in gastric emptying. No differences in symptom response were seen between treatment groups nor in relation to the loss or retention of ERBHAL. Breath hydrogen patterns after lactulose are poorly reproducible. No FMPP-specific effects on fermentation patterns or symptoms were observed. The presence of ERBHAL is not useful to predict symptomatic response to probiotic therapy in patients with IBS. © 2015 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

Beyond abuse: the association among parenting style, abdominal pain, and somatization in IBS patients.

PubMed

Lackner, Jeffrey M; Gudleski, Gregory D; Blanchard, Edward B

2004-01-01

This study assessed the relative strength of the association between abuse, negative parenting style, and somatization in irritable bowel syndrome (IBS) patients. Drawing from preclinical stress physiology and abuse research identifying the family social climate as a frequently stronger and independent determinant of long-term health effects than abuse-specific variables, we predicted that negative parenting behaviors would more strongly correlate with somatization than abuse. Subjects were 81 consecutively evaluated patients, who at baseline underwent psychological testing, measuring perceived parental style, abuse history, somatization, and pain. Although abuse correlated with maternal and paternal rejection, abuse was not associated with somatization. Higher levels of rejection and/or hostility among fathers (not mothers) were more strongly correlated with somatization than was abuse. Further, paternal parenting behaviors were more predictive of somatization than abuse, age, and gender. The lack of an association between abuse and somatization is discussed in light of limitations of biopsychosocial IBS models, whose strong focus on "pathological stressors" (e.g., abuse, trauma) as risk factors may overlook the importance of "less extreme" parenting variables in influencing somatic complaints. The relationship between parenting and somatization is discussed in the context of broader behavioral science research linking disruptions in the quality of parenting to dramatic and long-term changes in patterns of stress reactivity and brain abnormalities seen in IBS patients.

Diagnostic accuracy of enzyme-linked immunosorbent assay (ELISA) and immunoblot (IB) for the detection of antibodies against Neospora caninum in milk from dairy cows.

PubMed

Chatziprodromidou, I P; Apostolou, T

2018-04-01

The aim of the study was to estimate the sensitivity and specificity of enzyme-linked immunosorbent assay (ELISA) and immunoblot (IB) for detecting antibodies of Neospora caninum in dairy cows, in the absence of a gold standard. The study complies with STRADAS-paratuberculosis guidelines for reporting the accuracy of the test. We tried to apply Bayesian models that do not require conditional independence of the tests under evaluation, but as convergence problems appeared, we used Bayesian methodology, that does not assume conditional dependence of the tests. Informative prior probability distributions were constructed, based on scientific inputs regarding sensitivity and specificity of the IB test and the prevalence of disease in the studied populations. IB sensitivity and specificity were estimated to be 98.8% and 91.3%, respectively, while the respective estimates for ELISA were 60% and 96.7%. A sensitivity analysis, where modified prior probability distributions concerning IB diagnostic accuracy applied, showed a limited effect in posterior assessments. We concluded that ELISA can be used to screen the bulk milk and secondly, IB can be used whenever needed.

Opsonophagocytic Antibodies to Serotype Ia, Ib, and III Group B Streptococcus among Korean Infants and in Intravenous Immunoglobulin Products.

PubMed

Kim, Han Wool; Lee, Ji Hyen; Cho, Hye Kyung; Lee, Hyunju; Seo, Ho Seong; Lee, Soyoung; Kim, Kyung Hyo

2017-05-01

Group B streptococcus (GBS) infection is a leading cause of sepsis and meningitis among infants, and is associated with high rates of morbidity and mortality in many countries. Protection against GBS typically involves antibody-mediated opsonization by phagocytes and complement components. The present study evaluated serotype-specific functional antibodies to GBS among Korean infants and in intravenous immunoglobulin (IVIG) products. An opsonophagocytic killing assay (OPA) was used to calculate the opsonization indices (OIs) of functional antibodies to serotypes Ia, Ib, and III in 19 IVIG products from 5 international manufacturers and among 98 Korean infants (age: 0-11 months). The GBS Ia, Ib, and III serotypes were selected because they are included in a trivalent GBS vaccine formulation that is being developed. The OI values for the IVIG products were 635-5,706 (serotype Ia), 488-1,421 (serotype Ib), and 962-3,315 (serotype III), and none of the IVIG lots exhibited undetectable OI values (< 4). The geometric mean OI values were similar for all 3 serotypes when we compared the Korean manufacturers. The seropositive rate among infants was significantly lower for serotype Ia (18.4%), compared to serotype Ib and serotype III (both, 38.8%). Infant age of ≥ 3 months was positively correlated with the seropositive rates for each serotype. Therefore, only a limited proportion of infants exhibited protective immunity against serotype Ia, Ib, and III GBS infections. IVIG products that exhibit high antibody titers may be a useful therapeutic or preventive measure for infants. Further studies are needed to evaluate additional serotypes and age groups. © 2017 The Korean Academy of Medical Sciences.

Opsonophagocytic Antibodies to Serotype Ia, Ib, and III Group B Streptococcus among Korean Infants and in Intravenous Immunoglobulin Products

PubMed Central

2017-01-01

Group B streptococcus (GBS) infection is a leading cause of sepsis and meningitis among infants, and is associated with high rates of morbidity and mortality in many countries. Protection against GBS typically involves antibody-mediated opsonization by phagocytes and complement components. The present study evaluated serotype-specific functional antibodies to GBS among Korean infants and in intravenous immunoglobulin (IVIG) products. An opsonophagocytic killing assay (OPA) was used to calculate the opsonization indices (OIs) of functional antibodies to serotypes Ia, Ib, and III in 19 IVIG products from 5 international manufacturers and among 98 Korean infants (age: 0–11 months). The GBS Ia, Ib, and III serotypes were selected because they are included in a trivalent GBS vaccine formulation that is being developed. The OI values for the IVIG products were 635–5,706 (serotype Ia), 488–1,421 (serotype Ib), and 962–3,315 (serotype III), and none of the IVIG lots exhibited undetectable OI values (< 4). The geometric mean OI values were similar for all 3 serotypes when we compared the Korean manufacturers. The seropositive rate among infants was significantly lower for serotype Ia (18.4%), compared to serotype Ib and serotype III (both, 38.8%). Infant age of ≥ 3 months was positively correlated with the seropositive rates for each serotype. Therefore, only a limited proportion of infants exhibited protective immunity against serotype Ia, Ib, and III GBS infections. IVIG products that exhibit high antibody titers may be a useful therapeutic or preventive measure for infants. Further studies are needed to evaluate additional serotypes and age groups. PMID:28378545

Acetylation of TAF(I)68, a subunit of TIF-IB/SL1, activates RNA polymerase I transcription.

PubMed

Muth, V; Nadaud, S; Grummt, I; Voit, R

2001-03-15

Mammalian rRNA genes are preceded by a terminator element that is recognized by the transcription termination factor TTF-I. In exploring the functional significance of the promoter-proximal terminator, we found that TTF-I associates with the p300/CBP-associated factor PCAF, suggesting that TTF-I may target histone acetyltransferase to the rDNA promoter. We demonstrate that PCAF acetylates TAF(I)68, the second largest subunit of the TATA box-binding protein (TBP)-containing factor TIF-IB/SL1, and acetylation enhances binding of TAF(I)68 to the rDNA promoter. Moreover, PCAF stimulates RNA polymerase I (Pol I) transcription in a reconstituted in vitro system. Consistent with acetylation of TIF-IB/SL1 being required for rDNA transcription, the NAD(+)-dependent histone deacetylase mSir2a deacetylates TAF(I)68 and represses Pol I transcription. The results demonstrate that acetylation of the basal Pol I transcription machinery has functional consequences and suggest that reversible acetylation of TIF-IB/SL1 may be an effective means to regulate rDNA transcription in response to external signals.

`Science to the Glory of God'. The Popular Science Magazine Ibérica and its Coverage of Radioactivity, 1914-1936

NASA Astrophysics Data System (ADS)

Herran, Néstor

2012-03-01

This paper provides a first approach to the history of Ibérica, one of the most important popular science magazines published in Spain before the Civil War. Founded in 1914 by members of the Society of Jesus based at the Ebro Observatory, Ibérica reached a weekly circulation of about 10,000 in the mid 1920s, and was instrumental in extending science education in Jesuit education facilities and in developing a "reactionary modernist" culture that embraced Catholicism and modernisation. By focusing on its coverage of radioactivity and the radium industry, the article aims to examine the magazine's popularising style and ideology, and to determine its role in the debates regarding the cultural value of science in the first decades of twentieth century Spain.

Analysis of results of radiation therapy for stage IB carcinoma of the cervix.

PubMed

Montana, G S; Fowler, W C; Varia, M A; Walton, L A; Mack, Y

1987-11-01

From April of 1969 through December of 1980, 197 patients with Stage IB, invasive, epidermoid carcinoma of the cervix received radical radiation therapy. The treatment consisted of external beam and intracavitary therapy designed to deliver 7000 to 8000 rad to Point A and 5000 to 5500 rad to the pelvic lymph nodes. The 2-, 5-, and 10-year, disease-free survival rates were 87%, 83%, and 81%, respectively. Thirty-six patients developed recurrent and/or metastatic disease. The sites that failed to remain disease-free were: locoregional in five patients (3%), locoregional with distant metastases in 15 patients (8%), and distant metastases only in 14 patients (7%). In addition, there were two patients (1%) who are considered to have died of disease but the site or sites of recurrence could not be determined. Thirty-nine patients developed complications. The complications were mild and self-limiting--Grade I--in 24 patients (12%) and of moderate severity--Grade II--in eight patients (4%). Seven patients (4%) developed severe--Grade III--complications. A correlation was found between the dose to Point A, the bladder, and the rectum and the complications. The mean dose to Point A for patients without and with complications were 7453 rad (SE +/- 91) and 7737 (SE +/- 124), respectively, with a P value of .05. The mean dose to the bladder for patients without and with urinary complications was 5590 rad (SE +/- 103) and 6335 rad (SE +/- 411), respectively, with a P value of 0.14. The mean dose to the rectum for patients without and with intestinal complications was 5837 rad (SE +/- 103) and 6810 rad (SE +/- 236), respectively, with a P value of 0.001. No correlation was found between the dose to Point A and locoregional recurrences.

Instrumentation and monitoring of rustic road geosynthetic reinforced soil (GRS) integrated bridge system (IBS).

DOT National Transportation Integrated Search

2016-11-01

J. Erik Loehr ; orcid.org/0000-0001-6035-8416 : An instrumentation and monitoring system was implemented for a geosynthetic reinforced soil (GRS) integrated bridge : system (IBS) constructed in Boone County, Missouri in 2014. The project location is ...

Sparing Bilateral Neck Level IB in Oropharyngeal Carcinoma and Xerostomia Outcomes

PubMed Central

Tam, Moses; Riaz, Nadeem; Kannarunimit, Danita; Peña, Angela P.; Schupak, Karen D.; Gelblum, Daphna Y.; Wolden, Suzanne L.; Rao, Shyam; Lee, Nancy Y.

2017-01-01

Objectives To assess whether sparing neck level IB in target delineation of node positive (N+) oropharyngeal carcinoma (OPC) can improve xerostomia outcomes without compromising local-regional control (LRC). Methods 125 N+ OPC patients with a median age of 57 years underwent chemoradiation between 5/10 and 12/11. 74% of patients had T1-2 disease, 26% T3-4, 16% N1, 8% N2A, 48% N2B, 28% N2C; 53% base of tongue, 41% tonsil, and 6% other. Patients were divided into those who had target delineation sparing of bilateral level IB (the spared cohort) vs. no sparing (the treated cohort). Sparing of contralateral high level II nodes was also performed more consistently in the spared cohort. A prospective xerostomia questionnaire (patient reported) was given at each patient follow-up visit to this cohort of patients to assess late xerostomia. Clinical assessment (observer rated) at each patient follow-up visit was also recorded. Results The 2-year LRC for the spared and treated cohorts was 97.5% and 93.8%, respectively (median follow-up, 23.2 months). No local-regional failures occurred outside of treatment fields. The spared cohort experienced significant benefits in patient-reported xerostomia summary scores (P = 0.021) and observer-rated xerostomia scores (P = 0.006). In addition, there were significant reductions in mean doses to the ipsilateral submandibular gland (SMG; 63.9 Gy vs. 70.5 Gy; P < 0.001), contralateral SMG (45.0 Gy vs. 56.2 Gy; P < 0.001), oral cavity (35.9 Gy vs. 45.2 Gy; P < 0.001), and contralateral parotid gland (20.0 Gy vs. 24.4 Gy; P < 0.001). Conclusions Target delineation sparing of bilateral level IB nodes in N+ OPC reduced mean doses to salivary organs without compromising LRC. Patients with reduced target volumes had better patient-reported xerostomia outcomes. PMID:26208401

Photodynamic therapy with 3-(1'-hexyloxyethyl) pyropheophorbide-a for early-stage cancer of the larynx: Phase Ib study.

PubMed

Shafirstein, Gal; Rigual, Nestor R; Arshad, Hassan; Cooper, Michele T; Bellnier, David A; Wilding, Gregory; Tan, Wei; Merzianu, Mihai; Henderson, Barbara W

2016-04-01

The purpose of this study was for us to report results regarding the safety of 3-(1'-hexyloxyethyl) pyropheophorbide-a (HPPH) mediated photodynamic therapy (PDT) in early laryngeal disease, and offer preliminary information on treatment responses. A single-institution, phase Ib, open label, noncomparative study of HPPH-PDT in patients with high-risk dysplasia, carcinoma in situ, and T1 squamous cell carcinoma (SCC) of the larynx. The primary outcomes were safety and maximum tolerated dose (MTD), and the secondary outcome was response. Twenty-nine patients and 30 lesions were treated. The most common adverse event (AE) was transient hoarseness of voice. Severe edema, requiring tracheostomy, was the most serious AE, which occurred in 2 patients within several hours of therapy. The MTD was 100 J/cm(2) . Patients with T1 SCC seemed to have good complete response rate (82%) to HPPH-PDT at MTD. HPPH-PDT can be safely used to treat early-stage laryngeal cancer, with potential efficacy. © 2015 The Authors Head & Neck Published by Wiley Periodicals, Inc. Head Neck 38: E377-E383, 2016. © 2015 The Authors Head & Neck Published by Wiley Periodicals, Inc.

Gastrointestinal (GI) permeability correlates with trait anxiety and urinary norepinephrine/creatinine (CR)ratio in children with functional abdominal pain (FAP)and irritable bowel syndrome (IBS) but not in controls

USDA-ARS?s Scientific Manuscript database

FAP and IBS affect 10–15% of school age children and bear many similarities to irritable bowel syndrome (IBS) in adults (e.g., functional pain, visceral hyperalgesia). Animal models of IBS have suggested a relationship between neonatal stress/anxiety and increased GI permeability later in life. We h...

30 CFR 57.22222 - Ventilation materials (I-A, I-B, I-C, II-A, III, V-A, and V-B mines).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Ventilation materials (I-A, I-B, I-C, II-A, III, V-A, and V-B mines). 57.22222 Section 57.22222 Mineral Resources MINE SAFETY AND HEALTH....22222 Ventilation materials (I-A, I-B, I-C, II-A, III, V-A, and V-B mines). Brattice cloth and...

30 CFR 57.22222 - Ventilation materials (I-A, I-B, I-C, II-A, III, V-A, and V-B mines).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Ventilation materials (I-A, I-B, I-C, II-A, III, V-A, and V-B mines). 57.22222 Section 57.22222 Mineral Resources MINE SAFETY AND HEALTH....22222 Ventilation materials (I-A, I-B, I-C, II-A, III, V-A, and V-B mines). Brattice cloth and...

30 CFR 57.22234 - Actions at 1.0 percent methane (I-A, I-B, III, V-A, and V-B mines).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Actions at 1.0 percent methane (I-A, I-B, III...-UNDERGROUND METAL AND NONMETAL MINES Safety Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22234 Actions at 1.0 percent methane (I-A, I-B, III, V-A, and V-B mines). (a) If methane reaches 1.0...

IB2d: a Python and MATLAB implementation of the immersed boundary method.

PubMed

Battista, Nicholas A; Strickland, W Christopher; Miller, Laura A

2017-03-29

The development of fluid-structure interaction (FSI) software involves trade-offs between ease of use, generality, performance, and cost. Typically there are large learning curves when using low-level software to model the interaction of an elastic structure immersed in a uniform density fluid. Many existing codes are not publicly available, and the commercial software that exists usually requires expensive licenses and may not be as robust or allow the necessary flexibility that in house codes can provide. We present an open source immersed boundary software package, IB2d, with full implementations in both MATLAB and Python, that is capable of running a vast range of biomechanics models and is accessible to scientists who have experience in high-level programming environments. IB2d contains multiple options for constructing material properties of the fiber structure, as well as the advection-diffusion of a chemical gradient, muscle mechanics models, and artificial forcing to drive boundaries with a preferred motion.

Rapid detection of AAC(6')-Ib-cr production using a MALDI-TOF MS strategy.

PubMed

Pardo, C-A; Tan, R N; Hennequin, C; Beyrouthy, R; Bonnet, R; Robin, F

2016-12-01

Plasmid-mediated quinolone resistance mechanisms have become increasingly prevalent among Enterobacteriaceae strains since the 1990s. Among these mechanisms, AAC(6')-Ib-cr is the most difficult to detect. Different detection methods have been developed, but they require expensive procedures such as Sanger sequencing, pyrosequencing, polymerase chain reaction (PCR) restriction, or the time-consuming phenotypic method of Wachino. In this study, we describe a simple matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) method which can be easily implemented in clinical laboratories that use the MALDI-TOF technique for bacterial identification. We tested 113 strains of Enterobacteriaceae, of which 64 harbored the aac(6')-Ib-cr gene. We compared two MALDI-TOF strategies, which differed by their norfloxacin concentration (0.03 vs. 0.5 g/L), and the method of Wachino with the PCR and sequencing strategy used as the reference. The MALDI-TOF strategy, performed with 0.03 g/L norfloxacin, and the method of Wachino yielded the same high performances (Se = 98 %, Sp = 100 %), but the turnaround time of the MALDI-TOF strategy was faster (<5 h), simpler, and inexpensive (<1 Euro). Our study shows that the MALDI-TOF strategy has the potential to become a major method for the detection of many different enzymatic resistance mechanisms.

The Double-peaked SN 2013ge: A Type Ib/c SN with an Asymmetric Mass Ejection or an Extended Progenitor Envelope

NASA Astrophysics Data System (ADS)

Drout, M. R.; Milisavljevic, D.; Parrent, J.; Margutti, R.; Kamble, A.; Soderberg, A. M.; Challis, P.; Chornock, R.; Fong, W.; Frank, S.; Gehrels, N.; Graham, M. L.; Hsiao, E.; Itagaki, K.; Kasliwal, M.; Kirshner, R. P.; Macomb, D.; Marion, G. H.; Norris, J.; Phillips, M. M.

2016-04-01

We present extensive multiwavelength (radio to X-ray) observations of the Type Ib/c supernova (SN Ib/c) SN 2013ge from -13 to +457 days relative to maximum light, including a series of optical spectra and Swift UV-optical photometry beginning 2-4 days post-explosion. This data set makes SN 2013ge one of the best-observed normal SNe Ib/c at early times—when the light curve is particularly sensitive to the progenitor configuration and mixing of radioactive elements—and reveals two distinct light curve components in the UV bands. The first component rises over 4-5 days and is visible for the first week post-explosion. Spectra of the first component have blue continua and show a plethora of moderately high velocity (˜15,000 km s-1) but narrow (˜3500 km s-1) spectroscopic features, indicating that the line-forming region is restricted. The explosion parameters estimated for the bulk explosion ({M}{{ej}} ˜ 2-3 {M}⊙ ; {E}{{K}} ˜ (1-2) × 1051 erg) are standard for SNe Ib/c, and there is evidence for weak He features at early times—in an object that would have otherwise been classified as Type Ic. In addition, SN 2013ge exploded in a low-metallicity environment (˜0.5 {Z}⊙ ), and we have obtained some of the deepest radio and X-ray limits for an SN Ib/c to date, which constrain the progenitor mass-loss rate to be \\dot{M} < 4 × 10-6 {M}⊙ yr-1. We are left with two distinct progenitor scenarios for SN 2013ge, depending on our interpretation of the early emission. If the first component is cooling envelope emission, then the progenitor of SN 2013ge either possessed an extended (≳30 {R}⊙ ) envelope or ejected a portion of its envelope in the final ≲ 1 yr before core collapse. Alternatively, if the first component is due to outwardly mixed 56Ni, then our observations are consistent with the asymmetric ejection of a distinct clump of nickel-rich material at high velocities. Current models for the collision of an SN shock with a binary companion cannot

The Double-Peaked SN 2013ge: A Type Ib/c Sn with an Asymmetric Mass Ejection or an Extended Progenitor Envelope

NASA Technical Reports Server (NTRS)

Drout, M. R.; Milisavjlevic, D.; Parrent, J.; Margutti, R.; Kamble, A.; Soderberg, A.M.; Challis, P.; Chornock, P.; Fong, W.; Frank, S.;

Gut Microbiota Dysbiosis as Risk and Premorbid Factors of IBD and IBS Along the Childhood-Adulthood Transition.

