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  1. Recurrent Loss of STING Signaling in Melanoma Correlates with Susceptibility to Viral Oncolysis.

    Science.gov (United States)

    Xia, Tianli; Konno, Hiroyasu; Barber, Glen N

    2016-11-15

    The innate immunoregulator STING stimulates cytokine production in response to the presence of cytosolic DNA, which can arise following DNA damage. Extrinsic STING signaling is also needed for antigen-presenting cells to stimulate antitumor T-cell immunity. Here, we show that STING signaling is recurrently suppressed in melanoma cells, where this event may enable immune escape after DNA damage. Mechanistically, STING signaling was suppressed most frequently by epigenetic silencing of either STING or the cyclic GMP-AMP synthase, which generates STING-activating cyclic dinucleotides after binding cytosolic DNA species. Loss of STING function rendered melanoma cells unable to produce type I IFN and other immune cytokines after exposure to cytosolic DNA species. Consequently, such cells were highly susceptible to infection with DNA viruses including HSV1, a variant of which is being developed presently as a therapeutic oncolytic virus [talimogene laherparepvec (T-VEC)]. Our findings provide insight into the basis for susceptibility to viral oncolysis by agents such as HSV1. Cancer Res; 76(22); 6747-59. ©2016 AACR. ©2016 American Association for Cancer Research.

  2. Madurella mycetomatis is highly susceptible to ravuconazole

    NARCIS (Netherlands)

    Ahmed, Sarah Abdalla; Kloezen, Wendy; Duncanson, Frederick; Zijlstra, Ed E; de Hoog, G Sybren; Fahal, Ahmed H; van de Sande, Wendy W J

    The current treatment of eumycetoma utilizing ketoconazole is unsatisfactory because of high recurrence rates, which often leads to complications and unnecessary amputations, and its comparatively high cost in endemic areas. Hence, an effective and affordable drug is required to improve therapeutic

  3. Madurella mycetomatis is highly susceptible to ravuconazole

    NARCIS (Netherlands)

    Ahmed, S.A.; Kloezen, W.; Duncanson, F.; Zijlstra, E.E.; de Hoog, G.S.; Fahal, A.H.; van de Sande, W.W.J.

    2014-01-01

    The current treatment of eumycetoma utilizing ketoconazole is unsatisfactory because of high recurrence rates, which often leads to complications and unnecessary amputations, and its comparatively high cost in endemic areas. Hence, an effective and affordable drug is required to improve therapeutic

  4. Madurella mycetomatis Is Highly Susceptible to Ravuconazole

    NARCIS (Netherlands)

    S.A. Ahmed (Sarah Abdalla); W. Kloezen (Wendy); F. Duncanson (Frederick); E. Zijlstra (Ed); G.S. de Hoog; A.H. Fahal (Ahmed); W.W.J. van de Sande (Wendy)

    2014-01-01

    textabstractThe current treatment of eumycetoma utilizing ketoconazole is unsatisfactory because of high recurrence rates, which often leads to complications and unnecessary amputations, and its comparatively high cost in endemic areas. Hence, an effective and affordable drug is required to improve

  5. Species distribution and in vitro antifungal susceptibility of oral yeast isolates from Tanzanian HIV-infected patients with primary and recurrent oropharyngeal candidiasis

    Directory of Open Access Journals (Sweden)

    Rijs Antonius JMM

    2008-08-01

    Full Text Available Abstract Background In Tanzania, little is known on the species distribution and antifungal susceptibility profiles of yeast isolates from HIV-infected patients with primary and recurrent oropharyngeal candidiasis. Methods A total of 296 clinical oral yeasts were isolated from 292 HIV-infected patients with oropharyngeal candidiasis at the Muhimbili National Hospital, Dar es Salaam, Tanzania. Identification of the yeasts was performed using standard phenotypic methods. Antifungal susceptibility to fluconazole, itraconazole, miconazole, clotrimazole, amphotericin B and nystatin was assessed using a broth microdilution format according to the guidelines of the Clinical and Laboratory Standard Institute (CLSI; M27-A2. Results Candida albicans was the most frequently isolated species from 250 (84.5% patients followed by C. glabrata from 20 (6.8% patients, and C. krusei from 10 (3.4% patients. There was no observed significant difference in species distribution between patients with primary and recurrent oropharyngeal candidiasis, but isolates cultured from patients previously treated were significantly less susceptible to the azole compounds compared to those cultured from antifungal naïve patients. Conclusion C. albicans was the most frequently isolated species from patients with oropharyngeal candidiasis. Oral yeast isolates from Tanzania had high level susceptibility to the antifungal agents tested. Recurrent oropharyngeal candidiasis and previous antifungal therapy significantly correlated with reduced susceptibility to azoles antifungal agents.

  6. Identifying patients at high risk of tuberculosis recurrence

    Directory of Open Access Journals (Sweden)

    Ruxana T Sadikot

    2016-01-01

    Full Text Available Several studies have been done in relation to recurrence of tuberculosis (TB following completion of treatment. However, recurrence of TB is still a major problem from a public health perspective in high-burden countries, where no special attention is being given to this issue. Disease recurrence is an important indicator of the efficacy of antituberculosis treatment. The rate of recurrence is highly variable and has been estimated to range from 4.9% to 25%. This variability is not only a reflection of regional epidemiology of recurrence but differences in the definitions used by the TB control programs. In addition to treatment failure related to medication adherence, there are several key host factors that are associated with high rates of recurrence. The widely recognized host factors independent of treatment program that predispose to TB recurrence include: malnutrition; human immunodeficiency virus; substance abuse including tobacco use; comorbidity such as diabetes, renal failure and systemic diseases, especially immunosuppressive states; and environmental exposure such as silicosis. With improved understanding of the human genome, proteome, and metabolome, additional host-specific factors that predispose to recurrence are being discovered. Information on temporal and geographical trends of TB cases as well as genotyping might provide further information to enable us to fully understand TB recurrence and discriminate between reactivation and new infection. The recently launched World Health Organization End TB Strategy emphasizes the importance of integrated, patient-centered TB care. Continued improvement in diagnosis, treatment approaches, and defining host-specific factors are needed to fully understand the clinical epidemiological and social determinants of TB recurrence.

  7. Mannose binding lectin codon 54 polymorphism and susceptibility to recurrent respiratory tract infections in children: A meta-analysis.

    Science.gov (United States)

    Atan, Ozlem; Kucukcelebi, Ahmet; Atik, Tahir; Ozkınay, Ferda

    2016-02-01

    There have been studies focused on mannose binding lectin (MBL) polymorphism and susceptibility to recurrent respiratory tract infections (RRTI) with inconclusive results. This present study is a meta-analysis of possible MBL and RRTI association in children. A literature search was performed using Medline and PubMed and abstracts were reviewed for relevance. Any study was considered to be eligible for inclusion if it met the following criteria: the MBL gene polymorphism at codon 54 was determined, the outcome was recurrent respiratory tract infection in children and there were at least two comparison groups. The odds ratios(OR) of the genetic MBL polymorphisms were combined and calculated, and the forest plots of the OR value distributions were drawn. Chi-squared testing of heterogeneity was done (prespiratory tract infection in children. Summary of the article's main point Here are discrepancies regarding the importance of MBL polymorphism and its impact on recurrent respiratory tract infections. Our meta analysis did not find statistically significant association between MBL codon 54 polymorphism and recurrent respiratory tract infection in children. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  8. High grade leiomyosarcoma mimicking a recurrent angiomyxoma in the perineum

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    Neha Sood

    2015-05-01

    Full Text Available Perineal leiomyosarcoma is an extremely rare and aggressive cancer with a high metastatic potential and no defined standard treatment. There are only a few (six reported cases in the literature. We report the case of a 67-year-old woman with a perineal leiomyosarcoma arising at the same site of a previously resected superficial angiomyxoma. Initially, she was treated for a presumptive recurrence of angiomyxoma. As she did not respond to medical therapy, she underwent repeat surgical excision. Pathology revealed a high grade leiomyosarcoma, histologically strikingly distinct from the initial diagnosis. She received adjuvant local radiation therapy, and remains without evidence of recurrent disease 36 months after completion of all therapy. This is the first reported case of a high grade perineal leiomyosarcoma originating at the same site as a resected benign superficial angiomyxoma. Our case emphasizes the necessity of a prompt histological diagnosis in cases of presumed recurrent perineal angiomyxoma.

  9. Targeted Next-Generation Sequencing Identifies a Recurrent Mutation in MCPH1 Associating with Hereditary Breast Cancer Susceptibility.

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    Tuomo Mantere

    2016-01-01

    Full Text Available Breast cancer is strongly influenced by hereditary risk factors, a majority of which still remain unknown. Here, we performed a targeted next-generation sequencing of 796 genes implicated in DNA repair in 189 Finnish breast cancer cases with indication of hereditary disease susceptibility and focused the analysis on protein truncating mutations. A recurrent heterozygous mutation (c.904_916del, p.Arg304ValfsTer3 was identified in early DNA damage response gene, MCPH1, significantly associating with breast cancer susceptibility both in familial (5/145, 3.4%, P = 0.003, OR 8.3 and unselected cases (16/1150, 1.4%, P = 0.016, OR 3.3. A total of 21 mutation positive families were identified, of which one-third exhibited also brain tumors and/or sarcomas (P = 0.0007. Mutation carriers exhibited significant increase in genomic instability assessed by cytogenetic analysis for spontaneous chromosomal rearrangements in peripheral blood lymphocytes (P = 0.0007, suggesting an effect for MCPH1 haploinsufficiency on cancer susceptibility. Furthermore, 40% of the mutation carrier tumors exhibited loss of the wild-type allele. These findings collectively provide strong evidence for MCHP1 being a novel breast cancer susceptibility gene, which warrants further investigations in other populations.

  10. Increased seizure susceptibility and up-regulation of nNOS expression in hippocampus following recurrent early-life seizures in rats.

    Science.gov (United States)

    Kim, Doo-Kwun

    2010-06-01

    This study aimed to determine the long-term change of seizure susceptibility and the role of nNOS on brain development following recurrent early-life seizures in rats. Video-EEG recordings were conducted between postnatal days 50 and 60. Alterations in seizure susceptibility were assayed on day 22 or 50 using the flurothyl method. Changes in nNOS expression were determined by quantitative immunoblotting on day 50. On average, rats had 8.4+/-2.7 seizures during 10 daily 1 hr behavioral monitoring sessions. As adults (days 50-60), all rats displayed interictal spikes in the hippocampus and/or overlying cortex. Brief electrographic seizures were recorded in only one of five animals. Rats appeared to progress from a period of marked seizure susceptibility (day 22) to one of lessened seizure susceptibility (day 50). Up-regulation of nNOS expression following early-life recurrent seizures was observed on day 50. In conclusion, these data suggested that recurrent early-life seizures had the long-term effects on seizure susceptibility late in life and up-regulatory nNOS expression on the hippocampus during brain development, and nNOS appeared to contribute to the persistent changes in seizure susceptibility, and epileptogenesis.

  11. Tipifarnib in Treating Young Patients With Recurrent or Progressive High-Grade Glioma, Medulloblastoma, Primitive Neuroectodermal Tumor, or Brain Stem Glioma

    Science.gov (United States)

    2013-10-07

    Childhood High-grade Cerebral Astrocytoma; Childhood Oligodendroglioma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma

  12. Changes in bleaching susceptibility among corals subject to ocean warming and recurrent bleaching in Moorea, French Polynesia.

    Directory of Open Access Journals (Sweden)

    Morgan S Pratchett

    Full Text Available BACKGROUND: Climate-induced coral bleaching poses a major threat to coral reef ecosystems, mostly because of the sensitivities of key habitat-forming corals to increasing temperature. However, susceptibility to bleaching varies greatly among coral genera and there are likely to be major changes in the relative abundance of different corals, even if the wholesale loss of corals does not occur for several decades. Here we document variation in bleaching susceptibility among key genera of reef-building corals in Moorea, French Polynesia, and compare bleaching incidence during mass-bleaching events documented in 1991, 1994, 2002 and 2007. METHODOLOGY/PRINCIPAL FINDINGS: This study compared the proportion of colonies that bleached for four major genera of reef-building corals (Acropora, Montipora, Pocillopora and Porites, during each of four well-documented bleaching events from 1991 to 2007. Acropora and Montipora consistently bleached in far greater proportions (up to 98% than Pocillopora and Porites. However, there was an apparent and sustained decline in the proportion of colonies that bleached during successive bleaching events, especially for Acropora and Montipora. In 2007, only 77% of Acropora colonies bleached compared with 98% in 1991. Temporal variation in the proportion of coral colonies bleached may be attributable to differences in environmental conditions among years. Alternately, the sustained declines in bleaching incidence among highly susceptible corals may be indicative of acclimation or adaptation. CONCLUSIONS/SIGNIFICANCE: Coral genera that are highly susceptible to coral bleaching, and especially Acropora and Montipora, exhibit temporal declines in their susceptibility to thermal anomalies at Moorea, French Polynesia. One possible explanation for these findings is that gradual removal of highly susceptible genotypes (through selective mortality of individuals, populations, and/or species is producing a coral assemblage that is

  13. Changes in bleaching susceptibility among corals subject to ocean warming and recurrent bleaching in Moorea, French Polynesia.

    Science.gov (United States)

    Pratchett, Morgan S; McCowan, Dominique; Maynard, Jeffrey A; Heron, Scott F

    2013-01-01

    Climate-induced coral bleaching poses a major threat to coral reef ecosystems, mostly because of the sensitivities of key habitat-forming corals to increasing temperature. However, susceptibility to bleaching varies greatly among coral genera and there are likely to be major changes in the relative abundance of different corals, even if the wholesale loss of corals does not occur for several decades. Here we document variation in bleaching susceptibility among key genera of reef-building corals in Moorea, French Polynesia, and compare bleaching incidence during mass-bleaching events documented in 1991, 1994, 2002 and 2007. This study compared the proportion of colonies that bleached for four major genera of reef-building corals (Acropora, Montipora, Pocillopora and Porites), during each of four well-documented bleaching events from 1991 to 2007. Acropora and Montipora consistently bleached in far greater proportions (up to 98%) than Pocillopora and Porites. However, there was an apparent and sustained decline in the proportion of colonies that bleached during successive bleaching events, especially for Acropora and Montipora. In 2007, only 77% of Acropora colonies bleached compared with 98% in 1991. Temporal variation in the proportion of coral colonies bleached may be attributable to differences in environmental conditions among years. Alternately, the sustained declines in bleaching incidence among highly susceptible corals may be indicative of acclimation or adaptation. Coral genera that are highly susceptible to coral bleaching, and especially Acropora and Montipora, exhibit temporal declines in their susceptibility to thermal anomalies at Moorea, French Polynesia. One possible explanation for these findings is that gradual removal of highly susceptible genotypes (through selective mortality of individuals, populations, and/or species) is producing a coral assemblage that is more resistant to sustained and ongoing ocean warming.

  14. Species distribution and in vitro antifungal susceptibility of oral yeast isolates from Tanzanian HIV-infected patients with primary and recurrent oropharyngeal candidiasis.

    NARCIS (Netherlands)

    Hamza, O.J.M.; Matee, M.I.N.; Moshi, M.J.; Simon, E.N.; Mugusi, F.; Mikx, F.H.M.; Palenstein Helderman, W.H. van; Rijs, A.J.M.M.; Ven, A.J.A.M. van der; Verweij, P.E.

    2008-01-01

    BACKGROUND: In Tanzania, little is known on the species distribution and antifungal susceptibility profiles of yeast isolates from HIV-infected patients with primary and recurrent oropharyngeal candidiasis. METHODS: A total of 296 clinical oral yeasts were isolated from 292 HIV-infected patients

  15. High-throughput metal susceptibility testing of microbial biofilms

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    Turner Raymond J

    2005-10-01

    Full Text Available Abstract Background Microbial biofilms exist all over the natural world, a distribution that is paralleled by metal cations and oxyanions. Despite this reality, very few studies have examined how biofilms withstand exposure to these toxic compounds. This article describes a batch culture technique for biofilm and planktonic cell metal susceptibility testing using the MBEC assay. This device is compatible with standard 96-well microtiter plate technology. As part of this method, a two part, metal specific neutralization protocol is summarized. This procedure minimizes residual biological toxicity arising from the carry-over of metals from challenge to recovery media. Neutralization consists of treating cultures with a chemical compound known to react with or to chelate the metal. Treated cultures are plated onto rich agar to allow metal complexes to diffuse into the recovery medium while bacteria remain on top to recover. Two difficulties associated with metal susceptibility testing were the focus of two applications of this technique. First, assays were calibrated to allow comparisons of the susceptibility of different organisms to metals. Second, the effects of exposure time and growth medium composition on the susceptibility of E. coli JM109 biofilms to metals were investigated. Results This high-throughput method generated 96-statistically equivalent biofilms in a single device and thus allowed for comparative and combinatorial experiments of media, microbial strains, exposure times and metals. By adjusting growth conditions, it was possible to examine biofilms of different microorganisms that had similar cell densities. In one example, Pseudomonas aeruginosa ATCC 27853 was up to 80 times more resistant to heavy metalloid oxyanions than Escherichia coli TG1. Further, biofilms were up to 133 times more tolerant to tellurite (TeO32- than corresponding planktonic cultures. Regardless of the growth medium, the tolerance of biofilm and planktonic

  16. High-throughput metal susceptibility testing of microbial biofilms

    Science.gov (United States)

    Harrison, Joe J; Turner, Raymond J; Ceri, Howard

    2005-01-01

    Background Microbial biofilms exist all over the natural world, a distribution that is paralleled by metal cations and oxyanions. Despite this reality, very few studies have examined how biofilms withstand exposure to these toxic compounds. This article describes a batch culture technique for biofilm and planktonic cell metal susceptibility testing using the MBEC assay. This device is compatible with standard 96-well microtiter plate technology. As part of this method, a two part, metal specific neutralization protocol is summarized. This procedure minimizes residual biological toxicity arising from the carry-over of metals from challenge to recovery media. Neutralization consists of treating cultures with a chemical compound known to react with or to chelate the metal. Treated cultures are plated onto rich agar to allow metal complexes to diffuse into the recovery medium while bacteria remain on top to recover. Two difficulties associated with metal susceptibility testing were the focus of two applications of this technique. First, assays were calibrated to allow comparisons of the susceptibility of different organisms to metals. Second, the effects of exposure time and growth medium composition on the susceptibility of E. coli JM109 biofilms to metals were investigated. Results This high-throughput method generated 96-statistically equivalent biofilms in a single device and thus allowed for comparative and combinatorial experiments of media, microbial strains, exposure times and metals. By adjusting growth conditions, it was possible to examine biofilms of different microorganisms that had similar cell densities. In one example, Pseudomonas aeruginosa ATCC 27853 was up to 80 times more resistant to heavy metalloid oxyanions than Escherichia coli TG1. Further, biofilms were up to 133 times more tolerant to tellurite (TeO32-) than corresponding planktonic cultures. Regardless of the growth medium, the tolerance of biofilm and planktonic cell E. coli JM109 to metals

  17. Genetic Polymorphism of Toll-like Receptor 4 — Predictor of Susceptibility to Recurrent Course of Chronic Pyelonephritis in Children

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    T.A. Kryuchko

    2013-10-01

    Methods. We examined a group of children aged 1–15 years with chronic pyelonephritis in the active stage (n = 60. Control group consisted of 95 apparently healthy people. Results. There were revealed significantly higher prevalence of Toll-like receptor 4 Asp299Gly gene polymorphism among children with chronic pyelonephritis (n = 60, identified a statistically significant correlation of mutant genotypes Asp299Gly, Gly299Gly with manifestation of the disease before the age of 3, and frequent episodes of acute respiratory viral infections, torpid urinary syndrome, unstable remission and increased secretion of interleukin-6 (p < 0.001. Thus, genetically determined Toll-like receptor 4 Asp299Gly gene polymorphism is a marker of high risk of early manifestation of chronic inflammation in the kidney interstitium and prolonged recurrent clinical course of the disease in children.

  18. The Psychosocial Experience of High School Girls Highly Susceptible to Stereotype Threat: A Phenomenological Study

    Science.gov (United States)

    Picho, Katherine

    2016-01-01

    The author used phenomenology to explore the subjective experience of ninth-grade girls susceptible to mathematics-related stereotype threat in their authentic learning environments. The sample constituted students categorized as either having low or high susceptibility to stereotype threat (SST) enrolled in Honors mathematics classes at an urban…

  19. Drug combination may be highly effective in recurrent ovarian cancer

    Science.gov (United States)

    Significant improvement with the use of a combination drug therapy for recurrent ovarian cancer was reported at the annual meeting of the American Society of Clinical Oncology meeting in Chicago. The trial compared the activity of a combination of the dru

  20. High incidence of acute and recurrent patellar dislocations

    DEFF Research Database (Denmark)

    Gravesen, Kasper Skriver; Kallemose, Thomas; Blønd, Lars

    2017-01-01

    PURPOSE: The purpose of this study was to investigate the Danish population as a whole from 1994 to 2013 to find the incidence of acute and recurrent patellar dislocation. METHODS: The study was performed as a descriptive epidemiological study. The Danish National Patient Registry was retrospecti......PURPOSE: The purpose of this study was to investigate the Danish population as a whole from 1994 to 2013 to find the incidence of acute and recurrent patellar dislocation. METHODS: The study was performed as a descriptive epidemiological study. The Danish National Patient Registry...... was retrospectively searched from 1994 to 2013 to find the number of acute and recurrent patellar dislocation. National population data were collected from Statistics Denmark. RESULTS: The period 1994-2013 saw a total registration of 24,154 primary patellar dislocations. A mean incidence of 42 (95% CI 37-47) per 100......,000 person-years at risk was found, and young females aged 10-17 had the highest incidence of 108 (95% CI 101-116). In a 10-year follow-up, patients were at an overall risk of 22.7% (95% CI 22.2-23.2) of suffering a recurrent dislocation, with young girls aged 10-17 experiencing the highest risk, namely 36...

  1. Predictive factors of biochemical recurrence after radical prostatectomy for high-risk prostate cancer.

    Science.gov (United States)

    Murata, Yukiko; Tatsugami, Katsunori; Yoshikawa, Masahiro; Hamaguchi, Masumitsu; Yamada, Shigetomo; Hayakawa, Yusuke; Ueda, Kouhei; Momosaki, Seiya; Sakamoto, Naotaka

    2018-01-08

    To identify risk factors of biochemical recurrence after radical prostatectomy in high-risk patients. A total of 191 high-risk prostate cancer patients according to the D'Amico classification treated with radical prostatectomy at a single institution between April 2000 and December 2013 were enrolled. The pathological evaluation including intraductal carcinoma of prostate was reassessed, and the clinical and pathological risk factors of biochemical recurrence were analyzed. The median follow up after radical prostatectomy was 49 months. The 5-year biochemical recurrence-free survival rate after radical prostatectomy in high-risk prostate cancer patients was 41.6%. Initial prostate-specific antigen, pathological Gleason score, seminal vesicle invasion, extraprostatic extension and intraductal carcinoma of the prostate were significantly associated with biochemical recurrence-free survival. The 5-year biochemical recurrence-free survival rates in patients with zero, one, two and three of these risk factors were 92.9%, 70.7%, 38.3% and 28.8%, respectively. In patients with four or more factors, the biochemical recurrence-free survival rate was 6.1% after 18 months. In D'Amico high-risk patients treated with radical prostatectomy, risk factors for biochemical recurrence can be identified. Patients with fewer risk factors have longer biochemical recurrence-free survival, even among these high-risk cases. © 2018 The Japanese Urological Association.

  2. A Pilot Feasibility Study of Oral 5-Fluorocytosine and Genetically-Modified Neural Stem Cells Expressing E.Coli Cytosine Deaminase for Treatment of Recurrent High Grade Gliomas

    Science.gov (United States)

    2017-11-07

    Adult Anaplastic Astrocytoma; Recurrent Grade III Glioma; Recurrent Grade IV Glioma; Adult Anaplastic Oligodendroglioma; Adult Brain Tumor; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Mixed Glioma; Recurrent Adult Brain Tumor; Adult Anaplastic Oligoastrocytoma; Recurrent High Grade Glioma

  3. Association of rs1042658 Polymorphism of the CSF3 Gene with the Susceptibility of Recurrent Pregnancy Loss in Women of Fars Province

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    Kobra Jahangirizade

    2016-04-01

    Full Text Available Abstract Background: Recurrent pregnancy loss (RPL is a heterogeneous condition with the prevalence of more than 1% among women of reproductive age, which is defined as the occurrence of more than two miscarriages. Immune-mediators, cytokines, determine the role of immune cells in response to tissue incompatibility conditions. Colony stimulating factor 3 (CSF3 is a cytokine affecting the expression of other cytokines such as IL-4, and suppressing the immune response against semi-allograft embryo. This study was done for the first time on the association of the rs1042658 polymorphism at 3’UTR of the CSF3 gene with the susceptibility to recurrent pregnancy loss, supposing the effect of it on the expression level and stability of the CSF3 gene transcript. Materials and Methods: 122 RPL women and 140 healthy fertile women as a control group were enrolled in this case-control study. Genotype distribution of the selected polymorphism was evaluated by T-ARMS PCR method and the results were analyzed by logistic regression test. Results: comparison of the genotypic frequencies in the 3'UTR of the CSF3 gene in patients and controls resulted in the statistically significant difference in the incidence of pregnancy loss in order to the protection effect of the genotypes carrying T allele was observed between two groups (p<0.05. History of the abortion among the relatives of RPL women versus the relatives of controls showed significant differences (p=0.05. Conclusion: Findings showed significant relationship between rs1042658 polymorphism and the risk of recurrent pregnancy loss, which can affect the susceptibility of the condition.

  4. Salvage high-dose-rate brachytherapy for local prostate cancer recurrence after radical radiotherapy

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    V. A. Solodkiy

    2016-01-01

    Full Text Available Studies salvage interstitial radiation therapy for recurrent prostate cancer, launched at the end of the XX century. In recent years, more and more attention is paid to high-dose-rate brachytherapy (HDR-BT as a method of treating local recurrence.The purpose of research – preliminary clinical results of salvage high-dose-rate brachytherapy applied in cases of suspected local recurrence or of residual tumour after radiotherapy.Preliminary findings indicate the possibility of using HDR-BT, achieving local tumor control with low genitourinary toxicity.

  5. Short Communication Antibiotic Susceptibility Pattern and Beta ...

    African Journals Online (AJOL)

    The multiple drug resistance as evident in high MICs of the antibiotics tested could probably be due to abuse/misuse of antibiotics resulting in recurrence of furuncles in the patients. Keywords: Antibiotic susceptibility, β-lactamase, Recurrent furunculosis, Staphylococcus aureus. Received 08 August 2011/ Accepted 30 ...

  6. Breast Cancer Susceptibility Genes in High Risk Women

    National Research Council Canada - National Science Library

    Hamilton, Ann

    2003-01-01

    ...%. It has been hypothesized that susceptibility genes of lower penetrance may also affect breast cancer risk, and a likely group of such genes are those that regulate the production, intracellular...

  7. Breast Cancer Susceptibility Genes in High Risk Women

    National Research Council Canada - National Science Library

    Hamilton, Ann

    2004-01-01

    ...). It has been hypothesized that susceptibility genes of lower penetrance are more prevalent than among the latter, and a likely group of such genes are those that regulate the production, intracellular...

  8. Breast Cancer Susceptibility Genes in High Risk Women

    National Research Council Canada - National Science Library

    Hamilton, Ann

    2002-01-01

    ...%. It has been hypothesized that susceptibility genes of lower penetrance may also affect breast cancer risk, and a likely group of such genes are those that regulate the production, intracellular...

  9. Breast Cancer Susceptibility Genes in High Risk Women

    National Research Council Canada - National Science Library

    Hamilton, Ann

    2001-01-01

    ...%. It has been hypothesized that susceptibility genes of lower penetrance may also affect breast cancer risk, and a likely group of such genes are those that regulate the production, intracellular...

  10. Why a high statistical performance cannot be equated with a high plausibility of landslide susceptibility maps

    Science.gov (United States)

    Steger, Stefan; Brenning, Alexander; Bell, Rainer; Petschko, Helene; Glade, Thomas

    2015-04-01

    Statistical landslide susceptibility maps express a relative estimate of where landslides are more likely to occur in the future due to a set of geo-environmental conditions. Their predictive capability is regularly deduced by interpreting threshold independent performance measures like the area under the receiver operating characteristic curve (AUROC). These quantitative estimates frequently serve as a decision tool to favour a certain classifier over another and/or to select a suitable combination of predictors. Literature exposes that many authors consider their final maps as a valuable instrument for spatial planners and decision makers. However, most often the susceptibility maps are selected by solely interpreting such quantitative estimates. We assume that a high statistical quality is necessary but not sufficient in order to produce plausible landslide susceptibility maps. This assumption was tested by quantitatively and qualitatively validating 16 susceptibility models for a study area (1354 km²) located in Lower Austria. The models were generated by applying two statistical and two machine learning classifiers separately for two landslide inventories and two sets of predictors. Quantitative validation was conducted by estimating the AUROC with non spatial hold-out validation and a repeated spatial cross validation technique. The spatial differentiation of the final maps was evaluated at different scales by interpreting semivariograms. Maps of the location of major variations illustrate the spatial structure of the final susceptibility maps and allowed to deduce the most influential predictors and predictor classes. According to the hold-out validation, all 16 susceptibility models performed similarly well. However, spatial cross validation revealed considerable differences between models generated by different landslide inventories. Semivariograms exposed that the predicted landslide susceptibility pattern differs substantially between maps generated by

  11. Antimicrobial Resistance and Reduced Susceptibility in Clostridium difficile: Potential Consequences for Induction, Treatment, and Recurrence of C. difficile Infection

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    Simon D. Baines

    2015-07-01

    Full Text Available Clostridium difficile infection (CDI remains a substantial burden on healthcare systems and is likely to remain so given our reliance on antimicrobial therapies to treat bacterial infections, especially in an aging population in whom multiple co-morbidities are common. Antimicrobial agents are a key component in the aetiology of CDI, both in the establishment of the infection and also in its treatment. The purpose of this review is to summarise the role of antimicrobial agents in primary and recurrent CDI; assessing why certain antimicrobial classes may predispose to the induction of CDI according to a balance between antimicrobial activity against the gut microflora and C. difficile. Considering these aspects of CDI is important in both the prevention of the infection and in the development of new antimicrobial treatments.