PubMed

Putignani, Lorenza; Del Chierico, Federica; Vernocchi, Pamela; Cicala, Michele; Cucchiara, Salvatore; Dallapiccola, Bruno

2016-02-01

Gastrointestinal disorders, although clinically heterogeneous, share pathogenic mechanisms, including genetic susceptibility, impaired gut barrier function, altered microbiota, and environmental triggers (infections, social and behavioral factors, epigenetic control, and diet). Gut microbiota has been studied for inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) in either children or adults, while modifiable gut microbiota features, acting as risk and premorbid factors along the childhood-adulthood transition, have not been thoroughly investigated so far. Indeed, the relationship between variations of the entire host/microbiota/environmental scenario and clinical phenotypes is still not fully understood. In this respect, tracking gut dysbiosis grading may help deciphering host phenotype-genotype associations and microbiota shifts in an integrated top-down omics-based approach within large-scale pediatric and adult case-control cohorts. Large-scale gut microbiota signatures and host inflammation patterns may be integrated with dietary habits, under genetic and epigenetic constraints, providing gut dysbiosis profiles acting as risk predictors of IBD or IBS in preclinical cases. Tracking dysbiosis supports new personalized/stratified IBD and IBS prevention programmes, generating Decision Support System tools. They include (1) high risk or flare-up recurrence -omics-based dysbiosis profiles; (2) microbial and molecular biomarkers of health and disease; (3) -omics-based pipelines for laboratory medicine diagnostics; (4) health apps for self-management of score-based dietary profiles, which can be shared with clinicians for nutritional habit and lifestyle amendment; (5) -omics profiling data warehousing and public repositories for IBD and IBS profile consultation. Dysbiosis-related indexes can represent novel laboratory and clinical medicine tools preventing or postponing the disease, finally interfering with its natural history.

Associations of Cholesteryl Ester Transfer Protein TaqIB Polymorphism with the Composite Ischemic Cardiovascular Disease Risk and HDL-C Concentrations: A Meta-Analysis

PubMed Central

Guo, Shu-xia; Yao, Ming-hong; Ding, Yu-song; Zhang, Jing-yu; Yan, Yi-zhong; Liu, Jia-ming; Zhang, Mei; Rui, Dong-sheng; Niu, Qiang; He, Jia; Guo, Heng; Ma, Ru-lin

2016-01-01

Background: Previous studies have evaluated the associations between the cholesteryl ester transfer protein (CETP) TaqIB polymorphism (rs708272), the risk of developing composite ischemic cardiovascular disease (CVD) and the concentration of high-density lipoprotein cholesterol (HDL-C), but results remain controversial. The objective of this study was to investigate whether a relationship exists between these factors. Methods: We conducted a meta-analysis of available studies to clarify the associations of the CETP TaqIB polymorphism with HDL-C concentration and the composite ischemic CVD risk in both Asians and Caucasians. All statistical analyses were done with Stata 12.0. Results: Through utilization of the Cochrane Library, Embase, PubMed, Web of Science, Springer, China Science and Technology Journal Database, China National Knowledge Infrastructure, Google Scholar, and Baidu Library, a total of 45 studies from 44 papers with 20,866 cases and 21,298 controls were combined showing a significant association between the CETP TaqIB variant and composite ischemic CVD risk. Carriers of allele TaqIB-B1 were found to have a higher risk of composite ischemic CVD than non-carriers: OR = 1.15, 95% CI = 1.09–1.21, p < 0.001. Meanwhile, 28 studies with 23,959 subjects were included in the association between the CETP TaqIB polymorphism and the concentration of HDL-C. Results suggested that carriers of the B1B1 genotype had lower concentrations of HDL-C than those of the B2B2 genotype: SMD = 0.50, 95% CI = 0.36–0.65, p < 0.001. Conclusions: The synthesis of available evidence demonstrates that the CETP TaqIB polymorphism protects against composite ischemic CVD risk and is associated with a higher HDL-C concentration in both Asians and Caucasians. PMID:27608031

FABP4 blocker attenuates colonic hypomotility and modulates white adipose tissue-derived hormone levels in mouse models mimicking constipation-predominant IBS.

PubMed

Mosińska, P; Jacenik, D; Sałaga, M; Wasilewski, A; Cygankiewicz, A; Sibaev, A; Mokrowiecka, A; Małecka-Panas, E; Pintelon, I; Storr, M; Timmermans, J P; Krajewska, W M; Fichna, J

2018-05-01

The role of fatty acid binding protein 4 (FABP4) in lower gastrointestinal (GI) motility is unknown. We aimed to verify the effect of inhibition of FABP4 on GI transit in vivo, and to determine the expression of FABP4 in mouse and human tissues. Fatty acid binding protein 4 inhibitor, BMS309403, was administered acutely or chronically for 6 and 13 consecutive days and its effect on GI transit was assessed in physiological conditions and in loperamide-induced constipation. Intracellular recordings were made to examine the effects of BMS309403 on colonic excitatory and inhibitory junction potentials. Abdominal pain was evaluated using behavioral pain response. Localization and expression of selected adipokines were determined in the mouse colon and serum using immunohistochemistry and Enzyme-Linked ImmunoSorbent Assay respectively. mRNA expression of FABP4 and selected adipokines in colonic and serum samples from irritable bowel syndrome (IBS) patients and control group were assessed. Acute injection of BMS309403 significantly increased GI motility and reversed inhibitory effect of loperamide. BMS309403 did not change colonic membrane potentials. Chronic treatment with BMS309403 increased the number of pain-induced behaviors. In the mouse serum, level of resistin was significantly decreased after acute administration; no changes in adiponectin level were detected. In the human serum, level of adiponectin and resistin, but not of FABP4, were significantly elevated in patients with constipation-IBS (IBS-C). FABP4 mRNA expression was significantly downregulated in the human colon in IBS-C. Fatty acid binding protein 4 may be involved in IBS pathogenesis and become a novel target in the treatment of constipation-related diseases. © 2017 John Wiley & Sons Ltd.

Patient satisfaction and psychological well-being after internet-based cognitive behavioral stress management (IB-CBSM) for women with preterm labor: A randomized controlled trial.

PubMed

Scherer, S; Alder, J; Gaab, J; Berger, T; Ihde, K; Urech, C

2016-01-01

Despite its value for the management of psychological burden, little is known about the efficacy of and patient satisfaction with internet-based cognitive behavioral stress management (IB-CBSM) for women with preterm labor. The present study sets out to analyze stress/anxiety reduction, patient satisfaction and patient's working alliance in a group of 58 women with preterm labor participating in an online psychological stress management project. As part of the project, women were randomly assigned to online stress management or a control condition. Levels of stress and anxiety decreased significantly in both conditions from pre- to post-treatment measure. Participants in IB-CBSM reported significant higher working alliance inventory (WAI) scores in the task and goal subscale (p<.001; p<.05) than women in the control condition. In Addition the IB-CBSM group showed significant correlations of the WAI subscale task and goal and the stress/anxiety outcome. Regarding patient satisfaction, women in the IB-CBSM reported significantly higher satisfaction scores (p<.001) than women in the control condition. WAI explained nearly 40% of the variance in patient satisfaction. Furthermore, WAI mediates, at least in part, the relationship between group condition and patient satisfaction. The current analysis indicated that participants in IB-CBSM had higher WAI scores and were more satisfied with the program. In addition only the IB-CBSM group showed significant correlations of the WAI with the stress/anxiety reduction outcome. Based on these findings, it can be presumed that measures of agreement with working alliance parameters, especially task and goal components, are substantially important for more effective and satisfactory therapeutic interventions. Copyright © 2015 Elsevier Inc. All rights reserved.

IB4(+) nociceptors mediate persistent muscle pain induced by GDNF.

PubMed

Alvarez, Pedro; Chen, Xiaojie; Bogen, Oliver; Green, Paul G; Levine, Jon D

2012-11-01

Skeletal muscle is a well-known source of glial cell line-derived neurotrophic factor (GDNF), which can produce mechanical hyperalgesia. Since some neuromuscular diseases are associated with both increased release of GDNF and intense muscle pain, we explored the role of GDNF as an endogenous mediator in muscle pain. Intramuscularly injected GDNF induced a dose-dependent (0.1-10 ng/20 μl) persistent (up to 3 wk) mechanical hyperalgesia in the rat. Once hyperalgesia subsided, injection of prostaglandin E(2) at the site induced a prolonged mechanical hyperalgesia (>72 h) compared with naïve rats (<4 h; hyperalgesic priming). Selective neurotoxic destruction of IB4(+) nociceptors attenuated both GDNF hyperalgesia and hyperalgesic priming. Ergonomic muscular injury induced by eccentric exercise or mechanical vibration increased muscle GDNF levels at 24 h, a time point where rats also exhibited marked muscle hyperalgesia. Intrathecal antisense oligodeoxynucleotides to mRNA encoding GFRα1, the canonical binding receptor for GDNF, reversibly inhibited eccentric exercise- and mechanical vibration-induced muscle hyperalgesia. Finally, electrophysiological recordings from nociceptors innervating the gastrocnemius muscle in anesthetized rats, revealed significant increase in response to sustained mechanical stimulation after local GDNF injection. In conclusion, these data indicate that GDNF plays a role as an endogenous mediator in acute and induction of chronic muscle pain, an effect likely to be produced by GDNF action at GFRα1 receptors located in IB4(+) nociceptors.

30 CFR 57.22232 - Actions at 0.5 percent methane (I-B, II-A, II-B, IV, V-B, and VI mines).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Actions at 0.5 percent methane (I-B, II-A, II-B, IV, V-B, and VI mines). 57.22232 Section 57.22232 Mineral Resources MINE SAFETY AND HEALTH....22232 Actions at 0.5 percent methane (I-B, II-A, II-B, IV, V-B, and VI mines). If methane reaches 0.5...

30 CFR 57.22232 - Actions at 0.5 percent methane (I-B, II-A, II-B, IV, V-B, and VI mines).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Actions at 0.5 percent methane (I-B, II-A, II-B...-UNDERGROUND METAL AND NONMETAL MINES Safety Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22232 Actions at 0.5 percent methane (I-B, II-A, II-B, IV, V-B, and VI mines). If methane reaches 0.5...

Enantiomeric resolution of five chiral pesticides on a Chiralpak IB-H column by SFC.

PubMed

Jin, Lixia; Gao, Weiliang; Yang, Huayun; Lin, Chunmian; Liu, Weiping

2011-10-01

The enantiomeric separations of five chiral pesticides, diclofopmethyl, 1; benalaxy, 2; acetofenate, 3; myclobutanil, 4; and difenoconazole, 5, were conducted on a Chiralpak IB-H column by a packed-column supercritical fluid chromatography (p-SFC). All compounds, except difenoconazole and myclobutanil, were well resolved within 10 min. As the mobile phase polarity decreased through changing the percentage and the type of alcohol modifiers in the supercritical carbon dioxide (CO(2)), the retention time, the separation factors, and the resolution increased. However, based on the retention time and the resolution, the optimized separations were obtained with the mobile phase containing 10% 2-propanol for diclofop-methyl 1; benalaxy, 2; myclobutanil, 4; difenoconazole, 5; and containing 3% 2-propanol for acetofenate, 3. The optimized separation temperature was at 35°C under the supercritical fluid condition. The π-π interactions and the hydrogen bonding interactions between Chiralpak IB-H CSP and the analytes might be the main chiral discriminations on enantioseparation of these five pesticides.

Assessments of Sequential Intensity Modulated Radiation Therapy Boost (SqIB) Treatments Using HART

NASA Astrophysics Data System (ADS)

Pyakuryal, Anil

2009-05-01

A retrospective study was pursued to evaluate the SqIB treatments performed on ten head and neck cancer patients(n=10).Average prescription doses (PDs) of 39 Gy,15Gy and 17.8Gy were delivered consecutively from larger to smaller planning target volumes(ptvs) in three different treatment plans using 6 MV X-ray photon beams from a Linear accelerator (SLA Linac, Elekta) on BID weak on-weak off schedules. These plans were statistically evaluated on basis of plan indices (PIs),dose response of targets and critical structures, and dose tolerance(DT) of various organs utilizing the DVH analysis automated software known as Histogram Analysis in Radiation Therapy-HART(S.Jang et al., 2008, Med Phys 35, p.2812). Mean SqIB PIs were found consistent with the reported values for varying radio-surgical systems.The 95.5%(n=10)of each ptvs and the gross tumor volume also received 95% (n=10)of PDs in treatments. The average volume of ten organs (N=10) affected by each PDs shrank with decreasing size of ptvs in above plans.A largest volume of Oropharynx (79%,n=10,N=10) irradiated at PD, but the largest volume of Larynx (98%, n=10, N=10) was vulnerable to DT of structure (TD50).Thus, we have demonstrated the efficiency and accuracy of HART in the assessment of Linac based plans in radiation therapy treatments of cancer.

Concurrent Oncogene Mutation Profile in Chinese Patients With Stage Ib Lung Adenocarcinoma

PubMed Central

Wen, Ying-Sheng; Cai, Ling; Zhang, Xue-wen; Zhu, Jian-fei; Zhang, Zi-chen; Shao, Jian-yong; Zhang, Lan-Jun

2014-01-01

Abstract Molecular characteristics in lung cancer are associated with carcinogenesis, response to targeted therapies, and prognosis. With concurrent oncogene mutations being reported more often, the adjustment of treatment based on the driver gene mutations would improve therapy. We proposed to investigate the distribution of concurrent oncogene mutations in stage Ib lung adenocarcinoma in a Chinese population and find out the correlation between survival outcome and the most frequently mutated genes in EGFR and KRAS in Chinese population. Simultaneously, we tried to validate the Sequenom method by real time fluoresce qualification reverse transcription polymerase chain reaction (RT-PCR) in oncogene detection. One hundred fifty-six patients who underwent complete surgical resection in our hospital between 1999 and 2007 were retrospectively investigated. Using time-of-flight mass spectrometry, 238 mutation hotspots in 19 oncogenes were examined. Genetic mutations occurred in 86 of 156 patients (55.13%). EGFR was most frequently gene contained driver mutations, with a rate of 44.23%, followed by KRAS (8.33%), PIK3CA (3.84%), KIT (3.20%), BRAF (2.56%), AKT (1.28%), MET (0.64%), NRAS (0.64%), HRAS (0.64%), and ERBB2 (0.64%). No mutations were found in the RET, PDGFRA, FGFR1, FGFR3, FLT3, ABL, CDK, or JAK2 oncogenes. Thirteen patients (8.3%) were detected in multiple gene mutations. Six patients had PIK3CA mutations in addition to mutations in EGFR and KRAS. EGFR mutations can coexist with mutations in NRAS, KIT, ERBB2, and BRAF. Only one case was found to have a KRAS mutation coexisting with the EGFR T790M mutation. Otherwise, mutations in EGFR and KRAS seem to be mutually exclusive. There is no survival benefit in favor of EGFR/KRAS mutation. Several concomitant driver gene mutations were observed in our study. None of EFGR/KRAS mutation was demonstrated as a prognostic factor. Polygenic mutation testing by time-of-flight mass spectrometry was validated by RT

Fission Meter Information Barrier Attribute Measurement System: Task 1 Report: Document existing Fission Meter neutron IB system

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kerr, P. L.

An SNM attribute Information Barrier (IB) system was developed for a 2011 US/UK Exercise. The system was modified and extensively tested in a 2013-2014 US-UK Measurement Campaign. This work demonstrated rapid deployment of an IB system for potential treaty use. The system utilizes an Ortec Fission Meter neutron multiplicity counter and custom computer code. The system demonstrates a proof-of-principle automated Pu-240 mass determination with an information barrier. After a software start command is issued, the system automatically acquires and downloads data, performs an analysis, and displays the results. This system conveys the results of a Pu mass threshold measurements inmore » a way the does not reveal sensitive information. In full IB mode, only red/green ‘lights’ are displayed in the software. In test mode, more detailed information is displayed. The code can also read in, analyze, and display results from previously acquired or simulated data. Because the equipment is commercial-off-the-shelf (COTS), the system demonstrates a low-cost short-lead-time technology for treaty SNM attribute measurements. A deployed system will likely require integration of additional authentication and tamper-indicating technologies. This will be discussed for the project in this and future progress reports.« less

OC5 Project Phase Ib: Validation of hydrodynamic loading on a fixed, flexible cylinder for offshore wind applications

DOE Office of Scientific and Technical Information (OSTI.GOV)

Robertson, Amy N.; Wendt, Fabian; Jonkman, Jason M.

This paper summarizes the findings from Phase Ib of the Offshore Code Comparison, Collaboration, Continued with Correlation (OC5) project. OC5 is a project run under the International Energy Agency (IEA) Wind Research Task 30, and is focused on validating the tools used for modelling offshore wind systems through the comparison of simulated responses of select offshore wind systems (and components) to physical test data. For Phase Ib of the project, simulated hydrodynamic loads on a flexible cylinder fixed to a sloped bed were validated against test measurements made in the shallow water basin at the Danish Hydraulic Institute (DHI) withmore » support from the Technical University of Denmark (DTU). The first phase of OC5 examined two simple cylinder structures (Phase Ia and Ib) to focus on validation of hydrodynamic models used in the various tools before moving on to more complex offshore wind systems and the associated coupled physics. As a result, verification and validation activities such as these lead to improvement of offshore wind modelling tools, which will enable the development of more innovative and cost-effective offshore wind designs.« less

OC5 Project Phase Ib: Validation of hydrodynamic loading on a fixed, flexible cylinder for offshore wind applications

DOE PAGES

Robertson, Amy N.; Wendt, Fabian; Jonkman, Jason M.; ...

2016-10-13

This paper summarizes the findings from Phase Ib of the Offshore Code Comparison, Collaboration, Continued with Correlation (OC5) project. OC5 is a project run under the International Energy Agency (IEA) Wind Research Task 30, and is focused on validating the tools used for modelling offshore wind systems through the comparison of simulated responses of select offshore wind systems (and components) to physical test data. For Phase Ib of the project, simulated hydrodynamic loads on a flexible cylinder fixed to a sloped bed were validated against test measurements made in the shallow water basin at the Danish Hydraulic Institute (DHI) withmore » support from the Technical University of Denmark (DTU). The first phase of OC5 examined two simple cylinder structures (Phase Ia and Ib) to focus on validation of hydrodynamic models used in the various tools before moving on to more complex offshore wind systems and the associated coupled physics. As a result, verification and validation activities such as these lead to improvement of offshore wind modelling tools, which will enable the development of more innovative and cost-effective offshore wind designs.« less

Record of Lower Gondwana megafloral assemblage from Lower Kamthi Formation of Ib River Coalfield, Orissa, India.

PubMed

Goswami, Shreerup

2006-03-01

Recent investigations carried out in the Ib River Coalfield, Mahanadi Master Basin, Orissa, identified some fossilif-erous beds in the Lower Gondwana deposits. Two exposures of the Lower Kamthi Formation yielded diverse and abundant plant remains, which include Neomariopteris, Vertebraria, and a scale leaf along with 14 Glossopteris species otherwise mapped as Barren Measures and Upper Kamthi formations. Glossopteris indica dominates the flora (22.78%) followed by G. communis (17.72%) and G. browniana (13.92%). Based on megafloral assemblages, different beds exposed at Gopalpur and Laxamanpur Pahar are assigned here to the Lower Kamthi Formation (Late Permian). The floristic composition suggests that a warm and humid climate prevailed during the Late Permian. The status of the Kamthi Formation in the Ib River Coalfield has been redefined in the present study.

The Rhizoctonia solani AG1-IB (isolate 7/3/14) transcriptome during interaction with the host plant lettuce (Lactuca sativa L.).

PubMed

Verwaaijen, Bart; Wibberg, Daniel; Kröber, Magdalena; Winkler, Anika; Zrenner, Rita; Bednarz, Hanna; Niehaus, Karsten; Grosch, Rita; Pühler, Alfred; Schlüter, Andreas

2017-01-01

The necrotrophic pathogen Rhizoctonia solani is one of the most economically important soil-borne pathogens of crop plants. Isolates of R. solani AG1-IB are the major pathogens responsible for bottom-rot of lettuce (Lactuca sativa L.) and are also responsible for diseases in other plant species. Currently, there is lack of information regarding the molecular responses in R. solani during the pathogenic interaction between the necrotrophic soil-borne pathogen and its host plant. The genome of R. solani AG1-IB (isolate 7/3/14) was recently established to obtain insights into its putative pathogenicity determinants. In this study, the transcriptional activity of R. solani AG1-IB was followed during the course of its pathogenic interaction with the host plant lettuce under controlled conditions. Based on visual observations, three distinct pathogen-host interaction zones on lettuce leaves were defined which covered different phases of disease progression on tissue inoculated with the AG1-IB (isolate 7/3/14). The zones were defined as: Zone 1-symptomless, Zone 2-light brown discoloration, and Zone 3-dark brown, necrotic lesions. Differences in R. solani hyphae structure in these three zones were investigated by microscopic observation. Transcriptional activity within these three interaction zones was used to represent the course of R. solani disease progression applying high-throughput RNA sequencing (RNA-Seq) analysis of samples collected from each Zone. The resulting three transcriptome data sets were analyzed for their highest expressed genes and for differentially transcribed genes between the respective interaction zones. Among the highest expressed genes was a group of not previously described genes which were transcribed exclusively during early stages of interaction, in Zones 1 and 2. Previously described importance of up-regulation in R. solani agglutinin genes during disease progression could be further confirmed; here, the corresponding genes exhibited

The lignan glycosides lyoniside and saracoside poison the unusual type IB topoisomerase of Leishmania donovani and kill the parasite both in vitro and in vivo.

PubMed

Saha, Sourav; Mukherjee, Tulika; Chowdhury, Sayan; Mishra, Amartya; Chowdhury, Somenath Roy; Jaisankar, Parasuraman; Mukhopadhyay, Sibabrata; Majumder, Hemanta K

2013-12-15

Lignans are diphenyl propanoids with vast range of biological activities. The present study provides an important insight into the anti-leishmanial activities of two lignan glycosides, viz. lyoniside and saracoside. These compounds inhibit catalytic activities of topoisomerase IB (LdTopIB) of Leishmania donovani in non-competitive manner and stabilize the LdTopIB mediated cleavage complex formation both in vitro and in Leishmania promastigotes and subsequently inhibit the religation of cleaved strand. These two compounds not only poison LdTopIB but also can interact with the free enzyme LdTopIB. We have also shown that lyoniside and saracoside are cytotoxic to promastigotes and intracellular amastigotes. The protein-DNA complex formation leads to double strand breaks in DNA which ultimately triggers apoptosis-like cell death in the parasite. Along with their cytotoxicity towards sodium antimony gluconate (SAG) sensitive AG83 strain, their ability to kill SAG resistant GE1 strain makes these two compounds potential anti-leishmanial candidates. Not only they effectively kill L. donovani amastigotes inside macrophages in vitro, lyoniside and saracoside demonstrated strong anti-leishmanial efficacies in BALB/c mice model of leishmaniasis. Treatment with these lignan glycosides produce nitric oxide and reactive oxygen species which result in almost complete clearance of the liver and splenic parasite burden. These compounds do not inhibit human topoisomerase IB upto 200μM concentrations and had poor cytotoxic effect on uninfected cultured murine peritoneal macrophages upto 100μM concentrations. Taken together it can be concluded that these compounds can be developed into excellent therapeutic agent against deadly disease leishmaniasis. Copyright © 2013 Elsevier Inc. All rights reserved.

Suggestive association of major histocompatibility IB genetic markers with resistance to bacterial cold water disease in rainbow trout (Oncorhynchus mykiss).

PubMed

Johnson, Nathan A; Vallejo, Roger L; Silverstein, Jeffrey T; Welch, Timothy J; Wiens, Gregory D; Hallerman, Eric M; Palti, Yniv

2008-01-01

Genes within the major histocompatibility complex (MHC) are important for both innate and adaptive immune responses in mammals; however, much less is known regarding their contribution in teleost fishes. We examined the involvement of four major histocompatibility (MH) genomic regions in rainbow trout in resistance to the causative agent of bacterial coldwater disease (BCWD), Flavobacterium psychrophilum. Fish from the 2005 NCCCWA brood-year (71 full-sib families) were challenged with F. psychrophilum strain CSF 259-93. The overall mortality rate was 70%, with large variation in mortality between families. Disease resistance was quantified as post-challenge days to death. Phenotypic variation and additive genetic variation were estimated using mixed models of survival analysis. To examine association, eight microsatellite markers were isolated from MH gene-containing BAC clones and mapped onto the rainbow trout genetic linkage map. The parents and grandparents of the 2005 brood-year families were genotyped with these eight markers and another two markers tightly linked to the MH-IB region to assess the extent of linkage disequilibrium (LD) of MH genomic regions MH-IA, MH-IB, TAP1, and MH-II with survival post-challenge. MH-IB and MH-II markers were linked to BCWD survivability when data were analyzed by family. Tests for disease association at the population level substantiated the involvement of MH-IB, but not MH-II, with disease resistance. The impact of selective breeding for disease resistance on MH sequence variation is discussed in the context of aquaculture production.

A Novel EphA2 Inhibitor Exerts Beneficial Effects in PI-IBS in Vivo and in Vitro Models via Nrf2 and NF-κB Signaling Pathways.

PubMed

Zeng, Li; Li, Kaixue; Wei, Hong; Hu, Jingjing; Jiao, Lu; Yu, Shaoyong; Xiong, Ying

2018-01-01

Though the detailed pathological mechanism of post-infectious irritable bowel syndrome (PI-IBS) remains unclear, accumulating evidence indicates that oxidative stress and inflammation are implicated in the process of PI-IBS. Oxidative stress and inflammation are regulated by Nrf2 and NF-κB signaling pathways, respectively. EphA2, a member of Eph receptor family, promotes oxidative stress and inflammatory responses via regulation of Nrf2 and NF-κB signaling pathways in various types of human diseases. Understanding the mechanisms by which EphA2 regulate oxidative stress and inflammation in PI-IBS is important for the development of new strategies to treat PI-IBS. However, the effects of ALW-II-41-27, a novel EphA2 inhibitor on PI-IBS and the underlying molecular mechanisms have never been studied. In the present study, we showed that ALW-II-41-27 decreased gastrointestinal motility and abdominal withdrawal reflex (AWR) scores, markedly reduced the levels of oxidative stress markers [4-hydroxy-2-nonenal (4-HNE), protein carbonyl, and 8-hydroxy-2-de-axyguanine (8-OHdG)] and proinflammatory cytokines (TNF-α, IL-6, IL-17, and ICAM-1), and remarkably increased the level of anti-inflammatory cytokine (IL-10) in serum and colon of Trichinella spiralis -infected mice. Moreover, ALW-II-41-27 was effective in suppressing oxidative stress and inflammation in LPS-treated NCM460 colonic cells. Treatment of ALW-II-41-27 reversed the activation of NF-κB and inactivation of Nrf2 in LPS-treated NCM460 cells. Importantly, these protective effects of ALW-II-41-27 were partially inhibited by EphA2 KO and abolished by EphA2 overexpression. In conclusion, EphA2 may represent a promising therapeutic target for patients with PI-IBS and ALW-II-41-27 might function as a novel therapeutic agent for PI-IBS.

Mathematical, theoretical and experimental confirmations of IRS and IBS by R.M. Santilli

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kohale, Ritesh L.

The objective of present work is to put forward the Santilli’s experimental, physical and mathematical conception of IsoRedShift (IRS), IsoBlueShift (IBS) and NoIsoShift (NIS). Santilli has carried out a step-by step isotopic lifting of the physical laws of special relativity resulting in a new theory today specifically known Santilli isorelativity. In his 1991 hypothesis Santilli established the requirement to realize the light as electromagnetic waves propagating within a universal substratum. Furthermore Santilli has carried out a step-by step isotopic lifting of the physical laws of special relativity resulting in a new theory today specifically known Santilli isorelativity.

High prevalence of plasmid-mediated quinolone resistance determinants qnr, aac(6')-Ib-cr, and qepA among ceftiofur-resistant Enterobacteriaceae isolates from companion and food-producing animals.

PubMed

Ma, Junying; Zeng, Zhenling; Chen, Zhangliu; Xu, Xiaogang; Wang, Xiaoying; Deng, Yuting; Lü, Dianhong; Huang, Liangzong; Zhang, Yunyuan; Liu, Jianhua; Wang, Minggui

2009-02-01

Three kinds of plasmid-mediated quinolone resistance (PMQR) determinants have been discovered and have been shown to be widely distributed among clinical isolates: qnr genes, aac(6')-Ib-cr, and qepA. Few data on the prevalence of these determinants in strains from animals are available. The presence of PMQR genes in isolates from animals was determined by PCR amplification and DNA sequencing. The production of extended-spectrum beta-lactamases (ESBLs) and AmpC beta-lactamases in the strains was detected, and their genotypes were determined. The genetic environment of PMQR determinants in selected plasmids was analyzed. All samples of ceftiofur-resistant (MICs > or = 8 microg/ml) isolates of the family Enterobacteriaceae were selected from 36 companion animals and 65 food-producing animals in Guangdong Province, China, between November 2003 and April 2007, including 89 Escherichia coli isolates, 9 Klebsiella pneumoniae isolates, and isolates of three other genera. A total of 68.3% (69/101) of the isolates produced ESBLs and/or AmpC beta-lactamases, mainly those of the CTX-M and CMY types. Of the 101 strains, PMQR determinants were present in 35 (34.7%) isolates, with qnr, aac(6')-Ib-cr, and qepA detected alone or in combination in 8 (7.9%), 19 (18.8%), and 16 (15.8%) strains, respectively. The qnr genes detected included one qnrB4 gene, four qnrB6 genes, and three qnrS1 genes. Five strains were positive for both aac(6')-Ib-cr and qepA, while one strain was positive for qnrS1, aac(6')-Ib-cr, and qepA. qnrB6 was flanked by two copies of ISCR1 with an intervening dfr gene downstream and sul1 and qacEDelta1 genes upstream. In another plasmid, aac(6')-Ib-cr followed intI1 and arr-3 was downstream. PMQR determinants are highly prevalent in ceftiofur-resistant Enterobacteriaceae strains isolated from animals in China. This is the first report of the occurrence of PMQR determinants among isolates from companion animals.

Psychosexual Intervention in Patients With Stage I-III Gynecologic or Breast Cancer

ClinicalTrials.gov

2018-05-25

Ovarian Sarcoma; Ovarian Stromal Cancer; Stage I Uterine Sarcoma; Stage I Vaginal Cancer; Stage I Vulvar Cancer; Stage IA Cervical Cancer; Stage IA Endometrial Carcinoma; Stage IA Fallopian Tube Cancer; Stage IA Ovarian Epithelial Cancer; Stage IA Ovarian Germ Cell Tumor; Stage IA Primary Peritoneal Cavity Cancer; Stage IB Cervical Cancer; Stage IB Endometrial Carcinoma; Stage IB Fallopian Tube Cancer; Stage IB Ovarian Epithelial Cancer; Stage IB Ovarian Germ Cell Tumor; Stage IB Primary Peritoneal Cavity Cancer; Stage IC Fallopian Tube Cancer; Stage IC Ovarian Epithelial Cancer; Stage IC Ovarian Germ Cell Tumor; Stage IC Primary Peritoneal Cavity Cancer; Stage II Endometrial Carcinoma; Stage II Gestational Trophoblastic Tumor; Stage II Uterine Sarcoma; Stage II Vaginal Cancer; Stage II Vulvar Cancer; Stage IIA Cervical Cancer; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Epithelial Cancer; Stage IIA Ovarian Germ Cell Tumor; Stage IIA Primary Peritoneal Cavity Cancer; Stage IIB Cervical Cancer; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Epithelial Cancer; Stage IIB Ovarian Germ Cell Tumor; Stage IIB Primary Peritoneal Cavity Cancer; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Epithelial Cancer; Stage IIC Ovarian Germ Cell Tumor; Stage IIC Primary Peritoneal Cavity Cancer; Stage III Gestational Trophoblastic Tumor; Stage III Uterine Sarcoma; Stage III Vaginal Cancer; Stage III Vulvar Cancer; Stage IIIA Cervical Cancer; Stage IIIA Endometrial Carcinoma; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Epithelial Cancer; Stage IIIA Ovarian Germ Cell Tumor; Stage IIIA Primary Peritoneal Cavity Cancer; Stage IIIB Cervical Cancer; Stage IIIB Endometrial Carcinoma; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Epithelial Cancer; Stage IIIB Ovarian Germ Cell Tumor; Stage IIIB Primary Peritoneal Cavity Cancer; Stage IIIC Endometrial Carcinoma; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Epithelial Cancer; Stage IIIC Ovarian Germ Cell

Inhibition of aac(6′)-Ib-mediated amikacin resistance by nuclease-resistant external guide sequences in bacteria

PubMed Central

Soler Bistué, Alfonso J. C.; Martín, Fernando A.; Vozza, Nicolás; Ha, Hongphuc; Joaquín, Jonathan C.; Zorreguieta, Angeles; Tolmasky, Marcelo E.

2009-01-01

Inhibition of bacterial gene expression by RNase P-directed cleavage is a promising strategy for the development of antibiotics and pharmacological agents that prevent expression of antibiotic resistance. The rise in multiresistant bacteria harboring AAC(6′)-Ib has seriously limited the effectiveness of amikacin and other aminoglycosides. We have recently shown that recombinant plasmids coding for external guide sequences (EGS), short antisense oligoribonucleotides (ORN) that elicit RNase P-mediated cleavage of a target mRNA, induce inhibition of expression of aac(6′)-Ib and concomitantly induce a significant decrease in the levels of resistance to amikacin. However, since ORN are rapidly degraded by nucleases, development of a viable RNase P-based antisense technology requires the design of nuclease-resistant RNA analog EGSs. We have assayed a variety of ORN analogs of which selected LNA/DNA co-oligomers elicited RNase P-mediated cleavage of mRNA in vitro. Although we found an ideal configuration of LNA/DNA residues, there seems not to be a correlation between number of LNA substitutions and level of activity. Exogenous administration of as low as 50 nM of an LNA/DNA co-oligomer to the hyperpermeable E. coli AS19 harboring the aac(6′)-Ib inhibited growth in the presence of amikacin. Our experiments strongly suggest an RNase P-mediated mechanism in the observed antisense effect. PMID:19666539

Nurse-Administered, Gut-Directed Hypnotherapy in IBS: Efficacy and Factors Predicting a Positive Response.

PubMed

Lövdahl, Jenny; Ringström, Gisela; Agerforz, Pia; Törnblom, Hans; Simrén, Magnus

2015-07-01

Hypnotherapy is an effective treatment in irritable bowel syndrome (IBS). It is often delivered by a psychotherapist and is costly and time consuming. Nurse-administered hypnotherapy could increase availability and reduce costs. In this study the authors evaluate the effectiveness of nurse-administered, gut-directed hypnotherapy and identify factors predicting treatment outcome. Eighty-five patients were included in the study. Participants received hypnotherapy by a nurse once/week for 12 weeks. Patients reported marked improvement in gastrointestinal (GI) and extra-colonic symptoms after treatment, as well as a reduction in GI-specific anxiety, general anxiety, and depression. Fifty-eight percent were responders after the 12 weeks treatment period, and of these 82% had a favorable clinical response already at week 6. Women were more likely than men to respond favorably to the treatment. Nurse-administered hypnotherapy is an effective treatment for IBS. Being female and reporting a favorable response to treatment by week 6 predicted a positive treatment response at the end of the 12 weeks treatment period.

EHealth: self-management in inflammatory bowel disease and in irritable bowel syndrome using novel constant-care web applications. EHealth by constant-care in IBD and IBS.

PubMed

Pedersen, Natalia

2015-12-01

Inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) are chronic gastrointestinal disorders of unknown aetiology of increasing incidence and changing disease activity or severity. Approximately 60-80% of IBD patients suffer from IBS. Monitoring and treatment goals of IBD are to optimise the disease course by prolonging remission periods and preventing or shortening periods of active disease. Constant-care web-monitoring and treatment approaches with active patient involvement have been proven effective in UC, increasing patients' adherence and improving the disease outcomes.   To assess the feasibility and efficacy of the novel constant-care eHealth applications in: i) CD patients treated with infliximab (IFX), ii) UC patients with active disease on mesalazine, iii) IBS patients and iv) IBD patients with IBS on a low FODMAP diet (LFD).   New constant-care web applications www.cd.constant-care.dk, www.meza.constant-care.dk and www.ibs.constant-care.dk in IBD patients were developed and assessed in this thesis. An integrated inflammatory burden measure of disease activity, consisting of a subjective (clinical indices) and of an objective (faecal calprotectin) part and a treatment guide to drug doses and intervals, was incorporated into the web applications and used by patients. Web-guided IFX treatment in CD demonstrated patients' inter- and intra-individual variability in infusion intervals and provided patients with individualised treatment according to their needs. Web-guided treatment with multimatrix mesalazine was efficacious in a majority of UC patients with mild-to-moderate disease activity. Web-guided IBS-monitoring in IBD and in IBS patients on LFD was shown to be a feasible method that actively involved patients in their disease management and had a positive short-term impact on the disease. Moreover, the new constant-care concepts were demonstrated to be safe and to have a positive impact on quality of life and adherence to treatment and

Intellectually Gifted Females and Their Perspectives of Lived Experience in the AP and IB Programs

ERIC Educational Resources Information Center

Vanderbrook, Carrie M.

2006-01-01

The Advanced Placement (AP) and International Baccalaureate (IB) programs serve as popular choices for many intellectually gifted high school students. This article describes an aspect of a larger study that examined 5 intellectually gifted females' perceptions of their educational experience while enrolled in one of the programs. Using the…

30 CFR 57.22201 - Mechanical ventilation (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Mechanical ventilation (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines). 57.22201 Section 57.22201 Mineral Resources MINE SAFETY AND HEALTH....22201 Mechanical ventilation (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines). All mines shall...

30 CFR 57.22201 - Mechanical ventilation (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Mechanical ventilation (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines). 57.22201 Section 57.22201 Mineral Resources MINE SAFETY AND HEALTH....22201 Mechanical ventilation (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines). All mines shall...

Charlotte, N.C.'s Project L.I.F.T.: Ranson IB Middle School Launches an Opportunty Culture. An Opportunity Culture Case Study

ERIC Educational Resources Information Center

Barrett, Sharon Kebschull; Han, Jiye Grace

2015-01-01

Principal Alison Harris is blunt in describing what she confronted on her arrival to Ranson IB Middle School in 2011. "I was placed in what many people would call an impossible situation," she says. During her initial visit to the school in 2009-10, she watched as students changed classes--while teachers pressed against the lockers to…

Structural basis for decreased induction of class IB PI3-kinases expression by MIF inhibitors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Singh, Abhay Kumar; Pantouris, Georgios; Borosch, Sebastian

Macrophage migration inhibitory factor (MIF) is a master regulator of proinflammatory cytokines and plays pathological roles when not properly regulated in rheumatoid arthritis, lupus, atherosclerosis, asthma and cancer. Unlike canonical cytokines, MIF has vestigial keto-enol tautomerase activity. Most of the current MIF inhibitors were screened for the inhibition of this enzymatic activity. However, only some of the enzymatic inhibitors inhibit receptor-mediated biological functions of MIF, such as cell recruitment, through an unknown molecular mechanism. The goal of this study was to understand the molecular basis underlying the pharmacological inhibition of biological functions of MIF. Here, we demonstrate how the structuralmore » changes caused upon inhibitor binding translate into the alteration of MIF-induced downstream signalling. Macrophage migration inhibitory factor activates phosphoinositide 3-kinases (PI3Ks) that play a pivotal role in immune cell recruitment in health and disease. There are several different PI3K isoforms, but little is known about how they respond to MIF. We demonstrate that MIF up-regulates the expression of Class IB PI3Ks in leucocytes. We also demonstrate that MIF tautomerase active site inhibitors down-regulate the expression of Class IB PI3Ks as well as leucocyte recruitment in vitro and in vivo. Finally, based on our MIF:inhibitor complex crystal structures, we hypothesize that the reduction in Class IB PI3K expression occurs because of the displacement of Pro1 towards the second loop of MIF upon inhibitor binding, which results in increased flexibility of the loop 2 and sub-optimal MIF binding to its receptors. These results will provide molecular insights for fine-tuning the biological functions of MIF.« less

Deletion of the Noncoding GNAS Antisense Transcript Causes Pseudohypoparathyroidism Type Ib and Biparental Defects of GNAS Methylation in cis

PubMed Central

Chillambhi, Smitha; Turan, Serap; Hwang, Daw-Yang; Chen, Hung-Chun; Jüppner, Harald; Bastepe, Murat

2010-01-01

Context: GNAS encodes the α-subunit of the stimulatory G protein as well as additional imprinted transcripts including the maternally expressed NESP55 and the paternally expressed XLαs, antisense, and A/B transcripts. Most patients with pseudohypoparathyroidism type Ib (PHP-Ib) exhibit imprinting defects affecting the maternal GNAS allele, which are thought to reduce/abolish Gsα expression in renal proximal tubules and thereby cause resistance to PTH. Objective: Our objective was to define the genetic defect in a previously unreported family with autosomal dominant PHP-Ib. Design and Setting: Analyses of serum and urine chemistries and of genomic DNA and lymphoblastoid-derived RNA were conducted at a tertiary hospital and research laboratory. Patients: Affected individuals presented with muscle weakness and/or paresthesia and showed hypocalcemia, hyperphosphatemia, and elevated serum PTH. Obligate carriers were healthy and revealed no obvious abnormality in mineral ion homeostasis. Results: A novel 4.2-kb microdeletion was discovered in the affected individuals and the obligate carriers, ablating two noncoding GNAS antisense exons while preserving the NESP55 exon. On maternal transmission, the deletion causes loss of all maternal GNAS imprints, partial gain of NESP55 methylation, and PTH resistance. Paternal transmission of the mutation leads to epigenetic alterations in cis, including a partial loss of NESP55 methylation and a partial gain of A/B methylation. Conclusions: The identified deletion points to a unique cis-acting element located telomeric of the NESP55 exon that is critical for imprinting both GNAS alleles. These findings provide novel insights into the molecular mechanisms underlying PHP and GNAS imprinting. PMID:20444925

The neurokinin-2 receptor antagonist ibodutant improves overall symptoms, abdominal pain and stool pattern in female patients in a phase II study of diarrhoea-predominant IBS.