  12. Methylenetetrahydrofolate reductase gene A1298C polymorphism and susceptibility to recurrent pregnancy loss: a meta-analysis.

    Science.gov (United States)

    Rai, V

    2014-06-27

    Environmental and genetic factors are thought to be involved in the pathogenesis of recurrent pregnancy loss (RPL)/spontaneous abortions (SA), which include endocrine, anatomical abnormalities within the genital organs, autoimmune diseases and some gene variants. Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme of the folate/methionine metabolic pathway and it is well established fact that folate deficiency causes pregnancy complications like recurrent pregnancy loss, preeclempsia and birth defects affected pregnancies. MTHFR A1298C polymorphism reduces the enzymatic activity and mimics as folate deficiency. To date, many studies have investigated the association between MTHFR A1298C polymorphism and RPL risk; however, the result is still controversial and inconclusive. The aim of the present study was to address the association of MTHFR A1298C polymorphism with RPL risk by meta—analysis. By searching electronic databases, total seventeen studies were identified for present meta—analysis. Crude odds ratios (OR) with 95 % confidence intervals (CIs) was used to assess the strength of association between A1298C polymorphism and RPL. The results indicate that the A1298C polymorphism is not associated with RPL (ORCvs A = 1.13 ,95 % CI= 0.87—1.46, P = 0.36 ; ORACvs AA = 1.22 ,95 % CI= 0.94— 1.6, P = 0.13; ORCCvsAA =1.35, 95 % CI= 76—2.36, P = 0.30; ORCC+AC vs AA = 1.15, 95 % CI= 88 —1.49, P = 0.29; ORCCvs AC+AA = 1.29, 95 % CI= 76 —2.12, P = 0.34). Further prospective studies were needed to confirm the precise relationship between the MTHFR A1298C polymorphism and RPL.

  13. Nurses and Dietitians Differ in Food Safety Information Provided to Highly Susceptible Clients

    Science.gov (United States)

    Buffer, Janet; Kendall, Patricia; Medeiros, Lydia; Schroeder, Mary; Sofos, John

    2013-01-01

    Objective: To determine content, education channels, and motivational factors that influence what health professionals teach about safe food handling to populations who are highly susceptible for foodborne illnesses. To assess the differences in information provided by health professionals to highly susceptible populations. Design: Descriptive,…

  14. Identifying rheumatoid arthritis susceptibility genes using high-dimensional methods

    OpenAIRE

    Liang Xueying; Gao Ying; Lam Tram K; Li Qizhai; Falk Cathy; Yang Xiaohong R; Goldstein Alisa M; Goldin Lynn R

    2009-01-01

    Abstract Although several genes (including a strong effect in the human leukocyte antigen (HLA) region) and some environmental factors have been implicated to cause susceptibility to rheumatoid arthritis (RA), the etiology of the disease is not completely understood. The ability to screen the entire genome for association to complex diseases has great potential for identifying gene effects. However, the efficiency of gene detection in this situation may be improved by methods specifically des...

  15. Open retropubic reanastomosis for highly recurrent and complex bladder neck stenosis.

    Science.gov (United States)

    Pfalzgraf, Daniel; Beuke, Maike; Isbarn, Hendrik; Reiss, Christoph Philip; Meyer-Moldenhauer, Wolf-Hartmut; Dahlem, Roland; Fisch, Margit

    2011-11-01

    We assessed the success rate of open reanastomosis for highly recurrent bladder neck stenosis resistant to transurethral treatment. Due to the paucity of available data the success rate of this procedure is not well defined, although it can be a last treatment option before urinary diversion. A total of 158 patients were treated for bladder neck stenosis in 1998 to 2007, of whom 20 underwent open reanastomosis for highly recurrent or complex bladder neck stenosis after radical prostatectomy and were seen for followup 3 months postoperatively. They received a standardized questionnaire at the time of data acquisition in this retrospective analysis. The 20 patients underwent a mean of 3.7 previous surgeries. Median followup was 59.2 months. Stenosis recurred after reanastomosis in 8 patients (40%) while the remaining 60% were recurrence free. Seven recurrences were successfully treated endoscopically, resulting in an overall combined 95% success rate. Urinary diversion was performed in 1 patient with another recurrence after reanastomosis and transurethral resection. Four patients (31%) had new onset incontinence and 13 were completely incontinent, of whom 9 were successfully treated with artificial urinary sphincter implantation. In another patient artificial urinary sphincter implantation is scheduled and 3 elected no further treatment. Open reanastomosis for recurrent bladder neck stenosis is a good therapeutic option in cases of endoscopic treatment failure. The initial success rate after reanastomosis was 60%, which increased to 95% after secondary treatment. There was a relatively high risk of new onset incontinence after reconstructive surgery but this was successfully treated with artificial urinary sphincter implantation in most patients. Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  16. High-dose rate Ir-192 interstitial brachytherapy for recurrent pelvic tumors

    Energy Technology Data Exchange (ETDEWEB)

    Tsukiyama, Iwao; Katano, Susumu; Kotake, Kenjiro; Yamamoto, Seiichiro; Kamata, Hiroyuki; Sekiguchi, Isao [Tochigi Cancer Center, (Japan); Furuta, Masaya; Ohno, Tatsuya

    1999-06-01

    Recurrent pelvic tumors are difficult to control with external irradiation alone. We have conducted phase I and II clinical trials against recurrent pelvic tumors. From January 1995 through March 1997, 13 recurrent pelvic tumors in 10 patients were treated with high-dose rate Ir-192 interstitial brachytherapy. Complete responses were achieved for 2 tumors, partial responses for 5 tumors, and no response for 6 tumors; therefore, the response rate was 61% (8 of 13 tumors). Treatment-related morbidity was noted in 5 patients and included one case each of skin ulcer, rectovaginal fistula, sacral abscess, rectal bleeding, and vesicovaginal fistula. In January 1999, four patients were alive and had survived for 17, 18, 28, and 46 months. Six patients had died but had survived 4, 13, 15, 16, and 27 months. (author)

  17. High Dry Bean Intake and Reduced Risk of Advanced Colorectal Adenoma Recurrence among Participants in the Polyp Prevention Trial

    OpenAIRE

    Lanza, Elaine; Hartman, Terryl J.; Albert, Paul S.; Shields, Rusty; Slattery, Martha; Caan, Bette; Paskett, Electra; Iber, Frank; Kikendall, James Walter; Lance, Peter; Daston, Cassandra; Schatzkin, Arthur

    2006-01-01

    Adequate fruit and vegetable intake was suggested to protect against colorectal cancer and colorectal adenomas; however, several recent prospective studies reported no association. We examined the association between fruits and vegetables and adenomatous polyp recurrence in the Polyp Prevention Trial (PPT). The PPT was a low-fat, high-fiber, high-fruit, and vegetable dietary intervention trial of adenoma recurrence, in which there were no differences in the rate of adenoma recurrence in parti...

  18. Determination of Drug Susceptibility of Candida Strains Isolated From Patients With Recurrent Candida Vulvovaginitis and Investigation of Predisposing Factors of the Disease

    Directory of Open Access Journals (Sweden)

    Minooeianhaghighi MH

    2017-03-01

    Full Text Available Introduction: Recurrent Vulvovaginal Candidiasis RVVC(, which is mostly caused by Candida albicans C. albicans(, is the second common cause of genital tract infection in females. Th purpose of this research was to identify Candida isolates from RVVC, identify predisposing factors and determine antifungal effct of flconazole against Candida strains isolated from the patients. Methods: In this descriptive-laboratory study, 20 patients with confimed diagnosis of RVVC were selected. Yeast isolates were characterized using mycological standard methods, including culture on Sabouraud dextrose agar medium and CHROM agar, germ tube test and polymerase chain reaction-restriction fragment length polymorphism PCR-RFLP( technique. Th susceptibility of Candida isolates against flconazole was determined by microdilution broth method. Results: Th average age of the patients was 29.43 ± 4.63 years. Candida albicans was obtained from 100% of the samples. Th most common clinical sign was vaginal discharge 60%( in females with positive culture. Statistical correlations were observed between parturition frequency and low RVVC occurrence as well as between the previous antifungal therapy and RVVC occurrence. Th mean minimum inhibitory concentration MIC( and minimum fungicidal concentration MFC( of flconazole against diffrent C. albicans strains was determined as 45.3863 µg/mL and 63 µg/mL, respectively. Conclusion: Due to the uncertainty of diagnosis of this disease according to clinical symptoms and also, due to the resistance of Candida species, using culture and molecular methods are recommended as standard methods of diagnosis.

  19. Salvage high-dose-rate interstitial brachytherapy for locally recurrent rectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Pellizzon, Antonio Cassio Assis, E-mail: acapellizzon@hcancer.org.br [A.C. Camargo Cancer Center, Sao Paulo, SP (Brazil). Departamento de Radioterapia

    2016-05-15

    For tumors of the lower third of the rectum, the only safe surgical procedure is abdominal-perineal resection. High-dose-rate interstitial brachytherapy is a promising treatment for local recurrence of previously irradiated lower rectal cancer, due to the extremely high concentrated dose delivered to the tumor and the sparing of normal tissue, when compared with a course of external beam radiation therapy. (author)

  20. Deep Recurrent Neural Network for Mobile Human Activity Recognition with High Throughput

    OpenAIRE

    Inoue, Masaya; Inoue, Sozo; Nishida, Takeshi

    2016-01-01

    In this paper, we propose a method of human activity recognition with high throughput from raw accelerometer data applying a deep recurrent neural network (DRNN), and investigate various architectures and its combination to find the best parameter values. The "high throughput" refers to short time at a time of recognition. We investigated various parameters and architectures of the DRNN by using the training dataset of 432 trials with 6 activity classes from 7 people. The maximum recognition ...

  1. Usefulness of high-dose intravenous human immunoglobulins treatment for refractory recurrent pericarditis.

    Science.gov (United States)

    Moretti, Michele; Buiatti, Alessandra; Merlo, Marco; Massa, Laura; Fabris, Enrico; Pinamonti, Bruno; Sinagra, Gianfranco

    2013-11-01

    The management of refractory recurrent pericarditis is challenging. Previous clinical reports have noted a beneficial effect of high-dose intravenous human immunoglobulins (IvIgs) in isolated and systemic inflammatory disease-related forms. In this article, we analyzed retrospectively our clinical experience with IvIg therapy in a series of clinical cases of pericarditis refractory to conventional treatment. We retrospectively analyzed 9 patients (1994 to 2010) with refractory recurrent pericarditis, who received high-dose IvIg as a part of their medical treatment. Nonsteroidal anti-inflammatory drugs (NSAIDs), steroids, or colchicine treatment was not discontinued during IvIg treatment. No patients had a history of autoimmune or connective tissue diseases. During an average period of 11 months from the first recurrence, patients had experienced a mean of 5 relapses before the first IvIg treatment. In 4 cases, patients showed complete clinical remission with no further relapse after the first IvIg cycle. Two patients experienced a single minor relapse, responsive to short-term nonsteroidal anti-inflammatory drugs. In 2 patients, we performed a second cycle of IvIg after a recurrence of pericarditis, with subsequent complete remission. One patient did not respond to 3 cycles of IvIg and subsequently underwent pericardial window and long-term immunosuppressive treatment. No major adverse effect was observed in consequence of IvIg administration in all the cases. In conclusion, although IvIg mode of action is still poorly understood in this setting, this treatment can be considered as an option in patients with recurrent pericarditis refractory to conventional medical treatment and, in our small series, has proved to be effective in 8 of 9 cases. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. High-Grade Tumor Budding Stratifies Early-Stage Cervical Cancer with Recurrence Risk.

    Science.gov (United States)

    Huang, Bangxing; Cai, Jing; Xu, Xia; Guo, Shuang; Wang, Zehua

    2016-01-01

    This study investigated prognostic significance of tumor budding in early-stage cervical cancer (ESCC) following radical surgery and its contribution to improve the stratification of patients with recurrence risk. The archival medical records and H&E-stained slides of 643 patients with IA2-IIA stage cervical cancer who underwent radical surgery were retrospectively reviewed. Clinicopathological parameters were noted, and tumor buds were counted using immunohistochemistry for each case. The prognostic significance of tumor budding was analyzed. Prediction models that comprised tumor budding were established, and the performance was compared between the novel models and classic criteria via log-rank test and receiver operating characteristic analysis. Tumors with high-grade tumor budding (HTB) exhibited a substantially increased risk of recurrence (hazard ratio = 4.287, P tumor size ≥ 4 cm, deep stromal invasion of outer 1/3, and lymphovascular space invasion to stratify patients with an intermediate risk was most predictive of recurrence compared with the classic criteria. Tumor budding is an independent, unfavorable, prognostic factor for ESCC patients following radical surgery and holds promise for improved recurrence risk stratification.

  3. Perioperative Interstitial High-Dose-Rate Brachytherapy for the Treatment of Recurrent Keloids

    DEFF Research Database (Denmark)

    Jiang, Ping; Baumann, René; Dunst, Jürgen

    2016-01-01

    PURPOSE: To prospectively evaluate high-dose-rate brachytherapy in the treatment of therapy-resistant keloids and report first results, with emphasis on feasibility and early treatment outcome. METHODS AND MATERIALS: From 2009 to 2014, 24 patients with 32 recurrent keloids were treated...... with immediate perioperative high-dose-rate brachytherapy; 3 patients had been previously treated with adjuvant external beam radiation therapy and presented with recurrences in the pretreated areas. Two or more different treatment modalities had been tried in all patients and had failed to achieve remission....... After (re-)excision of the keloids, a single brachytherapy tube was placed subcutaneously before closing the wound. The target volume covered the scar in total length. Brachytherapy was given in 3 fractions with a single dose of 6 Gy in 5 mm tissue depth. The first fraction was given within 6 hours...

  4. Bladder wall recurrence of prostate cancer after high-dose-rate brachytherapy.

    Science.gov (United States)

    Raleigh, David R; Hsu, I-Chow; Braunstein, Steve; Chang, Albert J; Simko, Jeffry P; Roach, Mack

    2015-01-01

    Prostate cancer seeding after needle biopsy has been reported in the perineum, rectal wall, and periprostatic soft tissue. In this article, we report the results of a localized prostate cancer recurrence in the bladder following protrusion of a single high-dose-rate brachytherapy catheter through the bladder wall at the ultimate site of failure. A 62-year-old man with high-risk prostate adenocarcinoma was treated with long-term androgen deprivation therapy, intensity-modulated radiation, and high-dose-rate brachytherapy boost. He developed biochemical recurrence 4 years after treatment, and a CT scan of the pelvis revealed a nodule in the posterior, inferior bladder wall. Surgical pathology following transurethral resection of tumor within the bladder was consistent with high-grade prostate adenocarcinoma. The patient's prostate-specific antigen level fell to the range of normal postoperatively, and whole body imaging, including a multi-parametric MRI of the prostate with diffusion and spectroscopy, failed to reveal any other sites of disease. Review of the CT scan obtained for dosimetry at the time of brachytherapy demonstrated a lone catheter protruding through the bladder wall at the site of eventual recurrence. The tumor recurred in the bladder 12 months later, once more without evidence of disease within the prostate itself or distantly, and the patient was started on salvage androgen deprivation therapy. This case is the first report of prostate cancer recurrence in the bladder wall after brachytherapy and raises questions about prostate cancer biology, brachytherapy technique, and the timing of brachytherapy boost relative to whole pelvic radiotherapy for prostate cancer. Published by Elsevier Inc.

  5. The use of porcine small intestine submucosa implants might be associated with a high recurrence rate following laparoscopic herniorrhaphy

    Directory of Open Access Journals (Sweden)

    Chen-Hsun Ho

    2015-03-01

    Conclusion: Our data suggest that the use of SIS mesh in endoscopic TEP herniorrhaphy might be associated with a high recurrence rate. The second look laparoscopy in these recurrent cases revealed slow and inadequate integration of host tissue. More evidence is still required to further evaluate the efficacy of SIS mesh in endoscopic TEP herniorrhaphy.

  6. In vitro susceptibility of high virulence microorganisms isolated in heart valve banking.

    Science.gov (United States)

    Villalba, R; Solis, F; Fornés, G; Jimenez, A; Eisman, M; González, Ana I; Linares, M J; Casal, M; Gómez Villagrán, J L

    2012-08-01

    Storage preparation of human heart valves for implants generally includes incubation in an antimicrobial disinfection solution and cryopreservation. Changes in patterns of microorganisms susceptibility to antibiotics is a variable process of that promote its inefficiency. The aim of this study has been an evaluation of in vitro susceptibility of high virulence microorganisms isolated in our tissue bank for 14 years in order to evaluate the efficiency, and to promote changes for further antibiotics mixtures as well. Data presented in this study show that microorganisms isolates in valve banking display susceptibility patterns similar to those shown in other clinical circumstances, and the most commonly used antibiotics regimes are useful to date. An antibiotic cocktail containing aminoglicoside in addition to ciprofloxacin and vancomycin is an efficient mixture to be used in valve banking. Further studies will be necessary for monitoring patterns changes of in vitro susceptibility of microbiological isolates in tissue banking.

  7. High Rate of Recurrence Following Proximal Medial Opening Wedge Osteotomy for Correction of Moderate Hallux Valgus.

    Science.gov (United States)

    Iyer, Sravisht; Demetracopoulos, Constantine A; Sofka, Carolyn M; Ellis, Scott J

    2015-07-01

    The proximal medial opening wedge (PMOW) osteotomy has become more popular to treat moderate to severe hallux valgus with the recent development of specifically designed, low-profile modular plates. Despite the promising results previously reported in the literature, we have noted a high incidence of recurrence in patients treated with a PMOW. The purpose of this study was to report the clinical and radiographic outcomes of an initial cohort of patients treated with a PMOW osteotomy for moderate hallux valgus. We retrospectively analyzed prospectively gathered data on a cohort of 17 consecutive patients who were treated by the senior author using a PMOW osteotomy for moderate hallux valgus deformity. Average time to follow-up was 2.4 years (range, 1.0-3.5 years). The intermetatarsal angle (IMA), the hallux valgus angle (HVA), and the distal metatarsal articular angle (DMAA) were assessed on standard weightbearing radiographs of the foot preoperatively and at all follow-up visits. The Foot and Ankle Outcome Score (FAOS) was collected on all patients preoperatively and at final follow-up. Despite demonstrating good correction of their deformity initially, 11 of the 17 patients (64.7%) had evidence of recurrence of their hallux valgus deformity at final follow-up. Patients who recurred had a greater preoperative HVA (P = .023) and DMAA (P = .049) than patients who maintained their correction. Improvement in the quality-of-life subscale of the FAOS was noted at final follow-up for all patients (P = .05). There was no significant improvement in any of the other FAOS subscales. There was a high rate of recurrence of the hallux valgus deformity in this cohort of patients. Recurrence was associated with greater preoperative deformity and an increased preoperative DMAA. The PMOW without a concomitant distal metatarsal osteotomy may be best reserved for patients with mild hallux valgus deformity without an increased DMAA. Level IV, retrospective case series. © The Author

  8. Probability of high-risk colorectal neoplasm recurrence based on the results of two previous colonoscopies.

    Science.gov (United States)

    Park, Hye Won; Han, Seungbong; Lee, Ji Young; Chang, Hye-Sook; Choe, Jaewon; Choi, Yunsik; So, Hoonsub; Yang, Dong-Hoon; Myung, Seung-Jae; Yang, Suk-Kyun; Kim, Jin-Ho; Byeon, Jeong-Sik

    2015-01-01

    Current guidelines for the surveillance colonoscopy interval are largely based on the most recent colonoscopy findings. We aimed to evaluate differences in the probability of high-risk neoplasm recurrence according to the two previous colonoscopy findings. This was a retrospective cohort study from a tertiary-care center. A total of 4,143 subjects who underwent three or more colonoscopies for screening or surveillance purposes from January 2001 to December 2011 were enrolled. We compared the probability of high-risk neoplasm detection on follow-up colonoscopies after the second colonoscopy based on risk categories in both the second and first colonoscopies. At the final colonoscopy, 370 participants (8.9 %) had high-risk neoplasms. In patients with a normal second colonoscopy, the probability of high-risk neoplasm recurrence was different between those with normal, low-risk, and high-risk findings at the first colonoscopy (3.8, 6.8, and 17.7 %, respectively). The hazard ratio of a high-risk neoplasm at the final colonoscopy for patients with a normal second and low-risk first colonoscopy over a normal second and normal first colonoscopy was 3.07 (95 % CI 2.04-4.64, P neoplasm at the final colonoscopy for patients with a normal second and high-risk first colonoscopy over a normal second with normal first colonoscopy was 7.88 (95 % CI 4.90-12.67, P neoplasm recurrence differs according to the two previous colonoscopy findings. Therefore, surveillance intervals could be adjusted not just only by the most recent colonoscopy findings but also by considering two previous colonoscopy findings.

  9. Predictors of local recurrence in high-grade soft tissue sarcomas: hydrogen peroxide as a local adjuvant.

    Science.gov (United States)

    Wooldridge, Adam N; Kolovich, Gregory P; Crist, Martha K; Mayerson, Joel L; Scharschmidt, Thomas J

    2013-02-01

    Soft tissue sarcomas have a mortality rate of 40% to 60%, with local recurrence being a poor prognostic factor for overall survival. Three-percent nondiluted hydrogen peroxide is hypothesized to be an effective local adjuvant. The purpose of this study was to identify risk factors for local recurrence in high-grade soft tissue sarcomas and to determine whether using hydrogen peroxide as a local adjuvant reduced the risks of local recurrence and surgical-site infection. Retrospective data were collected for 106 patients surgically treated for high-grade soft tissue sarcomas between 2002 and 2010. The primary endpoint was local recurrence. Eighteen (16.98%) cases of local recurrence occurred. Predictors of local recurrence were margin status, estimated blood loss, and histology (ie, malignant peripheral nerve sheath tumor), with hazard ratios of 4.44 (95% confidence interval [CI], 1.32-14.95), 1.19 (95% CI, 1.06-1.35), and 9.21 (95% CI, 2.11-40.16), respectively. Hydrogen peroxide yielded a statistically insignificant improvement in local recurrence, with a hazard ratio of 0.81 (95% CI, 0.27-2.48) and a reduced risk of surgical site infection, with a hazard ratio of 0.52 (95% CI, 0.15-1.81). Margin status, increased blood loss, and histologic subtype are associated with increased local recurrence risk. Using hydrogen peroxide improved local control and infection rates, but the difference was not statistically significant. Copyright 2013, SLACK Incorporated.

  10. A Review of the Role of Re-Irradiation in Recurrent High-Grade Glioma (HGG)

    Energy Technology Data Exchange (ETDEWEB)

    Amichetti, Maurizio, E-mail: amichett@atrep.it; Amelio, Dante, E-mail: amichett@atrep.it [ATreP, Agenzia Provinciale per la Protonterapia, via Perini 181, 38122 Trento (Italy)

    2011-10-28

    Despite the use of more effective multimodal treatments in high-grade glioma (HGG), the outcome of patients affected by this disease is still dismal and recurrence is a very common event. Many therapeutic approaches, alone or combined (surgery, drugs, targeted agents, immunotherapy, radiotherapy, supportive therapy), are available in the clinical armamentarium so far. The attitude of physicians is increasingly interventionist, but recurrent HGG still remains a very difficult scenario to be treated. Radiotherapy with different re-irradiation techniques is increasingly proposed as a therapeutic option with interesting results, even though the resulting duration of response is usually quite short. Most lesions re-recur locally, with inadequate identification and targeting of viable tumor being the most important cause of failure. Prognosis is affected by many patient-, tumor-, and treatment-associated prognostic factors. Radiotherapy is delivered with many advanced modalities: 3D-CRT, intensity-modulated radiation therapy, stereotactic fractionated radiotherapy, radiosurgery, and brachitherapy with or without chemotherapy administration. In order to evaluate the feasibility and efficacy of re-irradiation in this setting, we reviewed the PubMed and MEDLINE databases restricting the search to original reports published from January 1990 to June 2011. The search resulted in a total of 155 reports: 78 of them covering 2,688 patients treated with different irradiation modalities overall fulfilled the entry criteria. Radiation therapy demonstrated to be an acceptable option in recurrent HGG with good response rates and acceptable toxicity.

  11. A Review of the Role of Re-Irradiation in Recurrent High-Grade Glioma (HGG

    Directory of Open Access Journals (Sweden)

    Maurizio Amichetti

    2011-10-01

    Full Text Available Despite the use of more effective multimodal treatments in high-grade glioma (HGG, the outcome of patients affected by this disease is still dismal and recurrence is a very common event. Many therapeutic approaches, alone or combined (surgery, drugs, targeted agents, immunotherapy, radiotherapy, supportive therapy, are available in the clinical armamentarium so far. The attitude of physicians is increasingly interventionist, but recurrent HGG still remains a very difficult scenario to be treated. Radiotherapy with different re-irradiation techniques is increasingly proposed as a therapeutic option with interesting results, even though the resulting duration of response is usually quite short. Most lesions re-recur locally, with inadequate identification and targeting of viable tumor being the most important cause of failure. Prognosis is affected by many patient-, tumor-, and treatment-associated prognostic factors. Radiotherapy is delivered with many advanced modalities: 3D-CRT, intensity-modulated radiation therapy, stereotactic fractionated radiotherapy, radiosurgery, and brachitherapy with or without chemotherapy administration. In order to evaluate the feasibility and efficacy of re-irradiation in this setting, we reviewed the PubMed and MEDLINE databases restricting the search to original reports published from January 1990 to June 2011. The search resulted in a total of 155 reports: 78 of them covering 2,688 patients treated with different irradiation modalities overall fulfilled the entry criteria. Radiation therapy demonstrated to be an acceptable option in recurrent HGG with good response rates and acceptable toxicity.

  12. [High recurrence and good functional results after arthroscopic resection of pigmented villonodular synovitis].

    Science.gov (United States)

    Isart, A; Gelber, P E; Besalduch, M; Pelfort, X; Erquicia, J I; Tey-Pons, M; Monllau, J C

    2015-01-01

    Pigmented villonodular synovitis (PVS) is a synovial proliferation disorder of uncertain aetiology, with some controversy as regards its proper treatment. The purpose of the study was to evaluate the functional outcome and recurrence rate in a series of patients diagnosed with both the diffuse and the localised type of PVS and treated by arthroscopic resection. Twenty-four patients diagnosed with PVS were retrospectively assessed. There were 11 cases with the diffuse type, and 13 cases with the localised type of PVS. They were followed-up for a median of 60 months (range, 34-204). They underwent arthroscopic synovectomy, and were functionally evaluated with IKDC, WOMET, and Kujala scores. There was recurrence in 8 out of 13 (61.5%) cases with the diffuse type of PVS. Two of these patients were treated with radiation. One patient underwent surgical resection with an open procedure due to extra-articular involvement. The remaining 5 patients underwent a second arthroscopic resection, and no recurrence was subsequently observed. Cases with localised PVS did not recur after a single arthroscopic resection. IKDC, WOMET and Kujala scores improved by 30.6, 37.4 and 34.03 points, respectively. Pigmented villonodular synovitis treated by arthroscopic resection showed good functional results at mid-term follow-up. A single arthroscopic resection was sufficient to treat the localised PVS, whereas the diffuse type of PVS required a second arthroscopic resection in most cases, due to its high rate of recurrence. Copyright © 2014 SECOT. Published by Elsevier Espana. All rights reserved.