PubMed

Tack, J; Schumacher, K; Tonini, G; Scartoni, S; Capriati, A; Maggi, C A

2017-08-01

Tachykinins have been implicated in the pathophysiology of IBS with diarrhoea (IBS-D). Our aim was to study the efficacy and safety of ibodutant, a selective neurokinin-2 (NK2) receptor antagonist, in patients with IBS-D. This multinational double-blind, placebo-controlled study recruited 559 patients with IBS-D according to Rome III criteria. After a 2-week treatment-free run-in, patients were randomised to ibodutant 1 mg, 3 mg, 10 mg or placebo once daily for eight consecutive weeks. Responders were those with a combined response of satisfactory relief (weekly binary question yes/no) of overall IBS symptoms and abdominal pain/discomfort on ≥75% weeks (primary end point). Secondary end points included abdominal pain and stool pattern. Data were also analysed according to US Food and Drug Administration (FDA)-approved interim end points (improvement of pain and stool consistency). Safety was assessed by monitoring adverse events and laboratory tests. Prespecified statistical analysis involved the whole group as well as gender subgroups. Demographics and baseline characteristics were comparable for all treatment arms. In the overall population, responsiveness tended to increase with escalating ibodutant doses. In the prespecified analysis by gender, ibodutant 10 mg demonstrated significant superiority over placebo in females (p=0.003), while no significant effect occurred in males. This was confirmed for secondary end points and for the responder analysis according to FDA-approved end points. The tolerability and safety of ibodutant was excellent at all doses. Ibodutant showed dose-dependent efficacy response in IBS-D, reaching statistical significance at the 10 mg dose in female patients. The safety and tolerability profile of ibodutant was similar to placebo. NCT01303224. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

De Novo STX16 Deletions: An Infrequent Cause of Pseudohypoparathyroidism Type Ib that Should Be Excluded in Sporadic Cases

PubMed Central

Turan, Serap; Ignatius, Jaakko; Moilanen, Jukka S.; Kuismin, Outi; Stewart, Helen; Mann, Nicholas P.; Linglart, Agnès; Bastepe, Murat

2012-01-01

Context: Maternally inherited 3-kb STX16 deletions cause autosomal dominant pseudohypoparathyroidism type Ib (PHP-Ib) characterized by PTH resistance with loss of methylation restricted to the GNAS exon A/B. Objective: The objective of the study was to search for the 3-kb STX16 deletion and to establish haplotypes for the GNAS region for two PHP-Ib patients and their families. Setting: The study was conducted at a research laboratory and tertiary care hospitals. Patients: The index cases presented at the ages 8 and 9.5 yr, respectively, with hypocalcemia, hyperphosphatemia, and elevated PTH. Interventions: There were no interventions. Results: DNA analyses of the index cases revealed an isolated loss of the GNAS exon A/B methylation and the 3-kb STX16 deletion. In the first family, the patient's healthy mother and sister showed no genetic or epigenetic abnormality, yet microsatellite analysis of the GNAS region indicated that both siblings share the same maternal allele, with the exception of an allelic loss for marker 261P9-CA1 (located within STX16), leading to the conclusion that a de novo mutation had occurred on the maternal allele. In the second family, three siblings of the index case are also affected, and an analysis of their DNA revealed the 3-kb STX16 deletion, which was also found in the healthy mother and a maternal uncle. Analysis of the siblings of the deceased maternal grandfather and some of their descendants excluded the 3-kb STX16 deletion, but haplotype analysis of the GNAS region suggested that he had acquired the mutation de novo. Conclusions: De novo 3-kb STX16 deletions, reported only once previously, are infrequent but should be excluded in all cases of PHP-Ib, even when the family history is negative for an inherited form of this disorder. PMID:23087324

αConotoxin ArIB[V11L,V16D] is a potent and selective antagonist at rat and human native α7 nicotinic acetylcholine receptors

PubMed Central

Innocent, Neal; Livingstone, Phil D.; Hone, Arik; Kimura, Atsuko; Young, Tracey; Whiteaker, Paul; McIntosh, J. Michael; Wonnacott, Susan

2008-01-01

A recently developed α-conotoxin, α-CtxArIB[V11L,V16D] is a potent and selective competitive antagonist at rat recombinant α7 nicotinic acetylcholine receptors (nAChRs), making it an attractive probe for this receptor subtype. α7 nAChRs are potential therapeutic targets that are widely expressed in both neuronal and non-neuronal tissues where they are implicated in a variety of functions. Here we evaluate this toxin at rat and human native nAChRs. Functional α7 nAChR responses were evoked by choline plus the allosteric potentiator PNU-120596 in rat PC12 cells and human SHSY5Y cells loaded with calcium indicators. α-CtxArIB[V11L,V16D] specifically inhibited α7 nAChR-mediated increases in Ca2+ in PC12 cells. Responses to other stimuli (5-iodo-A-85380, nicotine or KCl) that did not activate α7 nAChRs were unaffected. Human α7 nAChRs were also sensitive to α-CtxArIB[V11L,V16D]: ACh-evoked currents in X. laevis oocytes expressing human α7 nAChRs were inhibited by α-CtxArIB[V11L,V16D] (IC50 3.4 nM) in a slowly reversible manner, with full recovery taking 15 min. This is consistent with the timecourse of recovery from blockade of rat α7 nAChRs in PC12 cells. α-CtxArIB[V11L,V16D] inhibited human native α7 nAChRs in SHSY5Y cells, activated by either choline or AR-R17779 plus PNU-120596. Rat brain α7 nAChRs contribute to dopamine release from striatal minces: α-CtxArIB[V11L,V16D] (300 nM) selectively inhibited choline-evoked dopamine release without affecting responses evoked by nicotine that activates heteromeric nAChRs. This study establishes that α-CtxArIB[V11L,V16D] selectively inhibits human and rat native α7 nAChRs with comparable potency, making this a potentially useful antagonist for investigating α7 nAChR functions. PMID:18664588

Role of the protein in the DNA sequence specificity of the cleavage site stabilized by the camptothecin topoisomerase IB inhibitor: a metadynamics study

PubMed Central

Coletta, Andrea; Desideri, Alessandro

2013-01-01

Camptothecin (CPT) is a topoisomerase IB (TopIB) selective inhibitor whose derivatives are currently used in cancer therapy. TopIB cleaves DNA at any sequence, but in the presence of CPT the only stabilized protein–DNA covalent complex is the one having a thymine in position −1 with respect to the cleavage site. A metadynamics simulation of two TopIB–DNA–CPT ternary complexes differing for the presence of a thymine or a cytosine in position −1 indicates the occurrence of two different drug’s unbinding pathways. The free-energy difference between the bound state and the transition state is large when a thymine is present in position −1 and is strongly reduced in presence of a cytosine, in line with the different drug stabilization properties of the two systems. Such a difference is strictly related to the changes in the hydrogen bond network between the protein, the DNA and the drug in the two systems, indicating a direct role of the protein in determining the specificity of the cleavage site sequence stabilized by the CPT. Calculations carried out in presence of one compound of the indenoisoquinoline family (NSC314622) indicate a comparable energy difference between the bound and the transition state independently of the presence of a thymine or a cytosine in position −1, in line with the experimental results. PMID:24003027

30 CFR 57.22501 - Personal electric lamps (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Personal electric lamps (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines). 57.22501 Section 57.22501 Mineral Resources MINE SAFETY AND... Illumination § 57.22501 Personal electric lamps (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines...

30 CFR 57.22501 - Personal electric lamps (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Personal electric lamps (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines). 57.22501 Section 57.22501 Mineral Resources MINE SAFETY AND... Illumination § 57.22501 Personal electric lamps (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines...

30 CFR 57.22501 - Personal electric lamps (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines).

Code of Federal Regulations, 2014 CFR

2014-07-01

... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Personal electric lamps (I-A, I-B, I-C, II-A... Illumination § 57.22501 Personal electric lamps (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines). Electric lamps used for personal illumination shall be approved by MSHA under the requirements of 30 CFR...

30 CFR 57.22501 - Personal electric lamps (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines).

Code of Federal Regulations, 2012 CFR

2012-07-01

... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Personal electric lamps (I-A, I-B, I-C, II-A... Illumination § 57.22501 Personal electric lamps (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines). Electric lamps used for personal illumination shall be approved by MSHA under the requirements of 30 CFR...

30 CFR 57.22501 - Personal electric lamps (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines).

Code of Federal Regulations, 2013 CFR

2013-07-01

... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Personal electric lamps (I-A, I-B, I-C, II-A... Illumination § 57.22501 Personal electric lamps (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines). Electric lamps used for personal illumination shall be approved by MSHA under the requirements of 30 CFR...

Photodynamic therapy with 3‐(1′‐hexyloxyethyl) pyropheophorbide‐a for early‐stage cancer of the larynx: Phase Ib study

PubMed Central

Rigual, Nestor R.; Arshad, Hassan; Cooper, Michele T.; Bellnier, David A.; Wilding, Gregory; Tan, Wei; Merzianu, Mihai; Henderson, Barbara W.

2015-01-01

Abstract Background The purpose of this study was for us to report results regarding the safety of 3‐(1′‐hexyloxyethyl) pyropheophorbide‐a (HPPH) mediated photodynamic therapy (PDT) in early laryngeal disease, and offer preliminary information on treatment responses. Methods A single‐institution, phase Ib, open label, noncomparative study of HPPH‐PDT in patients with high‐risk dysplasia, carcinoma in situ, and T1 squamous cell carcinoma (SCC) of the larynx. The primary outcomes were safety and maximum tolerated dose (MTD), and the secondary outcome was response. Results Twenty‐nine patients and 30 lesions were treated. The most common adverse event (AE) was transient hoarseness of voice. Severe edema, requiring tracheostomy, was the most serious AE, which occurred in 2 patients within several hours of therapy. The MTD was 100 J/cm2. Patients with T1 SCC seemed to have good complete response rate (82%) to HPPH‐PDT at MTD. Conclusion HPPH‐PDT can be safely used to treat early‐stage laryngeal cancer, with potential efficacy. © 2015 The Authors Head & Neck Published by Wiley Periodicals, Inc. Head Neck 38: E377–E383, 2016 PMID:25580824

Meta-analysis of Cholesteryl Ester Transfer Protein TaqIB Polymorphism and Risk of Myocardial Infarction

PubMed Central

Cao, Min; Zhou, Zhi-Wen; Fang, Bang-Jiang; Zhao, Cheng-Gen; Zhou, Duan

2014-01-01

Abstract A number of studies have been conducted to explore the association between the cholesteryl ester transfer protein (CETP) TaqIB polymorphism and risk of myocardial infarction (MI); however, the results are inconsistent. Therefore, we conducted this meta-analysis to clarify the issue based on all the data available. Eligible studies were retrieved by searching PubMed, Embase, Web of Science, and Google Scholar. We calculated the crude odds ratios (ORs) and corresponding 95% confidence intervals (95% CIs) to assess the association between the TaqIB polymorphism and risk of MI. We included 13 studies involving 8733 MI cases and 8573 controls in the meta-analysis. The pooled results from all included studies showed decreased MI risk in the analysis of the B2B2 versus B1B1 (OR = 0.78, 95% CI = 0.68–0.91), dominant (OR = 0.88, 95% CI = 0.77–0.99), and recessive genetic models (OR = 0.84, 95% CI = 0.78–0.91). The frequency of the B2B2 genotype in MI patients was lower (OR = 0.87, 95% CI = 0.81–0.94). However, there was no significant association in the B1B2 versus B1B1 analysis (OR = 0.92, 95% CI = 0.81–1.05) and no significant difference for the B1B1 genotype (OR = 1.04, 95% CI = 0.98–1.11) and B1B2 genotype (OR = 1.03, 95% CI = 0.97–1.08). Cumulative analysis confirmed these results. Our results suggest that the B2B2 genotype of the CETP TaqIB polymorphism is a protective factor against the development of MI. PMID:25474428

Meta-analysis of cholesteryl ester transfer protein TaqIB polymorphism and risk of myocardial infarction.

PubMed

Cao, Min; Zhou, Zhi-Wen; Fang, Bang-Jiang; Zhao, Cheng-Gen; Zhou, Duan

2014-11-01

A number of studies have been conducted to explore the association between the cholesteryl ester transfer protein (CETP) TaqIB polymorphism and risk of myocardial infarction (MI); however, the results are inconsistent. Therefore, we conducted this meta-analysis to clarify the issue based on all the data available.Eligible studies were retrieved by searching PubMed, Embase, Web of Science, and Google Scholar. We calculated the crude odds ratios (ORs) and corresponding 95% confidence intervals (95% CIs) to assess the association between the TaqIB polymorphism and risk of MI.We included 13 studies involving 8733 MI cases and 8573 controls in the meta-analysis. The pooled results from all included studies showed decreased MI risk in the analysis of the B2B2 versus B1B1 (OR = 0.78, 95% CI = 0.68-0.91), dominant (OR = 0.88, 95% CI = 0.77-0.99), and recessive genetic models (OR = 0.84, 95% CI = 0.78-0.91). The frequency of the B2B2 genotype in MI patients was lower (OR = 0.87, 95% CI = 0.81-0.94). However, there was no significant association in the B1B2 versus B1B1 analysis (OR = 0.92, 95% CI = 0.81-1.05) and no significant difference for the B1B1 genotype (OR = 1.04, 95% CI = 0.98-1.11) and B1B2 genotype (OR = 1.03, 95% CI = 0.97-1.08). Cumulative analysis confirmed these results.Our results suggest that the B2B2 genotype of the CETP TaqIB polymorphism is a protective factor against the development of MI.

The Dimanganese(II) Site of Bacillus subtilis Class Ib Ribonucleotide Reductase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Boal, Amie K.; Cotruvo, Jr., Joseph A.; Stubbe, JoAnne

2014-10-02

Class Ib ribonucleotide reductases (RNRs) use a dimanganese-tyrosyl radical cofactor, Mn{sub 2}{sup III}-Y{sm_bullet}, in their homodimeric NrdF ({beta}2) subunit to initiate reduction of ribonucleotides to deoxyribonucleotides. The structure of the Mn{sub 2}{sup II} form of NrdF is an important component in understanding O{sub 2}-mediated formation of the active metallocofactor, a subject of much interest because a unique flavodoxin, NrdI, is required for cofactor assembly. Biochemical studies and sequence alignments suggest that NrdF and NrdI proteins diverge into three phylogenetically distinct groups. The only crystal structure to date of a NrdF with a fully ordered and occupied dimanganese site is thatmore » of Escherichia coli Mn{sub 2}{sup II}-NrdF, prototypical of the enzymes from actinobacteria and proteobacteria. Here we report the 1.9 {angstrom} resolution crystal structure of Bacillus subtilis Mn{sub 2}{sup II}-NrdF, representative of the enzymes from a second group, from Bacillus and Staphylococcus. The structures of the metal clusters in the {beta}2 dimer are distinct from those observed in E. coli Mn{sub 2}{sup II}-NrdF. These differences illustrate the key role that solvent molecules and protein residues in the second coordination sphere of the Mn{sub 2}{sup II} cluster play in determining conformations of carboxylate residues at the metal sites and demonstrate that diverse coordination geometries are capable of serving as starting points for Mn{sub 2}{sup III}-Y{sm_bullet} cofactor assembly in class Ib RNRs.« less

miR-16 and miR-125b are involved in barrier function dysregulation through the modulation of claudin-2 and cingulin expression in the jejunum in IBS with diarrhoea.

PubMed

Martínez, Cristina; Rodiño-Janeiro, Bruno K; Lobo, Beatriz; Stanifer, Megan L; Klaus, Bernd; Granzow, Martin; González-Castro, Ana M; Salvo-Romero, Eloisa; Alonso-Cotoner, Carmen; Pigrau, Marc; Roeth, Ralph; Rappold, Gudrun; Huber, Wolfgang; González-Silos, Rosa; Lorenzo, Justo; de Torres, Inés; Azpiroz, Fernando; Boulant, Steeve; Vicario, María; Niesler, Beate; Santos, Javier

2017-09-01

Micro-RNAs (miRNAs) play a crucial role in controlling intestinal epithelial barrier function partly by modulating the expression of tight junction (TJ) proteins. We have previously shown differential messenger RNA (mRNA) expression correlated with ultrastructural abnormalities of the epithelial barrier in patients with diarrhoea-predominant IBS (IBS-D). However, the participation of miRNAs in these differential mRNA-associated findings remains to be established. Our aims were (1) to identify miRNAs differentially expressed in the small bowel mucosa of patients with IBS-D and (2) to explore putative target genes specifically involved in epithelial barrier function that are controlled by specific dysregulated IBS-D miRNAs. Healthy controls and patients meeting Rome III IBS-D criteria were studied. Intestinal tissue samples were analysed to identify potential candidates by: (a) miRNA-mRNA profiling; (b) miRNA-mRNA pairing analysis to assess the co-expression profile of miRNA-mRNA pairs; (c) pathway analysis and upstream regulator identification; (d) miRNA and target mRNA validation. Candidate miRNA-mRNA pairs were functionally assessed in intestinal epithelial cells. IBS-D samples showed distinct miRNA and mRNA profiles compared with healthy controls. TJ signalling was associated with the IBS-D transcriptional profile. Further validation of selected genes showed consistent upregulation in 75% of genes involved in epithelial barrier function. Bioinformatic analysis of putative miRNA binding sites identified hsa-miR-125b-5p and hsa-miR-16 as regulating expression of the TJ genes CGN (cingulin) and CLDN2 (claudin-2), respectively. Consistently, protein expression of CGN and CLDN2 was upregulated in IBS-D, while the respective targeting miRNAs were downregulated. In addition, bowel dysfunction, perceived stress and depression and number of mast cells correlated with the expression of hsa-miR-125b-5p and hsa-miR-16 and their respective target proteins. Modulation of the

30 CFR 57.22227 - Approved testing devices (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Approved testing devices (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines). 57.22227 Section 57.22227 Mineral Resources MINE SAFETY AND... Ventilation § 57.22227 Approved testing devices (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines). (a...

MGOUN1 encodes an Arabidopsis type IB DNA topoisomerase required in stem cell regulation and to maintain developmentally regulated gene silencing.

PubMed

Graf, Philipp; Dolzblasz, Alicja; Würschum, Tobias; Lenhard, Michael; Pfreundt, Ulrike; Laux, Thomas

2010-03-01

Maintenance of stem cells in the Arabidopsis thaliana shoot meristem is regulated by signals from the underlying cells of the organizing center, provided through the transcription factor WUSCHEL (WUS). Here, we report the isolation of several independent mutants of MGOUN1 (MGO1) as genetic suppressors of ectopic WUS activity and enhancers of stem cell defects in hypomorphic wus alleles. mgo1 mutants have previously been reported to result in a delayed progression of meristem cells into differentiating organ primordia (Laufs et al., 1998). Genetic analyses indicate that MGO1 functions together with WUS in stem cell maintenance at all stages of shoot and floral meristems. Synergistic interactions of mgo1 with several chromatin mutants suggest that MGO1 affects gene expression together with chromatin remodeling pathways. In addition, the expression states of developmentally regulated genes are randomly switched in mgo1 in a mitotically inheritable way, indicating that MGO1 stabilizes epigenetic states against stochastically occurring changes. Positional cloning revealed that MGO1 encodes a putative type IB topoisomerase, which in animals and yeast has been shown to be required for regulation of DNA coiling during transcription and replication. The specific developmental defects in mgo1 mutants link topoisomerase IB function in Arabidopsis to stable propagation of developmentally regulated gene expression.

AmeriFlux US-IB2 Fermi National Accelerator Laboratory- Batavia (Prairie site)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Matamala, Roser

2016-01-01

This is the AmeriFlux version of the carbon flux data for the site US-IB2 Fermi National Accelerator Laboratory- Batavia (Prairie site). Site Description - Two eddy correlation systems are installed at Fermi National Accelerator Laboratory: one on a restored prairie (established October 2004) and one on a corn/soybean rotation agricultural field (established in July 2005). The prairie site had been farmed for more than 100 years, but was converted to prairie in 1989. April annual to bi-annual prescribed burns have taken place from 1994 - 2007.

SYMPOSIUM REPORT: An Evidence-Based Approach to IBS and CIC: Applying New Advances to Daily Practice: A Review of an Adjunct Clinical Symposium of the American College of Gastroenterology Meeting October 16, 2016 • Las Vegas, Nevada.

PubMed

Chey, William D

2017-02-01

Many nonpharmacologic and pharmacologic therapies are available to manage irritable bowel syndrome (IBS) and chronic idiopathic constipation (CIC). The American College of Gastroenterology (ACG) regularly publishes reviews on IBS and CIC therapies. The most recent of these reviews was published by the ACG Task Force on the Management of Functional Bowel Disorders in 2014. The key objective of this review was to evaluate the efficacy of therapies for IBS or CIC compared with placebo or no treatment in randomized controlled trials. Evidence-based approaches to managing diarrhea-predominant IBS include dietary measures, such as a diet low in gluten and fermentable oligo-, di-, and monosaccharides and polyols (FODMAPs); loperamide; antispasmodics; peppermint oil; probiotics; tricyclic antidepressants; alosetron; eluxadoline, and rifaximin. Evidence-based approaches to managing constipation-predominant IBS and CIC include fiber, stimulant laxatives, polyethylene glycol, selective serotonin reuptake inhibitors, lubiprostone, and guanylate cyclase agonists. With the growing evidence base for IBS and CIC therapies, it has become increasingly important for clinicians to assess the quality of evidence and understand how to apply it to the care of individual patients.

An Outbreak of Acute Hepatitis Caused by Genotype IB Hepatitis A Viruses Contaminating the Water Supply in Thailand.

PubMed

Ruchusatsawat, Kriangsak; Wongpiyabovorn, Jongkonnee; Kawidam, Chonthicha; Thiemsing, Laddawan; Sangkitporn, Somchai; Yoshizaki, Sayaka; Tatsumi, Masashi; Takeda, Naokazu; Ishii, Koji

2016-01-01

In 2000, an outbreak of acute hepatitis A was reported in a province adjacent to Bangkok, Thailand. To investigate the cause of the 2000 hepatitis A outbreaks in Thailand using molecular epidemiological analysis. Serum and stool specimens were collected from patients who were clinically diagnosed with acute viral hepatitis. Water samples from drinking water and deep-drilled wells were also collected. These specimens were subjected to polymerase chain reaction (PCR) amplification and sequencing of the VP1/2A region of the hepatitis A virus (HAV) genome. The entire genome sequence of one of the fecal specimens was determined and phylogenetically analyzed with those of known HAV sequences. Eleven of 24 fecal specimens collected from acute viral hepatitis patients were positive as determined by semi- nested reverse transcription PCR targeting the VP1/2A region of HAV. The nucleotide sequence of these samples had an identical genotype IB sequence, suggesting that the same causative agent was present. The complete nucleotide sequence derived from one of the samples indicated that the Thai genotype IB strain should be classified in a unique phylogenetic cluster. The analysis using an adjusted odds ratio showed that the consumption of groundwater was the most likely risk factor associated with the disease. © 2017 S. Karger AG, Basel.

H+ -pyrophosphatase IbVP1 promotes efficient iron use in sweet potato [Ipomoea batatas (L.) Lam.].

PubMed

Fan, Weijuan; Wang, Hongxia; Wu, Yinliang; Yang, Nan; Yang, Jun; Zhang, Peng

2017-06-01

Iron (Fe) deficiency is one of the most common micronutrient deficiencies limiting crop production globally, especially in arid regions because of decreased availability of iron in alkaline soils. Sweet potato [Ipomoea batatas (L.) Lam.] grows well in arid regions and is tolerant to Fe deficiency. Here, we report that the transcription of type I H + -pyrophosphatase (H + -PPase) gene IbVP1 in sweet potato plants was strongly induced by Fe deficiency and auxin in hydroponics, improving Fe acquisition via increased rhizosphere acidification and auxin regulation. When overexpressed, transgenic plants show higher pyrophosphate hydrolysis and plasma membrane H + -ATPase activity compared with the wild type, leading to increased rhizosphere acidification. The IbVP1-overexpressing plants showed better growth, including enlarged root systems, under Fe-sufficient or Fe-deficient conditions. Increased ferric precipitation and ferric chelate reductase activity in the roots of transgenic lines indicate improved iron uptake, which is also confirmed by increased Fe content and up-regulation of Fe uptake genes, e.g. FRO2, IRT1 and FIT. Carbohydrate metabolism is significantly affected in the transgenic lines, showing increased sugar and starch content associated with the increased expression of AGPase and SUT1 genes and the decrease in β-amylase gene expression. Improved antioxidant capacities were also detected in the transgenic plants, which showed reduced H 2 O 2 accumulation associated with up-regulated ROS-scavenging activity. Therefore, H + -PPase plays a key role in the response to Fe deficiency by sweet potato and effectively improves the Fe acquisition by overexpressing IbVP1 in crops cultivated in micronutrient-deficient soils. © 2016 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

Upregulation of Ih expressed in IB4-negative Aδ nociceptive DRG neurons contributes to mechanical hypersensitivity associated with cervical radiculopathic pain

PubMed Central

Liu, Da-Lu; Lu, Na; Han, Wen-Juan; Chen, Rong-Gui; Cong, Rui; Xie, Rou-Gang; Zhang, Yu-Fei; Kong, Wei-Wei; Hu, San-Jue; Luo, Ceng

2015-01-01

Cervical radiculopathy represents aberrant mechanical hypersensitivity. Primary sensory neuron’s ability to sense mechanical force forms mechanotransduction. However, whether this property undergoes activity-dependent plastic changes and underlies mechanical hypersensitivity associated with cervical radiculopathic pain (CRP) is not clear. Here we show a new CRP model producing stable mechanical compression of dorsal root ganglion (DRG), which induces dramatic behavioral mechanical hypersensitivity. Amongst nociceptive DRG neurons, a mechanically sensitive neuron, isolectin B4 negative Aδ-type (IB4− Aδ) DRG neuron displays spontaneous activity with hyperexcitability after chronic compression of cervical DRGs. Focal mechanical stimulation on somata of IB4- Aδ neuron induces abnormal hypersensitivity. Upregulated HCN1 and HCN3 channels and increased Ih current on this subset of primary nociceptors underlies the spontaneous activity together with neuronal mechanical hypersensitivity, which further contributes to the behavioral mechanical hypersensitivity associated with CRP. This study sheds new light on the functional plasticity of a specific subset of nociceptive DRG neurons to mechanical stimulation and reveals a novel mechanism that could underlie the mechanical hypersensitivity associated with cervical radiculopathy. PMID:26577374

Changes in Brain Function in Patients With Stage I, Stage II, Stage III, or Stage IV Ovarian, Primary Peritoneal, or Fallopian Tube Cancer Who Are Receiving Chemotherapy

ClinicalTrials.gov

2018-04-11

Cognitive Side Effects of Cancer Therapy; Malignant Ovarian Epithelial Tumor; Ovarian Brenner Tumor; Ovarian Carcinosarcoma; Ovarian Choriocarcinoma; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Dysgerminoma; Ovarian Embryonal Carcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mixed Germ Cell Tumor; Ovarian Mucinous Cystadenocarcinoma; Ovarian Polyembryoma; Ovarian Sarcoma; Ovarian Seromucinous Carcinoma; Ovarian Serous Cystadenocarcinoma; Ovarian Teratoma; Ovarian Yolk Sac Tumor; Stage I Ovarian Cancer; Stage IA Fallopian Tube Cancer; Stage IA Ovarian Cancer; Stage IA Ovarian Germ Cell Tumor; Stage IB Fallopian Tube Cancer; Stage IB Ovarian Cancer; Stage IB Ovarian Germ Cell Tumor; Stage IC Fallopian Tube Cancer; Stage IC Ovarian Cancer; Stage IC Ovarian Germ Cell Tumor; Stage II Ovarian Cancer; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Cancer; Stage IIA Ovarian Germ Cell Tumor; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Cancer; Stage IIB Ovarian Germ Cell Tumor; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Cancer; Stage IIC Ovarian Germ Cell Tumor; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Ovarian Germ Cell Tumor; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Ovarian Germ Cell Tumor; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Ovarian Germ Cell Tumor; Stage IIIC Primary Peritoneal Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Ovarian Germ Cell Tumor; Stage IV Primary Peritoneal Cancer; Undifferentiated Ovarian Carcinoma

A Global Study of the Practice and Impact of Distributed Instructional Leadership in International Baccalaureate (IB) Schools

ERIC Educational Resources Information Center

Hallinger, Philip; Lee, Moosung

2012-01-01

Over the last half century, international schools have come to represent an increasingly important sector in the changing global education context. International Baccalaureate (IB) schools in particular, and international schools more generally, can be viewed as specific types of educational contexts for leadership practice. In this article we…

A nonpolymorphic major histocompatibility complex class Ib molecule binds a large array of diverse self-peptides

PubMed Central

1994-01-01

Unlike the highly polymorphic major histocompatibility complex (MHC) class Ia molecules, which present a wide variety of peptides to T cells, it is generally assumed that the nonpolymorphic MHC class Ib molecules may have evolved to function as highly specialized receptors for the presentation of structurally unique peptides. However, a thorough biochemical analysis of one class Ib molecule, the soluble isoform of Qa-2 antigen (H-2SQ7b), has revealed that it binds a diverse array of structurally similar peptides derived from intracellular proteins in much the same manner as the classical antigen-presenting molecules. Specifically, we find that SQ7b molecules are heterodimers of heavy and light chains complexed with nonameric peptides in a 1:1:1 ratio. These peptides contain a conserved hydrophobic residue at the COOH terminus and a combination of one or more conserved residue(s) at P7 (histidine), P2 (glutamine/leucine), and/or P3 (leucine/asparagine) as anchors for binding SQ7b. 2 of 18 sequenced peptides matched cytosolic proteins (cofilin and L19 ribosomal protein), suggesting an intracellular source of the SQ7b ligands. Minimal estimates of the peptide repertoire revealed that at least 200 different naturally processed self-peptides can bind SQ7b molecules. Since Qa-2 molecules associate with a diverse array of peptides, we suggest that they function as effective presenting molecules of endogenously synthesized proteins like the class Ia molecules. PMID:8294869

Development and validation of the irritable bowel syndrome scale under the system of quality of life instruments for chronic diseases QLICD-IBS: combinations of classical test theory and generalizability theory.

PubMed

Lei, Pingguang; Lei, Guanghe; Tian, Jianjun; Zhou, Zengfen; Zhao, Miao; Wan, Chonghua

2014-10-01

This paper is aimed to develop the irritable bowel syndrome (IBS) scale of the system of Quality of Life Instruments for Chronic Diseases (QLICD-IBS) by the modular approach and validate it by both classical test theory and generalizability theory. The QLICD-IBS was developed based on programmed decision procedures with multiple nominal and focus group discussions, in-depth interview, and quantitative statistical procedures. One hundred twelve inpatients with IBS were used to provide the data measuring QOL three times before and after treatments. The psychometric properties of the scale were evaluated with respect to validity, reliability, and responsiveness employing correlation analysis, factor analyses, multi-trait scaling analysis, t tests and also G studies and D studies of generalizability theory analysis. Multi-trait scaling analysis, correlation, and factor analyses confirmed good construct validity and criterion-related validity when using SF-36 as a criterion. Test-retest reliability coefficients (Pearson r and intra-class correlation (ICC)) for the overall score and all domains were higher than 0.80; the internal consistency α for all domains at two measurements were higher than 0.70 except for the social domain (0.55 and 0.67, respectively). The overall score and scores for all domains/facets had statistically significant changes after treatments with moderate or higher effect size standardized response mean (SRM) ranging from 0.72 to 1.02 at domain levels. G coefficients and index of dependability (Ф coefficients) confirmed the reliability of the scale further with more exact variance components. The QLICD-IBS has good validity, reliability, responsiveness, and some highlights and can be used as the quality of life instrument for patients with IBS.

Detection of acrA, acrB, aac(6')-Ib-cr, and qepA genes among clinical isolates of Escherichia coli and Klebsiella pneumoniae.

PubMed

Heidary, Mohsen; Bahramian, Aghil; Hashemi, Ali; Goudarzi, Mehdi; Omrani, Vahid Fallah; Eslami, Gita; Goudarzi, Hossein

2017-03-01

The distribution of drug resistance among clinical isolates of Escherichia coli and Klebsiella pneumoniae has limited the therapeutic options. The aim of this study was to report the prevalence of quinolone resistance genes among E. coli and K. pneumoniae clinical strains isolated from three educational hospitals of Tehran, Iran. A total of 100 strains of E. coli from Labbafinejad and Taleghani Hospitals and 100 strains of K. pneumoniae from Mofid Children and Taleghani Hospitals were collected between January 2013 and May 2014. Antimicrobial susceptibility tests were done by disk diffusion method based on Clinical and Laboratory Standards Institute guidelines. Detection of qepA, aac(6')-Ib-cr, acrA, and acrB genes was done by polymerase chain reaction (PCR). In this study, fosfomycin and imipenem against E. coli and fosfomycin and tigecycline against K. pneumoniae had the best effect in antimicrobial susceptibility tests. PCR assay using specific primers demonstrated that the prevalence of qepA, aac(6')-Ib-cr, acrA, and acrB genes among the 100 E. coli isolates was 0 (0%), 87 (87%), 92 (92%), and 84 (84%), respectively. The prevalence of qepA, aac(6')-Ib-cr, acrA, and acrB genes among the 100 K. pneumoniae isolates was 4 (4%), 85 (85%), 94 (94%), and 87 (87%), respectively. The distribution of qepA, aac(6')-Ib-cr, acrA, and acrB resistance determinants in E. coli and K. pneumoniae is a great concern. Therefore, infection control and prevention of spread of drug-resistant bacteria need careful management of medication and identification of resistant isolates.

Quantifying women's stated benefit-risk trade-off preferences for IBS treatment outcomes.

PubMed

Johnson, F Reed; Hauber, A Brett; Ozdemir, Semra; Lynd, Larry

2010-01-01

The Food and Drug Administration, currently, is exploring quantitative benefit-risk methods to support regulatory decision-making. A scientifically valid method for assessing patients' benefit-risk trade-off preferences is needed to compare risks and benefits in a common metric. The study aims to quantify the maximum acceptable risk (MAR) of treatment-related adverse events (AEs) that women with diarrhea-predominant irritable bowel syndrome (IBS) are willing to accept in exchange for symptom relief. A stated-choice survey was used to elicit trade-off preferences among constructed treatment profiles, each defined by symptom severity and treatment-related AEs. Symptom attributes included frequency of abdominal pain and discomfort, frequency of diarrhea, and frequency of urgency. AE attributes included frequency of mild-to-moderate constipation and the risk of four possible serious AEs. A Web-enabled survey was administered to 589 female US residents at least 18 years of age with a self-reported diagnosis of diarrhea-predominant IBS. Preference weights and MAR were estimated using mixed-logit methods. SUBJECTS were willing to accept higher risks of serious AEs in return for treatments offering better symptom control. For an improvement from the lowest to the highest of four benefit levels, subjects were willing to tolerate a 2.65% increase in impacted-bowel risk, but only a 1.34% increase in perforated-bowel risk. Variation in MARs across AE types is consistent with the relative seriousness of the AEs. Stated-preference methods offer a scientifically valid approach to quantifying benefit-risk trade-off preferences that can be used to inform regulatory decision-making.

Wide-range antifungal antagonism of Paenibacillus ehimensis IB-X-b and its dependence on chitinase and beta-1,3-glucanase production.

PubMed

Aktuganov, G; Melentjev, A; Galimzianova, N; Khalikova, E; Korpela, T; Susi, P

2008-07-01

Previously, we isolated a strain of Bacillus that had antifungal activity and produced lytic enzymes with fungicidal potential. In the present study, we identified the bacterium as Paenibacillus ehimensis and further explored its antifungal properties. In liquid co-cultivation assays, P. ehimensis IB-X-b decreased biomass production of several pathogenic fungi by 45%-75%. The inhibition was accompanied by degradation of fungal cell walls and alterations in hyphal morphology. Residual medium from cultures of P. ehimensis IB-X-b inhibited fungal growth, indicating the inhibitors were secreted into the medium. Of the 2 major lytic enzymes, chitinases were only induced by chitin-containing substrates, whereas beta-1,3-glucanase showed steady levels in all carbon sources. Both purified chitinase and beta-1,3-glucanase degraded cell walls of macerated fungal mycelia, whereas only the latter also degraded cell walls of intact mycelia. The results indicate synergism between the antifungal action mechanisms of these enzymes in which beta-1,3-glucanase is the initiator of the cell wall hydrolysis, whereas the degradation process is reinforced by chitinases. Paenibacillus ehimensis IB-X-b has pronounced antifungal activity with a wide range of fungi and has potential as a biological control agent against plant pathogenic fungi.

Complete sequence of RNA3 of Cucumber mosaic virus isolates infecting Gerbera jamesonii suggests its grouping under IB subgroup.

PubMed

Gautum, K K; Raj, R; Kumar, S; Raj, S K; Roy, R K; Katiyar, R

2014-01-01

The complete RNA3 genome of Cucumber mosaic virus (CMV) was amplified by RT-PCR from three infected gerbera (Gerbera jamesonii) leaf samples exhibiting severe chlorotic mosaic and flower deformation symptoms. The amplicons obtained were cloned sequenced and deposited in GenBank under the accessions JN692495, JX913531 (from cv. Zingaro) and JX888093 (from cv. Silvester). These sequences shared 98-99 % identities to each other and with a strain of CMV-Banana reported from India, and 90-95 % identities with various strains of CMV reported worldwide. Phylogenetic analysis revealed their closest affinity with CMV-Banana strain, and close relationships with several other strains of CMV of subgroup IB. This study provides evidence of subgroup IB CMV causing severe chlorosis and flower deformation in two cultivars (Zingaro and Silvester) of G. jamesonii in India.

Electrophysiological characteristics of IB4-negative TRPV1-expressing muscle afferent DRG neurons.

PubMed

Lin, Yi-Wen; Chen, Chih-Cheng

2015-01-01

Muscle afferent neurons that express transient receptor potential vanilloid type I (TRPV1) are responsible for muscle pain associated with tissue acidosis. We have previously found that TRPV1 of isolectin B4 (IB4)-negative muscle nociceptors plays an important role in the acid-induced hyperalgesic priming and the development of chronic hyperalgesia in a mouse model of fibromyalgia. To understand the electrophysiological properties of the TRPV1-expressing muscle afferent neurons, we used whole-cell patch clamp recording to study the acid responsiveness and action potential (AP) configuration of capsaicin-sensitive neurons innervating to gastrocnemius muscle. Here we showed that IB4-negative TRPV1-expressing muscle afferent neurons are heterogeneous in terms of cell size, resting membrane potential, AP configuration, tetrodotoxin (TTX)-resistance, and acid-induced current (I acid), as well as capsaicin-induced current (I cap). TRPV1-expressing neurons were all acid-sensitive and could be divided into two acid-sensitive groups depending on an acid-induced sustained current (type I) or an acid-induced biphasic ASIC3-like current (type II). Type I TRPV1-expressing neurons were distinguishable from type II TRPV1-expressing neurons in AP overshoot, after-hyperpolarization duration, and all I acid parameters, but not in AP threshold, TTX-resistance, resting membrane potential, and I cap parameters. These differential biophysical properties of TRPV1-expressing neurons might partially annotate their different roles involved in the development and maintenance of chronic muscle pain.

Development of W/C soft x-ray multilayer mirror by ion beam sputtering (IBS) system for below 50A wavelength

DOE Office of Scientific and Technical Information (OSTI.GOV)

Biswas, A.; Bhattacharyya, D.

A home-made Ion Beam Sputtering (IBS) system has been developed in our laboratory. Using the IBS system single layer W and single layer C film has been deposited at 1000eV Ar ion energy and 10mA ion current. The W-film has been characterized by grazing Incidence X-ray reflectrometry (GIXR) technique and Atomic Force Microscope technique. The single layer C-film has been characterized by Spectroscopic Ellipsometric technique. At the same deposition condition 25-layer W/C multilayer film has been deposited which has been designed for using as mirror at 30 Degree-Sign grazing incidence angle around 50A wavelength. The multilayer sample has been characterizedmore » by measuring reflectivity of CuK{alpha} radiation and soft x-ray radiation around 50A wavelength.« less

Saturn Apollo Program

NASA Image and Video Library

1965-01-01

In one of the initial assembly steps for the first stage (S-IB stage) of the Saturn IB launch vehicle, workers at the Michoud Assembly Facility (MAF) near New Orleans, Louisiana, position a "Spider Beam" to the central liquid-oxygen tank of the S-IB stage. Developed by the Marshall Space Flight Center (MSFC) and built by the Chrysler Corporation at MAF, the S-IB stage utilized eight H-1 engines to produce a combined thrust of 1,600,000 pounds.