  13. Salvage high-dose-rate brachytherapy for isolated vaginal recurrence of endometrial cancer.

    Science.gov (United States)

    Baek, Sungjae; Isohashi, Fumiaki; Yamaguchi, Hiroko; Mabuchi, Seiji; Yoshida, Ken; Kotsuma, Tadayuki; Yamazaki, Hideya; Tanaka, Eiichi; Sumida, Iori; Tamari, Keisuke; Otani, Keisuke; Seo, Yuji; Suzuki, Osamu; Yoshioka, Yasuo; Kimura, Tadashi; Ogawa, Kazuhiko

    We have retrospectively analyzed the outcomes of high-dose-rate (HDR) brachytherapy as a salvage therapy for vaginal recurrence of endometrial cancer. From 1997 to 2012, salvage HDR brachytherapy was performed in 43 patients. The median age was 64 years (range, 41-88 years). HDR brachytherapy was performed by interstitial brachytherapy in 34 patients (79%) and by intracavity brachytherapy in nine patients (21%). Seventeen (40%) of the 43 patients were treated with external beam radiotherapy. The median followup period was 58 months (range, 6-179 months). The 5-year overall survival (OS), progression-free survival (PFS), and local control rates (LC) were 84%, 52%, and 78%, respectively. Patients who received brachytherapy with external beam radiotherapy experienced no nodal recurrence (0 of 17 patients), whereas 23% of the patients (6 of 26 patients) who received brachytherapy alone experienced nodal recurrence (p = 0.047). The pathologic grade at the time of initial surgery (G1-2 vs. G3) was found to be a significant prognostic factor for both OS and PFS. The respective 5-year OS was 96% vs. 40% (p brachytherapy vs. intracavity brachytherapy) were significant prognostic factors for LC. The respective 5-year LC was 74% vs. 100% (p = 0.020) and 85% vs. 56% (p = 0.035). HDR brachytherapy is effective and feasible in patients with isolated vaginal recurrence of endometrial cancer. Pathologic grade, age, and modality were significant prognostic factors. Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

  14. Predictive value of Escherichia coli susceptibility in strains causing asymptomatic bacteriuria for women with recurrent symptomatic urinary tract infections receiving prophylaxis

    NARCIS (Netherlands)

    Beerepoot, M. A. J.; den Heijer, C. D. J.; Penders, J.; Prins, J. M.; Stobberingh, E. E.; Geerlings, S. E.

    2012-01-01

    A significant proportion of women develop a recurrence following an initial urinary tract infection (UTI). In women with recurrent UTI, the predictive value of asymptomatic bacteriuria (ASB) for the development of a subsequent UTI has not yet been established and it is not known whether information

  15. High expression of IRE1 in lung adenocarcinoma is associated with a lower rate of recurrence.

    Science.gov (United States)

    Sakatani, Toshio; Maemura, Keita; Hiyama, Noriko; Amano, Yosuke; Watanabe, Kousuke; Kage, Hidenori; Fukayama, Masashi; Nakajima, Jun; Yatomi, Yutaka; Nagase, Takahide; Takai, Daiya

    2017-06-01

    Recent reports have shown that endoplasmic reticulum stress is associated with cancer. However, the impacts of endoplasmic reticulum stress on the prognosis of lung cancer are unknown. Therefore, in this study, we sought to reveal the relationship between the expression of endoplasmic reticulum stress-related genes (endoplasmic reticulum oxidoreductase 1L, protein kinase RNA-like endoplasmic reticulum kinase, activating transcription factor 6 and inositol-requiring kinase 1) and the outcome of lung adenocarcinoma. One hundred and twenty-six patients with surgically resected lung adenocarcinomas were subjected to an endoplasmic reticulum stress-related mRNA expression analysis using quantitative RT-PCR. The following parameters were analyzed for all the study patients: age, sex, disease stage, smoking status, lymph node invasion (ly), vascular invasion (v) and EGFR mutation status. We assigned patients to either a high-expression group or a low-expression group according to the expression levels of endoplasmic reticulum stress-related genes. High expressions of endoplasmic reticulum stress-related genes were observed in patients with lower stages of lung adenocarcinoma and minimal vascular invasion. A Kaplan-Meier analysis showed significant differences in recurrence-free survival and overall survival between high-expression group and low-expression group. High inositol-requiring kinase 1 expression was an independent predictor of recurrence-free survival among patients with lung adenocarcinoma (hazard ratio, 0.396; 95% confidence interval, 0.188-0.834; P = 0.015). Inositol-requiring kinase 1 may be a useful biomarker to predict recurrence in surgically resected lung adenocarcinoma patients.

  16. Palliative Care in Improving Quality of Life in Patients With High Risk Primary or Recurrent Gynecologic Malignancies

    Science.gov (United States)

    2015-10-15

    Cervical Carcinoma; Ovarian Carcinoma; Primary Peritoneal Carcinoma; Recurrent Cervical Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Uterine Corpus Carcinoma; Recurrent Vulvar Carcinoma; Uterine Corpus Cancer; Vulvar Carcinoma; Peritoneal Neoplasms

  17. A rare case of recurrent pregnancy loss associated with high-titer positivity for perinuclear anti-neutrophilic cytoplasmic antibodies

    Directory of Open Access Journals (Sweden)

    Akhila Vasudeva

    2012-01-01

    Full Text Available We present a case of recurrent pregnancy loss associated with unusual constellation of utoimmunity-related features such as hypertension, severe hrombocytopenia, hypothyroidism and persistent high titers of perinuclear antineutrophilic cytoplasmic antibodies. Her clinical features did not fit into a particular diagnosis of vasculitides, systemic lupus erythematosis (SLE or other known autoimmune diseases where this autoantibody is found in high titers. We report the unusual association of this autoantibody with recurrent early fetal demise in this case.

  18. IASCC susceptibility of austenitic stainless steels and alloy 690 in high dissolved oxygen water environment

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Y.; Chopra, O.K.; Soppet, W.K. [Argonne National Lab., Nuclear Engineering Div., Argonne, Illinois (United States); Dietz Rago, N.L. [Argonne National Lab., Chemical Engineering Div., Argonne, Illinois (United States); Shack, W.J. [Argonne National Lab., Nuclear Engineering Div., Argonne, Illinois (United States)

    2007-07-01

    The influences of grain boundary engineering, alloying elements, and neutron dose on irradiation-assisted stress corrosion cracking (IASCC) of austenitic stainless steels and Alloy 690 were investigated. Flat dog-bone specimens irradiated in the Halden boiling heavy water reactor to {approx}2 dpa were tested in slow strain rate tensile tests in high dissolved oxygen water at 289 {sup o}C. The area fractions of intergranular or transgranular fracture were measured using a scanning electron microscope. All tested materials showed significant hardening and loss of ductility after irradiation. The area fractions of the intergranular cracking decreased with increase of uniform elongation, and were used to rank IASCC susceptibility. The grain boundary engineering treatment employed in this study does not have a significant impact on IASCC susceptibility for austenitic SSs at {approx}2 dpa, but does affect the cracking behavior of Alloy 690. High-sulfur and low-carbon SSs are more susceptible to IASCC. Oxygen content also contributes to the IASCC susceptibility in high-purity Type 304L SS. (author)

  19. High-definition colonoscopy and risk factors for recurrence of advanced adenomas in patients with a personal history of polyps.

    Science.gov (United States)

    Lorenzo-Zúñiga, Vicente; Moreno de Vega, Vicente; Domènech, Eugeni; Mañosa, Míriam; Cabré, Eduard; Planas, Ramon; Boix, Jaume

    2011-05-01

    Postpolypectomy surveillance is one of the most common reasons for performing colonoscopy. Our purpose was to assess characteristics of basal adenomas related to the recurrence of advanced adenomas, and to compare the patterns observed in recurrent adenomas with the use of conventional colonoscopy (CC) (1995-1998 period) or high-definition colonoscopy (HDC) (2005-2008 period). Analyses were based on 612 patients with recurrent adenomas (n=306) or no adenomas (control group; n=306), with at least two follow-up colonoscopies. A total of 56 patients with recurrent adenomas during the 1995-1998 period were compared with 116 patients in the 2005-2008 period. Morphology, size, location, and pathological diagnosis of each polyp were recorded. Multiple logistic regressions were used to calculate relative risk (RR) for recurrence. The study population was predominantly male (68.8%), with a mean age of 61.1 years and a mean follow-up period of 90.6±59.4 months. Advanced adenomas were found during follow-up evaluation in 120 patients (39.2%). The RR of advanced adenoma recurrence was 1.64 [95% confidence interval (CI): 1.01-2.64] among patients with baseline high-risk adenoma and 0.61 (CI: 0.38-0.98) among those with baseline low-risk adenoma. In the multivariable analyses, patients with larger adenomas were more likely to develop advanced recurrence (RR 1.02; 95% CI: 1.01-1.04). Both techniques (CC and HDC) detected a similar number (2.37±3.28 vs. 3.11±4.63; P=0.406) at qualifying colonoscopy. During follow-up both periods showed comparable adenoma characteristics. Patients with larger adenomas were more likely to develop advanced recurrence. HDC did not detect significantly more adenomas than CC. Characteristics of recurrent adenomas were comparable in both periods.

  20. Treatment of recurrent pregnancy loss by Levothyroxine in women with high Anti-TPO antibody.

    Science.gov (United States)

    Mosaddegh, Mohammad Hosein; Ghasemi, Nasrin; Jahaninejad, Tahere; Mohsenifar, Fatemeh; Aflatoonian, Abbas

    2012-07-01

    Recurrent pregnancy loss (RPL) is defined as two or more consecutive pregnancy losses before twenty weeks of gestation. It is caused by a variety of genetics and non-genetics factors. Thyroid autoimmunity could associate with pregnancy loss. To investigate the effectiveness of Levothyroxine in treatment of RPL in women with high auto-thyroid antibodies. In this observational cross sectional study, 900 women who had a history of recurrent pregnancy loss were studied. All women with high anti-TPO antibody without any other problems entered in this study. Levothyroxine was given to them two months before pregnancy till the end of pregnancy. The doses of levothyroxine were depended on the anti-TPO levels, which were decided by endocrinologist. Women followed for the results of pregnancies. The success rate of pregnancy in women with abnormal anti-TPO with Levothyroxine therapy was 82.85%. Mean of anti-TPO in women with treatment before taking medication was 488.35 and after that it was 123.35 UI/ml. This difference was significant (pTPO antibody. It decreased anti-TPO antibody levels after 2-3 months treatment.

  1. Spinal cord stimulation as adjuvant during chemotherapy and reirradiation treatment of recurrent high-grade gliomas.

    Science.gov (United States)

    Clavo, Bernardino; Robaina, Francisco; Jorge, Ignacio J; Cabrera, Raquel; Ruiz-Egea, Eugenio; Szolna, Adam; Otermin, Emilio; Llontop, Pedro; Carames, Miguel A; Santana-Rodríguez, Norberto; Sminia, Peter

    2014-11-01

    Relapsed high-grade gliomas (HGGs) have poor prognoses and there is no standard treatment. HGGs have ischemia/hypoxia associated and, as such, drugs and oxygen have low access, with increased resistance to chemotherapy and radiotherapy. Tumor hypoxia modification can improve outcomes and overall survival in some patients with these tumors. In previous works, we have described that cervical spinal cord stimulation can modify tumor microenvironment in HGG by increasing tumor blood flow, oxygenation, and metabolism. The aim of this current, preliminary, nonrandomized, study was to assess the clinical effect of spinal cord stimulation during brain reirradiation and chemotherapy deployed for the treatment of recurrent HGG; the hypothesis being that an improvement in oxygenated blood supply would facilitate enhanced delivery of the scheduled therapy. Seven patients had spinal cord stimulation applied during the scheduled reirradiation and chemotherapy for the treatment of recurrent HGG (6 anaplastic gliomas and 1 glioblastoma). Median dose of previous irradiation was 60 Gy (range = 56-72 Gy) and median dose of reirradiation was 46 Gy (range = 40-46 Gy). Primary end point of the study was overall survival (OS) following confirmation of HGG relapse. From the time of diagnosis of last tumor relapse before reirradiation, median OS was 39 months (95% CI = 0-93) for the overall study group: 39 months (95% CI = 9-69) for those with anaplastic gliomas and 16 months for the patient with glioblastoma. Posttreatment, doses of corticosteroids was significantly decreased (P = .026) and performance status significantly improved (P = .046). Spinal cord stimulation during reirradiation and chemotherapy is feasible and well tolerated. In our study, spinal cord stimulation was associated with clinical improvement and longer survival than previously reported in recurrent anaplastic gliomas. Spinal cord stimulation as adjuvant during chemotherapy and reirradiation in relapsed HGGs merits

  2. History of High Motion Sickness Susceptibility Predicts Vestibular Dysfunction Following Sport/Recreation-Related Concussion.

    Science.gov (United States)

    Sufrinko, Alicia M; Kegel, Nathan E; Mucha, Anne; Collins, Michael W; Kontos, Anthony P

    2017-11-20

    To compare vestibular dysfunction at 1 to 10 and 11 to 20 days following sport/recreation-related concussion (SRC) in athletes with and without history of motion sickness susceptibility. Secondary aims of this study were to investigate differences in neurocognitive performance and affective symptoms in these groups. Cross-sectional. Concussion Specialty Clinic. One hundred twenty-four adolescents and adults (82 males, 42 females) aged 14 to 26 (16.36 ± 2.10) years, diagnosed with SRC in the past 10 (4.56 ± 2.54) days; 47 participants composed the sample for quartile analyses. Motion sickness susceptibility questionnaire short form score. Computerized neurocognitive test scores, vestibular/oculomotor screening scores (VOMS), and symptom factor scores from a standardized concussion symptom inventory. There was no association between history of motion sickness susceptibility and VOMS scores (above or below clinical cutoff) at 1 to 10 days after injury, although at 11 to 20 days after injury there was an association between high motion sickness susceptibility and symptoms above clinical cutoff on 5 of the 6 VOMS items (P values 0.01-0.04). The high motion sickness group had more affective symptoms on the symptom inventory than the no motion sickness group (P = 0.002) at 1 to 10 days after injury. Groups did not differ on computerized neurocognitive testing (P = 0.11). Athletes with a preexisting history of motion sensitivity may exhibit more prolonged vestibular dysfunction following SRC, and may experience more affective symptoms early in recovery.

  3. Modified mean-field theory of the magnetic properties of concentrated, high-susceptibility, polydisperse ferrofluids

    Science.gov (United States)

    Solovyova, Anna Yu.; Elfimova, Ekaterina A.; Ivanov, Alexey O.; Camp, Philip J.

    2017-11-01

    The effects of particle-size polydispersity on the magnetostatic properties of concentrated ferrofluids are studied using theory and computer simulation. The second-order modified mean-field (MMF2) theory of Ivanov and Kuznetsova [Phys. Rev. E 64, 041405 (2001), 10.1103/PhysRevE.64.041405] has been extended by calculating additional terms of higher order in the dipolar coupling constant in the expansions of the initial magnetic susceptibility and the magnetization curve. The theoretical predictions have been tested rigorously against results from Monte Carlo simulations of model monodisperse, bidisperse, and highly polydisperse ferrofluids. Comparisons have been made between systems with the same Langevin susceptibility and the same saturation magnetization. In all cases, the new theoretical magnetization curve shows better agreement with simulation data than does the MMF2 theory. As for the initial susceptibility, MMF2 theory is most accurate for the monodisperse model, while the new theory works best for polydisperse systems with a significant proportion of large particles. These results are important for the analysis and characterization of recently synthesized polydisperse ferrofluids with record-breaking values of the initial magnetic susceptibility.

  4. High-resolution SNP genotyping platform identified recurrent and novel CNVs in autism multiplex families.

    Science.gov (United States)

    AlAyadhi, Laila Y; Hashmi, Jamil A; Iqbal, Muhammad; Albalawi, Alia M; Samman, Mohammad I; Elamin, Nadra E; Bashir, Shahid; Basit, Sulman

    2016-12-17

    Single nucleotide polymorphisms (SNPs)-based genotyping using microarray platform is now frequently used to detect copy number variants (CNVs) in the human genome. Here, we report CNVs identified using Illumina Human Omni 2.5M oligonucleotide microarrays in 11 multiplex families with autism spectrum disorder (ASD) referred to Autism Research and Treatment Center (ART) and Madinah Maternity and Children Hospital (MMCH). Of the 11 families, 22 patients with ASD (all males) and their parents, were recruited for the present study. In total, 43 individuals were genotyped with high-resolution array. Abnormal microarray results were seen in all 22 patients with ASD. A total of 17 shared CNVs were selected for further analysis. Out of these 17 CNVs, we discovered one novel CNV, previously not described, and 16 recurrent CNVs that overlap with the genomic imbalances defined in the autism database, autism chromosome rearrangement database and database of genomic variants. Recurrent CNVs include 11 common and 5 rare CNVs. All rare CNVs are duplications except a 16-kb deletion on chr2q36.3. Rare gain of copy numbers includes a 2-kb duplication on chr9q21.13, overlapping duplications of 107kb and 181kb on chrXp22.33 in 2 different families and a 10-kb duplication on chr18q21.13. A novel loss of copy number on chr3q23 was found in four ASD cases. This CNV results in deletion of intron 2 of calsyntenin 2 (CLSTN2) encoding synaptic protein calsyntenin 2. CLSTN2 is expressed exclusively in the brain, with high levels occurring in cortical gamma-aminobutyric acid (GABA)ergic interneurons and in medial temporal lobe regions. These results verify the diagnostic relevance of genome-wide small common and rare CNVs and provide further evidence of the high diagnostic yield of microarray for genetic testing in children with ASD. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  5. Highly improved acarbose production of Actinomyces through the combination of ARTP and penicillin susceptible mutant screening.

    Science.gov (United States)

    Ren, Fei; Chen, Long; Tong, Qunyi

    2017-01-01

    Atmospheric and room temperature plasma (ARTP) was first employed to generate mutants of Actinomyces JN537 for improving acarbose production. To obtain higher acarbose producing strains, the method of screening the strains for susceptibility to penicillin was used after treatment with ARTP. The rationale for the strategy was that mutants showing penicillin susceptibility were likely to be high acarbose producers, as their ability to synthesize cell walls was weak which might enhance metabolic flux to the pathway of acarbose biosynthesis. Acarbose yield of the mutant strain M37 increased by 62.5 % than that of the original strain. The contents of monosaccharides and amino acids of the cell wall of M37 were lower than that of the original strain. The acarbose production ability in mutant strain remained relatively stable after 10 generations. This work provides a promising strategy for obtaining high acarbose-yield strains by combination of ARTP mutation method and efficient screening technique.

  6. Mice lacking functional STAT1 are highly susceptible to lethal infection with Lassa virus.

    Science.gov (United States)

    Yun, Nadezhda E; Seregin, Alexey V; Walker, David H; Popov, Vsevolod L; Walker, Aida G; Smith, Jeanon N; Miller, Milagros; de la Torre, Juan C; Smith, Jennifer K; Borisevich, Viktoriya; Fair, Joseph N; Wauquier, Nadia; Grant, Donald S; Bockarie, Bayon; Bente, Dennis; Paessler, Slobodan

    2013-10-01

    Lassa fever (LF) is a potentially lethal human disease that is caused by the arenavirus Lassa virus (LASV). Annually, around 300,000 infections with up to 10,000 deaths occur in regions of Lassa fever endemicity in West Africa. Here we demonstrate that mice lacking a functional STAT1 pathway are highly susceptible to infection with LASV and develop lethal disease with pathology similar to that reported in humans.

  7. High susceptibility prevalence for F4+and F18+Escherichia coli in Flemish pigs.

    Science.gov (United States)

    Nguyen, Ut V; Coddens, Annelies; Melkebeek, Vesna; Devriendt, Bert; Goetstouwers, Tiphanie; Poucke, Mario Van; Peelman, Luc; Cox, Eric

    2017-04-01

    F4 and/or F18 enterotoxigenic Escherichia coli (F4 + /F18 + ETEC) are responsible for diarrhea while F18 + verotoxigenic E. coli (F18 + VTEC) cause edema disease in pigs. Both infections can result in severe economic losses, which are mainly the result of the medication, growth retardation and mortality. The susceptibility of piglets to these pathogens is determined by the presence of F4 and F18 receptors (F4R and F18R). Understanding the composition of the susceptibility phenotypes of pigs is useful for animal health and breeding management. This study aimed to determine the prevalence of the F4 ETEC susceptibility phenotypes and F18 + E. coli susceptibility among Flemish pig breeds by using the in vitro villous adhesion assay. In this study, seven F4 ETEC susceptibility phenotypes were found, namely A (F4 ab R + , ac R + , ad R + ; 59.16%), B (F4 ab R + , ac R + , ad R - ; 6.28%), C (F4 ab R + , ac R - , ad R + ; 2.62%), D (F4 ab R - , ac R - , ad R + ; 6.28%), E (F4 ab R - , ac R - , ad R - ; 24.08%), F (F4 ab R + , ac R - , ad R - ; 1.05%) and G (F4 ab R - , ac R + , ad R - ; 0.52%). F4ab and F4ac E. coli showed a stronger degree of adhesion to the intestinal villi (53.40% and 52.88% strong adhesion, respectively), compared to F4ad E. coli (43.46% strong adhesion). Furthermore, the correlation between F4ac and F4ab adhesion was higher (r=0.78) than between F4ac and F4ad adhesion (r=0.41) and between F4ab and F4ad adhesion (r=0.57). For F18 + E. coli susceptibility, seven out of 82 pigs were F18R negative (8.54%), but only two of these seven pigs (2.44%) were also negative for F4R. As such, the chance to identify a pig that is positive for a F4 ETEC variant or F18 + E. coli is 97.56%. Therefore, significant economic losses will arise due to F4 + and/or F18 + E. coli infections in the Flemish pig population due to the high susceptibility prevalence. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. High Dose Involved Field Radiation Therapy as Salvage for Loco-Regional Recurrence of Non-Small Cell Lung Cancer

    Science.gov (United States)

    Bae, Sun Hyun; Nam, Heerim; Park, Hee Chul; Pyo, Hong Ryull; Shim, Young Mog; Kim, Jhingook; Kim, Kwhanmien; Ahn, Jin Seok; Ahn, Myung-Ju; Park, Keunchil

    2012-01-01

    Purpose To determine the effectiveness of salvage radiation therapy (RT) in patients with loco-regional recurrences (LRR) following initial complete resection of non-small cell lung cancer (NSCLC) and assess prognostic factors affecting survivals. Materials and Methods Between 1994 and 2007, 64 patients with LRR after surgery of NSCLC were treated with high dose RT alone (78.1%) or concurrent chemo-radiation therapy (CCRT, 21.9%) at Samsung Medical Center. Twenty-nine patients (45.3%) had local recurrence, 26 patients (40.6%) had regional recurrence and 9 patients (14.1%) had recurrence of both components. The median RT dose was 54 Gy (range, 44-66 Gy). The radiation target volume included the recurrent lesions only. Results The median follow-up time from the start of RT in survivors was 32.0 months. The rates of in-field failure free survival, intra-thoracic failure free survival and extra-thoracic failure free survival at 2 years were 52.3%, 33.9% and 59.4%, respectively. The median survival after RT was 18.5 months, and 2-year overall survival (OS) rate was 47.9%. On both univariate and multivariate analysis, the interval from surgery till recurrence and CCRT were significant prognostic factors for OS. Conclusion The current study demonstrates that involved field salvage RT is effective for LRR of NSCLC following surgery. PMID:23074111

  9. The association between high on-treatment platelet reactivity and early recurrence of ischemic events after minor stroke or TIA.

    Science.gov (United States)

    Rao, Zilong; Zheng, Huaguang; Wang, Fei; Wang, Anxin; Liu, Liping; Dong, Kehui; Zhao, Xingquan; Wang, Yilong; Cao, Yibin

    2017-08-01

    To evaluate the role of HTPR in predicting early recurrence of ischemic events in patients with minor ischemic stroke or high-risk TIA. From January 2014 to September 2014, a single center continuously enrolled patients with minor ischemic stroke or high-risk TIA and gave them antiplatelet therapy consisting of aspirin with clopidogrel. HTPR was assessed by TEG after 7 days of antiplatelet therapy and detected CYP2C19 genotype. The incidence of recurrent ischemic events was assessed 3 months after onset. The incidence of recurrent ischemic events was compared between the HTPR and NTPR groups with the Kaplan-Meier method, and multivariate Cox proportional hazards models were used to determine the risk factors associated with recurrent ischemic events. We enrolled 278 eligible patients with minor ischemic stroke or high-risk TIA. Through TEG testing, patients with HTPR were 22.7%, and carriers were not associated with HTPR to ADP by TEG-ADP(%) (p = 0.193). A total of 265 patients completed 3 months of follow-up, and Kaplan-Meier analysis showed that patients with HTPR had a higher percentage of recurrent ischemic events compared with patients with NTPR (p = 0.002). In multivariate Cox proportional hazards models, history of ischemic stroke or TIA (HR 4.45, 95% CI 1.77-11.16, p = 0.001) and HTPR (HR 3.34, 95% CI 1.41-7.91, p = 0.006) was independently associated with recurrent ischemic events. In patients with minor stroke or TIA, the prevalence of HTPR was 22.7%, and HTPR was independently associated with recurrent ischemic events.

  10. Urbanized South Asians' susceptibility to coronary heart disease: The high-heat food preparation hypothesis.

    Science.gov (United States)

    Kakde, Smitha; Bhopal, Raj S; Bhardwaj, Swati; Misra, Anoop

    2017-01-01

    Known risk factors do not fully explain the comparatively high susceptibility to coronary heart disease (CHD) in South Asians (Indian, Pakistani, Bangladeshi, and Sri Lankan populations in South Asia and overseas). The search for explanatory hypotheses and cofactors that raise susceptibility of South Asians to CHD continues. The aim of this study was to propose "the high-heat food preparation hypothesis," where neo-formed contaminants (NFCs) such as trans-fatty acids (TFAs) and advanced glycation end-products (AGEs) are the cofactors. We reviewed the actions of AGEs and TFAs, the burden of these products in tissues and blood in South Asians, the relationship between these products and CHD, the effects of preparing food and reheating oils at high temperatures on NFCs, and the foods and mode of preparation in South Asian and Chinese cuisines. Animal and human studies show NFCs increase the risk for CHD. Evidence on the consumption and body burden of these products across ethnic groups is not available, and comparable data on the NFC content of the cuisine of South Asians and potential comparison populations (e.g., the Chinese with lower CHD rates) are limited. South Asians' cuisine is dominated by frying and roasting techniques that use high temperatures. South Asian foods have high TFA content primarily through the use of partially hydrogenated fats, reheated oils, and high-heat cooking. Reheating oils greatly increases the TFA content. In comparison, Chinese cuisine involves mostly braising, steaming, and boiling rather than frying. We hypothesize that South Asians' susceptibility to CHD is partly attributable to high-heat treated foods producing high NFCs. Research to accrue direct evidence is proposed. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. New and Recurrent Concussions in High-School Athletes Before and After Traumatic Brain Injury Laws, 2005-2016.

    Science.gov (United States)

    Yang, Jingzhen; Comstock, R Dawn; Yi, Honggang; Harvey, Hosea H; Xun, Pengcheng

    2017-12-01

    To examine the trends of new and recurrent sports-related concussions in high-school athletes before and after youth sports traumatic brain injury laws. We used an interrupted time-series design and analyzed the concussion data (2005-2016) from High School Reporting Injury Online. We examined the trends of new or recurrent concussion rates among US representative high-school athletes participating in 9 sports across prelaw, immediate-postlaw, and postlaw periods by using general linear models. We defined 1 athlete exposure as attending 1 competition or practice. We included a total of 8043 reported concussions (88.7% new, 11.3% recurrent). The average annual concussion rate was 39.8 per 100 000 athlete exposures. We observed significantly increased trends of reported new and recurrent concussions from the prelaw, through immediate-postlaw, into the postlaw period. However, the recurrent concussion rate showed a significant decline 2.6 years after the laws went into effect. Football exhibited different trends compared with other boys' sports and girls' sports. Observed trends of increased concussion rates are likely attributable to increased identification and reporting. Additional research is needed to evaluate intended long-term impact of traumatic brain injury laws.

  12. Improving NMR Diffusion Logs by Accounting for High Magnetic Susceptibility in Sediments

    Science.gov (United States)

    Fay, E. L.; Knight, R. J.

    2013-12-01

    Nuclear magnetic resonance (NMR) well-logging can be used to measure the apparent diffusion coefficient of fluids in the soil or rock around a well. NMR diffusion logs have several potential applications in the field of hydrogeophysics, such as improving estimates of permeability and characterizing LNAPL contamination. Near-surface environments, however, offer an added challenge to measuring diffusion with NMR due to the high variability in the magnetic mineral content of soils. In this work, we were able to improve the accuracy of diffusion measurements from an NMR log by accounting for the magnetic susceptibility of the sediments. NMR diffusion measurements have been used extensively both in laboratory and logging applications to measure the relative saturation of water, gas, and oil in reservoir rocks, due to the contrasting diffusion coefficients of these fluids. Laboratory diffusion measurements have also been used to study restricted diffusion in pore systems, which yields information on the pore size and the connectivity of the pore space, both critical to predicting the permeability of a material. NMR diffusion measurements rely on the application of an external magnetic field gradient across the measured volume. This magnetic field gradient is used to measure the displacement of fluid molecules during a specified diffusion time interval. The magnitude of the effective field gradient, i.e. the gradient experienced in the measured volume, must be known in order to calculate of the diffusion coefficient of the fluid from the NMR signal. Common practice in NMR logging is to assume that internal gradients are negligible and that the effective gradient is equal to the externally applied gradient, which is typically well characterized. In materials with low magnetic susceptibility, this is a valid assumption. Complications arise in materials with high magnetic susceptibility, because magnetic field gradients will be present within these materials before the

  13. 32. Incidence and predictors of progression of Coronary Artery Disease among high risk patients with recurrent symptoms

    Directory of Open Access Journals (Sweden)

    M. Bassam Bdeir

    2015-10-01

    Conclusions: Among high risk patients with recurrent symptoms, the short term rate of progression of CAD is high. A drop in LVEF >5% is the best predictor of progression of CAD. Further studies are needed to determine the prognostic value of CAD progression in the era of potent medical therapy.