Carboplatin and Paclitaxel With or Without Cisplatin and Radiation Therapy in Treating Patients With Stage I, Stage II, Stage III, or Stage IVA Endometrial Cancer

ClinicalTrials.gov

2018-01-09

Endometrial Clear Cell Adenocarcinoma; Endometrial Serous Adenocarcinoma; Stage IA Uterine Corpus Cancer; Stage IB Uterine Corpus Cancer; Stage II Uterine Corpus Cancer; Stage IIIA Uterine Corpus Cancer; Stage IIIB Uterine Corpus Cancer; Stage IIIC Uterine Corpus Cancer; Stage IVA Uterine Corpus Cancer

An appraisal of the Permian palaeobiodiversity and geology of the Ib-River Basin, eastern coastal area, India

NASA Astrophysics Data System (ADS)

Goswami, Shreerup; Saxena, Anju; Singh, Kamal Jeet; Chandra, Shaila; Cleal, Christopher J.

2018-05-01

The Ib-River Basin situated in the east coastal area of India, in Odisha State is a south-eastern part of the Mahanadi Master Basin. A large number of plant macrofossils belonging to the Glossopteris flora were described and documented between 2006 and 2010 from various localities of the Barakar and Lower Kamthi formations of this basin. The floral components representing leaves, roots and fructifications in these assemblages belong to the Lycopodiales, Equisetales, Sphenophyllales, Filicales, Cordaitales, Cycadales, Ginkgoales, Coniferales and Glossopteridales. In the present study, all the available data pertaining to the biological remains, petrological analyses as well as the geology of this basin are reviewed and analyzed to deduce and reconstruct the biostratigraphy, palaeoclimate, palaeoenvironment and the landscape of this basin during Permian time in general and during the deposition of Barakar (Artinskian - Kungurian) and Lower Kamthi (Lopingian) formations in particular. The floral composition suggests the prevalence of a temperate climate with a slight change from warm moist to warm dry conditions during the deposition of the Barakar Formation and warm and humid during the deposition of Lower Kamthi sediments. Distribution of various plant groups in the Barakar and Lower Kamthi formations have been shown to depict the biodiversity trends. Vegetational reconstructions during the deposition of the Barakar and Lower Kamthi formations around the Ib-River Basin have also been attempted based on all the fossil records from this area. The status of unclassified Barakar and Kamthi formations has been redefined. Apart from megafloristics, the palynology of the basin is also discussed. Possible marine incursions and marine marginal environment in the Ib-Basin during Permian are overtly summarized on the basis of records of acritarchs, typical marine ichnofossils and evidences of wave activity in Lower Gondwana sediments of this Basin.

Saturn Apollo Program

NASA Image and Video Library

1965-04-01

S-IB-1, the first flight version of the Saturn IB launch vehicle's first stage (S-IB stage), undergoes a full-duration static firing in Saturn IB static test stand at the Marshall Space Flight Center (MSFC) on April 13, 1965. Developed by the MSFC and built by the Chrysler Corporation at the Michoud Assembly Facility (MAF) in New Orleans, Louisiana, the 90,000-pound booster utilized eight H-1 engines to produce a combined thrust of 1,600,000 pounds. Between April 1965 and July 1968, MSFC performed thirty-two static tests on twelve different S-IB stages.

Does adjuvant therapy improve overall survival for stage IA/B pancreatic adenocarcinoma?

PubMed

Ostapoff, Katherine T; Gabriel, Emmanuel; Attwood, Kristopher; Kuvshinoff, Boris W; Nurkin, Steven J; Hochwald, Steven N

2017-07-01

Current guidelines recommend adjuvant chemotherapy for resected pancreatic adenocarcinoma (PDAC). However, no studies have addressed its survival benefit for stage I patients as they comprise <10% of PDAC. Using the NCDB 2006-2012, resected PDAC patients with stage I disease who received adjuvant therapy (chemotherapy or chemoradiation) were analyzed. Factors associated with overall survival (OS) were identified. 3909 patients with resected stage IA or IB PDAC were identified. Median OS was 60.3 months (mo) for stage IA and 36.9 mo for IB. 45.5% received adjuvant chemotherapy; 19.9% received adjuvant chemoradiation. There was OS benefit for both stage IA/IB patients with adjuvant chemotherapy (HR = 0.73 and 0.76 for IA and IB, respectively, p = 0.002 and <0.001). For patients with Stage IA disease (n = 1,477, 37.8%), age ≥70 (p < 0.001), higher grade (p < 0.001), ≤10 lymph nodes examined (p = 0.008), positive margins (p < 0.001), and receipt of adjuvant chemoradiation (p = 0.002) were associated with worse OS. For stage IB patients (n = 2,432, 62.2%), similar associations were observed with the exception of adjuvant chemoradiation whereby there was no significant association (p = 0.35). Adjuvant chemotherapy was associated with an OS benefit for patients with stage I PDAC; adjuvant chemoradiation was either of no benefit or associated with worse OS. Copyright © 2017 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.

Polygalacturonase: production of pectin depolymerising enzyme from Bacillus licheniformis KIBGE IB-21.

PubMed

Rehman, Haneef Ur; Qader, Shah Ali Ul; Aman, Afsheen

2012-09-01

Polygalacturonase is an enzyme that hydrolyzes external and internal α (1-4) glycosidic bonds of pectin to decrease the viscosity of fruits juices and vegetable purees. Several bacterial strains were isolated from soil and rotten vegetables and screened for polygalacturonase production. The strain which produced maximum polygalacturonase was identified Bacillus licheniformis on the basis of taxonomic studies and 16S rDNA analysis. The isolated bacterial strain produced maximum polygalacturonase at 37 °C after 48 h of fermentation. Among various carbon sources apple pectin (1.0%) showed maximum enzyme production. Different agro industrial wastes were also used as substrate in batch fermentation and it was found that wheat bran is capable of producing high yield of enzyme. Maximum polygalacturonase production was obtained by using yeast extract (0.3%) as a nitrogen source. It was observed that B. licheniformis KIBGE IB-21 is capable of producing 1015 U/mg of polygalacturonase at neutral pH. Copyright © 2012 Elsevier Ltd. All rights reserved.

Saturn Apollo Program

NASA Image and Video Library

1969-01-01

In the "clustering" procedure, an initial assembly step for the first stage (S-IB stage) of the Saturn IB launch vehicle, workers at the Michoud Assembly Facility (MAF) near New Orleans, Louisiana, place the first of eight outboard fuel tanks (left) next to the central liquid-oxygen tank of S-IB stage. Developed by the Marshall Space Flight Center (MSFC) and built by the Chrysler Corporation at MAF, the S-IB stage utilized eight H-1 engines to produce a combined thrust of 1,600,000 pounds.

Saturn Apollo Program

NASA Image and Video Library

1969-01-01

In the clustering procedure, an initial assembly step for the first stage (S-IB stage) of the Saturn IB launch vehicle, workers at the Michoud Assembly Facility (MAF) near New Orleans, Louisiana, place the first of eight outboard fuel tanks next to the central liquid-oxygen tank of the S-IB stage. Developed by the Marshall Space Flight Center (MSFC) and built by the Chrysler Corporation at MAF, the S-IB stage utilized eight H-1 engines to produce a combined thrust of 1,600,000 pounds.

In vivo body composition in autochthonous and conventional pig breeding groups by dual-energy X-ray absorptiometry and magnetic resonance imaging under special consideration of Cerdo Ibérico.

PubMed

Kremer, P V; Fernández-Fígares, I; Förster, M; Scholz, A M

2012-12-01

The improvement of carcass quality is one of the main breeding goals in pig production. To select appropriate breeding animals, it is of major concern to exactly and reliably analyze the body composition in vivo. Therefore, the objective of the study was to examine whether the combination of dual-energy X-ray absorptiometry (DXA) and magnetic resonance imaging (MRI) offers the opportunity to reliably analyze quantitative and qualitative body composition characteristics of different pig breeding groups in vivo. In this study, a total of 77 pigs were studied by DXA and MRI at an average age of 154 days. The pigs originated from different autochthonous or conventional breeds or crossbreeds and were grouped into six breed types: Cerdo Ibérico (Ib); Duroc × Ib (Du_Ib); White Sow Lines (WSL, including German Landrace and German Large White); Hampshire/Pietrain (Pi_Ha, including Hampshire, Pietrain × Hampshire (PiHa) and Pietrain × PiHa); Pietrain/Duroc (Pi_Du, including Pietrain × Duroc (PiDu) and Pietrain × PiDu); crossbred WSL (PiDu_WSL, including Pietrain × WSL and PiDu × WSL). A whole-body scan was performed by DXA with a GE Lunar DPX-IQ in order to measure the amount and percentage of fat tissue (FM; %FM), lean tissue (LM; %LM) and bone mineral, whereas a Siemens Magnetom Open with a large body coil was used for MRI in the thorax region between 13th and 14th vertebrae in order to measure the area of the loin (LA) and the above back fat area (FA) of both body sides. A GLM procedure using SAS 9.2 was used to analyze the data. As expected, the native breed Ib followed by Du_Ib crossbreeds showed the highest %FM (27.2%, 25.0%) combined with the smallest LA (46.2 cm2, 73.6 cm2), whereas Ib had the lowest BW at an average age of 154 days. Pigs with Pi_Ha origin presented the least %FM (12.4%) and largest LA (99.5 cm2). The WSL and PiDu_WSL showed an intermediate body composition. Therefore, it could be concluded that DXA and MRI and especially their combination

External Guide Sequences Targeting the aac(6′)-Ib mRNA Induce Inhibition of Amikacin Resistance▿

PubMed Central

Bistué, Alfonso J. C. Soler; Ha, Hongphuc; Sarno, Renee; Don, Michelle; Zorreguieta, Angeles; Tolmasky, Marcelo E.

2007-01-01

The dissemination of AAC(6′)-I-type acetyltransferases have rendered amikacin and other aminoglycosides all but useless in some parts of the world. Antisense technologies could be an alternative to extend the life of these antibiotics. External guide sequences are short antisense oligoribonucleotides that induce RNase P-mediated cleavage of a target RNA by forming a precursor tRNA-like complex. Thirteen-nucleotide external guide sequences complementary to locations within five regions accessible for interaction with antisense oligonucleotides in the mRNA that encodes AAC(6′)-Ib were analyzed. While small variations in the location targeted by different external guide sequences resulted in big changes in efficiency of binding to native aac(6′)-Ib mRNA, most of them induced high levels of RNase P-mediated cleavage in vitro. Recombinant plasmids coding for selected external guide sequences were introduced into Escherichia coli harboring aac(6′)-Ib, and the transformant strains were tested to determine their resistance to amikacin. The two external guide sequences that showed the strongest binding efficiency to the mRNA in vitro, EGSC3 and EGSA2, interfered with expression of the resistance phenotype at different degrees. Growth curve experiments showed that E. coli cells harboring a plasmid coding for EGSC3, the external guide sequence with the highest mRNA binding affinity in vitro, did not grow for at least 300 min in the presence of 15 μg of amikacin/ml. EGSA2, which had a lower mRNA-binding affinity in vitro than EGSC3, inhibited the expression of amikacin resistance at a lesser level; growth of E. coli harboring a plasmid coding for EGSA2, in the presence of 15 μg of amikacin/ml was undetectable for 200 min but reached an optical density at 600 nm of 0.5 after 5 h of incubation. Our results indicate that the use of external guide sequences could be a viable strategy to preserve the efficacy of amikacin. PMID:17387154

MK2206 in Treating Patients With Stage I, Stage II, or Stage III Breast Cancer

ClinicalTrials.gov

2017-08-01

Estrogen Receptor Negative; Estrogen Receptor Positive; HER2/Neu Negative; HER2/Neu Positive; Progesterone Receptor Negative; Progesterone Receptor Positive; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Triple-Negative Breast Carcinoma

Saturn Apollo Program

NASA Image and Video Library

1967-10-01

S-IB-211, the flight version of the Saturn IB launch vehicle's first (S-IVB) stage, arrives at Marshall Space Flight Center's (MSFC's) S-IB static test stand. Between December 1967 and April 1968, the stage would undergo seven static test firings. The S-IB, developed by the MSFC and built by the Chrysler Corporation at the Michoud Assembly Facility near New Orleans, Louisiana, utilized eight H-1 engines and each produced 200,000 pounds of thrust.

Saturn Apollo Program

NASA Image and Video Library

1967-10-01

S-IB-211, the flight version of the Saturn IB launch vehicle's (S-IVB) first stage, after installation at the Marshall Space Flight Center's (MSFC's) S-IB static test stand. Between December 1967 and April 1968, the stage would undergo seven static test firings. The S-IB, developed by the MSFC and built by the Chrysler Corporation at the Michoud Assembly Facility near New Orleans, Louisiana, utilized eight H-1 engines and each produced 200,000 pounds of thrust.

77 FR 76109 - IAS Energy, Inc., IB3 Networks, Inc., IBroadband, Inc., ICP Solar Technologies, Inc., IdentiPHI...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-26

... SECURITIES AND EXCHANGE COMMISSION [File No. 500-1] IAS Energy, Inc., IB3 Networks, Inc., IBroadband, Inc., ICP Solar Technologies, Inc., IdentiPHI, Inc., iDNA, Inc., Immune Network Ltd., Inca Designs, Inc., Indico Technologies, Inc. (n/k/a Indico Resources Ltd.), Infopage, Inc. (a/k/a Tamija Gold & Diamond Exploration, Inc.), Innofone.com , Inc...

More Accurate Definition of Clinical Target Volume Based on the Measurement of Microscopic Extensions of the Primary Tumor Toward the Uterus Body in International Federation of Gynecology and Obstetrics Ib-IIa Squamous Cell Carcinoma of the Cervix

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xie, Wen-Jia; Wu, Xiao; Xue, Ren-Liang

Purpose: To more accurately define clinical target volume for cervical cancer radiation treatment planning by evaluating tumor microscopic extension toward the uterus body (METU) in International Federation of Gynecology and Obstetrics stage Ib-IIa squamous cell carcinoma of the cervix (SCCC). Patients and Methods: In this multicenter study, surgical resection specimens from 318 cases of stage Ib-IIa SCCC that underwent radical hysterectomy were included. Patients who had undergone preoperative chemotherapy, radiation, or both were excluded from this study. Microscopic extension of primary tumor toward the uterus body was measured. The association between other pathologic factors and METU was analyzed. Results: Microscopicmore » extension toward the uterus body was not common, with only 12.3% of patients (39 of 318) demonstrating METU. The mean (±SD) distance of METU was 0.32 ± 1.079 mm (range, 0-10 mm). Lymphovascular space invasion was associated with METU distance and occurrence rate. A margin of 5 mm added to gross tumor would adequately cover 99.4% and 99% of the METU in the whole group and in patients with lymphovascular space invasion, respectively. Conclusion: According to our analysis of 318 SCCC specimens for METU, using a 5-mm gross tumor volume to clinical target volume margin in the direction of the uterus should be adequate for International Federation of Gynecology and Obstetrics stage Ib-IIa SCCC. Considering the discrepancy between imaging and pathologic methods in determining gross tumor volume extent, we recommend a safer 10-mm margin in the uterine direction as the standard for clinical practice when using MRI for contouring tumor volume.« less

Classification of ulnar triangular fibrocartilage complex tears. A treatment algorithm for Palmer type IB tears.

PubMed

Atzei, A; Luchetti, R; Garagnani, L

2017-05-01

The classical definition of 'Palmer Type IB' triangular fibrocartilage complex tear, includes a spectrum of clinical conditions. This review highlights the clinical and arthroscopic criteria that enable us to categorize five classes on a treatment-oriented classification system of triangular fibrocartilage complex peripheral tears. Class 1 lesions represent isolated tears of the distal triangular fibrocartilage complex without distal radio-ulnar joint instability and are amenable to arthroscopic suture. Class 2 tears include rupture of both the distal triangular fibrocartilage complex and proximal attachments of the triangular fibrocartilage complex to the fovea. Class 3 tears constitute isolated ruptures of the proximal attachment of the triangular fibrocartilage complex to the fovea; they are not visible at radio-carpal arthroscopy. Both Class 2 and Class 3 tears are diagnosed with a positive hook test and are typically associated with distal radio-ulnar joint instability. If required, treatment is through reattachment of the distal radio-ulnar ligament insertions to the fovea. Class 4 lesions are irreparable tears due to the size of the defect or to poor tissue quality and, if required, treatment is through distal radio-ulnar ligament reconstruction with tendon graft. Class 5 tears are associated with distal radio-ulnar joint arthritis and can only be treated with salvage procedures. This subdivision of type IB triangular fibrocartilage complex tear provides more insights in the pathomechanics and treatment strategies. II.

Genomic characterization of two novel SAR11 isolates from the Red Sea, including the first strain of the SAR11 Ib clade.

PubMed

Jimenez-Infante, Francy; Ngugi, David Kamanda; Vinu, Manikandan; Blom, Jochen; Alam, Intikhab; Bajic, Vladimir B; Stingl, Ulrich

2017-07-01

The SAR11 clade (Pelagibacterales) is a diverse group that forms a monophyletic clade within the Alphaproteobacteria, and constitutes up to one third of all prokaryotic cells in the photic zone of most oceans. Pelagibacterales are very abundant in the warm and highly saline surface waters of the Red Sea, raising the question of adaptive traits of SAR11 populations in this water body and warmer oceans through the world. In this study, two pure cultures were successfully obtained from surface waters on the Red Sea: one isolate of subgroup Ia and one of the previously uncultured SAR11 Ib lineage. The novel genomes were very similar to each other and to genomes of isolates of SAR11 subgroup Ia (Ia pan-genome), both in terms of gene content and synteny. Among the genes that were not present in the Ia pan-genome, 108 (RS39, Ia) and 151 genes (RS40, Ib) were strain specific. Detailed analyses showed that only 51 (RS39, Ia) and 55 (RS40, Ib) of these strain-specific genes had not reported before on genome fragments of Pelagibacterales. Further analyses revealed the potential production of phosphonates by some SAR11 members and possible adaptations for oligotrophic life, including pentose sugar utilization and adhesion to marine particulate matter. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Saturn Apollo Program

NASA Image and Video Library

1967-08-02

Developed by the Marshall Space Flight Center (MSFC) as an interim vehicle in MSFC’s “building block” approach to the Saturn rocket development, the Saturn IB utilized Saturn I technology to further develop and refine the larger boosters and the Apollo spacecraft capabilities required for the manned lunar missions. The Saturn IB vehicle was a two-stage rocket and had a payload capability about 50 percent greater than the Saturn I vehicle. The first stage, S-IB stage, was a redesigned first stage of the Saturn I. This photograph is of the S-IB nose cone #3 during assembly in building 4752.

Prelaunch - Apollo VII (Erection of First Stage) - KSC

NASA Image and Video Library

1968-04-15

S68-29781 (22 April 1968) --- Low angle view at the Kennedy Space Center's Pad 34 showing the erection of the first stage of the Saturn 205 launch vehicle. The two-stage Saturn IB will be the launch vehicle for the first unmanned Apollo space mission, Apollo 7 (Spacecraft 101/Saturn 205).

Saturn Apollo Program

NASA Image and Video Library

1965-01-01

Marshall Space Flight Center (MSFC) workers lower S-IB-200D, a dynamic test version of the Saturn IB launch vehicle's first stage (S-IB stage), into the Center's Dynamic Test Stand on January 12, 1965. Test Laboratory persornel assembled a complete Saturn IB to test the structural soundness of the launch vehicle. Developed by the MSFC as an interim vehicle in MSFC's "building block" approach to Saturn rocket development, the Saturn IB utilized Saturn I technology to further develop and refine large boosters and the Apollo spacecraft capabilities required for the manned lunar missions.

Segal crystallinity index revisited by the simulation of x-ray diffraction patterns of cotton cellulose IB and cellulose II

USDA-ARS?s Scientific Manuscript database

The Segal method estimates the amorphous fraction of cellulose IB materials simply based on intensity at 18o 20 in an X-ray diffraction pattern and was extended to cellulose II using 16o 2O intensity. To address the dependency of Segal amorphous intensity on crystal size, cellulose polymorph, and th...

Saturn Apollo Program

NASA Image and Video Library

1965-03-01

S-IB-1, the first flight version of the Saturn IB launch vehicle's first stage (S-IB stage), sat in the Marshall Space Flight Center (MSFC) Saturn IB static test stand on March 15, 1965. Developed by the MSFC and built by the Chrysler Corporation at the Michoud Assembly Facility (MAF) in New Orleans, Louisiana, the 90,000-pound booster utilized eight H-1 engines to produce a combined thrust of 1,600,000 pounds.

Ovarian Cancer Stage I

MedlinePlus

... Stage I Description: Three-panel drawing of stage IA, IB, and IC; the first panel (stage IA) shows cancer inside one ovary. The second panel ( ... fallopian tubes, uterus, cervix, and vagina. In stage IA, cancer is found inside a single ovary or ...

Are We Appropriately Selecting Therapy For Patients With Cervical Cancer? Longitudinal Patterns-of-Care Analysis for Stage IB-IIB Cervical Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Carlson, Julie A., E-mail: Julie.A2.Carlson@ucdenver.edu; Rusthoven, Chad; DeWitt, Peter E.

Purpose: We performed a patterns-of-care analysis evaluating the effects of newer technology and recent research findings on treatment decisions over 26 years to determine whether patients with cervical cancer are being appropriately selected for treatment to optimize the therapeutic ratio. Methods and Materials: A retrospective analysis was conducted using the Surveillance, Epidemiology and End Results (SEER) program from 1983 to 2009. We identified 10,933 women with stage IB-IIB cervical carcinoma. Results: Of the 10,933 subjects identified, 40.1% received surgery, 26.8% received radiation (RT), and 33.1% received surgery plus RT. RT use increased after 2000 compared to prior to 2000, with amore » corresponding decrease in surgery and surgery plus RT. Among patients with risk factors including tumor size >4 cm, positive parametria, and positive lymph nodes, declining use of surgery plus RT was observed. However, 23% of patients with tumors >4 cm, 20% of patients with positive parametria, and 55% of node-positive patients continued to receive surgery plus RT as of 2009. Factors associated with increased use of surgery plus RT included patient age <50 and node-positive status. Conclusions: In this largest patterns-of-care analysis to date for patients with locally advanced cervical cancer, we found a substantial proportion of patients continue to undergo surgery followed by radiation, despite randomized data supporting the use of definitive radiation therapy, with lower morbidity than surgery and radiation.« less

Young Children with Functional Abdominal Pain (FAP) and Irritable Bowel Syndrome (IBS) Followed in Tertiary vs. Primary Care: Differences in Outcomes

USDA-ARS?s Scientific Manuscript database

Despite the fact that the American Academy of Pediatrics suggests that general pediatricians (PED) manage children with FAP/IBS without alarm signs many children are cared for by pediatric gastroenterologists (GI). In a longitudinal examination of physical symptoms, healthcare use, quality of life (...

Platelet GpIbα Binding to von Willebrand Factor Under Fluid Shear: Contributions of the D'D3‐Domain, A1‐Domain Flanking Peptide and O‐Linked Glycans

PubMed Central

Madabhushi, Sri R.; Zhang, Changjie; Kelkar, Anju; Dayananda, Kannayakanahalli M.; Neelamegham, Sriram

2014-01-01

Background Von Willebrand Factor (VWF) A1‐domain binding to platelet receptor GpIbα is an important fluid‐shear dependent interaction that regulates both soluble VWF binding to platelets, and platelet tethering onto immobilized VWF. We evaluated the roles of different structural elements at the N‐terminus of the A1‐domain in regulating shear dependent platelet binding. Specifically, the focus was on the VWF D′D3‐domain, A1‐domain N‐terminal flanking peptide (NFP), and O‐glycans on this peptide. Methods and Results Full‐length dimeric VWF (ΔPro‐VWF), dimeric VWF lacking the D′D3 domain (ΔD′D3‐VWF), and ΔD′D3‐VWF variants lacking either the NFP (ΔD′D3NFP─‐VWF) or just O‐glycans on this peptide (ΔD′D3OG─‐VWF) were expressed. Monomeric VWF‐A1 and D′D3‐A1 were also produced. In ELISA, the apparent dissociation constant (KD) of soluble ΔPro‐VWF binding to immobilized GpIbα (KD≈100 nmol/L) was 50‐ to 100‐fold higher than other proteins lacking the D′D3 domain (KD~0.7 to 2.5 nmol/L). Additionally, in surface plasmon resonance studies, the on‐rate of D′D3‐A1 binding to immobilized GpIbα (kon=1.8±0.4×104 (mol/L)−1·s−1; KD=1.7 μmol/L) was reduced compared with the single VWF‐A1 domain (kon=5.1±0.4×104 (mol/L)−1·s−1; KD=1.2 μmol/L). Thus, VWF‐D′D3 primarily controls soluble VWF binding to GpIbα. In contrast, upon VWF immobilization, all molecular features regulated A1‐GpIbα binding. Here, in ELISA, the number of apparent A1‐domain sites available for binding GpIbα on ΔPro‐VWF was ≈50% that of the ΔD′D3‐VWF variants. In microfluidics based platelet adhesion measurements on immobilized VWF and thrombus formation assays on collagen, human platelet recruitment varied as ΔPro‐VWF<ΔD′D3‐VWF<ΔD′D3NFP─‐VWF<ΔD′D3OG─‐VWF. Conclusions Whereas VWF‐D′D3 is the major regulator of soluble VWF binding to platelet GpIbα, both the D′D3‐domain and N�

IB-LBM study on cell sorting by pinched flow fractionation.

PubMed

Ma, Jingtao; Xu, Yuanqing; Tian, Fangbao; Tang, Xiaoying

2014-01-01

Separation of two categories of cells in pinched flow fractionation(PFF) device is simulated by employing IB-LBM. The separation performances at low Reynolds number (about 1) under different pinched segment widths, flow ratios, cell features, and distances between neighboring cells are studied and the results are compared with those predicted by the empirical formula. The simulation indicates that the diluent flow rate should approximate to or more than the flow rate of particle solution in order to get a relatively ideal separation performance. The discrepancy of outflow position between numerical simulation and the empirical prediction enlarges, when the cells become more flexible. Too short distance between two neighboring cells could lead to cell banding which would result in incomplete separation, and the relative position of two neighboring cells influences the banding of cells. The present study will probably provide some new applications of PFF, and make some suggestions on the design of PFF devices.

Theoretical prediction of the vibrational spectra of group IB trimers

PubMed Central

Richtsmeier, Steven C.; Gole, James L.; Dixon, David A.

1980-01-01

The molecular structures of the group IB trimers, Cu3, Ag3, and Au3, have been determined by using the semi-empirical diatomics-in-molecules theory. The trimers are found to have C2v symmetry with bond angles between 65° and 80°. The trimers are bound with respect to dissociation to the asymptotic limit of an atom plus a diatom. The binding energies per atom for Cu3, Ag3, and Au3 are 1.08, 0.75, and 1.16 eV, respectively. The vibrational frequencies of the trimers have been determined for comparison with experimental results. The vibrational frequencies are characterized by low values for the bending and asymmetric stretch modes. The frequency of the symmetric stretch of the trimer is higher than the stretching frequency of the corresponding diatomic. A detailed comparison of the theoretical results with the previously measured Raman spectra of matrix isolated Ag3 is presented. PMID:16592885

Saturn Apollo Program

NASA Image and Video Library

1965-03-15

Workers at the Marshall Space Flight Center (MSFC) hoist S-IB-1, the first flight version of the Saturn IB launch vehicle's first stage (S-IB stage), into the Saturn IB static test stand on March 15, 1965. Developed by the MSFC and built by the Chrysler Corporation at the Michoud Assembly Facility (MAF) in New Orleans, Louisiana, the 90,000-pound booster utilized eight H-1 engines to produce a combined thrust of 1,600,000 pounds.

Simulations of flow induced structural transition of the β-switch region of glycoprotein Ibα.

PubMed

Han, Mengzhi; Xu, Ji; Ren, Ying; Li, Jinghai

2016-02-01

Binding of glycoprotein Ibα to von Willebrand factor induces platelet adhesion to injured vessel walls and initiates a multistep hemostatic process. It has been hypothesized that the flow condition could induce a loop to β-sheet conformational change in the β-switch region of glycoprotein Ibα, which regulates it binding to the von Willebrand factor and facilitates the blood clot formation and wound healing. In this work, direct molecular dynamics (MD), flow MD and metadynamics, were employed to investigate the mechanisms of this flow induced conformational transition process. Specifically, the free energy landscape of the whole transition process was drawn by metadynamics with the path collective variable approach. The results reveal that without flow, the free energy landscape has two main basins, including a random loop basin stabilized by large conformational entropy and a partially folded β-sheet basin. The free energy barrier separating these two basins is relatively high and the β-switch could not fold from loop to β-sheet state spontaneously. The fully β-sheet conformations located in high free energy regions, which are also unstable and gradually unfold into partially folded β-sheet state with flow. Relatively weak flow could trigger some folding of the β-switch but could not fold it into fully β-sheet state. Under strong flow conditions, the β-switch could readily overcome the high free energy barrier and fold into fully β-sheet state. Copyright © 2015 Elsevier B.V. All rights reserved.

Assessment and analysis of noise levels in and around Ib river coalfield, Orissa, India.

PubMed

Mohapatra, Haraprasad; Goswami, Shreerup

2012-05-01

Heavy earth moving machineries, different capacities of dumpers and loaders, blasting and drilling make the mining environment noisy. A study was carried out to assess the noise level in different opencast projects in and around Belpahar and Brajarajnagar areas of Ib river coalfield. Noise assessment was carried out in various residential, commercial and industrial places. The noise levels, especially L(eq) values of different wheel loaders, dumpers, shovel and crusher units were also assessed and were more than permissible limit (90dB) in some of their operating conditions. Sound ressure level measurements while drilling into coal and overburden at Lakhanpur opencast project yielded noise levels (L(eq)) of 81.33 to 96.2 dB. Thus, these L(eq) values of drilling machines in most of the operating conditions were above permissible limit. The average noise intensities (6 a.m.-10 p.m.: 51.6-60.875dB and 10 p.m.-6 a.m.: 42.6-49.8dB) and L(eq) values (6 a.m.-10 p.m.: 50.9-67.0dB and 10 p.m.-6 a.m.: 40.8-53.3dB) during both day and night time of the residential areas around the Ib river coalfield were in close proximity or beyond the permissible limit. The L(eq) values at some of the commercial and industrial places were beyond (6 a.m.-10 p.m.: 61.6-88.3 dB and 10 p.m.-6 a.m.: 55.4-64.8dB) permissible limit. However, in most of the cases, the L(max) noise values were more (6 a.m.-10 p.m.: 68.5-91.4 dB and 10 p.m.-6 a.m.: 69.3-76.4dB) than the permissible limit. Analysis of variance was also computed for heavy earth moving machineries in different operating conditions and also for different residential, commercial and industrial places to infer the level of significance. The difference of noise intensity produced by different wheel loaders at Lakhanpur and Lilari opencast projects, drilling machines at Lakhanpur opencast project, 50 tons capacity dumpers at various conditions of Ib river coalfield within the same operating condition was significant at both 5% and 1% levels

A randomised clinical trial (RCT) of a symbiotic mixture in patients with irritable bowel syndrome (IBS): effects on symptoms, colonic transit and quality of life.

PubMed

Cappello, Carmelina; Tremolaterra, Fabrizio; Pascariello, Annalisa; Ciacci, Carolina; Iovino, Paola

2013-03-01

The aim of this study is to test in a double-blinded, randomised placebo-controlled study the effects of a commercially available multi-strain symbiotic mixture on symptoms, colonic transit and quality of life in irritable bowel syndrome (IBS) patients who meet Rome III criteria. There is only one other double-blinded RCT on a single-strain symbiotic mixture in IBS. This is a double-blinded, randomised placebo-controlled study of a symbiotic mixture (Probinul, 5 g bid) over 4 weeks after 2 weeks of run-in. The primary endpoints were global satisfactory relief of abdominal flatulence and bloating. Responders were patients who reported at least 50 % of the weeks of treatment with global satisfactory relief. The secondary endpoints were change in abdominal bloating, flatulence, pain and urgency by a 100-mm visual analog scale, stool frequency and bowel functions on validated adjectival scales (Bristol Scale and sense of incomplete evacuation). Pre- and post-treatment colonic transit time (Metcalf) and quality of life (SF-36) were assessed. Sixty-four IBS patients (symbiotic n = 32, 64 % females, mean age 38.7 ± 12.6 years) were studied. This symbiotic mixture reduced flatulence over a 4-week period of treatment (repeated-measures analysis of covariance, p < 0.05). Proportions of responders were not significantly different between groups. At the end of the treatment, a longer rectosigmoid transit time and a significant improvement in most SF-36 scores were observed in the symbiotic group. This symbiotic mixture has shown a beneficial effect in decreasing the severity of flatulence in IBS patients, a lack of adverse events and a good side-effect profile; however, it failed to achieve an improvement in global satisfactory relief of abdominal flatulence and bloating. Further studies are warranted.

Berberine Improves Intestinal Motility and Visceral Pain in the Mouse Models Mimicking Diarrhea-Predominant Irritable Bowel Syndrome (IBS-D) Symptoms in an Opioid-Receptor Dependent Manner

PubMed Central

Pan, Qiuhui; Fichna, Jakub; Zheng, Lijun; Wang, Kesheng; Yu, Zhen; Li, Yongyu; Li, Kun; Song, Aihong; Liu, Zhongchen; Song, Zhenshun; Kreis, Martin

2015-01-01

Background and Aims Berberine and its derivatives display potent analgesic, anti-inflammatory and anticancer activity. Here we aimed at characterizing the mechanism of action of berberine in the gastrointestinal (GI) tract and cortical neurons using animal models and in vitro tests. Methods The effect of berberine was characterized in murine models mimicking diarrhea-predominant irritable bowel syndrome (IBS-D) symptoms. Then the opioidantagonists were used to identify the receptors involved. Furthermore, the effect of berberineon opioid receptors expression was established in the mouse intestine and rat fetal cortical neurons. Results In mouse models, berberine prolonged GI transit and time to diarrhea in a dose-dependent manner, and significantly reduced visceral pain. In physiological conditions the effects of berberine were mediated by mu- (MOR) and delta- (DOR) opioidreceptors; hypermotility, excessive secretion and nociception were reversed by berberine through MOR and DOR-dependent action. We also found that berberine increased the expression of MOR and DOR in the mouse bowel and rat fetal cortical neurons. Conclusion Berberine significantly improved IBS-D symptoms in animal models, possibly through mu- and delta- opioid receptors. Berberine may become a new drug candidate for the successful treatment of IBS-D in clinical conditions. PMID:26700862

Saturn Apollo Program

NASA Image and Video Library

1967-10-01

Workmen at the Marshall Space Flight Center's (MSFC's) dock on the Ternessee River unload S-IB-211, the flight version of the Saturn IB launch vehicle's first stage, from the NASA barge Palaemon. Between December 1967 and April 1968, the stage would undergo seven static test firings in MSFC's S-IB static test stand.

Saturn Apollo Program

NASA Image and Video Library

1967-10-01

Workmen at the Marshall Space Flight Center's (MSFC's) dock on the Ternessee River unload S-IB-211, the flight version of the Saturn IB launch vehicle's first stage, from the NASA barge Palaemon. Between December 1967 and April 1968, the stage would undergo seven static test firings in Marshall's S-IB static test stand.

Is There "Space" for International Baccalaureate? A Case Study Exploring Space and the Adoption of the IB Middle Year Programme

ERIC Educational Resources Information Center

Monreal, Timothy

2016-01-01

Henri Lefebvre (1991) wrote, "[representational] space is alive: it speaks" (p. 42). This article explores how we might "listen" to space in education by examining the role of space in one school's decision to adopt the International Baccalaureate's Middle Years Programme [IB MYP]. It builds upon recent scholarship that applies…

Fragmentation of the CRISPR-Cas Type I-B signature protein Cas8b.

PubMed

Richter, Hagen; Rompf, Judith; Wiegel, Julia; Rau, Kristina; Randau, Lennart

2017-11-01

CRISPR arrays are transcribed into long precursor RNA species, which are further processed into mature CRISPR RNAs (crRNAs). Cas proteins utilize these crRNAs, which contain spacer sequences that can be derived from mobile genetic elements, to mediate immunity during a reoccurring virus infection. Type I CRISPR-Cas systems are defined by the presence of different Cascade interference complexes containing large and small subunits that play major roles during target DNA selection. Here, we produce the protein and crRNA components of the Type I-B CRISPR-Cas complex of Clostridium thermocellum and Methanococcus maripaludis. The C. thermocellum Cascade complexes were reconstituted and analyzed via size-exclusion chromatography. Activity of the heterologous M. maripaludis CRISPR-Cas system was followed using phage lambda plaques assays. The reconstituted Type-I-B Cascade complex contains Cas7, Cas5, Cas6b and the large subunit Cas8b. Cas6b can be omitted from the reconstitution protocol. The large subunit Cas8b was found to be represented by two tightly associated protein fragments and a small C-terminal Cas8b segment was identified in recombinant complexes and C. thermocellum cell lysate. Production of Cas8b generates a small C-terminal fragment, which is suggested to fulfill the role of the missing small subunit. A heterologous, synthetic M. maripaludis Type I-B system is active in E. coli against phage lambda, highlighting a potential for genome editing using endogenous Type-I-B CRISPR-Cas machineries. This article is part of a Special Issue entitled "Biochemistry of Synthetic Biology - Recent Developments" Guest Editor: Dr. Ilka Heinemann and Dr. Patrick O'Donoghue. Copyright © 2017 Elsevier B.V. All rights reserved.

Parameters of blood count and tumor markers in patients with borderline ovarian tumors: a retrospective analysis and relation to staging.

PubMed

Nomelini, Rosekeila Simões; da Silva, Taísa Morete; Tavares Murta, Beatriz Martins; Murta, Eddie Fernando Candido

2012-01-01

The aim of this paper was to evaluate the parameters of blood count and tumor markers in borderline ovarian tumors. We evaluated 21 patients who had confirmed histopathologic diagnosis of borderline ovarian tumor. We recorded age, parity, tumor type, stage of cancer, serum levels of tumor markers (CA-125, CA-15.3, CA-19.9, CEA, AFP), and the parameters of blood count, fasting glucose, disease-free survival and overall. The patients were divided into two groups, stage IA (n = 13) and stage IB-IIIC (n = 8). The unpaired t-test and Fisher's exact test were used, with P values of less than 0.05 being considered to indicate statistical significance. Levels of red blood cells, hematocrit, and hemoglobin were significantly higher in stage IA when compared with stage IB-IIIC (P < 0.05). The levels of tumor marker CEA had a tendency to be higher in the group stage IB-IIIC (0.08). Abnormal levels of CEA and CA-19.9 were found more frequently in stages IB-IIIC. Therefore, parameters of blood count, CEA, and CA-19.9 should be targeted for further research in identifying prognostic factors in borderline tumors.

Dimerization of glycoprotein Ibα is not sufficient to induce platelet clearance.

PubMed

Liang, X; Syed, A K; Russell, S R; Ware, J; Li, R

2016-02-01

ESSENTIALS: Many anti-glycoprotein (GP)Ibα antibodies induce platelet clearance in a dimer-dependent manner. Characterization of monoclonal antibodies that bind the mechanosensitive domain (MSD) of GPIbα. An anti-MSD antibody binds two copies of GPIbα in platelets but does not induce platelet clearance. The prevailing clustering model of GPIbα signaling is incorrect or needs revision. The mechanism of platelet clearance is not clear. Many antibodies binding the membrane-distal ligand-binding domain of glycoprotein (GP)Ibα induce rapid clearance of platelets and acute thrombocytopenia, which requires the bifurcated antibody structure. It was thought that binding of these antibodies induced lateral dimerization or clustering of GPIbα in the plasma membrane, which leads to downstream signaling and platelet clearance. However, many antibodies targeting GPIbβ and GPIX, which are associated with GPIbα in the GPIb-IX complex, do not induce platelet clearance, which is in contradiction to the clustering model. To test whether dimerization or clustering of GPIbα is sufficient to transmit the signal that leads to platelet clearance. We have recently raised several mAbs targeting the mechanosensitive domain (MSD) of GPIbα. Binding of these anti-MSD antibodies was characterized with biochemical methods. Their ability to stimulate platelets and induce platelet clearance in mice was assessed. Infusion of anti-MSD antibodies does not cause thrombocytopenia in mice. These antibodies show no detectable effects on platelet activation and aggregation in vitro. Further biochemical investigation showed that the anti-MSD antibody 3D1 binds two copies of GPIbα on the platelet surface. Therefore, lateral dimerization of GPIbα induced by antibody binding is not sufficient to initiate GPIb-IX signaling and induce platelet clearance. Our results suggest that a factor other than or in addition to clustering of GPIbα is required to induce platelet clearance. © 2015 International

Arachidonic acid depletion extends survival of cold-stored platelets by interfering with the [glycoprotein Ibα – 14-3-3ζ] association

PubMed Central

van der Wal, Dianne E.; Gitz, Eelo; Du, Vivian X.; Lo, Kimberly S.L.; Koekman, Cornelis A.; Versteeg, Sabine; Akkerman, Jan Willem N.