  14. Attentional bias and metacognitions in cancer survivors with high fear of cancer recurrence.

    Science.gov (United States)

    Butow, P; Kelly, S; Thewes, B; Hruby, G; Sharpe, L; Beith, J

    2015-04-01

    Fear of cancer recurrence (FCR) is a common and severe problem amongst cancer survivors, but mechanisms to explain its development and maintenance are still lacking. The self-regulatory executive function (S-REF) model suggests that metacognitions and attentional bias to cancer-related words may explain high FCR. Thus, this study aimed to explore relationships between FCR, metacognitions and attentional bias in a mixed group of cancer survivors. Sixty-three early-stage breast or prostate cancer survivors, diagnosed within 6 months to 5 years prior to participation and who had completed all hospital-based treatment with no evidence of cancer recurrence were recruited through two metropolitan oncology clinics. Participants completed a questionnaire battery and the dot-probe task. Survivors with clinical FCR had significantly greater positive beliefs about worry (10.1 vs 7.4, p = 0.002) and beliefs about the uncontrollability and danger of worry (12.0 vs 7.7, p = 0.000) than those with non-clinical FCR, whereas the total metacognition score significantly predicted FCR in multiple regression analysis (β = 0.371, p = 0.001). No significant differences were detected between participants scoring above and below clinical FCR levels in attention bias indices. This study found partial support for the S-REF model of FCR, with metacognitions but not attentional bias found to be related to FCR. Further research is needed to explore attentional biases in more detail. Copyright © 2014 John Wiley & Sons, Ltd.

  15. Microstructural investigation of vintage pipeline steels highly susceptible to stress corrosion cracking

    Science.gov (United States)

    Torres, Monica

    The use of pipelines for the transmission of gas offers not only efficiency, but a number of economic advantages. Nevertheless, pipelines are subject to aggressive operating conditions and environments which can lead to in-service degradation [1] and thus to failures. These failures can have catastrophic consequences, such as environmental damage and loss of life [2]. One of the most dangerous threats to pipeline integrity is stress corrosion cracking (SCC). Despite the substantial progress that has been achieved in the field, due to the complex nature of this phenomenon there is still not a complete understanding of this form of external corrosion. This makes its detection and prevention a challenge and therefore a risk to pipeline integrity, and most importantly, to the safety of the population. SCC cracks are the result of the interaction between a corrosive environment, applied stresses, and a susceptible microstructure. To date, what defines a susceptible microstructure remains ambiguous, as SCC has been observed in a range of steel grades, microstructures, chemical composition, and grain sizes. Therefore, in order to be able to accurately predict and prevent this hazardous form of corrosion, it is imperative to advance our knowledge on the subject and gain a better understanding on the microstructural features of highly susceptible pipeline materials, especially in the subsurface zone where crack nucleation must take place. Therefore, a microstructural characterization of the region near the surface layer was carried-out utilizing TEM. TEM analysis revealed the dislocation character, ferrite morphology, and apparent carbide precipitation in some grain boundaries. Furthermore, light microscopy, SEM, and hardness testing were performed to expand our knowledge on the microscopical features of highly SCC susceptible service components. This investigation presents a new approach to SCC characterization, which exposed the sub-surface region microscopical

  16. Mortality and recurrence rates among systemically untreated high risk breast cancer patients included in the DBCG 77 trials

    DEFF Research Database (Denmark)

    Jensen, Maj Britt; Nielsen, Torsten O.; Knoop, Ann S.

    2018-01-01

    Background: Following loco-regional treatment for early breast cancer accurate prognostication is essential for communicating benefits of systemic treatment. The aim of this study was to determine time to recurrence and long-term mortality rates in high risk patients according to patient characte......Background: Following loco-regional treatment for early breast cancer accurate prognostication is essential for communicating benefits of systemic treatment. The aim of this study was to determine time to recurrence and long-term mortality rates in high risk patients according to patient...

  17. Alloy and composition dependence of hydrogen embrittlement susceptibility in high-strength steel fasteners

    Science.gov (United States)

    Brahimi, S. V.; Yue, S.; Sriraman, K. R.

    2017-06-01

    High-strength steel fasteners characterized by tensile strengths above 1100 MPa are often used in critical applications where a failure can have catastrophic consequences. Preventing hydrogen embrittlement (HE) failure is a fundamental concern implicating the entire fastener supply chain. Research is typically conducted under idealized conditions that cannot be translated into know-how prescribed in fastener industry standards and practices. Additionally, inconsistencies and even contradictions in fastener industry standards have led to much confusion and many preventable or misdiagnosed fastener failures. HE susceptibility is a function of the material condition, which is comprehensively described by the metallurgical and mechanical properties. Material strength has a first-order effect on HE susceptibility, which increases significantly above 1200 MPa and is characterized by a ductile-brittle transition. For a given concentration of hydrogen and at equal strength, the critical strength above which the ductile-brittle transition begins can vary due to second-order effects of chemistry, tempering temperature and sub-microstructure. Additionally, non-homogeneity of the metallurgical structure resulting from poorly controlled heat treatment, impurities and non-metallic inclusions can increase HE susceptibility of steel in ways that are measurable but unpredictable. Below 1200 MPa, non-conforming quality is often the root cause of real-life failures. This article is part of the themed issue 'The challenges of hydrogen and metals'.

  18. Global lung cancer risk from PAH exposure highly depends on emission sources and individual susceptibility

    Science.gov (United States)

    Shen, Huizhong; Tao, Shu; Liu, Junfeng; Huang, Ye; Chen, Han; Li, Wei; Zhang, Yanyan; Chen, Yuanchen; Su, Shu; Lin, Nan; Xu, Yinyin; Li, Bengang; Wang, Xilong; Liu, Wenxin

    2014-10-01

    The health impacts of polycyclic aromatic hydrocarbons (PAHs), the most concerning organic pollutants, depend not only on the locations and strengths of emission sources, but also on individual susceptibility. Moreover, trans-boundary transport makes them a global concern. In this study, a comprehensive analysis of the global health impacts of polycyclic aromatic hydrocarbons (PAHs) in ambient air is presented. Model resolution is critical in exposure modelling. Globally, incremental lifetime lung cancer risk (ILCR) induced by ambient PAH exposure is 3.1 × 10-5. If the individual susceptibility was not taken into consideration, the overall risk would be underestimated by 55% and the proportion of highly vulnerable population would be underestimated by more than 90%. Emphasizing on individual susceptibility, our study provides an instrumental revision of current risk assessment methodology. In terms of lung cancer risk, the most important sources are combustion of biomass fuels (40%) and fossil fuels (14%) in the residential/commercial sector, coke (13%) and aluminium (12%) production, and motor vehicles (9%). PAHs can travel long distance globally especially within the Eurasian continent. Still, the risk is dominantly contributed by local.

  19. A survey for Batrachochytrium dendrobatidis in endangered and highly susceptible Vietnamese salamanders (Tylototriton spp.).

    Science.gov (United States)

    Thien, Tao Nguyen; Martel, An; Brutyn, Melanie; Bogaerts, Sergé; Sparreboom, Max; Haesebrouck, Freddy; Fisher, Matthew C; Beukema, Wouter; Van, Tang Duong; Chiers, Koen; Pasmans, Frank

    2013-09-01

    Until now, Asian amphibians appear to have largely escaped declines driven by chytridiomycosis. Vietnamese salamanders that belong to the genus Tylototriton are rare and have a patchy distribution in mountainous areas, falling within the proposed environmental envelope of chytrid infections, surrounded by Batrachochytrium dendrobatidis infected regions. If these salamanders are susceptible to chytridiomycosis, then their populations could be highly vulnerable after the introduction of B. dendrobatidis. Examination for the presence of the chytrid fungus in skin swabs from 19 Tylototriton asperrimus and 104 Tylototriton vietnamensis by using quantitative polymerase chain reaction was performed. Susceptibility of T. asperrimus to experimental infection by using the global panzootic lineage (BdGPL) strain of B. dendrobatidis was examined. The fungus was absent in all samples from all wild salamanders examined. Inoculation with the BdGPL strain resulted in mortality of all five inoculated salamanders within 3 weeks after inoculation with infected animals that manifested severe orthokeratotic hyperkeratosis, epidermal hyperplasia, and spongiosis. Although infection by B. dendrobatidis currently appears absent in Vietnamese Tylototriton populations, the rarity of these animals, their pronounced susceptibility to chytridiomycosis, an apparently suitable environmental context and increasing likelihood of the pathogen being introduced, together suggest the need of urgent measures to avoid future scenarios of extinction as witnessed in Central America and Australia.

  20. Ulysses high energy particle observation of the effects of recurrent high speed streams

    Science.gov (United States)

    Droege, W.; Kunow, H.; Heber, B.; Mueller-Mellin, R.; Sierks, H.; Wibberenz, G.; Raviart, A.; Paizis, C.; Ducros, R.; Ferrando, P.

    1995-01-01

    Since June 1992 The Kiel Electron Telescope on board Ulysses measures variations of more than 10% in the fluxes of high energy H and He showing a periodicity of about 27 days, which are coincident with the passage of corotating interaction refios (CIR). At low energies MeV protons are accelerared at the shocks of the CIRs. These effects were observed up to high southern latitudes, where the signature of time of the conference Ulysses will have passed the solar equator and climbed up to 70 deg N at solar distance of 1.7 AU. In this paper we study the intensity variations with latitude as a function of magnetic rigidity.

  1. SURGICAL TREATMENT FOR VERY HIGH-RISK LOCALLY RECURRENT PROSTATE CANCER AFTER RADICAL RETROPUBIC PROSTATECTOMY: A CLINICAL CASE

    Directory of Open Access Journals (Sweden)

    E. I. Veliyev

    2014-07-01

    Full Text Available Locally recurrent prostate cancer (PC in the bladder neck can substantially worsen quality of life in patients and hinder further treatment when castration-resistant PC develops. The paper describes a clinical case of very high-risk PC in a 55-year-old patient in whom radical cystectomy (RCE with removal of metastases in the bladder neck and the Bricker ileal conduit were performed for a local recurrence after radical retropubic prostatectomy (RPE. It gives the data of preoperative examination, the technical features of the primary operation RPE, the data of postoperative observation, the technical aspects and outcomes of еру surgery for a local recurrence, as well as the results of a 1.5-year follow-up after RCE. 

  2. SURGICAL TREATMENT FOR VERY HIGH-RISK LOCALLY RECURRENT PROSTATE CANCER AFTER RADICAL RETROPUBIC PROSTATECTOMY: A CLINICAL CASE

    Directory of Open Access Journals (Sweden)

    E. I. Veliyev

    2014-01-01

    Full Text Available Locally recurrent prostate cancer (PC in the bladder neck can substantially worsen quality of life in patients and hinder further treatment when castration-resistant PC develops. The paper describes a clinical case of very high-risk PC in a 55-year-old patient in whom radical cystectomy (RCE with removal of metastases in the bladder neck and the Bricker ileal conduit were performed for a local recurrence after radical retropubic prostatectomy (RPE. It gives the data of preoperative examination, the technical features of the primary operation RPE, the data of postoperative observation, the technical aspects and outcomes of еру surgery for a local recurrence, as well as the results of a 1.5-year follow-up after RCE. 

  3. Acute exposure of mice to high-dose ultrafine carbon black decreases susceptibility to pneumococcal pneumonia

    Directory of Open Access Journals (Sweden)

    Gordon Stephen

    2010-10-01

    Full Text Available Abstract Background Epidemiological studies suggest that inhalation of carbonaceous particulate matter from biomass combustion increases susceptibility to bacterial pneumonia. In vitro studies report that phagocytosis of carbon black by alveolar macrophages (AM impairs killing of Streptococcus pneumoniae. We have previously reported high levels of black carbon in AM from biomass smoke-exposed children and adults. We therefore aimed to use a mouse model to test the hypothesis that high levels of carbon loading of AM in vivo increases susceptibility to pneumococcal pneumonia. Methods Female outbred mice were treated with either intranasal phosphate buffered saline (PBS or ultrafine carbon black (UF-CB in PBS; 500 μg on day 1 and day 4, and then infected with S. pneumoniae strain D39 on day 5. Survival was assessed over 72 h. The effect of UF-CB on AM carbon loading, airway inflammation, and a urinary marker of pulmonary oxidative stress was assessed in uninfected animals. Results Instillation of UF-CB in mice resulted a pattern of AM carbon loading similar to that of biomass-smoke exposed humans. In uninfected animals, UF-CB treated animals had increased urinary 8-oxodG (P = 0.055, and an increased airway neutrophil differential count (P . pneumoniae, whereas morbidity and mortality after infection was reduced in UF-CB treated animals (median survival 48 h vs. 30 h, P . pneumoniae colony forming unit counts, and lower airway levels of keratinocyte-derived chemokine/growth-related oncogene (KC/GRO, and interferon gamma. Conclusion Acute high level loading of AM with ultrafine carbon black particles per se does not increase the susceptibility of mice to pneumococcal infection in vivo.

  4. Murine Alveolar Macrophages Are Highly Susceptible to Replication of Coxiella burnetii Phase II In Vitro

    Science.gov (United States)

    Fernandes, Talita D.; Cunha, Larissa D.; Ribeiro, Juliana M.; Massis, Liliana M.; Lima-Junior, Djalma S.

    2016-01-01

    Coxiella burnetii is a Gram-negative bacterium that causes Q fever in humans. Q fever is an atypical pneumonia transmitted through inhalation of contaminated aerosols. In mammalian lungs, C. burnetii infects and replicates in several cell types, including alveolar macrophages (AMs). The innate immunity and signaling pathways operating during infection are still poorly understood, in part because of the lack of relevant host cell models for infection in vitro. In the study described here, we investigated and characterized the infection of primary murine AMs by C. burnetii phase II in vitro. Our data reveal that AMs show a pronounced M2 polarization and are highly permissive to C. burnetii multiplication in vitro. Murine AMs present an increased susceptibility to infection in comparison to primary bone marrow-derived macrophages. AMs support more than 2 logs of bacterial replication during 12 days of infection in culture, similar to highly susceptible host cells, such as Vero and THP-1 cells. As a proof of principle that AMs are useful for investigation of C. burnetii replication, we performed experiments with AMs from Nos2−/− or Ifng−/− mice. In the absence of gamma interferon and nitric oxide synthase 2 (NOS2), AMs were significantly more permissive than wild-type cells. In contrast, AMs from Il4−/− mice were more restrictive to C. burnetii replication, supporting the importance of M2 polarization for the permissiveness of AMs to C. burnetii replication. Collectively, our data account for understanding the high susceptibility of alveolar macrophages to bacterial replication and support the use of AMs as a relevant model of C. burnetii growth in primary macrophages. PMID:27297388

  5. Recurrent Word Combinations in EAP Test-Taker Writing: Differences between High- and Low-Proficiency Levels

    Science.gov (United States)

    Appel, Randy; Wood, David

    2016-01-01

    The correct use of frequently occurring word combinations represents an important part of language proficiency in spoken and written discourse. This study investigates the use of English-language recurrent word combinations in low-level and high-level L2 English academic essays sourced from the Canadian Academic English Language (CAEL) assessment.…

  6. Haptoglobin phenotype is not a predictor of recurrence free survival in high-risk primary breast cancer patients

    NARCIS (Netherlands)

    M.C.W. Gast; H. van Tinteren (Harm); M. Bontenbal (Marijke); R.Q.G.C.M. van Hoesel (René); M.A. Nooij; S. Rodenhuis (Sjoerd); P.N. Span (Paul); V.C.G. Tjan-Heijnen (Vivianne); E. de Vries (Esther); N. Harris (Nathan); J.W.R. Twisk (Jos); J.H.M. Schellens (Jan); J.H. Beijnen (Jos)

    2008-01-01

    textabstractBackground: Better breast cancer prognostication may improve selection of patients for adjuvant therapy. We conducted a retrospective follow-up study in which we investigated sera of high-risk primary breast cancer patients, to search for proteins predictive of recurrence free survival.

  7. Haptoglobin phenotype is not a predictor of recurrence free survival in high-risk primary breast cancer patients

    NARCIS (Netherlands)

    Gast, Marie-Christine W.; van Tinteren, Harm; Bontenbal, Marijke; van Hoesel, Rene Q. G. C. M.; Nooij, Marianne A.; Rodenhuis, Sjoerd; Span, Paul N.; Tjan-Heijnen, Vivianne C. G.; de Vries, Elisabeth G. E.; Harris, Nathan; Twisk, Jos W. R.; Schellens, Jan H. M.; Beijnen, Jos H.

    2008-01-01

    Background: Better breast cancer prognostication may improve selection of patients for adjuvant therapy. We conducted a retrospective follow-up study in which we investigated sera of high-risk primary breast cancer patients, to search for proteins predictive of recurrence free survival. Methods: Two

  8. Haptoglobin phenotype is not a predictor of recurrence free survival in high-risk primary breast cancer patients.

    NARCIS (Netherlands)

    Gast, M.C.; Tinteren, H van; Bontenbal, M.; Hoesel, R.Q. van; Nooij, M.A.; Rodenhuis, S.; Span, P.N.; Tjan-Heijnen, V.C.; Vries, E.G.F. de; Harris, N.; Twisk, J.W.; Schellens, J.H.M.; Beijnen, J.H.

    2008-01-01

    BACKGROUND: Better breast cancer prognostication may improve selection of patients for adjuvant therapy. We conducted a retrospective follow-up study in which we investigated sera of high-risk primary breast cancer patients, to search for proteins predictive of recurrence free survival. METHODS: Two

  9. High recurrence rates of bacterial vaginosis over the course of 12 months after oral metronidazole therapy and factors associated with recurrence.

    Science.gov (United States)

    Bradshaw, Catriona S; Morton, Anna N; Hocking, Jane; Garland, Suzanne M; Morris, Margaret B; Moss, Lorna M; Horvath, Leonie B; Kuzevska, Irene; Fairley, Christopher K

    2006-06-01

    We wished to determine recurrences of bacterial vaginosis (BV) after treatment over the course of 12 months and to establish factors associated with recurrence. Women with symptomatic BV (a Nugent score [NS] of 7-10 or of 4-6 with >or=3 Amsel criteria) were enrolled. BV was treated with 400 mg of oral metronidazole twice a day for 7 days. Participants completed a questionnaire and vaginal swabs were collected at 1, 3, 6, and 12 months; the study end point was an NS of 7-10. A total of 121 (87%) women with an NS of 7-10 and 18 (13%) with an NS of 4-6 and >or=3 Amsel criteria were enrolled; 130 (94%) returned >or=1 vaginal samples. Sixty-eight women (58% [95% confidence interval {CI}, 49%-66%]) had a recurrence of BV (NS 7-10), and 84 (69% [95% CI, 61%-77%]) had a recurrence of abnormal vaginal flora (NS 4-10) by 12 months. A past history of BV, a regular sex partner throughout the study, and female sex partners were significantly associated with recurrence of BV and abnormal vaginal flora by multivariate analysis; the use of hormonal contraception had a negative association with recurrence. Current recommended treatment is not preventing the recurrence of BV or abnormal vaginal flora in the majority of women; factors associated with recurrence support a possible role for sexual transmission in the pathogenesis of recurrent BV.

  10. Bafetinib in Treating Patients With Recurrent High-Grade Glioma or Brain Metastases

    Science.gov (United States)

    2013-03-18

    Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Oligodendroglioma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Mixed Glioma; Recurrent Adult Brain Tumor; Tumors Metastatic to Brain; Adult Anaplastic Oligoastrocytoma

  11. Development of a test method for determining the cracking susceptibility of resistance spot welded high strength steel sheets

    OpenAIRE

    Rethmeier, Michael; Suwala, Hubert

    2014-01-01

    In this study a test method for determining the cracking susceptibility of resistance spot welded high strength steel sheets was investigated. The development of a suitable test procedure is based on the External-Loaded Hot Crack Test (PVC-Test). The test modification for resistance spot welding contains a constant tensile force load. The test method for determining the cracking susceptibility was experimentally verified for a high strength steel, a transformation induced plasticity steel (TR...

  12. Likelihood of Bone Recurrence in Prior Sites of Metastasis in Patients With High-Risk Neuroblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Polishchuk, Alexei L. [Department of Radiation Oncology, University of California at San Francisco School of Medicine and UCSF Benioff Children' s Hospital, San Francisco, California (United States); Li, Richard [Division of Radiation Oncology, Dana Farber/Boston Children' s Cancer and Blood Disorders Center, Brigham and Women' s Hospital, Harvard Medical School, Boston, Massachusetts (United States); Hill-Kayser, Christine [Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania (United States); Little, Anthony [Division of Oncology, Children' s Hospital of Philadelphia, Philadelphia, Pennsylvania (United States); Hawkins, Randall A. [Department of Radiology, University of California at San Francisco School of Medicine and UCSF Benioff Children' s Hospital, San Francisco, California (United States); Hamilton, Jeffrey; Lau, Michael [Department of Radiation Oncology, University of California at San Francisco School of Medicine and UCSF Benioff Children' s Hospital, San Francisco, California (United States); Tran, Hung Chi [Division of Hematology/Oncology, Children' s Hospital of Los Angeles, Los Angeles, California (United States); Strahlendorf, Caron [Division of Hematology and Oncology, Department of Pediatrics, The University of British Columbia, Vancouver, British Columbia (Canada); Lemons, Richard S. [Division of Pediatric Hematology/Oncology, University of Utah School of Medicine, Salt Lake City, Utah (United States); Weinberg, Vivian [Department of Radiation Oncology, University of California at San Francisco School of Medicine and UCSF Benioff Children' s Hospital, San Francisco, California (United States); Matthay, Katherine K.; DuBois, Steven G. [Department of Pediatrics, University of California at San Francisco School of Medicine and UCSF Benioff Children' s Hospital, San Francisco, California (United States); and others

    2014-07-15

    Purpose/Objectives: Despite recent improvements in outcomes, 40% of children with high-risk neuroblastoma will experience relapse, facing a guarded prognosis for long-term cure. Whether recurrences are at new sites or sites of original disease may guide decision making during initial therapy. Methods and Materials: Eligible patients were retrospectively identified from institutional databases at first metastatic relapse of high-risk neuroblastoma. Included patients had disease involving metaiodobenzylguanidine (MIBG)-avid metastatic sites at diagnosis and first relapse, achieved a complete or partial response with no more than one residual MIBG-avid site before first relapse, and received no total body irradiation or therapy with {sup 131}I-MIBG before first relapse. Anatomically defined metastatic sites were tracked from diagnosis through first relapse to determine tendency of disease to recur at previously involved versus uninvolved sites and to assess whether this pattern was influenced by site irradiation. Results: Of 159 MIBG-avid metastatic sites identified among 43 patients at first relapse, 131 (82.4%) overlapped anatomically with the set of 525 sites present at diagnosis. This distribution was similar for bone sites, but patterns of relapse were more varied for the smaller subset of soft tissue metastases. Among all metastatic sites at diagnosis in our subsequently relapsed patient cohort, only 3 of 19 irradiated sites (15.8%) recurred as compared with 128 of 506 (25.3%) unirradiated sites. Conclusions: Metastatic bone relapse in neuroblastoma usually occurs at anatomic sites of previous disease. Metastatic sites identified at diagnosis that did not receive radiation during frontline therapy appeared to have a higher risk of involvement at first relapse relative to previously irradiated metastatic sites. These observations support the current paradigm of irradiating metastases that persist after induction chemotherapy in high-risk patients. Furthermore

  13. Tumour volume and high grade tumour volume are the best predictors of pathologic stage and biochemical recurrence after radical prostatectomy.

    Science.gov (United States)

    Chun, Felix K-H; Briganti, Alberto; Jeldres, Claudio; Gallina, Andrea; Erbersdobler, Andreas; Schlomm, Thorsten; Walz, Jochen; Eichelberg, Christian; Salomon, Georg; Haese, Alexander; Currlin, Eike; Ahyai, Sascha A; Bénard, François; Huland, Hartwig; Graefen, Markus; Karakiewicz, Pierre I

    2007-02-01

    Our goal was to examine to what extent tumour volume (TV) and percentage of high grade tumour volume (%HGTV) affect the rate of positive surgical margins and the rate of biochemical recurrence after radical prostatectomy. TV and %HGTV were routinely planimetrically quantified in a cohort of 780 consecutive patients. Mean follow-up was 46.7 months. Multivariable regression models addressed two separate endpoints: positive surgical margins and biochemical recurrence. The increase in model predictive accuracy related to the addition of TV and %HGTV to radical prostatectomy stage and grade was assessed, after 200 bootstrap resamples to reduce overfit bias. In multivariable logistic regression models addressing positive surgical margins rate, predictive accuracy increased by 1.9% (p<0.001) when TV was added to other covariates. No further increment was noted when %HGTV was added (p=0.3). In multivariable Cox regression models addressing biochemical recurrence, accuracy increased by 0.6% (p=0.002) when TV was added and an additional increase of 0.7% was recorded when %HGTV (p<0.001) was added. Tumour bulk reflected by TV affects local cancer control rate, which is reflected in the rate of positive surgical margins. Conversely, high grade cancer determines the rate of biochemical recurrence. These two variables represent the most powerful predictors of cancer control in men treated for localised prostate cancer. Moreover, they increase the ability of established predictors to predict the outcomes of interest. In consequence, they warrant consideration in future predictive and prognostic tools.

  14. Higher Grades and Repeated Recurrence of Hepatic Encephalopathy May Be Related to High Serum Manganese Levels.

    Science.gov (United States)

    Kobtan, Abdelrahman A; El-Kalla, Ferial S; Soliman, Hanan H; Zakaria, Soha S; Goda, Mohamed A

    2016-02-01

    Hepatic encephalopathy is a serious complication of liver failure. Until now, the precise pathophysiologic mechanisms are not fully determined. It has been demonstrated that manganese plays an important role in the pathogenesis of hepatic encephalopathy. Therefore, we studied manganese levels in serum of cirrhotic patients with hepatic encephalopathy in relation to grading and recurrence of hepatic encephalopathy. One hundred persons were enrolled in the study, 80 cirrhotic patients with or without encephalopathy and 20 healthy controls. Hepatic encephalopathy was diagnosed clinically and by laboratory findings. Serum manganese levels were measured in all participants. The grading of hepatic encephalopathy was significantly correlated to the severity of liver dysfunction. The mean serum manganese level was significantly higher in cirrhotic patients than in controls and in cirrhotic patients with encephalopathy than in those without encephalopathy. It was also significantly higher in patients with advanced grading of hepatic encephalopathy. Serum manganese level was positively correlated to number of recurrences of encephalopathy during a 6-month follow-up period. Serum manganese levels were able to predict recurrence of hepatic encephalopathy within 6 months following the episode. Serum manganese levels are positively correlated to the modified Child-Pugh score of cirrhosis as well as grading and number of recurrences of hepatic encephalopathy. Higher manganese levels seem to be related to worsening of the condition, and its measurement may be used as a predictor of repeated recurrences.

  15. Susceptibility to enhanced chemical migration from depression-focused preferential flow, High Plains aquifer

    Science.gov (United States)

    Gurdak, J.J.; Walvoord, Michelle Ann; McMahon, P.B.

    2008-01-01

    Aquifer susceptibility to contamination is controlled in part by the inherent hydrogeologic properties of the vadose zone, which includes preferential-flow pathways. The purpose of this study was to investigate the importance of seasonal ponding near leaky irrigation wells as a mechanism for depression-focused preferential flow and enhanced chemical migration through the vadose zone of the High Plains aquifer. Such a mechanism may help explain the widespread presence of agrichemicals in recently recharged groundwater despite estimates of advective chemical transit times through the vadose zone from diffuse recharge that exceed the historical period of agriculture. Using a combination of field observations, vadose zone flow and transport simulations, and probabilistic neural network modeling, we demonstrated that vadose zone transit times near irrigation wells range from 7 to 50 yr, which are one to two orders of magnitude faster than previous estimates based on diffuse recharge. These findings support the concept of fast and slow transport zones and help to explain the previous discordant findings of long vadose zone transit times and the presence of agrichemicals at the water table. Using predictions of aquifer susceptibility from probabilistic neural network models, we delineated approximately 20% of the areal extent of the aquifer to have conditions that may promote advective chemical transit times to the water table of practices.

  16. The usefulness of high-resolution ultrasound in detecting invasive disease in recurrent basal cell carcinoma after nonsurgical treatment.

    Science.gov (United States)

    Hernández-Ibáñez, C; Aguilar-Bernier, M; Fúnez-Liébana, R; Del Boz, J; Blázquez, N; de Troya, M

    2014-12-01

    Accurate subtyping of basal cell carcinoma (BCC) is crucial for the effective management of this disease and it is particularly important to distinguish between aggressive and nonaggressive histologic variants. Histologic subtype is not always accurately identified by biopsy and this can have serious implications. High-resolution ultrasound (HRUS) is a recent technique that has proven to be of value in differentiating between variants of BCC. The aim of this study was to investigate the potential usefulness of HRUS for detecting invasive disease in recurrent BCC treated nonsurgically following an initial diagnosis of noninvasive BCC by biopsy. This was a prospective observational study of consecutive cases of BCC with clinical suspicion of recurrence following nonsurgical treatment and a pretreatment diagnosis of superficial BCC by punch biopsy. Before surgical excision, the recurrent lesions were evaluated by HRUS followed by a punch biopsy of the site of suspected recurrence. The diagnostic agreement between HRUS, punch biopsy, and excisional biopsy was then evaluated. Eight lesions were studied. HRUS identified invasive disease in 3 of the 4 cases that were incorrectly classified as superficial subtypes by punch biopsy. HRUS could be useful for detecting persistent tumor after nonsurgical treatment and for choosing the site most likely to harbor invasive disease for punch biopsy. Copyright © 2013 Elsevier España, S.L.U. y AEDV. All rights reserved.

  17. A blinded, randomized controlled trial of high-dose vitamin D supplementation to reduce recurrence of bacterial vaginosis

    Science.gov (United States)

    TURNER, Abigail Norris; REESE, Patricia CARR; FIELDS, Karen S.; ANDERSON, Julie; ERVIN, Melissa; DAVIS, John A.; FICHOROVA, Raina N.; ROBERTS, Mysheika Williams; KLEBANOFF, Mark A.; JACKSON, Rebecca D.

    2014-01-01

    Objective Low serum vitamin D levels have been associated with increased prevalence of the reproductive tract condition bacterial vaginosis (BV). The objective of this trial was to evaluate the effect of high-dose vitamin D supplementation on BV recurrence. Study design This randomized, placebo-controlled, double-blinded trial enrolled 118 women with symptomatic BV from an urban STD clinic (clinicaltrials.gov registration NCT01450462). All participants received 500mg oral metronidazole twice daily for seven days. Intervention participants (n=59) also received nine doses of 50,000 international units of cholecalciferol (vitamin D3) over 24 weeks; control women (n=59) received matching placebo. Recurrent BV was assessed via Nugent scoring after 4, 12 and 24 weeks. We assessed the effect of the intervention using an intention-to-treat approach, fitting Cox proportional hazards models to evaluate recurrent BV over the follow-up period. Results Most participants (74%) were black, with a median age of 26 years. Median presupplementation serum 25-hydroxyvitamin D [25(OH)D] was similar across randomization arms: 16.6 ng/mL in the vitamin D arm and 15.8 ng/mL in the control arm. At trial completion, median 25(OH)D among women receiving vitamin D was 30.5 ng/mL, vs 17.8 ng/mL in control women; 16% of women receiving vitamin D and 57% receiving placebo remained vitamin D deficient (vitamin D was very similar to those randomized to placebo at the 4- and 12-week visits, but by the 24-week visit, BV prevalence was 65% among women in the vitamin D arm and 48% among control women. BV recurrence was not reduced by vitamin D supplementation (intention-to-treat hazard ratio, 1.11; 95% confidence interval, 0.68-1.81). Among women experiencing recurrent BV, median time to recurrence was 13.7 weeks in the vitamin D arm and 14.3 weeks in the control arm. Conclusions Women receiving vitamin D experienced significant increases in serum 25(OH)D, but this increase was not associated with

  18. High-Dose Viscum album Extract Treatment in the Prevention of Recurrent Bladder Cancer: A Retrospective Case Series.

    Science.gov (United States)

    von Schoen-Angerer, Tido; Wilkens, Johannes; Kienle, Gunver S; Kiene, Helmut; Vagedes, Jan

    2015-01-01

    Viscum album extract (European mistletoe), containing immuno-active compounds with dose-dependent cytotoxic activity, is being used as an adjuvant cancer treatment in Europe. Few studies have yet been done with high-dose, fever-inducing Viscum album treatment. To explore whether subcutaneous injections of high-dose Viscum album have a preventive effect on risk of recurrence of bladder cancer. We retrospectively analyzed the case records of patients with resectable bladder cancer who underwent initiation of high-dose Viscum album treatment at our clinic between January 2006 and December 2012. We calculated tumor recurrence and progression risk and explored case records to assess whether treatment had a likely, possible, or unlikely beneficial effect. Eight patients were identified, 7 of whom had nonmuscle-invasive bladder cancer and 1 with muscle-invasive cancer. Four patients had frequently recurring tumors before treatment. Among the 8 patients, 28 episodes of recurrence were observed. Median tumor-free follow-up duration was 48.5 months. High-dose Viscum album showed a possible beneficial effect in 5 of 8 patients, could not be assessed in 2 patients, and had an uncertain effect in 1 patient. No tumor progression was observed. Treatment was generally well tolerated and no patient stopped treatment because of side effects. High-dose Viscum album treatment may have interrupted frequently recurring tumors in individual patients with recurrent bladder cancer. Prospective studies are needed to assess whether this treatment offers an additional, bladder-sparing preventive option for patients with intermediate- to high-risk nonmuscle-invasive bladder cancer.. Treatment was generally well tolerated and no patient stopped treatment because of side effects.

  19. Brain Microglial Cells Are Highly Susceptible to HIV-1 Infection and Spread.

    Science.gov (United States)

    Cenker, Jennifer J; Stultz, Ryan D; McDonald, David

    2017-11-01

    Macrophages are a target of human immunodeficiency virus type 1 (HIV-1) infection and may serve as an important reservoir of the virus in the body, particularly after depletion of CD4+ T cells in HIV/AIDS. Recently, sterile alpha motif and histidine/aspartic acid domain-containing protein 1 (SAMHD1) was identified as the major restriction factor of HIV-1 infection in myeloid cells. SAMHD1 is targeted for proteolytic degradation by Vpx, a viral protein encoded by HIV-2 and many simian immunodeficiency viruses but not HIV-1. In this study, we assessed SAMHD1 restriction in in vitro differentiated macrophages and in freshly isolated macrophages from the lungs, abdomen, and brain. We found that infection and spread in in vitro cultured monocyte-derived macrophages were highly limited and that Vpx largely relieved the restriction to initial infection, as expected. We observed nearly identical infection and restriction profiles in freshly isolated peripheral blood monocytes, as well as lung (alveolar) and abdominal (peritoneal) macrophages. In contrast, under the same infection conditions, primary brain macrophages (microglia) were highly susceptible to HIV-1 infection despite levels of endogenous SAMHD1 comparable to the other macrophage populations. Addition of Vpx further increased HIV-1 infection under conditions of limiting virus input, and viral spread was robust whether or not SAMHD1 was depleted. These results suggest that HIV-1 infection of peripherally circulating macrophages is effectively restricted by SAMHD1; however, microglia are highly susceptible to infection despite SAMHD1 expression. These data may explain the long-standing observation that HIV-1 infection is often detected in macrophages in the brain, but seldom in other tissues of the body.

  20. Attentional bias and metacognitions in cancer survivors with high fear of cancer recurrence

    NARCIS (Netherlands)

    Butow, P.; Kelly, S.; Thewes, B.; Hruby, G.; Sharpe, L.; Beith, J.

    2015-01-01

    BACKGROUND: Fear of cancer recurrence (FCR) is a common and severe problem amongst cancer survivors, but mechanisms to explain its development and maintenance are still lacking. The self-regulatory executive function (S-REF) model suggests that metacognitions and attentional bias to cancer-related

  1. Alisertib and Fractionated Stereotactic Radiosurgery in Treating Patients With Recurrent High Grade Gliomas

    Science.gov (United States)

    2017-10-25

    Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Diffuse Astrocytoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Mixed Glioma; Adult Oligodendroglioma; Adult Pilocytic Astrocytoma; Adult Pineal Gland Astrocytoma; Adult Subependymal Giant Cell Astrocytoma; Recurrent Adult Brain Tumor

  2. High serum folate is associated with reduced biochemical recurrence after radical prostatectomy: Results from the SEARCH Database

    Directory of Open Access Journals (Sweden)

    Daniel M. Moreira

    2013-06-01

    Full Text Available Introduction To analyze the association between serum levels of folate and risk of biochemical recurrence after radical prostatectomy among men from the Shared Equal Access Regional Cancer Hospital (SEARCH database. Materials and Methods Retrospective analysis of 135 subjects from the SEARCH database treated between 1991-2009 with available preoperative serum folate levels. Patients' characteristics at the time of the surgery were analyzed with ranksum and linear regression. Uni- and multivariable analyses of folate levels (log-transformed and time to biochemical recurrence were performed with Cox proportional hazards. Results The median preoperative folate level was 11.6ng/mL (reference = 1.5-20.0ng/mL. Folate levels were significantly lower among African-American men than Caucasians (P = 0.003. In univariable analysis, higher folate levels were associated with more recent year of surgery (P < 0.001 and lower preoperative PSA (P = 0.003. In univariable analysis, there was a trend towards lower risk of biochemical recurrence among men with high folate levels (HR = 0.61, 95%CI = 0.37-1.03, P = 0.064. After adjustments for patients characteristics' and pre- and post-operative clinical and pathological findings, higher serum levels of folate were independently associated with lower risk for biochemical recurrence (HR = 0.42, 95%CI = 0.20-0.89, P = 0.023. Conclusion In a cohort of men undergoing radical prostatectomy at several VAs across the country, higher serum folate levels were associated with lower PSA and lower risk for biochemical failure. While the source of the folate in the serum in this study is unknown (i.e. diet vs. supplement, these findings, if confirmed, suggest a potential role of folic acid supplementation or increased consumption of folate rich foods to reduce the risk of recurrence.

  3. Perinatal hypoxia increases susceptibility to high-altitude polycythemia and attendant pulmonary vascular dysfunction.

    Science.gov (United States)

    Julian, Colleen Glyde; Gonzales, Marcelino; Rodriguez, Armando; Bellido, Diva; Salmon, Carlos Salinas; Ladenburger, Anne; Reardon, Lindsay; Vargas, Enrique; Moore, Lorna G

    2015-08-15

    Perinatal exposures exert a profound influence on physiological function, including developmental processes vital for efficient pulmonary gas transfer throughout the lifespan. We extend the concept of developmental programming to chronic mountain sickness (CMS), a debilitating syndrome marked by polycythemia, ventilatory impairment, and pulmonary hypertension that affects ∼10% of male high-altitude residents. We hypothesized that adverse perinatal oxygenation caused abnormalities of ventilatory and/or pulmonary vascular function that increased susceptibility to CMS in adulthood. Subjects were 67 male high-altitude (3,600-4,100 m) residents aged 18-25 yr with excessive erythrocytosis (EE, Hb concentration ≥18.3 g/dl), a preclinical form of CMS, and 66 controls identified from a community-based survey (n = 981). EE subjects not only had higher Hb concentrations and erythrocyte counts, but also lower alveolar ventilation, impaired pulmonary diffusion capacity, higher systolic pulmonary artery pressure, lower pulmonary artery acceleration time, and more frequent right ventricular hypertrophy, than controls. Compared with controls, EE subjects were more often born to mothers experiencing hypertensive complications of pregnancy and hypoxia during the perinatal period, with each increasing the risk of developing EE (odds ratio = 5.25, P = 0.05 and odds ratio = 6.44, P = 0.04, respectively) after other factors known to influence EE status were taken into account. Adverse perinatal oxygenation is associated with increased susceptibility to EE accompanied by modest abnormalities of the pulmonary circulation that are independent of increased blood viscosity. The association between perinatal hypoxia and EE may be due to disrupted alveolarization and microvascular development, leading to impaired gas exchange and/or pulmonary hypertension. Copyright © 2015 the American Physiological Society.

  4. Recurrent varicocele

    Directory of Open Access Journals (Sweden)

    Katherine Rotker

    2016-01-01

    Full Text Available Varicocele recurrence is one of the most common complications associated with varicocele repair. A systematic review was performed to evaluate varicocele recurrence rates, anatomic causes of recurrence, and methods of management of recurrent varicoceles. The PubMed database was evaluated using keywords "recurrent" and "varicocele" as well as MESH criteria "recurrent" and "varicocele." Articles were not included that were not in English, represented single case reports, focused solely on subclinical varicocele, or focused solely on a pediatric population (age <18. Rates of recurrence vary with the technique of varicocele repair from 0% to 35%. Anatomy of recurrence can be defined by venography. Management of varicocele recurrence can be surgical or via embolization.

  5. Palbociclib Isethionate in Treating Younger Patients With Recurrent, Progressive, or Refractory Central Nervous System Tumors

    Science.gov (United States)

    2017-09-27

    Childhood Choroid Plexus Tumor; Childhood Ependymoblastoma; Childhood Grade III Meningioma; Childhood High-grade Cerebellar Astrocytoma; Childhood High-grade Cerebral Astrocytoma; Childhood Medulloepithelioma; Recurrent Childhood Anaplastic Astrocytoma; Recurrent Childhood Anaplastic Oligoastrocytoma; Recurrent Childhood Anaplastic Oligodendroglioma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Giant Cell Glioblastoma; Recurrent Childhood Glioblastoma; Recurrent Childhood Gliomatosis Cerebri; Recurrent Childhood Gliosarcoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor

  6. A cell-based high-throughput screening assay for radiation susceptibility using automated cell counting.

    Science.gov (United States)

    Hodzic, Jasmina; Dingjan, Ilse; Maas, Mariëlle Jp; van der Meulen-Muileman, Ida H; de Menezes, Renee X; Heukelom, Stan; Verheij, Marcel; Gerritsen, Winald R; Geldof, Albert A; van Triest, Baukelien; van Beusechem, Victor W

    2015-02-27

    Radiotherapy is one of the mainstays in the treatment for cancer, but its success can be limited due to inherent or acquired resistance. Mechanisms underlying radioresistance in various cancers are poorly understood and available radiosensitizers have shown only modest clinical benefit. There is thus a need to identify new targets and drugs for more effective sensitization of cancer cells to irradiation. Compound and RNA interference high-throughput screening technologies allow comprehensive enterprises to identify new agents and targets for radiosensitization. However, the gold standard assay to investigate radiosensitivity of cancer cells in vitro, the colony formation assay (CFA), is unsuitable for high-throughput screening. We developed a new high-throughput screening method for determining radiation susceptibility. Fast and uniform irradiation of batches up to 30 microplates was achieved using a Perspex container and a clinically employed linear accelerator. The readout was done by automated counting of fluorescently stained nuclei using the Acumen eX3 laser scanning cytometer. Assay performance was compared to that of the CFA and the CellTiter-Blue homogeneous uniform-well cell viability assay. The assay was validated in a whole-genome siRNA library screening setting using PC-3 prostate cancer cells. On 4 different cancer cell lines, the automated cell counting assay produced radiation dose response curves that followed a linear-quadratic equation and that exhibited a better correlation to the results of the CFA than did the cell viability assay. Moreover, the cell counting assay could be used to detect radiosensitization by silencing DNA-PKcs or by adding caffeine. In a high-throughput screening setting, using 4 Gy irradiated and control PC-3 cells, the effects of DNA-PKcs siRNA and non-targeting control siRNA could be clearly discriminated. We developed a simple assay for radiation susceptibility that can be used for high-throughput screening. This will

  7. Avian infectious bronchitis virus in Brazil: a highly complex virus meets a highly susceptible host population

    Directory of Open Access Journals (Sweden)

    PE Brandão

    2010-06-01

    Full Text Available Infectious bronchitis (IB is a highly aggressive disease for poultry in terms of symptoms and economic losses, and the control of this disease is difficult if flocks are not protected against type-specific challenges by the Avian infectious bronchitis virus (IBV. This article summarizes data presented by the author at the Workshop on Infectious Bronchitis 2009 on IB and IBV, including future developments on the field.

  8. Highly variable recurrence of tsunamis in the 7,400 years before the 2004 Indian Ocean tsunami

    Science.gov (United States)

    Rubin, Charles M.; Horton, Benjamin P.; Sieh, Kerry; Pilarczyk, Jessica E.; Daly, Patrick; Ismail, Nazli; Parnell, Andrew C.

    2017-07-01

    The devastating 2004 Indian Ocean tsunami caught millions of coastal residents and the scientific community off-guard. Subsequent research in the Indian Ocean basin has identified prehistoric tsunamis, but the timing and recurrence intervals of such events are uncertain. Here we present an extraordinary 7,400 year stratigraphic sequence of prehistoric tsunami deposits from a coastal cave in Aceh, Indonesia. This record demonstrates that at least 11 prehistoric tsunamis struck the Aceh coast between 7,400 and 2,900 years ago. The average time period between tsunamis is about 450 years with intervals ranging from a long, dormant period of over 2,000 years, to multiple tsunamis within the span of a century. Although there is evidence that the likelihood of another tsunamigenic earthquake in Aceh province is high, these variable recurrence intervals suggest that long dormant periods may follow Sunda megathrust ruptures as large as that of the 2004 Indian Ocean tsunami.

  9. Highly variable recurrence of tsunamis in the 7,400 years before the 2004 Indian Ocean tsunami.

    Science.gov (United States)

    Rubin, Charles M; Horton, Benjamin P; Sieh, Kerry; Pilarczyk, Jessica E; Daly, Patrick; Ismail, Nazli; Parnell, Andrew C

    2017-07-19

    The devastating 2004 Indian Ocean tsunami caught millions of coastal residents and the scientific community off-guard. Subsequent research in the Indian Ocean basin has identified prehistoric tsunamis, but the timing and recurrence intervals of such events are uncertain. Here we present an extraordinary 7,400 year stratigraphic sequence of prehistoric tsunami deposits from a coastal cave in Aceh, Indonesia. This record demonstrates that at least 11 prehistoric tsunamis struck the Aceh coast between 7,400 and 2,900 years ago. The average time period between tsunamis is about 450 years with intervals ranging from a long, dormant period of over 2,000 years, to multiple tsunamis within the span of a century. Although there is evidence that the likelihood of another tsunamigenic earthquake in Aceh province is high, these variable recurrence intervals suggest that long dormant periods may follow Sunda megathrust ruptures as large as that of the 2004 Indian Ocean tsunami.

  10. Highly variable recurrence of tsunamis in the 7,400 years before the 2004 Indian Ocean tsunami

    Science.gov (United States)

    Rubin, Charles M.; Horton, Benjamin P.; Sieh, Kerry; Pilarczyk, Jessica E.; Daly, Patrick; Ismail, Nazli; Parnell, Andrew C.

    2017-01-01

    The devastating 2004 Indian Ocean tsunami caught millions of coastal residents and the scientific community off-guard. Subsequent research in the Indian Ocean basin has identified prehistoric tsunamis, but the timing and recurrence intervals of such events are uncertain. Here we present an extraordinary 7,400 year stratigraphic sequence of prehistoric tsunami deposits from a coastal cave in Aceh, Indonesia. This record demonstrates that at least 11 prehistoric tsunamis struck the Aceh coast between 7,400 and 2,900 years ago. The average time period between tsunamis is about 450 years with intervals ranging from a long, dormant period of over 2,000 years, to multiple tsunamis within the span of a century. Although there is evidence that the likelihood of another tsunamigenic earthquake in Aceh province is high, these variable recurrence intervals suggest that long dormant periods may follow Sunda megathrust ruptures as large as that of the 2004 Indian Ocean tsunami. PMID:28722009

  11. Pediatric peri-operative fractionated high-dose-rate brachytherapy for recurrent Wilms’ tumor using a reconstructed Freiburg flap

    Directory of Open Access Journals (Sweden)

    Emily Flower

    2016-10-01

    Full Text Available Purpose : To report peri-operative fractionated high-dose-rate (HDR brachytherapy with a 3D customized Freiburg flap applicator to treat locally recurrent Wilms’ tumor, followed by immediate hyperthermic intraperitoneal chemotherapy for a 16-year-old with a second recurrence of nephroblastoma (Wilms’ tumor. Material and methods: The tumor was excised and surgical bed was treated with fractionated HDR brachytherapy using a Freiburg flap applicator. Hyperthermic intraperitoneal chemotherapy was performed immediately after the removal of brachytherapy applicator. Results: The Freiburg flap was successfully reconstructed to enable delivery of conformable peri-operative HDR brachytherapy. The clinical target volume (CTV D90 was 26 Gy in 5 fractions. Conclusions : Peri-operative fractionated HDR brachytherapy with a customized Freiburg flap applicator was delivered successfully across a large multi-disciplinary team.

  12. Evaluation of HLA-G 14-bp ins/del and +3142G>C polymorphisms with susceptibility to recurrent spontaneous abortion.

    Science.gov (United States)

    Hashemi, Mohammad; Mokhtari, Mojgan; Khazaeian, Safura; Bahari, Gholamreza; Rezaei, Maryam; Nakhaee, Alireza; Taheri, Mohsen

    2017-06-01

    HLA-G is critically important for successful implantation during pregnancy. Increasing evidence supposed that HLA-G plays a key role in tolerance of the semi-allogeneic graft in pregnancy by inhibiting the cytotoxic functions of T and NK cells. The present study aimed to evaluate the impact of HLA-G rs1063320 (+3142G>C) and 14-bp insertion (ins)/deletion (del) polymorphisms on recurrent spontaneous abortion (RSA). Genomic DNA from 93 RSA patients and 93 normal fertile women was isolated using the salting out method. Genotyping of HLA-G +3142G>C and 14-bp ins/del variants was done by polymerase chain reaction restriction fragment length polymorphism (PCR-RFP) and PCR method, respectively. The HLA-G +3142G>C polymorphism increased the risk of RSA in codominant (OR = 2.39, 95%CI = 1.27-4.49, p = 0.010, GC vs GG; OR = 3.28, 95%CI = 1.16-9.72, p = 0.040, CC vs GG) and dominant (OR = 2.52, 95%CI = 1.37-4.64, p = 0.004, GC + CC vs GG) tested inheritance models. HLA-G rs1063320 C allele was associated with increased risk of RSA (OR = 1.84, 95%CI = 1.20-2.83, p = 0.007). The del/del genotype as well as del allele of 14-bp ins/del variant increased that risk of RSA (OR = 3.02, 95%CI = 1.23-7.41, p = 0.025 and OR = 1.65, 95%CI = 1.09-2.50, p = 0.022, respectively). In summary, our results showed that HLA-G gene polymorphisms significantly increased the risk of RSA in a sample of the Iranian population. Copyright © 2017. Published by Elsevier B.V.

  13. Irradiation Programs and Test Plans to Assess High-Fluence Irradiation Assisted Stress Corrosion Cracking Susceptibility.

    Energy Technology Data Exchange (ETDEWEB)

    Teysseyre, Sebastien [Idaho National Lab. (INL), Idaho Falls, ID (United States)

    2015-03-01

    . Irradiation assisted stress corrosion cracking (IASCC) is a known issue in current reactors. In a 60 year lifetime, reactor core internals may experience fluence levels up to 15 dpa for boiling water reactors (BWR) and 100+ dpa for pressurized water reactors (PWR). To support a safe operation of our fleet of reactors and maintain their economic viability it is important to be able to predict any evolution of material behaviors as reactors age and therefore fluence accumulated by reactor core component increases. For PWR reactors, the difficulty to predict high fluence behavior comes from the fact that there is not a consensus of the mechanism of IASCC and that little data is available. It is however possible to use the current state of knowledge on the evolution of irradiated microstructure and on the processes that influences IASCC to emit hypotheses. This report identifies several potential changes in microstructure and proposes to identify their potential impact of IASCC. The susceptibility of a component to high fluence IASCC is considered to not only depends on the intrinsic IASCC susceptibility of the component due to radiation effects on the material but to also be related to the evolution of the loading history of the material and interaction with the environment as total fluence increases. Single variation type experiments are proposed to be performed with materials that are representative of PWR condition and with materials irradiated in other conditions. To address the lack of IASCC propagation and initiation data generated with material irradiated in PWR condition, it is proposed to investigate the effect of spectrum and flux rate on the evolution of microstructure. A long term irradiation, aimed to generate a well-controlled irradiation history on a set on selected materials is also proposed for consideration. For BWR, the study of available data permitted to identify an area of concern for long term performance of component. The efficiency of

  14. Susceptibility correction for improved tractography using high field DT-EPI

    Science.gov (United States)

    Pintjens, W.; Poot, D. H. J.; Verhoye, M.; Van Der Linden, A.; Sijbers, J.

    2008-03-01

    Diffusion Tensor Magnetic Resonance Imaging (DTI) is a well known technique that can provide information about the neuronal fiber structure of the brain. However, since DTI requires a large amount of data, a high speed MRI acquisition technique is needed to acquire these data within a reasonable time. Echo Planar Imaging (EPI) is a technique that provides the desired speed. Unfortunately, the advantage of speed is overshadowed by image artifacts, especially at high fields. EPI artifacts originate from susceptibility differences in adjacent tissues and correction techniques are required to obtain reliable images. In this work, the fieldmap method, which tries to measure distortion effects, is optimized by using a non linear least squares estimator for calculating pixel shifts. This method is tested on simulated data and proves to be more robust against noise compared to previously suggested methods. Another advantage of this new method is that other parameters like relaxation and the odd/even phase difference are estimated. This new way of estimating the field map is demonstrated on a hardware phantom, which consists of parallel bundles made of woven strands of Micro Dyneema fibers. Using a modified EPI-sequence, reference data was measured for the calculation of fieldmaps. This allows one to reposition the pixels in order to obtain images with less distortions. The correction is applied to non-diffusion weighted images as well as diffusion weighted images and fiber tracking is performed on this corrected data.

  15. Formation of Linear Gradient of Antibiotics on Microfluidic Chips for High-throughput Antibiotic Susceptibility Testing

    Science.gov (United States)

    Kim, Seunggyu; Lee, Seokhun; Jeon, Jessie S.

    2017-11-01

    To determine the most effective antimicrobial treatments of infectious pathogen, high-throughput antibiotic susceptibility test (AST) is critically required. However, the conventional AST requires at least 16 hours to reach the minimum observable population. Therefore, we developed a microfluidic system that allows maintenance of linear antibiotic concentration and measurement of local bacterial density. Based on the Stokes-Einstein equation, the flow rate in the microchannel was optimized so that linearization was achieved within 10 minutes, taking into account the diffusion coefficient of each antibiotic in the agar gel. As a result, the minimum inhibitory concentration (MIC) of each antibiotic against P. aeruginosa could be immediately determined 6 hours after treatment of the linear antibiotic concentration. In conclusion, our system proved the efficacy of a high-throughput AST platform through MIC comparison with Clinical and Laboratory Standards Institute (CLSI) range of antibiotics. This work was supported by the Climate Change Research Hub (Grant No. N11170060) of the KAIST and by the Brain Korea 21 Plus project.

  16. Long-term prognosis of acute lateral ankle ligamentous sprains: high incidence of recurrences and residual symptoms.

    Science.gov (United States)

    Kemler, Ellen; Thijs, Karin M; Badenbroek, Ilse; van de Port, Ingrid G L; Hoes, Arno W; Backx, Frank J G

    2016-12-01

    Acute lateral ankle ligamentous sprains (ALALS) are common injuries. This injury does not always have a favourable long-term outcome. Studies reporting the prognosis of ALALS after functional treatment are scarce. To determine the prognosis of functionally treated ALALS, in terms of recurrent ALALS and residual symptoms. Retrospective cohort study. Patients were recruited from 20 family practices, nine physical therapy practices, the emergency departments of a regional hospital and a university hospital. Adult patients with an ALALS caused by an inversion trauma were invited to participate in this study 2.5-5 years after their initial injury. Functional treatment of the initial ALALS. Acute lateral ankle ligamentous sprain recurrences and residual symptoms. A total of 44 patients were included, with an average follow-up period after the initial ankle sprain of 204 weeks (range 150-274 weeks). Eight patients (18.1%) had reinjured their ankle. Explicit pain around the ankle joint at physical examination was experienced by 45.5%. Clinical symptoms of anterior ankle impingement were present in 25% (all athletes), with radiologically confirmed tibiotalar osteophyte bone formation in 82% of them. A large proportion of patients with ALALS experience recurrences and persistent symptoms after their initial ankle injury. The high percentage of patients with anterior ankle impingement syndromes illustrates the need for early assessment of this impairment in patients with persistent complaints. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  17. MR imaging in recurrent pain after back surgery. A comparative study using standard and high doses of gadolinium contrast agents

    Energy Technology Data Exchange (ETDEWEB)

    Aakeson, P. [Univ. Hospital, Lund (Sweden). Dept. of Radiology; Annertz, M. [Univ. Hospital, Lund (Sweden). Dept. of Radiology; Kristoffersen, D.T. [Nycomed Imaging AS, Oslo (Norway); Jonsson, E. [Nycomed AB, Stockholm (Sweden); Holtaas, S. [Univ. Hospital, Lund (Sweden). Dept. of Radiology

    1996-11-01

    Purpose: To compare the diagnostic results following injection of (a) a high dose (0.3 mmol/kg b.w.) of gadodiamide injection and (b) the standard dose (0.1 mmol/kg b.w.) of Gd-DTPA, in patients with recurrent symptoms after surgery for lumbar disc herniation. Material and Methods: Twenty patients with recurrent or sustained symptoms after surgery for lumbar disc herniations were examined. MR imaging (0.3 T) was first performed before and after Gd-DTPA at 0.1 mmol/kg b.w., and then within one month (17 patients) or within 3 months (3 patients) before and after gadodiamide injection at 0.3 mmol/kg b.w. The examinations were first evaluated by 2 neuroradiologists blinded to dose but not to patient as the images were presented in pairs. Six months later the same investigators evaluated the examinations again, this time blinded to both dose and patient. Results: At the evaluation in pairs (with the investigators blinded to dose only) the high-dose examinations were considered the most informative (p=0.05). However, at the later evaluation (with the investigators blinded both to dose and patient) no significant difference between high and standard dose was found regarding diagnosis or diagnostic certainty. Conclusion: In this study the high-dose contrast enhancement of MR imaging at 0.3 T did not increase the diagnostic information for differentiating between scar and recurrent hernia. The high-dose images were considered more informative when evaluated in pairs, but gave no additional or different information when evaluated separately. The study also indicated that comparisons in pairs should be interpreted with caution. (orig.).

  18. Identification of subpopulations of prairie voles differentially susceptible to peer influence to decrease high alcohol intake.

    Science.gov (United States)

    Anacker, Allison M J; Ryabinin, Andrey E

    2013-01-01

    Peer influences are critical in the decrease of alcohol (ethanol) abuse and maintenance of abstinence. We previously developed an animal model of inhibitory peer influences on ethanol drinking using prairie voles and here sought to understand whether this influential behavior was due to specific changes in drinking patterns and to variation in a microsatellite sequence in the regulatory region of the vasopressin receptor 1a gene (avpr1a). Adult prairie voles' drinking patterns were monitored in a lickometer apparatus that recorded each lick a subject exhibited during continuous access to water and 10% ethanol during periods of isolation, pair housing of high and low drinkers, and subsequent isolation. Analysis of fluid consumption confirmed previous results that high drinkers typically decrease ethanol intake when paired with low drinkers, but that a subset of voles do not decrease. Analysis of bout structure revealed differences in the number of ethanol drinking bouts in the subpopulations of high drinkers when paired with low drinkers. Lickometer drinking patterns analyzed by visual and by cross-correlation analyses demonstrated that pair housing did not increase the rate of subjects drinking in bouts occurring at the same time. The length of the avpr1a microsatellite did not predict susceptibility to peer influence or any other drinking behaviors. In summary, subpopulations of high drinkers were identified, by fluid intake and number of drinking bouts, which did or did not lower their ethanol intake when paired with a low drinking peer, and these subpopulations should be explored for testing the efficacy of treatments to decrease ethanol use in groups that are likely to be responsive to different types of therapy.

  19. Identification of subpopulations of prairie voles differentially susceptible to peer influence to decrease high alcohol intake

    Directory of Open Access Journals (Sweden)

    Allison M.J. Anacker

    2013-07-01

    Full Text Available Peer influences are critical in the decrease of alcohol (ethanol abuse and maintenance of abstinence. We previously developed an animal model of inhibitory peer influences on ethanol drinking using prairie voles and here sought to understand whether this influential behavior was due to specific changes in drinking patterns and to variation in a microsatellite sequence in the regulatory region of the vasopressin receptor 1a gene (avpr1a. Adult prairie voles’ drinking patterns were monitored in a lickometer apparatus that recorded each lick a subject exhibited during continuous access to water and 10% ethanol during periods of isolation, pair housing of high and low drinkers, and subsequent isolation. Analysis of fluid consumption confirmed previous results that high drinkers typically decrease ethanol intake when paired with low drinkers, but that a subset of voles do not decrease. Analysis of bout structure revealed differences in the number of ethanol drinking bouts in the subpopulations of high drinkers when paired with low drinkers. Lickometer drinking patterns analyzed by visual and by cross-correlation analyses demonstrated that pair housing did not increase the rate of subjects drinking in bouts occurring at the same time. The length of the avpr1a microsatellite did not predict susceptibility to peer influence or any other drinking behaviors. In summary, subpopulations of high drinkers were identified by fluid intake and number of drinking bouts, which did or did not lower their ethanol intake when paired with a low drinking peer, and these subpopulations should be explored for testing the efficacy of treatments to decrease ethanol use in groups that are likely to be responsive to different types of therapy.

  20. Pro-Tobacco Influences and Susceptibility to Smoking Cigarettes Among Middle and High School Students—United States, 2011

    Science.gov (United States)

    Dube, Shanta R.; Arrazola, René A.; Lee, Joann; Engstrom, Martha; Malarcher, Ann

    2015-01-01

    Purpose Smoking is a leading cause of cancer, and most smokers begin during adolescence. We examined the proportion of adolescents exposed to pro-tobacco advertising and assessed the association between this exposure and susceptibility to smoking. Methods Data from the 2011 National Youth Tobacco Survey were used to calculate the proportion of susceptible middle school (MS) and high school (HS) students exposed to pro-tobacco advertisements through stores, magazines, and the Internet. Following previous work, susceptibility to smoking cigarettes was defined as “never smoked but open to trying cigarettes.” Results In 2011, 81.5% of MS students and 86.9% of HS students were exposed to tobacco advertisements in stores; 48.2% of MS students and 54.0% of HS students were exposed to such advertising in magazines. Exposure to tobacco advertisements on the Internet was similar for MS (40.8%) and HS students (40.2%). Of those surveyed, 22.5% of MS students and 24.2% of HS students were susceptible to trying cigarettes. Exposure to magazine advertising declined from 71.8% in 2000 to 46.1% in 2009 among susceptible MS students; however, exposure increased to 55.4% in 2011. Tobacco advertising seen through the Internet among susceptible HS students increased from 25.9% in 2000 to 44.7% in 2011. Conclusions Adolescents continue to be exposed to pro-tobacco advertisements. Adolescents susceptible to smoking are more likely to report exposure to pro-tobacco advertisements. In addition to continued monitoring, more effective interventions to eliminate youth exposure to pro-tobacco marketing are needed. PMID:23601611

  1. High expression of micro RNA-135A in hepatocellular carcinoma is associated with recurrence within 12 months after resection.

    Science.gov (United States)

    von Felden, Johann; Heim, Denise; Schulze, Kornelius; Krech, Till; Ewald, Florian; Nashan, Björn; Lohse, Ansgar W; Wege, Henning

    2017-01-18

    Hepatocellular carcinoma has a dismal prognosis due to recurrence rates of up to 70% after curative resection. Early recurrence is driven by synchronous microscopic intrahepatic metastases. The predictive value of histological parameters is discussed controversially and adjuvant therapy is not established. The aim of this study was to identify patients at high risk for early intrahepatic recurrence by expression profiling of selected micro RNAs. In 52 patients undergoing HCC resection between 2011 and 2014, liver and tumor tissue was collected during surgery. Twelve patients with incomplete data regarding HCC recurrence, secondary liver transplantation, or perioperative death were excluded, leaving 40 patients with early recurrence 24 months (R-) to compare grading, T, L, V, and R status. If tissue quality permitted, micro RNAs were measured in HCC and liver tissue. Ten women and 30 men (64.0 ± 10.2 years) were analyzed. R+ occurred in 29 patients 6.2 ± 4.5 months after resection. Surveillance of R- was 26.2 ± 5.2 months. High intratumoral expression of miR-135a was associated with high risk of recurrence (HR = 4.2, p = 0.024, time to recurrence 8.8 ± 2.0 vs. 24.8 ± 4.4 months in patients with low miR-135a expression). As expected, T3 status was correlated with early recurrence, while other histological parameters and expression of miR-21, miR-122, and miR-125a did not. We show a significant association between high expression of miR-135a and early HCC recurrence. Therefore, high intratumoral miR-135a expression might serve as a novel biomarker to identify patients urgently requiring adjuvant therapy post resection.

  2. High susceptibility to fatty liver disease in two-pore channel 2-deficient mice.

    Science.gov (United States)

    Grimm, Christian; Holdt, Lesca M; Chen, Cheng-Chang; Hassan, Sami; Müller, Christoph; Jörs, Simone; Cuny, Hartmut; Kissing, Sandra; Schröder, Bernd; Butz, Elisabeth; Northoff, Bernd; Castonguay, Jan; Luber, Christian A; Moser, Markus; Spahn, Saskia; Lüllmann-Rauch, Renate; Fendel, Christina; Klugbauer, Norbert; Griesbeck, Oliver; Haas, Albert; Mann, Matthias; Bracher, Franz; Teupser, Daniel; Saftig, Paul; Biel, Martin; Wahl-Schott, Christian

    2014-08-21

    Endolysosomal organelles play a key role in trafficking, breakdown and receptor-mediated recycling of different macromolecules such as low-density lipoprotein (LDL)-cholesterol, epithelial growth factor (EGF) or transferrin. Here we examine the role of two-pore channel (TPC) 2, an endolysosomal cation channel, in these processes. Embryonic mouse fibroblasts and hepatocytes lacking TPC2 display a profound impairment of LDL-cholesterol and EGF/EGF-receptor trafficking. Mechanistically, both defects can be attributed to a dysfunction of the endolysosomal degradation pathway most likely on the level of late endosome to lysosome fusion. Importantly, endolysosomal acidification or lysosomal enzyme function are normal in TPC2-deficient cells. TPC2-deficient mice are highly susceptible to hepatic cholesterol overload and liver damage consistent with non-alcoholic fatty liver hepatitis. These findings indicate reduced metabolic reserve of hepatic cholesterol handling. Our results suggest that TPC2 plays a crucial role in trafficking in the endolysosomal degradation pathway and, thus, is potentially involved in the homoeostatic control of many macromolecules and cell metabolites.

  3. High miR-124-3p expression identifies smoking individuals susceptible to atherosclerosis.

    Science.gov (United States)

    de Ronde, Maurice W J; Kok, Maayke G M; Moerland, Perry D; Van den Bossche, Jan; Neele, Annette E; Halliani, Amalia; van der Made, Ingeborg; de Winther, Menno P J; Meijers, Joost C M; Creemers, Esther E; Pinto-Sietsma, Sara-Joan

    2017-08-01

    The risk of developing cardiovascular disease (CVD) is twice as high among smoking individuals compared to non-smokers. Monocytes are involved in smoking-related atherosclerotic plaque formation. In this study, we investigated whether smokers with an increased risk of developing CVD can be identified on the basis of monocyte-derived miRNA expression levels. We performed a miRNA microarray experiment on isolated monocytes from smoking, former smoking and non-smoking individuals in a cohort of patients with premature CVD and healthy controls (Cohort I, n = 76). We found miR-124-3p to be heterogeneously expressed among all smoking individuals, whereas expression was low in non-smokers. Subsequently, RT-qPCR measurements on whole blood showed that among smoking individuals an increase in miR-124-3p is associated with an increased risk for advanced atherosclerotic disease (cohort II, n = 24) (OR 11.72 95% CI 1.09-126.53) and subclinical atherosclerosis (coronary artery calcium score ≥ 80(th) percentile, cohort III n = 138) (OR 2.71, 95% CI 1.05-7.01). This was not observed among former smokers or non-smoking individuals. Flow cytometric analysis demonstrated that high miR-124-3p expression was associated with upregulation of the monocyte surface markers CD45RA, CD29 and CD206, indicating an altered monocyte phenotype. Finally, overexpression of miR-124-3p resulted in an upregulation of CD206 surface expression on monocytes. High miR-124-3p expression is associated with an increased risk of subclinical atherosclerosis in smoking individuals and with an altered monocyte phenotype. This may suggest that miR-124-3p identifies which smoking individuals are susceptible to the atherogenic effects of smoking. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. High Smac/DIABLO expression is associated with early local recurrence of cervical cancer

    Directory of Open Access Journals (Sweden)

    Maldonado Vilma

    2006-10-01

    Full Text Available Abstract Background In a recent pilot report, we showed that Smac/DIABLO mRNA is expressed de novo in a subset of cervical cancer patients. We have now expanded this study and analyzed Smac/DIABLO expression in the primary lesions in 109 cervical cancer patients. Methods We used immunohistochemistry of formalin-fixed, paraffin-embedded tissue sections to analyze Smac/DIABLO expression in the 109 primary lesions. Seventy-eight samples corresponded to epidermoid cervical cancer and 31 to cervical adenocarcinoma. The median follow up was 46.86 months (range 10–186. Results Smac/DIABLO was expressed in more adenocarcinoma samples than squamous tumours (71% vs 50%; p = 0.037. Among the pathological variables, a positive correlation was found between Smac/DIABLO immunoreactivity and microvascular density, a marker for angiogenesis (p = 0.04. Most importantly, Smac/DIABLO immunoreactivity was associated with a higher rate of local recurrence in squamous cell carcinoma (p = 0.002, log rank test. No association was found between Smac/DIABLO and survival rates. Conclusion Smac/DIABLO expression is a potential marker for local recurrence in cervical squamous cell carcinoma patients.

  5. Reverberation Chamber Uniformity Validation and Radiated Susceptibility Test Procedures for the NASA High Intensity Radiated Fields Laboratory

    Science.gov (United States)

    Koppen, Sandra V.; Nguyen, Truong X.; Mielnik, John J.

    2010-01-01

    The NASA Langley Research Center's High Intensity Radiated Fields Laboratory has developed a capability based on the RTCA/DO-160F Section 20 guidelines for radiated electromagnetic susceptibility testing in reverberation chambers. Phase 1 of the test procedure utilizes mode-tuned stirrer techniques and E-field probe measurements to validate chamber uniformity, determines chamber loading effects, and defines a radiated susceptibility test process. The test procedure is segmented into numbered operations that are largely software controlled. This document is intended as a laboratory test reference and includes diagrams of test setups, equipment lists, as well as test results and analysis. Phase 2 of development is discussed.

  6. High temperature series expansions for the susceptibility of Ising model on the Kagome lattice with nearest neighber interactions

    Directory of Open Access Journals (Sweden)

    Z Jalali mola

    2011-12-01

    Full Text Available  The Ising model is one of the simplest models describing the interacting particles. In this work, we calculate the high temperature series expansions of zero field susceptibility of ising model with ferromagnetic, antiferromagnetic and one antiferromagnetic interactions on two dimensional kagome lattice. Using the Pade´ approximation, we calculate the susceptibility of critical exponent of ferromagnetic ising model γ ≈ 1.75, which is consistent with universality hypothesis. However, antiferromagnetic and one antiferromagnetic interaction ising model doesn’t show any transition at finite temperature because of the effect of magnetic frustration.

  7. Perioperative Interstitial High-Dose-Rate Brachytherapy for the Treatment of Recurrent Keloids: Feasibility and Early Results

    Energy Technology Data Exchange (ETDEWEB)

    Jiang, Ping, E-mail: ping.jiang@uksh.de [Department of Radiation Oncology, University Clinic Schleswig-Holstein, Campus Kiel, Kiel (Germany); Baumann, René [Department of Radiation Oncology, University Clinic Schleswig-Holstein, Campus Kiel, Kiel (Germany); Dunst, Juergen [Department of Radiation Oncology, University Clinic Schleswig-Holstein, Campus Kiel, Kiel (Germany); Department of Radiation Oncology, University of Copenhagen, Copenhagen (Denmark); Geenen, Matthias [Department of Reconstructive Surgery, Lubinus Clinic Kiel, Kiel (Germany); Siebert, Frank-André [Department of Radiation Oncology, University Clinic Schleswig-Holstein, Campus Kiel, Kiel (Germany); Niehoff, Peter [Department of Radiation Oncology, University Clinic Schleswig-Holstein, Campus Kiel, Kiel (Germany); Department of Radiation Oncology, Community Clinic Köln, Köln (Germany); Department of Radiation Oncology, University Witten/Herdecke, Witten (Germany); Bertolini, Julia; Druecke, Daniel [Department of Reconstructive Surgery, University Clinic Schleswig-Holstein, Campus Kiel, Kiel (Germany)

    2016-03-01

    Purpose: To prospectively evaluate high-dose-rate brachytherapy in the treatment of therapy-resistant keloids and report first results, with emphasis on feasibility and early treatment outcome. Methods and Materials: From 2009 to 2014, 24 patients with 32 recurrent keloids were treated with immediate perioperative high-dose-rate brachytherapy; 3 patients had been previously treated with adjuvant external beam radiation therapy and presented with recurrences in the pretreated areas. Two or more different treatment modalities had been tried in all patients and had failed to achieve remission. After (re-)excision of the keloids, a single brachytherapy tube was placed subcutaneously before closing the wound. The target volume covered the scar in total length. Brachytherapy was given in 3 fractions with a single dose of 6 Gy in 5 mm tissue depth. The first fraction was given within 6 hours after surgery, the other 2 fractions on the first postoperative day. Thus, a total dose of 18 Gy in 3 fractions was administered within 36 hours after the resection. Results: The treatment was feasible in all patients. No procedure-related complications (eg, secondary infections) occurred. Nineteen patients had keloid-related symptoms before treatment like pain and pruritus; disappearance of symptoms was noticed in all patients after treatment. After a median follow-up of 29.4 months (range, 7.9-72.4 months), 2 keloid recurrences and 2 mildly hypertrophied scars were observed. The local control rate was 94%. Pigmentary abnormalities were detected in 3 patients, and an additional 6 patients had a mild delay in the wound-healing process. Conclusions: The early results of this study prove the feasibility and the efficacy of brachytherapy for the prevention of keloids. The results also suggest that brachytherapy may be advantageous in the management of high-risk keloids or as salvage treatment for failure after external beam therapy.

  8. Haptoglobin phenotype is not a predictor of recurrence free survival in high-risk primary breast cancer patients

    Directory of Open Access Journals (Sweden)

    Harris Nathan

    2008-12-01

    Full Text Available Abstract Background Better breast cancer prognostication may improve selection of patients for adjuvant therapy. We conducted a retrospective follow-up study in which we investigated sera of high-risk primary breast cancer patients, to search for proteins predictive of recurrence free survival. Methods Two sample sets of high-risk primary breast cancer patients participating in a randomised national trial investigating the effectiveness of high-dose chemotherapy were analysed. Sera in set I (n = 63 were analysed by surface enhanced laser desorption ionisation time-of-flight mass spectrometry (SELDI-TOF MS for biomarker finding. Initial results were validated by analysis of sample set II (n = 371, using one-dimensional gel-electrophoresis. Results In sample set I, the expression of a peak at mass-to-charge ratio 9198 (relative intensity ≤ 20 or > 20, identified as haptoglobin (Hp alpha-1 chain, was strongly associated with recurrence free survival (global Log-rank test; p = 0.0014. Haptoglobin is present in three distinct phenotypes (Hp 1-1, Hp 2-1, and Hp 2-2, of which only individuals with phenotype Hp 1-1 or Hp 2-1 express the haptoglobin alpha-1 chain. As the expression of the haptoglobin alpha-1 chain, determined by SELDI-TOF MS, corresponds to the phenotype, initial results were validated by haptoglobin phenotyping of the independent sample set II by native one-dimensional gel-electrophoresis. With the Hp 1-1 phenotype as the reference category, the univariate hazard ratio for recurrence was 0.87 (95% CI: 0.56 – 1.34, p = 0.5221 and 1.03 (95% CI: 0.65 – 1.64, p = 0.8966 for the Hp 2-1 and Hp 2-2 phenotypes, respectively, in sample set II. Conclusion In contrast to our initial results, the haptoglobin phenotype was not identified as a predictor of recurrence free survival in high-risk primary breast cancer in our validation set. Our initial observation in the discovery set was probably the result of a type I error (i.e. false positive

  9. High postnatal susceptibility of hippocampal cytoskeleton in response to ethanol exposure during pregnancy and lactation.

    Science.gov (United States)

    Reis, Karina Pires; Heimfarth, Luana; Pierozan, Paula; Ferreira, Fernanda; Loureiro, Samanta Oliveira; Fernandes, Carolina Gonçalves; Carvalho, Rônan Vivian; Pessoa-Pureur, Regina

    2015-11-01

    Ethanol exposure to offspring during pregnancy and lactation leads to developmental disorders, including central nervous system dysfunction. In the present work, we have studied the effect of chronic ethanol exposure during pregnancy and lactation on the phosphorylating system associated with the astrocytic and neuronal intermediate filament (IF) proteins: glial fibrillary acidic protein (GFAP), and neurofilament (NF) subunits of low, medium, and high molecular weight (NFL, NFM, and NFH, respectively) in 9- and 21-day-old pups. Female rats were fed with 20% ethanol in their drinking water during pregnancy and lactation. The homeostasis of the IF phosphorylation was not altered in the cerebral cortex, cerebellum, or hippocampus of 9-day-old pups. However, GFAP, NFL, and NFM were hyperphosphorylated in the hippocampus of 21-day-old pups. PKA had been activated in the hippocampus, and Ser55 in the N-terminal region of NFL was hyperphosphorylated. In addition, JNK/MAPK was activated and KSP repeats in the C-terminal region of NFM were hyperphosphorylated in the hippocampus of 21-day-old pups. Decreased NFH immunocontent but an unaltered total NFH/phosphoNFH ratio suggested altered stoichiometry of NFs in the hippocampus of ethanol-exposed 21-day-old pups. In contrast to the high susceptibility of hippocampal cytoskeleton in developing rats, the homeostasis of the cytoskeleton of ethanol-fed adult females was not altered. Disruption of the cytoskeletal homeostasis in neural cells supports the view that regions of the brain are differentially vulnerable to alcohol insult during pregnancy and lactation, suggesting that modulation of JNK/MAPK and PKA signaling cascades target the hippocampal cytoskeleton in a window of vulnerability in 21-day-old pups. Our findings are relevant, since disruption of the cytoskeleton in immature hippocampus could contribute to later hippocampal damage associated with ethanol toxicity. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Depression and emotional stress is highly prevalent among women with recurrent pregnancy loss

    DEFF Research Database (Denmark)

    Kolte, A M; Olsen, Line Rørbæk; Mikkelsen, E M

    2015-01-01

    STUDY QUESTION: Is the prevalence of psychological stress and moderate/severe depression higher for women with recurrent pregnancy loss (RPL) than pregnancy planners trying to conceive naturally? SUMMARY ANSWER: Both psychological stress and major depression are significantly more common among...... women with RPL than in those trying to conceive naturally. WHAT IS KNOWN ALREADY: RPL has a significant emotional impact on couples, especially the woman. Previous studies have shown inconclusive results. STUDY DESIGN, SIZE, DURATION: In this cross-sectional study, we compared the prevalence of stress......, and Cohen's Perceived Stress Scale (PSS) was used to measure stress. Relevant demographic data were also retrieved. MAIN RESULTS AND THE ROLE OF CHANCE: Of the RPL patients, 26 (8.6%) had a score on the MDI corresponding to moderate/severe depression, as did 40 (2.2%) of the women in Soon Parents Study...

  11. Treatment of Recurrent Posttransplant Lymphoproliferative Disorder of the Central Nervous System with High-Dose Methotrexate

    Directory of Open Access Journals (Sweden)

    Clare J. Twist

    2013-01-01

    Full Text Available Posttransplant lymphoproliferative disorder (PTLD is a frequent complication of intestinal transplantation and is associated with a poor prognosis. There is currently no consensus on optimal therapy. Recurrent PTLD involving the central nervous system (CNS represents a particularly difficult therapeutic challenge. We report the successful treatment of CNS PTLD in a pediatric patient after liver/small bowel transplantation. Initial immunosuppression (IS was with thymoglobulin, solucortef, tacrolimus, and mycophenolate mofetil. EBV viremia developed 8 weeks posttransplantation, and despite treatment with cytogam and valganciclovir the patient developed a polymorphic, CD20+, EBV+ PTLD with peripheral lymphadenopathy. Following treatment with rituximab, the lymphadenopathy resolved, but a new monomorphic CD20−, EBV+, lambda-restricted, plasmacytoid PTLD mesenteric mass emerged. Complete response of this PTLD was achieved with 6 cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP chemotherapy; however, 4 months off therapy he developed CNS PTLD (monomorphic CD20−, EBV+, lambda-restricted, plasmacytoid PTLD of the brain and spine. IS was discontinued and HD-MTX (2.5–5 gm/m2/dose followed by intrathecal HD-MTX (2 mg/dose ×2-3 days Q 7–10 days per cycle was administered Q 4–7 weeks. After 3 cycles of HD-MTX, the CSF was negative for malignant cells, MRI of head/spine showed near-complete response, and PET/CT was negative. The patient remains in complete remission now for 3.5 years after completion of systemic and intrathecal chemotherapy. Conclusion. HD-MTX is an effective therapy for CNS PTLD and recurrent PTLD that have failed rituximab and CHOP chemotherapy.

  12. Cluster of Neisseria gonorrhoeae Isolates With High-level Azithromycin Resistance and Decreased Ceftriaxone Susceptibility, Hawaii, 2016.

    Science.gov (United States)

    Katz, Alan R; Komeya, Alan Y; Kirkcaldy, Robert D; Whelen, A Christian; Soge, Olusegun O; Papp, John R; Kersh, Ellen N; Wasserman, Glenn M; O'Connor, Norman P; O'Brien, Pamela S; Sato, Douglas T; Maningas, Eloisa V; Kunimoto, Gail Y; Tomas, Juval E

    2017-09-15

    The Centers for Disease Control and Prevention (CDC) currently recommends dual therapy with ceftriaxone and azithromycin for gonorrhea to ensure effective treatment and slow emergence of antimicrobial resistance. Since 2013, the prevalence of reduced azithromycin susceptibility increased in the United States; however, these strains were highly susceptible to cephalosporins. We identified a cluster of Neisseria gonorrhoeae isolates with high-level azithromycin resistance, several of which also demonstrated decreased ceftriaxone susceptibility. Eight N. gonorrhoeae isolates collected from 7 patients on Oahu, Hawaii, seen 21 April 2016 through 10 May 2016 underwent routine Etest antimicrobial susceptibility testing by the Hawaii Department of Health. All demonstrated elevated azithromycin minimum inhibitory concentrations (MICs) >256 μg/mL and elevated ceftriaxone MICs (≥0.125 μg/mL). Isolates were sent to the University of Washington and CDC for confirmatory agar dilution testing; sequence data were sent to CDC for analysis. All patients were interviewed and treated, and when possible, partners were interviewed, tested, and treated. All isolates had azithromycin MICs >16 µg/mL and 5 had ceftriaxone MICs = 0.125 µg/mL by agar dilution. All isolates were β-lactamase positive and were resistant to penicillin, tetracycline, and ciprofloxacin. Genomic analysis revealed genetic relatedness. No patients reported recent travel or antibiotic use, and no male patients reported male sex partners. All patients were successfully treated. This cluster of genetically related gonococcal isolates with decreased ceftriaxone susceptibility and high-level azithromycin resistance may bring the threat of treatment failure in the United States with the current recommended dual therapy one step closer.

  13. Does high intelligence improve prognosis? The association of intelligence with recurrence and mortality among Swedish men with coronary heart disease.

    Science.gov (United States)

    Sörberg Wallin, Alma; Falkstedt, Daniel; Allebeck, Peter; Melin, Bo; Janszky, Imre; Hemmingsson, Tomas

    2015-04-01

    Lower intelligence early in life is associated with increased risks for coronary heart disease (CHD) and mortality. Intelligence level might affect compliance to treatment but its prognostic importance in patients with CHD is unknown. A cohort of 1923 Swedish men with a measure of intelligence from mandatory military conscription in 1969-1970 at age 18-20, who were diagnosed with CHD 1991-2007, were followed to the end of 2008. recurrent CHD event. Secondary outcome: case fatality from the first event, cardiovascular and all-cause mortality. National registers provided information on CHD events, comorbidity, mortality and socioeconomic factors. The fully adjusted HRs for recurrent CHD for medium and low intelligence, compared with high intelligence, were 0.98, (95% CIs 0.83 to 1.16) and 1.09 (0.89 to 1.34), respectively. The risks were increased for cardiovascular and all-cause mortality with lower intelligence, but were attenuated in the fully adjusted models (fully adjusted HRs for cardiovascular mortality 1.92 (0.94 to 3.94) and 1.98 (0.89 to 4.37), respectively; for all-cause mortality 1.63 (1.00 to 2.65) and 1.62 (0.94 to 2.78), respectively). There was no increased risk for case-fatality at the first event (fully adjusted ORs 1.06 (0.73 to 1.55) and 0.97 (0.62 to 1.50), respectively). Although we found lower intelligence to be associated with increased mortality in middle-aged men with CHD, there was no evidence for its possible effect on recurrence in CHD. 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.

  14. Image-guided high-dose-rate interstitial brachytherapy – a valuable salvage treatment approach for loco-regional recurrence of papillary thyroid cancer

    Directory of Open Access Journals (Sweden)

    Ning Wu

    2016-04-01

    Full Text Available Purpose : To report the treatment effect of image-guided high-dose-rate (HDR interstitial brachytherapy for refractory recurrence of papillary thyroid cancer (PTC. Case report: This 66-year-old female presented with recurrence 5 years after thyroidectomy for PTC. Despite external irradiation and radioactive 131I, the lesion expanded as 3.7 × 3.0 × 2.3 cm3 and 2.0 × 1.5 × 1.5 cm3. The locoregional recurrent tumor was treated with image-guided HDR interstitial brachytherapy. The total dose of 30 Gy in 6 fractions were delivered on the whole recurrent tumor. Results: Removal of the recurrent tumor was securely achieved by HDR interstitial brachytherapy guided with ultrasound, computed tomography (CT, and magnetic resonance imaging (MRI scanning. The refractory tumor in the patients healed uneventfully after HDR interstitial brachytherapy without recurrence during the 14 months of follow-up. Conclusions : The image-guided HDR interstitial brachytherapy may be a valuable salvage treatment approach for refractory recurrence of PTC.

  15. High Incidence of Celiac Disease in a Long-term Study of Adolescents With Susceptibility Genotypes.

    Science.gov (United States)

    Liu, Edwin; Dong, Fran; Barón, Anna E; Taki, Iman; Norris, Jill M; Frohnert, Brigitte I; Hoffenberg, Edward J; Rewers, Marian

    2017-05-01

    Little is known about the incidence of celiac disease in the general population of children in the United States. We aimed to estimate the cumulative incidence of celiac disease in adolescents born in the Denver metropolitan area. We collected data on HLA-DR, DQ genotypes of 31,766 infants, born from 1993 through 2004 at St. Joseph's Hospital in Denver, from the Diabetes Autoimmunity Study in the Young. Subjects with susceptibility genotypes for celiac disease and type 1 diabetes were followed up for up to 20 years for development of tissue transglutaminase autoantibodies (tTGA). Outcomes were the development of celiac disease autoimmunity (CDA) or celiac disease. CDA was defined as persistence of tTGA for at least 3 months or development of celiac disease. Celiac disease was defined based on detection of Marsh 2 or greater lesions in biopsy specimens or persistent high levels of tTGA. For each genotype, the cumulative incidence of CDA and celiac disease were determined. To estimate the cumulative incidence in the Denver general population, outcomes by each genotype were weighted according to the frequency of each of these genotypes in the general population. Of 1339 subjects followed up, 66 developed CDA and met criteria for celiac disease and 46 developed only CDA. Seropositivity for tTGA resolved spontaneously, without treatment, in 21 of the 46 subjects with only CDA (46%). The estimated cumulative incidence for CDA in the Denver general population at 5, 10, and 15 years of age was 2.4%, 4.3%, and 5.1%, respectively, and incidence values for celiac disease were 1.6%, 2.8%, and 3.1%, respectively. In a 20-year prospective study of 1339 children with genetic risk factors for celiac disease, we found the cumulative incidence of CDA and celiac disease to be high within the first 10 years. Although more than 5% of children may experience a period of CDA, not all children develop celiac disease or require gluten-free diets. Copyright © 2017 AGA Institute. Published

  16. Fault slip and earthquake recurrence along strike-slip faults — Contributions of high-resolution geomorphic data

    KAUST Repository

    Zielke, Olaf

    2015-01-01

    Understanding earthquake (EQ) recurrence relies on information about the timing and size of past EQ ruptures along a given fault. Knowledge of a fault\\'s rupture history provides valuable information on its potential future behavior, enabling seismic hazard estimates and loss mitigation. Stratigraphic and geomorphic evidence of faulting is used to constrain the recurrence of surface rupturing EQs. Analysis of the latter data sets culminated during the mid-1980s in the formulation of now classical EQ recurrence models, now routinely used to assess seismic hazard. Within the last decade, Light Detection and Ranging (lidar) surveying technology and other high-resolution data sets became increasingly available to tectono-geomorphic studies, promising to contribute to better-informed models of EQ recurrence and slip-accumulation patterns. After reviewing motivation and background, we outline requirements to successfully reconstruct a fault\\'s offset accumulation pattern from geomorphic evidence. We address sources of uncertainty affecting offset measurement and advocate approaches to minimize them. A number of recent studies focus on single-EQ slip distributions and along-fault slip accumulation patterns. We put them in context with paleoseismic studies along the respective faults by comparing coefficients of variation CV for EQ inter-event time and slip-per-event and find that a) single-event offsets vary over a wide range of length-scales and the sources for offset variability differ with length-scale, b) at fault-segment length-scales, single-event offsets are essentially constant, c) along-fault offset accumulation as resolved in the geomorphic record is dominated by essentially same-size, large offset increments, and d) there is generally no one-to-one correlation between the offset accumulation pattern constrained in the geomorphic record and EQ occurrence as identified in the stratigraphic record, revealing the higher resolution and preservation potential of

  17. Fault slip and earthquake recurrence along strike-slip faults - Contributions of high-resolution geomorphic data

    Science.gov (United States)

    Zielke, Olaf; Klinger, Yann; Arrowsmith, J. Ramon

    2015-01-01

    Understanding earthquake (EQ) recurrence relies on information about the timing and size of past EQ ruptures along a given fault. Knowledge of a fault's rupture history provides valuable information on its potential future behavior, enabling seismic hazard estimates and loss mitigation. Stratigraphic and geomorphic evidence of faulting is used to constrain the recurrence of surface rupturing EQs. Analysis of the latter data sets culminated during the mid-1980s in the formulation of now classical EQ recurrence models, now routinely used to assess seismic hazard. Within the last decade, Light Detection and Ranging (lidar) surveying technology and other high-resolution data sets became increasingly available to tectono-geomorphic studies, promising to contribute to better-informed models of EQ recurrence and slip-accumulation patterns. After reviewing motivation and background, we outline requirements to successfully reconstruct a fault's offset accumulation pattern from geomorphic evidence. We address sources of uncertainty affecting offset measurement and advocate approaches to minimize them. A number of recent studies focus on single-EQ slip distributions and along-fault slip accumulation patterns. We put them in context with paleoseismic studies along the respective faults by comparing coefficients of variation CV for EQ inter-event time and slip-per-event and find that a) single-event offsets vary over a wide range of length-scales and the sources for offset variability differ with length-scale, b) at fault-segment length-scales, single-event offsets are essentially constant, c) along-fault offset accumulation as resolved in the geomorphic record is dominated by essentially same-size, large offset increments, and d) there is generally no one-to-one correlation between the offset accumulation pattern constrained in the geomorphic record and EQ occurrence as identified in the stratigraphic record, revealing the higher resolution and preservation potential of the

  18. RECURRENT ABORTIONS

    African Journals Online (AJOL)

    recurrent abortion and intrauterine foetal deaths are not uncommon due to paucity of information on LA and its obstetrics manifestations. Our aim therefore was to determine the prevalence of LA in women with recurrent abortions in our community, with view of proffering therapeutic interventions. SUBJECTS AND METHODS.

  19. Handling high predictor dimensionality in slope-unit-based landslide susceptibility models through LASSO-penalized Generalized Linear Model

    KAUST Repository

    Camilo, Daniela Castro

    2017-08-30

    Grid-based landslide susceptibility models at regional scales are computationally demanding when using a fine grid resolution. Conversely, Slope-Unit (SU) based susceptibility models allows to investigate the same areas offering two main advantages: 1) a smaller computational burden and 2) a more geomorphologically-oriented interpretation. In this contribution, we generate SU-based landslide susceptibility for the Sado Island in Japan. This island is characterized by deep-seated landslides which we assume can only limitedly be explained by the first two statistical moments (mean and variance) of a set of predictors within each slope unit. As a consequence, in a nested experiment, we first analyse the distributions of a set of continuous predictors within each slope unit computing the standard deviation and quantiles from 0.05 to 0.95 with a step of 0.05. These are then used as predictors for landslide susceptibility. In addition, we combine shape indices for polygon features and the normalized extent of each class belonging to the outcropping lithology in a given SU. This procedure significantly enlarges the size of the predictor hyperspace, thus producing a high level of slope-unit characterization. In a second step, we adopt a LASSO-penalized Generalized Linear Model to shrink back the predictor set to a sensible and interpretable number, carrying only the most significant covariates in the models. As a result, we are able to document the geomorphic features (e.g., 95% quantile of Elevation and 5% quantile of Plan Curvature) that primarily control the SU-based susceptibility within the test area while producing high predictive performances. The implementation of the statistical analyses are included in a parallelized R script (LUDARA) which is here made available for the community to replicate analogous experiments.

  20. Injury Recurrence Among High School Athletes in the United States: A Decade of Patterns and Trends, 2005-2006 Through 2015-2016.

    Science.gov (United States)

    Welton, K Linnea; Kraeutler, Matthew J; Pierpoint, Lauren A; Bartley, Justin H; McCarty, Eric C; Comstock, R Dawn

    2018-01-01

    As participation in high school athletics increases, so does the number of adolescents experiencing sports-related injury. Understanding injury patterns is an important component to developing and evaluating prevention and rehabilitation programs. To analyze recurrent injury rates and patterns among high school athletes, to compare recurrent injuries with new injuries, and to evaluate injury trends over time. Descriptive epidemiology study. High school sports injury data on 24 sports were collected from 2005-2006 through 2015-2016 via the High School RIO (Reporting Information Online) surveillance system. Injury rates were calculated as number of injuries per 10,000 athletic exposures (AEs). Injury rate ratios and injury proportion ratios (IPRs) were calculated to compare differences among subgroups. Overall, 78,005 injuries were sustained during 40,195,806 AEs, for an injury rate of 19.41 per 10,000 AEs. Of these, 69,821 (89.5%) were new injuries, and 8184 (10.5%) were recurrent. The ankle was the most commonly injured body part among recurrent injuries, while the head/face was the most common body part that sustained new injuries. Ligament sprains were more often recurrent, while concussions were more commonly diagnosed as new, although concussions represented 16.7% of recurrent injuries. Trends for recurrent injuries over time were relatively stable. The proportion of athletes who had >3 weeks of time loss or medical disqualification (15.8% vs 13.3%; IPR, 1.19; 95% CI, 1.13-1.26) or who voluntarily withdrew from sport (2.5% vs 1.1%; IPR, 2.33; 95% CI, 2.00-2.73) was significantly greater for recurrent injuries than new injuries. Furthermore, a greater proportion of recurrent injuries resulted in surgery (8.1% vs 6.0%; IPR, 1.34; 95% CI, 1.24-1.46). Although only 10.5% of all injuries were recurrent, they more frequently resulted in missing >3 weeks of playing time and were more often managed surgically when compared with new injuries. The rate of recurrent

  1. Recurrent Meningitis.

    Science.gov (United States)

    Rosenberg, Jon; Galen, Benjamin T

    2017-07-01

    Recurrent meningitis is a rare clinical scenario that can be self-limiting or life threatening depending on the underlying etiology. This review describes the causes, risk factors, treatment, and prognosis for recurrent meningitis. As a general overview of a broad topic, the aim of this review is to provide clinicians with a comprehensive differential diagnosis to aide in the evaluation and management of a patient with recurrent meningitis. New developments related to understanding the pathophysiology of recurrent meningitis are as scarce as studies evaluating the treatment and prevention of this rare disorder. A trial evaluating oral valacyclovir suppression after HSV-2 meningitis did not demonstrate a benefit in preventing recurrences. The data on prophylactic antibiotics after basilar skull fractures do not support their use. Intrathecal trastuzumab has shown promise in treating leptomeningeal carcinomatosis from HER-2 positive breast cancer. Monoclonal antibodies used to treat cancer and autoimmune diseases are new potential causes of drug-induced aseptic meningitis. Despite their potential for causing recurrent meningitis, the clinical entities reviewed herein are not frequently discussed together given that they are a heterogeneous collection of unrelated, rare diseases. Epidemiologic data on recurrent meningitis are lacking. The syndrome of recurrent benign lymphocytic meningitis described by Mollaret in 1944 was later found to be closely related to HSV-2 reactivation, but HSV-2 is by no means the only etiology of recurrent aseptic meningitis. While the mainstay of treatment for recurrent meningitis is supportive care, it is paramount to ensure that reversible and treatable causes have been addressed for further prevention.

  2. Nasal Immunization Confers High Avidity Neutralizing Antibody Response and Immunity to Primary and Recurrent Genital Herpes in Guinea Pigs.

    Science.gov (United States)

    Persson, Josefine; Zhang, Yuan; Olafsdottir, Thorunn A; Thörn, Karolina; Cairns, Tina M; Wegmann, Frank; Sattentau, Quentin J; Eisenberg, Roselyn J; Cohen, Gary H; Harandi, Ali M

    2016-01-01

    Genital herpes is one of the most prevalent sexually transmitted infections in both the developing and developed world. Following infection, individuals experience life-long latency associated with sporadic ulcerative outbreaks. Despite many efforts, no vaccine has yet been licensed for human use. Herein, we demonstrated that nasal immunization with an adjuvanted HSV-2 gD envelope protein mounts significant protection to primary infection as well as the establishment of latency and recurrent genital herpes in guinea pigs. Nasal immunization was shown to elicit specific T cell proliferative and IFN-γ responses as well as systemic and vaginal gD-specific IgG antibody (Ab) responses. Furthermore, systemic IgG Abs displayed potent HSV-2 neutralizing properties and high avidity. By employing a competitive surface plasmon resonance (SPR) analysis combined with a battery of known gD-specific neutralizing monoclonal Abs (MAbs), we showed that nasal immunization generated IgG Abs directed to two major discontinuous neutralizing epitopes of gD. These results highlight the potential of nasal immunization with an adjuvanted HSV-2 envelope protein for induction of protective immunity to primary and recurrent genital herpes.

  3. High Rate of Recurrent De Novo Mutations in Developmental and Epileptic Encephalopathies.

    Science.gov (United States)

    Hamdan, Fadi F; Myers, Candace T; Cossette, Patrick; Lemay, Philippe; Spiegelman, Dan; Laporte, Alexandre Dionne; Nassif, Christina; Diallo, Ousmane; Monlong, Jean; Cadieux-Dion, Maxime; Dobrzeniecka, Sylvia; Meloche, Caroline; Retterer, Kyle; Cho, Megan T; Rosenfeld, Jill A; Bi, Weimin; Massicotte, Christine; Miguet, Marguerite; Brunga, Ledia; Regan, Brigid M; Mo, Kelly; Tam, Cory; Schneider, Amy; Hollingsworth, Georgie; FitzPatrick, David R; Donaldson, Alan; Canham, Natalie; Blair, Edward; Kerr, Bronwyn; Fry, Andrew E; Thomas, Rhys H; Shelagh, Joss; Hurst, Jane A; Brittain, Helen; Blyth, Moira; Lebel, Robert Roger; Gerkes, Erica H; Davis-Keppen, Laura; Stein, Quinn; Chung, Wendy K; Dorison, Sara J; Benke, Paul J; Fassi, Emily; Corsten-Janssen, Nicole; Kamsteeg, Erik-Jan; Mau-Them, Frederic T; Bruel, Ange-Line; Verloes, Alain; Õunap, Katrin; Wojcik, Monica H; Albert, Dara V F; Venkateswaran, Sunita; Ware, Tyson; Jones, Dean; Liu, Yu-Chi; Mohammad, Shekeeb S; Bizargity, Peyman; Bacino, Carlos A; Leuzzi, Vincenzo; Martinelli, Simone; Dallapiccola, Bruno; Tartaglia, Marco; Blumkin, Lubov; Wierenga, Klaas J; Purcarin, Gabriela; O'Byrne, James J; Stockler, Sylvia; Lehman, Anna; Keren, Boris; Nougues, Marie-Christine; Mignot, Cyril; Auvin, Stéphane; Nava, Caroline; Hiatt, Susan M; Bebin, Martina; Shao, Yunru; Scaglia, Fernando; Lalani, Seema R; Frye, Richard E; Jarjour, Imad T; Jacques, Stéphanie; Boucher, Renee-Myriam; Riou, Emilie; Srour, Myriam; Carmant, Lionel; Lortie, Anne; Major, Philippe; Diadori, Paola; Dubeau, François; D'Anjou, Guy; Bourque, Guillaume; Berkovic, Samuel F; Sadleir, Lynette G; Campeau, Philippe M; Kibar, Zoha; Lafrenière, Ronald G; Girard, Simon L; Mercimek-Mahmutoglu, Saadet; Boelman, Cyrus; Rouleau, Guy A; Scheffer, Ingrid E; Mefford, Heather C; Andrade, Danielle M; Rossignol, Elsa; Minassian, Berge A; Michaud, Jacques L

    2017-11-02

    Developmental and epileptic encephalopathy (DEE) is a group of conditions characterized by the co-occurrence of epilepsy and intellectual disability (ID), typically with developmental plateauing or regression associated with frequent epileptiform activity. The cause of DEE remains unknown in the majority of cases. We performed whole-genome sequencing (WGS) in 197 individuals with unexplained DEE and pharmaco-resistant seizures and in their unaffected parents. We focused our attention on de novo mutations (DNMs) and identified candidate genes containing such variants. We sought to identify additional subjects with DNMs in these genes by performing targeted sequencing in another series of individuals with DEE and by mining various sequencing datasets. We also performed meta-analyses to document enrichment of DNMs in candidate genes by leveraging our WGS dataset with those of several DEE and ID series. By combining these strategies, we were able to provide a causal link between DEE and the following genes: NTRK2, GABRB2, CLTC, DHDDS, NUS1, RAB11A, GABBR2, and SNAP25. Overall, we established a molecular diagnosis in 63/197 (32%) individuals in our WGS series. The main cause of DEE in these individuals was de novo point mutations (53/63 solved cases), followed by inherited mutations (6/63 solved cases) and de novo CNVs (4/63 solved cases). De novo missense variants explained a larger proportion of individuals in our series than in other series that were primarily ascertained because of ID. Moreover, these DNMs were more frequently recurrent than those identified in ID series. These observations indicate that the genetic landscape of DEE might be different from that of ID without epilepsy. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  4. High Frequency of Interactions between Lung Cancer Susceptibility Genes in the Mouse : Mapping of Sluc5 to Sluc14

    NARCIS (Netherlands)

    Fijneman, Remond J.A.; Jansen, Ritsert C.; Valk, Martin A. van der; Demant, Peter

    1998-01-01

    Although several genes that cause monogenic familial cancer syndromes have been identified, susceptibility to sporadic cancer remains unresolved. Animal experiments have demonstrated multigenic control of tumor susceptibility. Recently, we described four mouse lung cancer susceptibility (Sluc) loci,

  5. Effectivity of intravescical thermo-chemotherapy prophylaxis for patients with high recurrence and progression risk for non-muscle invasive bladder cancer

    Directory of Open Access Journals (Sweden)

    Ali Serdar Gözen

    2017-06-01

    Full Text Available Background&Aim: High grade non-muscle invasive bladder cancer (NMIBC is common in urological practice. Most of these cancers are or become refractory to intravesical immunotherapy and chemotherapy. Here we evaluated the efficacy of combined local bladder hyperthermia and intravesical mitomycin-C (MMC instillation in patients with high-risk recurrent NMIBC. Materials and methods: Between February 2014 and December 2015, 18 patients with high risk NMIBC were enrolled. Patients were treated in an outpatient basis with 6 weekly induction sessions followed by monthly maintenance sessions with intravesical MMC in local hyperthermia with bladder wall thermo-chemotherapy (BWT system (PelvixTT system, Elmedical Ltd., Hod Hasharon, Israel. The follow-up regimen included cystoscopy after the induction cycle and thereafter with regular intervals. Time to disease recurrence was defined as time from the first intravesical treatment to endoscopic or histological documentation of a new bladder tumour. Adverse events were recorded according to CTC 4.0 (Common Toxicity Criteria score system. Results: Mean age was 72 (32-87 years. 10 patients had multifocal disease, 9 had CIS, 6 had recurrent disease and 2 had highly recurrent disease (> 3 recurrences in a 24 months period. 6 patients underwent previous intravesical chemotherapy with MMC. The average number of maintenance sessions per patient was 7.6. After a mean follow-up of 433 days, 15 patients (83.3% were recurrence-free. 3 patients had tumour recurrence after a mean period of 248 days without progression. Side effects were limited to grade 1 in 2 patients and grade 2 in 1 patient. Conclusions: BWT seems to be feasible and safe in high grade NMIBC. More studies are needed to identify the subgroup of patients who may benefit more from this treatment.

  6. High susceptibility of Bt maize to aphids enhances the performance of parasitoids of lepidopteran pests.

    Directory of Open Access Journals (Sweden)

    Cristina A Faria

    Full Text Available Concerns about possible undesired environmental effects of transgenic crops have prompted numerous evaluations of such crops. So-called Bt crops receive particular attention because they carry bacteria-derived genes coding for insecticidal proteins that might negatively affect non-target arthropods. Here we show a remarkable positive effect of Bt maize on the performance of the corn leaf aphid Rhopalosiphum maidis, which in turn enhanced the performance of parasitic wasps that feed on aphid honeydew. Within five out of six pairs that were evaluated, transgenic maize lines were significantly more susceptible to aphids than their near-isogenic equivalents, with the remaining pair being equally susceptible. The aphids feed from the phloem sieve element content and analyses of this sap in selected maize lines revealed marginally, but significantly higher amino acid levels in Bt maize, which might partially explain the observed increased aphid performance. Larger colony densities of aphids on Bt plants resulted in an increased production of honeydew that can be used as food by beneficial insects. Indeed, Cotesia marginiventris, a parasitoid of lepidopteran pests, lived longer and parasitized more pest caterpillars in the presence of aphid-infested Bt maize than in the presence of aphid-infested isogenic maize. Hence, depending on aphid pest thresholds, the observed increased susceptibility of Bt maize to aphids may be either a welcome or an undesirable side effect.

  7. Intrauterine Growth Retardation Increases the Susceptibility of Pigs to High-Fat Diet-Induced Mitochondrial Dysfunction in Skeletal Muscle

    Science.gov (United States)

    Liu, Jingbo; Chen, Daiwen; Yao, Ying; Yu, Bing; Mao, Xiangbing; He, Jun; Huang, Zhiqing; Zheng, Ping

    2012-01-01

    It has been recognized that there is a relationship between prenatal growth restriction and the development of metabolic-related diseases in later life, a process involved in mitochondrial dysfunction. In addition, intrauterine growth retardation (IUGR) increases the susceptibility of offspring to high-fat (HF) diet-induced metabolic syndrome. Recent findings suggested that HF feeding decreased mitochondrial oxidative capacity and impaired mitochondrial function in skeletal muscle. Therefore, we hypothesized that the long-term consequences of IUGR on mitochondrial biogenesis and function make the offspring more susceptible to HF diet-induced mitochondrial dysfunction. Normal birth weight (NBW), and IUGR pigs were allotted to control or HF diet in a completely randomized design, individually. After 4 weeks of feeding, growth performance and molecular pathways related to mitochondrial function were determined. The results showed that IUGR decreased growth performance and plasma insulin concentrations. In offspring fed a HF diet, IUGR was associated with enhanced plasma leptin levels, increased concentrations of triglyceride and malondialdehyde (MDA), and reduced glycogen and ATP contents in skeletal muscle. High fat diet-fed IUGR offspring exhibited decreased activities of lactate dehydrogenase (LDH) and glucose-6-phosphate dehydrogenase (G6PD). These alterations in metabolic traits of IUGR pigs were accompanied by impaired mitochondrial respiration function, reduced mitochondrial DNA (mtDNA) contents, and down-regulated mRNA expression levels of genes responsible for mitochondrial biogenesis and function. In conclusion, our results suggest that IUGR make the offspring more susceptible to HF diet-induced mitochondrial dysfunction. PMID:22523560

  8. Test of linkage between candidate loci and a prostate cancer susceptibility locus in a set of high risk kindreds

    Energy Technology Data Exchange (ETDEWEB)

    Cannon-Albright, L.A.; Neuhausen, S.; Goldgar, D.E. [Univ. of Utah, Salt Lake City, UT (United States)] [and others

    1994-09-01

    Although no prostate cancer susceptibility locus has yet been mapped, candidate loci have been suggested by a series of allele loss studies in prostate tumors. We have used linkage analysis to investigate each locus previously shown to be lost in at least 30 percent of tumors. Seven high risk cases were screened with 31 markers representing loci on 11 chromosome arms to test for cosegregation of the markers and prostate cancer. Age of cancer onset for prostate cancer cases was not considered for ascertainment. A variety of models were utilized in linkage analysis, as well as model-free methods. A subset of Lod scored at {theta}=.01 are shown for a low penetrance affected-only model which assumed a rare dominant susceptibility and allowed sporadic cases. Multiple markers were run for each locus considered. Positive Lod scores >1.0 in specific kindreds are being investigated further and an exclusion map will be presented.

  9. The Effect of Acclimation to Sublethal Temperature on Subsequent Susceptibility of Sitophilus zeamais Mostchulsky (Coleoptera: Curculionidae) to High Temperatures.

    Science.gov (United States)

    Lü, Jianhua; Zhang, Huina

    2016-01-01

    Heat treatment is a popular alternative to synthetic pesticides in disinfesting food-processing facilities and empty grain storages. Sitophilus zeamais Mostchulsky is one of the most cosmopolitan and destructive insects found in empty grain storage facilities and processing facilities. The effect of acclimation in S. zeamais adults to sublethal high temperature on their subsequent susceptibility to high temperatures was investigated. S. zeamais adults were acclimated to 36°C for 0 (as a control), 1, 3, and 5 h, and then were exposed at 43, 47, 51, and 55°C for different time intervals respectively. Acclimation to sublethal high temperature significantly reduced subsequent susceptibility of S. zeamais adults to lethal high temperatures of 43, 47, 51, and 55°C, although the mortality of S. zeamais adults significantly increased with increasing exposure time at lethal high temperatures. The mortality of S. zeamais adults with 1, 3, and 5 h of acclimation to 36°C was significantly lower than that of S. zeamais adults without acclimation when exposed to the same lethal high temperatures. The present results suggest that the whole facility should be heated to target lethal high temperature as soon as possible, avoiding decreasing the control effectiveness of heat treatment due to the acclimation in stored product insects to sublethal temperature.

  10. High Nuclear Hypoxia-Inducible Factor 1 Alpha Expression Is a Predictor of Distant Recurrence in Patients With Resected Pancreatic Adenocarcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Colbert, Lauren E. [Department of Radiation Oncology, Emory University, Atlanta, Georgia (United States); Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Fisher, Sarah B. [Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Division of Surgical Oncology, Department of Surgery, Emory University, Atlanta, Georgia (United States); Balci, Serdar; Saka, Burcu [Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Department of Pathology, Emory University, Atlanta, Georgia (United States); Chen, Zhengjia; Kim, Sungjin [Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Biostatistics and Bioinformatics Shared Resource, Emory University, Atlanta, Georgia (United States); El-Rayes, Bassel F. [Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Department of Hematology and Medical Oncology, Emory University, Atlanta, Georgia (United States); Adsay, N. Volkan [Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Department of Pathology, Emory University, Atlanta, Georgia (United States); Biostatistics and Bioinformatics Shared Resource, Emory University, Atlanta, Georgia (United States); Maithel, Shishir K. [Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Division of Surgical Oncology, Department of Surgery, Emory University, Atlanta, Georgia (United States); Biostatistics and Bioinformatics Shared Resource, Emory University, Atlanta, Georgia (United States); Landry, Jerome C. [Department of Radiation Oncology, Emory University, Atlanta, Georgia (United States); Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Biostatistics and Bioinformatics Shared Resource, Emory University, Atlanta, Georgia (United States); and others

    2015-03-01

    Purpose: To evaluate nuclear hypoxia-inducible factor 1α (HIF-1α) expression as a prognostic factor for distant recurrence (DR) and local recurrence (LR) after pancreatic adenocarcinoma resection. Methods and Materials: Tissue specimens were collected from 98 patients with pancreatic adenocarcinoma who underwent resection without neoadjuvant therapy between January 2000 and December 2011. Local recurrence was defined as radiographic or pathologic evidence of progressive disease in the pancreas, pancreatic bed, or associated nodal regions. Distant recurrence was defined as radiographically or pathologically confirmed recurrent disease in other sites. Immunohistochemical staining was performed and scored by an independent pathologist blinded to patient outcomes. High HIF-1α overall expression score was defined as high percentage and intensity staining and thus score >1.33. Univariate analysis was performed for HIF-1α score with LR alone and with DR. Multivariate logistic regression was used to determine predictors of LR and DR. Results: Median follow-up time for all patients was 16.3 months. Eight patients (8%) demonstrated isolated LR, 26 patients (26.5%) had isolated DR, and 13 patients had both LR and DR. Fifty-three patients (54%) had high HIF-1α expression, and 45 patients (46%) had low HIF-1α expression. High HIF-1α expression was significantly associated with DR (P=.03), and low HIF-1α expression was significantly associated with isolated LR (P=.03). On multivariate logistic regression analysis, high HIF-1α was the only significant predictor of DR (odds ratio 2.46 [95% confidence interval 1.06-5.72]; P=.03). In patients with a known recurrence, an HIF-1α score ≥2.5 demonstrated a specificity of 100% for DR. Conclusions: High HIF-1α expression is a significant predictor of distant failure versus isolated local failure in patients undergoing resection of pancreatic adenocarcinoma. Expression of HIF-1α may have utility in determining candidates for

  11. A Novel Episcleral Macular Buckling: Wire-Strengthened Sponge Exoplant for Recurrent Macular Hole and Retinal Detachment in High Myopic Eyes

    OpenAIRE

    Mortada, Hassan A.

    2013-01-01

    The purpose would be to describe and evaluate a novel technique of episcleral macular buckling in postvitrectomy recurrent macular hole retinal detachment in highly myopic eyes. A 7mm silicone sponge strengthened with a U-shaped 0.5mm orthodontics stainless steel wire fed along its length and hand-bent to produce L-shaped buckle of appropriate shape and length, is used. The episcleral macular buckling has performed on 15 highly myopic eyes (axial length > 30mm) with recurrent macular hole ret...

  12. Susceptibility to superhelically driven DNA duplex destabilization: a highly conserved property of yeast replication origins.

    Directory of Open Access Journals (Sweden)

    2005-06-01

    Full Text Available Strand separation is obligatory for several DNA functions, including replication. However, local DNA properties such as A+T content or thermodynamic stability alone do not determine the susceptibility to this transition in vivo. Rather, superhelical stresses provide long-range coupling among the transition behaviors of all base pairs within a topologically constrained domain. We have developed methods to analyze superhelically induced duplex destabilization (SIDD in genomic DNA that take into account both this long-range stress-induced coupling and sequence-dependent local thermodynamic stability. Here we apply this approach to examine the SIDD properties of 39 experimentally well-characterized autonomously replicating DNA sequences (ARS elements, which function as replication origins in the yeast Saccharomyces cerevisiae. We find that these ARS elements have a strikingly increased susceptibility to SIDD relative to their surrounding sequences. On average, these ARS elements require 4.78 kcal/mol less free energy to separate than do their immediately surrounding sequences, making them more than 2,000 times easier to open. Statistical analysis shows that the probability of this strong an association between SIDD sites and ARS elements arising by chance is approximately 4 x 10. This local enhancement of the propensity to separate to single strands under superhelical stress has obvious implications for origin function. SIDD properties also could be used, in conjunction with other known origin attributes, to identify putative replication origins in yeast, and possibly in other metazoan genomes.

  13. Fatty acid composition of the anterior cingulate cortex indicates a high susceptibility to lipid peroxidation in Parkinson's disease.

    Science.gov (United States)

    Abbott, Sarah K; Jenner, Andrew M; Spiro, Adena S; Batterham, Marijka; Halliday, Glenda M; Garner, Brett

    2015-01-01

    Oxidative stress contributes to Parkinson's disease (PD) etiology. Although previous studies have focused on sources of free radical formation in brain regions affected by PD, less is known regarding changes in lipid composition and the implications for susceptibility to peroxidation. To assess fatty acid profiles from control and PD tissues that are susceptible to PD pathology but devoid of severe destruction. We used gas chromatography methods to assess fatty acid profiles from control (n = 10) and PD (n = 9) postmortem tissues. We focused on the anterior cingulate cortex (ACC), a region that accumulates alpha-synuclein, but does not undergo severe destruction, and compared this to the occipital cortex, a region that is pathologically spared. Our data indicate a significant 33% increase in the proportion of polyunsaturated fatty acids (mol%) present in the PD ACC as compared to control ACC. Increases in highly unsaturated 22:5n-6 and 22:6n-3 fatty acids were particularly pronounced (109% and 73%, respectively). Calculation of a peroxidation index (accounting for total fatty acyl double bounds) indicated a 44% increase in susceptibility of the PD ACC to lipid peroxidation compared to control ACC. Such differences were not detected in the occipital cortex from the same donors. Assessment of F2-isprostane levels confirmed that PD tissue lipids were more oxidized than controls. The global composition of fatty acids in the PD ACC is altered in a way that increases susceptibility to peroxidation in a region-specific manner. This has important implications for PD, supporting the oxidative stress hypothesis of PD pathogenesis.

  14. Association between recurrence of sporadic colorectal cancer, high level of microsatellite instability, and loss of heterozygosity at chromosome 18q.

    Science.gov (United States)

    Sarli, Leopoldo; Bottarelli, Lorena; Bader, Giovanni; Iusco, Domenico; Pizzi, Silvia; Costi, Renato; D'Adda, Tiziana; Bertolani, Marco; Roncoroni, Luigi; Bordi, Cesare

    2004-09-01

    Microsatellite instability and loss of heterozygosity of chromosomes 18q, 8p, and 4p are genetic alterations commonly found in colorectal cancer. We investigated whether these genetic markers allow for the stratification of patients with Stage II to III colorectal cancer into groups with different recurrence risks, and with different prognoses. Tumors of 113 patients were evaluated for loss of heterozygosity of chromosomes 18q, 8p, and 4p and for microsatellite instability by use of six microsatellite markers. Genetic alterations involving each of these genetic markers were examined for association with disease recurrences and survival. Loss of heterozygosity of chromosomes 18q, informative in 96 percent of cases, in Stage III tumors was associated with higher risk of overall recurrence ( Pcolorectal cancer were independent of loss of heterozygosity of chromosome 18q. Stage III and loss of heterozygosity of chromosome 8p also were associated with a higher risk of recurrences when these factors were considered individually. In multivariate analysis, only loss of heterozygosity of chromosome 18q was independently associated with risk of recurrences ( P microsatellite instability and recurrence rates. However, microsatellite instability was associated with improved overall survival ( P= 0.04) and with a longer disease-free interval ( P= 0.002). Only in five cases (16.7 percent) was it possible to perform resection of recurrences; two of these patients had microsatellite instability tumor. In no cases was it possible to resect recurrence of tumors with loss of heterozygosity of chromosome 18q. Loss of heterozygosity of chromosome 18q is an informative genetic marker, which in resected Stage III colorectal cancer can be used to predict recurrences and survival. Microsatellite instability identified cases that, even in the case of recurrence, have a more favorable prognosis.

  15. High-dose-rate brachytherapy as salvage modality for locally recurrent prostate cancer after definitive radiotherapy. A systematic review

    Energy Technology Data Exchange (ETDEWEB)

    Chatzikonstantinou, Georgios; Zamboglou, Nikolaos; Roedel, Claus; Tselis, Nikolaos [J.W. Goethe University of Frankfurt, Department of Radiotherapy and Oncology, Frankfurt am Main (Germany); Zoga, Eleni [Sana Klinikum Offenbach, Department of Radiotherapy and Oncology, Offenbach am Main (Germany); Strouthos, Iosif [Medical Center - University of Freiburg, Department of Radiotherapy and Oncology, University of Freiburg, Freiburg (Germany); Butt, Saeed Ahmed [Sana Klinikum Offenbach, Department of Medical Physics and Engineering, Offenbach am Main (Germany)

    2017-09-15

    To review the current status of interstitial high-dose-rate brachytherapy as a salvage modality (sHDR BRT) for locally recurrent prostate cancer after definitive radiotherapy (RT). A literature search was performed in PubMed using ''high-dose-rate, brachytherapy, prostate cancer, salvage'' as search terms. In all, 51 search results published between 2000 and 2016 were identified. Data tables were generated and summary descriptions created. The main outcome parameters used were biochemical control (BC) and toxicity scores. Eleven publications reported clinical outcome and toxicity with follow-up ranging from 4-191 months. A variety of dose and fractionation schedules were described, including 19.0 Gy in 2 fractions up to 42.0 Gy in 6 fractions. The 5-year BC ranged from 18-77%. Late grade 3 genitourinary and gastrointestinal toxicity was 0-32% and 0-5.1%, respectively. sHDR BRT appears as safe and effective salvage modality for the reirradiation of locally recurrent prostate cancer after definitive RT. (orig.) [German] Zusammenfassende Darstellung relevanter Literatur zur interstitiellen High-Dose-Rate-Brachytherapie als Salvage-Modalitaet (sHDR-BRT) bei der Behandlung des lokal rezidivierten Prostatakarzinoms nach vorausgegangener definitiver Radiotherapie (RT). In der PubMed-Datenbank wurde eine Literaturrecherche mit den Suchbegriffen ''high-dose-rate, brachytherapy, prostate cancer, salvage'' durchgefuehrt. Zwischen den Jahren 2000 und 2016 wurden 51 Publikationen identifiziert. Die biochemische Kontrolle (BC) sowie das assoziierte Toxizitaetsprofil waren onkologische Hauptpunkte in der Analyse der beruecksichtigten Literatur. Von onkologischen Ergebnissen und Toxizitaeten berichteten 11 Publikationen bei einer medianen Nachbeobachtungszeit von 4-191 Monaten. Eine Variabilitaet von Dosis- und Fraktionierungsregimen wurde beschrieben mit totalen physikalischen Dosen von 19,0 Gy in 2 Fraktionen bis zu 42,0 Gy in 6 Fraktionen

  16. High susceptibility of activated lymphocytes to oxidative stress-induced cell death

    Directory of Open Access Journals (Sweden)

    Giovanna R. Degasperi

    2008-03-01

    Full Text Available The present study provides evidence that activated spleen lymphocytes from Walker 256 tumor bearing rats are more susceptible than controls to tert-butyl hydroperoxide (t-BOOH-induced necrotic cell death in vitro. The iron chelator and antioxidant deferoxamine, the intracellular Ca2+ chelator BAPTA, the L-type Ca2+ channel antagonist nifedipine or the mitochondrial permeability transition inhibitor cyclosporin A, but not the calcineurin inhibitor FK-506, render control and activated lymphocytes equally resistant to the toxic effects of t-BOOH. Incubation of activated lymphocytes in the presence of t-BOOH resulted in a cyclosporin A-sensitive decrease in mitochondrial membrane potential. These results indicate that the higher cytosolic Ca2+ level in activated lymphocytes increases their susceptibility to oxidative stress-induced cell death in a mechanism involving the participation of mitochondrial permeability transition.O presente estudo demonstra que linfócitos ativados de baço de ratos portadores do tumor de Walker 256 são mais susceptíveis à morte celular necrótica induzida por tert-butil hidroperóxido (t-BOOH in vitro quando comparados aos controles. O quelante de ferro e antioxidante deferoxamina, o quelante intracelular de Ca2+ BAPTA, o antagonista de canal de Ca2+ nifedipina ou o inibidor da transição de permeabilidade mitocondrial ciclosporina-A, mas não o inibidor de calcineurina FK-506, inibiram de maneira similar a morte celular induzida por t-BOOH em linfócitos ativados e controles. Os linfócitos ativados apresentaram redução do potencial de membrana mitocondrial induzida por t-BOOH num mecanismo sensível a ciclosporina-A. Nossos resultados indicam que o aumento da concentração de Ca2+ citosólico em linfócitos ativados aumenta a susceptibilidade dos mesmos à morte celular induzida por estresse oxidativo, num mecanismo envolvendo a participação do poro de transição de permeabilidade mitocondrial.

  17. Current status of boron neutron capture therapy of high grade gliomas and recurrent head and neck cancer

    Directory of Open Access Journals (Sweden)

    Barth Rolf F

    2012-08-01

    Full Text Available Abstract Boron neutron capture therapy (BNCT is a biochemically targeted radiotherapy based on the nuclear capture and fission reactions that occur when non-radioactive boron-10, which is a constituent of natural elemental boron, is irradiated with low energy thermal neutrons to yield high linear energy transfer alpha particles and recoiling lithium-7 nuclei. Clinical interest in BNCT has focused primarily on the treatment of high grade gliomas, recurrent cancers of the head and neck region and either primary or metastatic melanoma. Neutron sources for BNCT currently have been limited to specially modified nuclear reactors, which are or until the recent Japanese natural disaster, were available in Japan, United States, Finland and several other European countries, Argentina and Taiwan. Accelerators producing epithermal neutron beams also could be used for BNCT and these are being developed in several countries. It is anticipated that the first Japanese accelerator will be available for therapeutic use in 2013. The major hurdle for the design and synthesis of boron delivery agents has been the requirement for selective tumor targeting to achieve boron concentrations in the range of 20 μg/g. This would be sufficient to deliver therapeutic doses of radiation with minimal normal tissue toxicity. Two boron drugs have been used clinically, a dihydroxyboryl derivative of phenylalanine, referred to as boronophenylalanine or “BPA”, and sodium borocaptate or “BSH” (Na2B12H11SH. In this report we will provide an overview of other boron delivery agents that currently are under evaluation, neutron sources in use or under development for BNCT, clinical dosimetry, treatment planning, and finally a summary of previous and on-going clinical studies for high grade gliomas and recurrent tumors of the head and neck region. Promising results have been obtained with both groups of patients but these outcomes must be more rigorously evaluated in larger

  18. Scenarios Susceptible to Induced Liquefaction Caused by High Magnitude Earthquakes in Santiago de Cuba

    Directory of Open Access Journals (Sweden)

    Liuska Fernández-Diéguez

    2016-05-01

    Full Text Available The objective of this investigation was to define the zoning of soil liquefaction potential for the Guillermón Moncada Popular Council in the municipality of Santiago de Cuba. The engineering and geological conditions and seismic peculiarities favoring a seism to take place were assessed. The safety factor was re-calculated after determining possible maximum intensity values based on seismic magnitudes that can trigger the soil of the investigated area to liquefy. A scheme of the area´s soil susceptibility to liquefaction was obtained. Based on this result, it was concluded that the sectors that are most likely to experience soil liquefaction if an earthquake of magnitudes ranging between 7,75 and 8 occurs are located towards the center-east of the Popular Council with sandy-clayey soils being predominant. This information is very useful for the location and planning of engineering construction works in the area.

  19. Recurrence of anxiety disorders and its predictors

    NARCIS (Netherlands)

    Scholten, Willemijn D.; Batelaan, Neeltje M.; van Balkom, Anton J. L. M.; Penninx, Brenda; Smit, Johannes H.; van Oppen, Patricia

    Background: The chronic course of anxiety disorders and its high burden of disease are partly due to the recurrence of anxiety disorders after remission. However, knowledge about recurrence rates and predictors of recurrence is scarce. This article reports on recurrence rates of anxiety disorders

  20. Recurrent pericarditis.

    Science.gov (United States)

    Imazio, M; Battaglia, A; Gaido, L; Gaita, F

    2017-05-01

    Recurrent pericarditis is the most troublesome complication of pericarditis occurring in 15 to 30% of cases. The pathogenesis is often presumed to be immune-mediated although a specific rheumatologic diagnosis is commonly difficult to find. The clinical diagnosis is based on recurrent pericarditis chest pain and additional objective evidence of disease activity (e.g. pericardial rub, ECG changes, pericardial effusion, elevation of markers of inflammation, and/or imaging evidence of pericardial inflammation by CT or cardiac MR). The mainstay of medical therapy for recurrent pericarditis is aspirin or a non-steroidal anti-inflammatory drug (NSAID) plus colchicine. Second-line therapy is considered after failure of such treatments and it is generally based on low to moderate doses of corticosteroids (e.g. prednisone 0.2 to 0.5 mg/kg/day or equivalent) plus colchicine. More difficult cases are treated with combination of aspirin or NSAID, colchicine and corticosteroids. Refractory cases are managed by alternative medical options, including azathioprine, or intravenous human immunoglobulins or biological agents (e.g. anakinra). When all medical therapies fail, the last option may be surgical by pericardiectomy to be recommended in well-experienced centres. Despite a significant impairment of the quality of life, the most common forms of recurrent pericarditis (usually named as "idiopathic recurrent pericarditis" since without a well-defined etiological diagnosis) have good long-term outcomes with a negligible risk of developing constriction and rarely cardiac tamponade during follow-up. The present article reviews current knowledge on the definition, diagnosis, aetiology, therapy and prognosis of recurrent pericarditis with a focus on the more recent available literature. Copyright © 2016 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  1. Examining Whether Offspring Psychopathology Influences Illness Course in Mothers With Recurrent Depression Using a High-Risk Longitudinal Sample

    Science.gov (United States)

    2016-01-01

    Depression is known to be influenced by psychosocial stressors. For mothers with recurrent depressive illness, the presence of psychopathology in their children may have important effects on their own mental health. Although the impact of maternal depression on child mental health is well-established, no study to date, as far as we are aware, has examined the extent to which offspring psychopathology influences the course of depression in mothers with a history of recurrent depressive illness, what types of child psychopathology impact maternal mental health, or whether risks vary by child gender. Aims were to (a) Use a longitudinal design to examine whether adolescent psychopathology (depression, disruptive behavior disorder; DBD) predicts recurrence of a depressive episode and depression symptom course in women with a history of recurrent depression; and (b) To test if observed effects vary by child gender. 299 mothers with recurrent major depressive disorder and their adolescent offspring were assessed on 2 occasions, 29 months apart. Maternal depression and offspring psychopathology were assessed using semistructured interview measures. Cross-generational links across time were assessed using structural equation modeling. Analyses were adjusted for past severity of maternal depression. Offspring depression symptoms but not DBD symptoms at baseline predicted future episode recurrence in mothers. Depression symptoms in daughters (β = .16, p = .039) but not sons (β = −.07, p = .461), predicted an increase in maternal depression symptoms across time. Psychopathology in daughters is associated with long-term depressive symptoms in women (mothers) with a history of recurrent depression. Findings highlight the importance of careful assessment and management of mental health problems in adolescents for more effective management of maternal depression. This study suggests that offspring symptoms of depression may be important for the recurrence of maternal

  2. Prediction of Low versus High Recurrence Scores in Estrogen Receptor-Positive, Lymph Node-Negative Invasive Breast Cancer on the Basis of Radiologic-Pathologic Features: Comparison with Oncotype DX Test Recurrence Scores.

    Science.gov (United States)

    Dialani, Vandana; Gaur, Shantanu; Mehta, Tejas S; Venkataraman, Shambhavi; Fein-Zachary, Valerie; Phillips, Jordana; Brook, Alexander; Slanetz, Priscilla J

    2016-08-01

    Purpose To review mammographic, ultrasonographic (US), and magnetic resonance (MR) imaging features and pathologic characteristics of estrogen receptor (ER)-positive, lymph node-negative invasive breast cancer and to determine the relationship of these characteristics to Oncotype DX (Genomic Health, Redwood City, Calif) test recurrence scores (ODRS) for breast cancer recurrence. Materials and Methods This institutional review board-approved retrospective study was performed in a single large academic medical center. The study population included patients with ER-positive, lymph node-negative invasive breast cancer who underwent genomic testing from January 1, 2009, to December 31, 2013. Imaging features of the tumor were classified according to the Breast Imaging Reporting and Data System lexicon by breast imagers who were blinded to the ODRS. Mammography was performed in 86% of patients, US was performed in 84%, and MR imaging was performed in 33%, including morphologic and kinetic evaluation. Images from each imaging modality were evaluated. Each imaging finding, progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) status, and tumor grade were then individually correlated with ODRS. Analysis of variance was used to determine differences for each imaging feature. Regression analysis was used to calculate prediction of recurrence on the basis of imaging features combined with histopathologic features. Results The 319 patients had a mean age ± standard deviation of 55 years ± 8.7 (range, 31-82 years). Imaging features with a positive correlation with ODRS included a well-circumscribed oval mass (P = .024) at mammography, vascularity (P = .047) and posterior enhancement (P = .004) at US, and lobulated mass (P = .002) at MR imaging. Recurrence scores were predicted by using these features in combination with PR and HER2 status and tumor grade by using the threshold of more than 30 as a high recurrence score. With a regression tree, there

  3. Establishment and Characterization of GSA-1, a Human Cell Line Highly Susceptible to Apoptosis after Free-fall

    OpenAIRE

    JUN, NOMURA; JYUNI, HIMEDA; Zheng, Chen; Shigeru, SUGAYA; Shunji, TAKAHASHI; Kazuko, KITA; Masaharu, ICHINOSE; Nobuo, Suzuki; Department of Environmental Medicine, Faculty of Education, Chiba University; Plastic and Reconstructive Surgery, Chiba University; Department of Environmental Biochemistry, Graduate School of Medicine, Chiba University

    2002-01-01

    The induction of apoptosis by microgravity and/or gravity-changing stress is considered to be one of the important causes of cell death, although the molecular mechanisms of the apoptotic event remain unclarified. In this study, we established a cell line, GSA-1, from ethyl methanesulfonate-treated human RSa cells. GSA-1 cells were highly susceptible to apoptosis after a free-fall; 24.4% of these cells underwent apoptosis after free-fall, compared with only 6% of the RSa cells. The apoptosis ...

  4. Methylation of PITX2, HOXD3, RASSF1 and TDRD1 predicts biochemical recurrence in high-risk prostate cancer.

    Science.gov (United States)

    Litovkin, Kirill; Joniau, Steven; Lerut, Evelyne; Laenen, Annouschka; Gevaert, Olivier; Spahn, Martin; Kneitz, Burkhard; Isebaert, Sofie; Haustermans, Karin; Beullens, Monique; Van Eynde, Aleyde; Bollen, Mathieu

    2014-11-01

    To explore differential methylation of HAAO, HOXD3, LGALS3, PITX2, RASSF1 and TDRD1 as a molecular tool to predict biochemical recurrence (BCR) in patients with high-risk prostate cancer (PCa). A multiplexed nested methylation-specific PCR was applied to quantify promoter methylation of the selected markers in five cell lines, 42 benign prostatic hyperplasia (BPH) and 71 high-risk PCa tumor samples. Uni- and multivariate Cox regression models were used to assess the importance of the methylation level in predicting BCR. A PCa-specific methylation marker HAAO in combination with HOXD3 and a hypomethylation marker TDRD1 distinguished PCa samples (>90 % of tumor cells each) from BPH with a sensitivity of 0.99 and a specificity of 0.95. High methylation of PITX2, HOXD3 and RASSF1, as well as low methylation of TDRD1, appeared to be significantly associated with a higher risk for BCR (HR 3.96, 3.44, 2.80 and 2.85, correspondingly) after correcting for established risk factors. When DNA methylation was treated as a continuous variable, a two-gene model PITX2 × 0.020677 + HOXD3 × 0.0043132 proved to be the best predictor of BCR (HR 4.85) compared with the individual markers. This finding was confirmed in an independent set of 52 high-risk PCa tumor samples (HR 11.89). Differential promoter methylation of HOXD3, PITX2, RASSF1 and TDRD1 emerges as an independent predictor of BCR in high-risk PCa patients. A two-gene continuous DNA methylation model "PITX2 × 0.020677 + HOXD3 × 0.0043132" is a better predictor of BCR compared with individual markers.

  5. Neuropathogenesis of Zika Virus in a Highly Susceptible Immunocompetent Mouse Model after Antibody Blockade of Type I Interferon.

    Directory of Open Access Journals (Sweden)

    Darci R Smith

    2017-01-01

    Full Text Available Animal models are needed to better understand the pathogenic mechanisms of Zika virus (ZIKV and to evaluate candidate medical countermeasures. Adult mice infected with ZIKV develop a transient viremia, but do not demonstrate signs of morbidity or mortality. Mice deficient in type I or a combination of type I and type II interferon (IFN responses are highly susceptible to ZIKV infection; however, the absence of a competent immune system limits their usefulness for studying medical countermeasures. Here we employ a murine model for ZIKV using wild-type C57BL/6 mice treated with an antibody to disrupt type I IFN signaling to study ZIKV pathogenesis. We observed 40% mortality in antibody treated mice exposed to ZIKV subcutaneously whereas mice exposed by intraperitoneal inoculation were highly susceptible incurring 100% mortality. Mice infected by both exposure routes experienced weight loss, high viremia, and severe neuropathologic changes. The most significant histopathological findings occurred in the central nervous system where lesions represent an acute to subacute encephalitis/encephalomyelitis that is characterized by neuronal death, astrogliosis, microgliosis, scattered necrotic cellular debris, and inflammatory cell infiltrates. This model of ZIKV pathogenesis will be valuable for evaluating medical countermeasures and the pathogenic mechanisms of ZIKV because it allows immune responses to be elicited in immunologically competent mice with IFN I blockade only induced at the time of infection.

  6. Extreme genomic erosion after recurrent demographic bottlenecks in the highly endangered Iberian lynx.

    Science.gov (United States)

    Abascal, Federico; Corvelo, André; Cruz, Fernando; Villanueva-Cañas, José L; Vlasova, Anna; Marcet-Houben, Marina; Martínez-Cruz, Begoña; Cheng, Jade Yu; Prieto, Pablo; Quesada, Víctor; Quilez, Javier; Li, Gang; García, Francisca; Rubio-Camarillo, Miriam; Frias, Leonor; Ribeca, Paolo; Capella-Gutiérrez, Salvador; Rodríguez, José M; Câmara, Francisco; Lowy, Ernesto; Cozzuto, Luca; Erb, Ionas; Tress, Michael L; Rodriguez-Ales, Jose L; Ruiz-Orera, Jorge; Reverter, Ferran; Casas-Marce, Mireia; Soriano, Laura; Arango, Javier R; Derdak, Sophia; Galán, Beatriz; Blanc, Julie; Gut, Marta; Lorente-Galdos, Belen; Andrés-Nieto, Marta; López-Otín, Carlos; Valencia, Alfonso; Gut, Ivo; García, José L; Guigó, Roderic; Murphy, William J; Ruiz-Herrera, Aurora; Marques-Bonet, Tomas; Roma, Guglielmo; Notredame, Cedric; Mailund, Thomas; Albà, M Mar; Gabaldón, Toni; Alioto, Tyler; Godoy, José A

    2016-12-14

    Genomic studies of endangered species provide insights into their evolution and demographic history, reveal patterns of genomic erosion that might limit their viability, and offer tools for their effective conservation. The Iberian lynx (Lynx pardinus) is the most endangered felid and a unique example of a species on the brink of extinction. We generate the first annotated draft of the Iberian lynx genome and carry out genome-based analyses of lynx demography, evolution, and population genetics. We identify a series of severe population bottlenecks in the history of the Iberian lynx that predate its known demographic decline during the 20th century and have greatly impacted its genome evolution. We observe drastically reduced rates of weak-to-strong substitutions associated with GC-biased gene conversion and increased rates of fixation of transposable elements. We also find multiple signatures of genetic erosion in the two remnant Iberian lynx populations, including a high frequency of potentially deleterious variants and substitutions, as well as the lowest genome-wide genetic diversity reported so far in any species. The genomic features observed in the Iberian lynx genome may hamper short- and long-term viability through reduced fitness and adaptive potential. The knowledge and resources developed in this study will boost the research on felid evolution and conservation genomics and will benefit the ongoing conservation and management of this emblematic species.

  7. Efficacy of Blended Cognitive Behavior Therapy for High Fear of Recurrence in Breast, Prostate, and Colorectal Cancer Survivors: The SWORD Study, a Randomized Controlled Trial

    NARCIS (Netherlands)

    Wal, M.A. van de; Thewes, B.; Gielissen, M.; Speckens, A.; Prins, J.B.

    2017-01-01

    Purpose Fear of cancer recurrence (FCR) is a common problem experienced by cancer survivors. Approximately one third of survivors report high FCR. This study aimed to evaluate whether blended cognitive behavior therapy (bCBT) can reduce the severity of FCR in cancer survivors curatively treated for

  8. Intrauterine growth retardation increases the susceptibility of pigs to high-fat diet-induced mitochondrial dysfunction in skeletal muscle.

    Directory of Open Access Journals (Sweden)

    Jingbo Liu

    Full Text Available It has been recognized that there is a relationship between prenatal growth restriction and the development of metabolic-related diseases in later life, a process involved in mitochondrial dysfunction. In addition, intrauterine growth retardation (IUGR increases the susceptibility of offspring to high-fat (HF diet-induced metabolic syndrome. Recent findings suggested that HF feeding decreased mitochondrial oxidative capacity and impaired mitochondrial function in skeletal muscle. Therefore, we hypothesized that the long-term consequences of IUGR on mitochondrial biogenesis and function make the offspring more susceptible to HF diet-induced mitochondrial dysfunction. Normal birth weight (NBW, and IUGR pigs were allotted to control or HF diet in a completely randomized design, individually. After 4 weeks of feeding, growth performance and molecular pathways related to mitochondrial function were determined. The results showed that IUGR decreased growth performance and plasma insulin concentrations. In offspring fed a HF diet, IUGR was associated with enhanced plasma leptin levels, increased concentrations of triglyceride and malondialdehyde (MDA, and reduced glycogen and ATP contents in skeletal muscle. High fat diet-fed IUGR offspring exhibited decreased activities of lactate dehydrogenase (LDH and glucose-6-phosphate dehydrogenase (G6PD. These alterations in metabolic traits of IUGR pigs were accompanied by impaired mitochondrial respiration function, reduced mitochondrial DNA (mtDNA contents, and down-regulated mRNA expression levels of genes responsible for mitochondrial biogenesis and function. In conclusion, our results suggest that IUGR make the offspring more susceptible to HF diet-induced mitochondrial dysfunction.

  9. [Cloxacillin-susceptible Staphylococcus aureus with high MIC to glycopeptides. Ever we use cloxacillin?].

    Science.gov (United States)

    Morales-Cartagena, Alejandra; Lalueza, Antonio; San Juan, Rafael; Aguado, José María

    2015-09-01

    Staphylococcus aureus infections are yet an important cause of morbidity and mortality despite of numerous effective anti-staphylococcal antibiotics available. There has been an increasing incidence of methicillin-resistant strains which might have led to a wider use of vancomycin. This seems to ride alongside a covert progressive increase of S. aureus vancomycin minimum inhibitory concentration. In this way, the emergence of vancomycin-intermediate S. aureus (VISA) strains and heteroresistant-VISA has raised concern for the scarcity of alternative treatment options. Equally alarming, though fortunately less frequent, is the emergence of vancomycin-resistant S. aureus. Ultimately, various debate issues have arisen regarding the emergence of S. aureus strains with decreased vancomycin susceptibility, within the range still considered sensitive. These strains have shown a different clinical behaviour regardless of vancomycin use, both in methicillin resistant and sensitive S. aureus. The emergence of increasing vancomycin-resistance in S. aureus isolates, has stirred up the basis of therapeutic approach in staphylococcal infections. There is yet much to explore to better define the impact of higher vancomycin minimum inhibitory concentration in staphylococcal infections.

  10. Ethical issues