2012-01-01

Background Cold storage of platelets reduces bacterial growth and preserves their hemostatic properties better than current procedures do. However, storage at 0°C induces [14-3-3ζ-glycoprotein Ibα] association, 14-3-3ζ release from phospho-Bad, Bad activation and apoptosis. Design and Methods We investigated whether arachidonic acid, which also binds 14-3-3ζ, contributes to coldinduced apoptosis. Results Cold storage activated P38-mitogen-activated protein kinase and released arachidonic acid, which accumulated due to cold inactivation of cyclooxygenase-1/thromboxane synthase. Accumulated arachidonic acid released 14-3-3ζ from phospho-Bad and decreased the mitochondrial membrane potential, which are steps in the induction of apoptosis. Addition of arachidonic acid did the same and its depletion made platelets resistant to cold-induced apoptosis. Incubation with biotin-arachidonic acid revealed formation of an [arachidonic acid-14-3-3ζ-glycoprotein Ibα] complex. Indomethacin promoted complex formation by accumulating arachidonic acid and released 14-3-3ζ from cyclo-oxygenase-1. Arachidonic acid depletion prevented the cold-induced reduction of platelet survival in mice. Conclusions We conclude that cold storage induced apoptosis through an [arachidonic acid-14-3-3ζ-glycoprotein Ibα] complex, which released 14-3-3ζ from Bad in an arachidonic acid-dependent manner. Although arachidonic acid depletion reduced agonist-induced thromboxane A2 formation and aggregation, arachidonic acid repletion restored these functions, opening ways to reduce apoptosis during storage without compromising hemostatic functions post-transfusion. PMID:22371179

Carboplatin and Paclitaxel or Oxaliplatin and Capecitabine With or Without Bevacizumab as First-Line Therapy in Treating Patients With Newly Diagnosed Stage II-IV or Recurrent Stage I Epithelial Ovarian or Fallopian Tube Cancer

ClinicalTrials.gov

2017-08-21

Borderline Ovarian Mucinous Tumor; Ovarian Mucinous Cystadenocarcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Stage IA Fallopian Tube Cancer; Stage IA Ovarian Cancer; Stage IB Fallopian Tube Cancer; Stage IB Ovarian Cancer; Stage IC Fallopian Tube Cancer; Stage IC Ovarian Cancer; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Cancer; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Cancer; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer

Single line source with and without vaginal loading and the impact on target coverage and organ at risk doses for cervix cancer Stages IB, II, and IIIB: treatment planning simulation in patients treated with MRI-guided adaptive brachytherapy in a multicentre study (EMBRACE).

PubMed

Nkiwane, Karen S; Pötter, Richard; Tanderup, Kari; Federico, Mario; Lindegaard, Jacob C; Kirisits, Christian

2013-01-01

Three-dimensional evaluation and comparison of target and organs at risk (OARs) doses from two traditional standard source loading patterns in the frame of MRI-guided cervical cancer brachytherapy for various clinical scenarios based on patient data collected in a multicenter trial setting. Two nonoptimized three-dimensional MRI-based treatment plans, Plan 1 (tandem and vaginal loading) and Plan 2 (tandem loading only), were generated for 134 patients from seven centers participating in the EMBRACE study. Both plans were normalized to point A (Pt. A). Target and OAR doses were evaluated in terms of minimum dose to 90% of the high-risk clinical target volume (HRCTV D90) grouped by tumor stage and minimum dose to the most exposed 2cm³ of the OARs volume. An HRCTV D90 ≥ Pt. A was achieved in 82% and 44% of the patients with Plans 1 and 2, respectively. Median HRCTV D90 with Plans 1 and 2 was 120% and 90% of Pt. A dose, respectively. Both plans had optimal dose coverage in 88% of Stage IB tumors; however, the tandem-only plan resulted in about 50% of dose reduction to the vagina and rectum. For Stages IIB and IIIB, Plan 1 had on average 35% better target coverage but with significant doses to OARs. Standard tandem loading alone results in good target coverage in most Stage IB tumors without violating OAR dose constraints. For Stage IIB tumors, standard vaginal loading improves the therapeutic window, however needs optimization to fulfill the dose prescription for target and OAR. In Stage IIIB, even optimized vaginal loading often does not fulfill the needs for dose prescription. The significant dose variation across various clinical scenarios for both target and OARs indicates the need for image-guided brachytherapy for optimal dose adaptation both for limited and advanced diseases. Copyright © 2013 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

Developmental Stage, Muscle and Genetic Type Modify Muscle Transcriptome in Pigs: Effects on Gene Expression and Regulatory Factors Involved in Growth and Metabolism.

PubMed

Ayuso, Miriam; Fernández, Almudena; Núñez, Yolanda; Benítez, Rita; Isabel, Beatriz; Fernández, Ana I; Rey, Ana I; González-Bulnes, Antonio; Medrano, Juan F; Cánovas, Ángela; López-Bote, Clemente J; Óvilo, Cristina

2016-01-01

Iberian pig production includes purebred (IB) and Duroc-crossbred (IBxDU) pigs, which show important differences in growth, fattening and tissue composition. This experiment was conducted to investigate the effects of genetic type and muscle (Longissimus dorsi (LD) vs Biceps femoris (BF)) on gene expression and transcriptional regulation at two developmental stages. Nine IB and 10 IBxDU piglets were slaughtered at birth, and seven IB and 10 IBxDU at four months of age (growing period). Carcass traits and LD intramuscular fat (IMF) content were measured. Muscle transcriptome was analyzed on LD samples with RNA-Seq technology. Carcasses were smaller in IB than in IBxDU neonates (p < 0.001), while growing IB pigs showed greater IMF content (p < 0.05). Gene expression was affected (p < 0.01 and Fold change > 1.5) by the developmental stage (5,812 genes), muscle type (135 genes), and genetic type (261 genes at birth and 113 at growth). Newborns transcriptome reflected a highly proliferative developmental stage, while older pigs showed upregulation of catabolic and muscle functioning processes. Regarding the genetic type effect, IBxDU newborns showed enrichment of gene pathways involved in muscle growth, in agreement with the higher prenatal growth observed in these pigs. However, IB growing pigs showed enrichment of pathways involved in protein deposition and cellular growth, supporting the compensatory gain experienced by IB pigs during this period. Moreover, newborn and growing IB pigs showed more active glucose and lipid metabolism than IBxDU pigs. Moreover, LD muscle seems to have more active muscular and cell growth, while BF points towards lipid metabolism and fat deposition. Several regulators controlling transcriptome changes in both genotypes were identified across muscles and ages (SIM1, PVALB, MEFs, TCF7L2 or FOXO1), being strong candidate genes to drive expression and thus, phenotypic differences between IB and IBxDU pigs. Many of the identified regulators

Combined approach for finding susceptibility genes in DISH/chondrocalcinosis families: whole-genome-wide linkage and IBS/IBD studies.

PubMed

Couto, Ana Rita; Parreira, Bruna; Thomson, Russell; Soares, Marta; Power, Deborah M; Stankovich, Jim; Armas, Jácome Bruges; Brown, Matthew A

2017-01-01

Twelve families with exuberant and early-onset calcium pyrophosphate dehydrate chondrocalcinosis (CC) and diffuse idiopathic skeletal hyperostosis (DISH), hereafter designated DISH/CC, were identified in Terceira Island, the Azores, Portugal. Ninety-two (92) individuals from these families were selected for whole-genome-wide linkage analysis. An identity-by-descent (IBD) analysis was performed in 10 individuals from 5 of the investigated pedigrees. The chromosome area with the maximal logarithm of the odds score (1.32; P =0.007) was not identified using the IBD/identity-by-state (IBS) analysis; therefore, it was not investigated further. From the IBD/IBS analysis, two candidate genes, LEMD3 and RSPO4 , were identified and sequenced. Nine genetic variants were identified in the RSPO4 gene; one regulatory variant (rs146447064) was significantly more frequent in control individuals than in DISH/CC patients ( P =0.03). Four variants were identified in LEMD3 , and the rs201930700 variant was further investigated using segregation analysis. None of the genetic variants in RSPO4 or LEMD3 segregated within the studied families. Therefore, although a major genetic effect was shown to determine DISH/CC occurrence within these families, the specific genetic variants involved were not identified.

Combined approach for finding susceptibility genes in DISH/chondrocalcinosis families: whole-genome-wide linkage and IBS/IBD studies

PubMed Central

Couto, Ana Rita; Parreira, Bruna; Thomson, Russell; Soares, Marta; Power, Deborah M; Stankovich, Jim; Armas, Jácome Bruges; Brown, Matthew A

2017-01-01

Twelve families with exuberant and early-onset calcium pyrophosphate dehydrate chondrocalcinosis (CC) and diffuse idiopathic skeletal hyperostosis (DISH), hereafter designated DISH/CC, were identified in Terceira Island, the Azores, Portugal. Ninety-two (92) individuals from these families were selected for whole-genome-wide linkage analysis. An identity-by-descent (IBD) analysis was performed in 10 individuals from 5 of the investigated pedigrees. The chromosome area with the maximal logarithm of the odds score (1.32; P=0.007) was not identified using the IBD/identity-by-state (IBS) analysis; therefore, it was not investigated further. From the IBD/IBS analysis, two candidate genes, LEMD3 and RSPO4, were identified and sequenced. Nine genetic variants were identified in the RSPO4 gene; one regulatory variant (rs146447064) was significantly more frequent in control individuals than in DISH/CC patients (P=0.03). Four variants were identified in LEMD3, and the rs201930700 variant was further investigated using segregation analysis. None of the genetic variants in RSPO4 or LEMD3 segregated within the studied families. Therefore, although a major genetic effect was shown to determine DISH/CC occurrence within these families, the specific genetic variants involved were not identified. PMID:29104755

Nerve-sparing radical hysterectomy for stage IA2-IIB cervical cancer: 5-year survival of 501 consecutive cases.

PubMed

Papp, Z; Csapó, Zs; Hupuczi, P; Mayer, A

2006-01-01

The purpose of this study was to assess the 5-year survival and morbidity in cases with radical hysterectomy and pelvic lymphadenectomy with pre- and postoperative irradiation performed to treat Stage IA2-IIB cervical cancer. During a 10(1/2)-year period between July 1990 and December 2000, 501 consecutive radical hysterectomies with bilateral pelvic lymphadenectomy were performed by the same gynecological surgeon in Stage IA2, IB, IIA and IIB cervical cancer. The patients were treated by pre- and postoperative irradiation as well. Apart from recurrence, perioperative complications were minimal with no long-term morbidity. The absolute 5-year survival rates for the patients in Stage IA2, IB1, IB2, IIA and IIB were 94.4%, 90.7%, 84.1%, 71.1%, and 55.4%, respectively. The respective 5-year survival rates for patients without or with lymph node metastasis were 94.5% and 33.3% in Stage IB2, 81.7% and 48.7% in Stage IIA and 70.2% and 36.5% in Stage IIB, respectively. Nerve-sparing radical hysterectomy with pelvic lymph node dissection and pre- and postoperative irradiation remains the treatment of choice for most patients with early-stage and even Stage IIB cervical cancer. The radicalism and extent of lymph node dissection and parametrial resection should be individualized and tailored to tumor- and patient-related risk factors.

Treatment Patterns and Health Resource Utilization Among Patients Diagnosed With Early Stage Resected Non-Small Cell Lung Cancer at US Community Oncology Practices.

PubMed

Buck, Philip O; Saverno, Kimberly R; Miller, Paul J E; Arondekar, Bhakti; Walker, Mark S

2015-11-01

Data on adjuvant therapy in resected non-small cell lung cancer (NSCLC) in routine practice are lacking in the United States. This retrospective observational database study included 609 community oncology patients with resected stage IB to IIIA NSCLC. Use of adjuvant therapy was 39.1% at disease stage IB and 64.9% to 68.2% at stage II to IIIA. The most common regimen at all stages was carboplatin and paclitaxel. Platin-based adjuvant chemotherapy has extended survival in clinical trials in patients with completely resected non-small cell lung cancer (NSCLC). There are few data on the use of adjuvant therapy in community-based clinical practice in the United States. This was a retrospective observational study using electronic medical record and billing data collected during routine care at US community oncology sites in the Vector Oncology Data Warehouse between January 2007 and January 2014. Patients aged ≥ 18 years with a primary diagnosis of stage IB to IIIA NSCLC were eligible if they had undergone surgical resection. Treatment patterns, health care resource use, and cost were recorded, stratified by stage at diagnosis. The study included 609 patients (mean age, 64.8 years, 52.9% male), of whom 215 had stage IB disease, 130 stage IIA/II, 110 stage IIB, and 154 stage IIIA. Adjuvant systemic therapy after resection was provided to 345 (56.7%) of 609 patients, with lower use in patients with stage IB disease (39.1%) than stage II to IIIA disease (64.9-68.2%) (P < .0001). The most common adjuvant regimen at all stages was the combination of carboplatin and paclitaxel. There were no statistically significant differences in office visits or incidence of hospitalization by disease stage. During adjuvant treatment, the total monthly median cost per patient was $17,389.75 (interquartile range, $8,815.61 to $23,360.85). Adjuvant systemic therapy was used in some patients with stage IB NSCLC and in the majority of patients with stage IIA to IIIA disease. There were few

Seventh edition (2010) of the AJCC/UICC staging system for gastric adenocarcinoma: is there room for improvement?

PubMed

Patel, Manali I; Rhoads, Kim F; Ma, Yifei; Ford, James M; Visser, Brendan C; Kunz, Pamela L; Fisher, George A; Chang, Daniel T; Koong, Albert; Norton, Jeffrey A; Poultsides, George A

2013-05-01

The gastric cancer AJCC/UICC staging system recently underwent significant revisions, but studies on Asian patients have reported a lack of adequate discrimination between various consecutive stages. We sought to validate the new system on a U.S. population database. California Cancer Registry data linked to the Office of Statewide Health Planning and Development discharge abstracts were used to identify patients with gastric adenocarcinoma (esophagogastric junction and gastric cardia tumors excluded) who underwent curative-intent surgical resection in California from 2002 to 2006. AJCC/UICC stage was recalculated based on the latest seventh edition. Overall survival probabilities were calculated using the Kaplan-Meier method. Of 1905 patients analyzed, 54 % were males with a median age of 70 years. Median number of pathologically examined lymph nodes was 12 (range, 1-90); 40 % of patients received adjuvant chemotherapy, and 31 % received adjuvant radiotherapy. The seventh edition AJCC/UICC system did not distinguish outcome adequately between stages IB and IIA (P = 0.40), or IIB and IIIA (P = 0.34). By merging stage II into 1 category and moving T2N1 to stage IB and T2N2, T1N3 to stage IIIA, we propose a new grouping system with improved discriminatory ability In this first study validating the new seventh edition AJCC/UICC staging system for gastric cancer on a U.S. population with a relatively limited number of lymph nodes examined, we found stages IB and IIA, as well as IIB and IIIA to perform similarly. We propose a revised stage grouping for the AJCC/UICC staging system that better discriminates between outcomes.

Saturn Apollo Program

NASA Image and Video Library

1971-01-01

This 1968 cutaway drawing illustrates the Saturn IB launch vehicle with its two booster stages, the S-IB (first stage) and S-IVB (second stage), and provides the vital statistics in metric units. Developed by the Marshall Space Flight Center (MSFC) as an interim vehicle in MSFC's "building block" approach to the Saturn rocket development, the Saturn IB utilized Saturn I technology to further develop and refine the larger boosters and the Apollo spacecraft capabilities required for the marned lunar missions.

Aspirations and Tensions in Developing International Mindedness: Case Study of Two Students in an IB School in an Indian Ocean Island Nation

ERIC Educational Resources Information Center

Poonoosamy, Mico

2016-01-01

International mindedness is considered by many educational researchers and organizations as a determining feature in international education. This article used data as part of a PhD case study inquiry to explore how international mindedness is developed by two students in an IB school in an Indian Ocean Island Nation. Through a qualitative…

Saturn Apollo Program

NASA Image and Video Library

1967-10-01

S-IB-211, the flight version of the Saturn IB launch vehicle's first (S-IVB) stage, on its way to Marshall Space Flight Center's (MSFC's) west test area. Between December 1967 and April 1968, the stage would undergo seven static test firings. The S-IB, developed by the MSFC and built by the Chrysler Corporation at the Michoud Assembly Facility near New Orleans, Louisiana, utilized eight H-1 engines and each produced 200,000 pounds of thrust.

Tailoring the field and indication of adjuvant pelvic radiation for patients with FIGO stage Ib lymph nodes-negative cervical carcinoma following radical surgery based on the GOG score--a pilot study.

PubMed

Rushdan, M N; Tay, E H; Khoo-Tan, H S; Lee, K M; Low, J H; Ho, T H; Yam, K L

2004-07-01

The traditional indications for adjuvant pelvic radiotherapy (RT) for International Federation of Obstetrics and Gynecology (FIGO) stage Ib1 lymph nodes-negative cervix carcinoma following radical surgery based on histopathological factors, such as deep stromal invasion and lymphovascular space invasion (LVSI), were often inconsistently applied. The perceived risk of relapse was subjectively determined. This pilot study attempts to determine if the treatment outcome will be affected when the indication for RT is based on the Gynecologic Oncology Group (GOG) Risk Score (RS) and the field of adjuvant RT is tailored to the RS. From 1997 to 1999, 55 patients with FIGO stage Ib1 lymph nodes-negative cervical carcinoma limited to the cervix were prescribed RT following radical surgery, based on their RS, as follows: RS <40, RT is omitted; RS >40 to <120, modified (smaller) field RT; and RS >120, standard field pelvic RT. Their incidence and site of recurrence were compared with a similar cohort of 40 patients who were treated prior to 1997. Prior to 1997, of the 40 patients, 10 patients were given standard field RT. There were 2 (5%) recurrent diseases. The mean duration of follow-up was 61.6 months (range, 1 to 103 months). The RS of 23 of the 30 patients who were not given RT were available. The mean RS was 22 with 5 patients having a score of >40. From 1997 onwards, of the 55 patients, 28 (51%) did not require RT, 13 (23%) were treated with modified (smaller) field RT and 14 (26%) were given standard field RT. There were 2 (3.6%) cases of relapse. The mean duration of follow-up was 36.4 months (range, 5 to 60 months). All patients with a RS of <40 did not suffer any relapse. Their survival outcomes were better when compared to patients who did not have any RT in the GOG Study. The results of this study indicated that postoperative adjuvant RT given to patients with a high GOG RS of >120, significantly improved their 5-year recurrence rate and disease-free survival, as

A myo-inositol-1-phosphate synthase gene, IbMIPS1, enhances salt and drought tolerance and stem nematode resistance in transgenic sweet potato.

PubMed

Zhai, Hong; Wang, Feibing; Si, Zengzhi; Huo, Jinxi; Xing, Lei; An, Yanyan; He, Shaozhen; Liu, Qingchang

2016-02-01

Myo-inositol-1-phosphate synthase (MIPS) is a key rate limiting enzyme in myo-inositol biosynthesis. The MIPS gene has been shown to improve tolerance to abiotic stresses in several plant species. However, its role in resistance to biotic stresses has not been reported. In this study, we found that expression of the sweet potato IbMIPS1 gene was induced by NaCl, polyethylene glycol (PEG), abscisic acid (ABA) and stem nematodes. Its overexpression significantly enhanced stem nematode resistance as well as salt and drought tolerance in transgenic sweet potato under field conditions. Transcriptome and real-time quantitative PCR analyses showed that overexpression of IbMIPS1 up-regulated the genes involved in inositol biosynthesis, phosphatidylinositol (PI) and ABA signalling pathways, stress responses, photosynthesis and ROS-scavenging system under salt, drought and stem nematode stresses. Inositol, inositol-1,4,5-trisphosphate (IP3 ), phosphatidic acid (PA), Ca(2+) , ABA, K(+) , proline and trehalose content was significantly increased, whereas malonaldehyde (MDA), Na(+) and H2 O2 content was significantly decreased in the transgenic plants under salt and drought stresses. After stem nematode infection, the significant increase of inositol, IP3 , PA, Ca(2+) , ABA, callose and lignin content and significant reduction of MDA content were found, and a rapid increase of H2 O2 levels was observed, peaked at 1 to 2 days and thereafter declined in the transgenic plants. This study indicates that the IbMIPS1 gene has the potential to be used to improve the resistance to biotic and abiotic stresses in plants. © 2015 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

30 CFR 57.22234 - Actions at 1.0 percent methane (I-A, I-B, III, V-A, and V-B mines).

Code of Federal Regulations, 2011 CFR

2011-07-01

....22234 Actions at 1.0 percent methane (I-A, I-B, III, V-A, and V-B mines). (a) If methane reaches 1.0... methane reaches 1.0 percent at a main exhaust fan, electrical power underground shall be deenergized..., and all persons shall be withdrawn from the mine. (c) If methane reaches 1.0 percent at a work place...

Hypofractionated Radiation Therapy in Treating Patients With Stage 0-IIB Breast Cancer

ClinicalTrials.gov

2018-05-11

Ductal Breast Carcinoma In Situ; Invasive Breast Carcinoma; Stage 0 Breast Cancer; Stage I Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer

Chemotherapy Toxicity On Quality of Life in Older Patients With Stage I, Stage II, Stage III, or Stage IV Ovarian Epithelial, Primary Peritoneal Cavity, or Fallopian Tube Cancer

ClinicalTrials.gov

2017-05-03

Stage I Ovarian Cancer; Stage IA Fallopian Tube Cancer; Stage IB Fallopian Tube Cancer; Stage IC Fallopian Tube Cancer; Stage II Ovarian Cancer; Stage IIA Fallopian Tube Cancer; Stage IIB Fallopian Tube Cancer; Stage IIC Fallopian Tube Cancer; Stage III Ovarian Cancer; Stage III Primary Peritoneal Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIC Fallopian Tube Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer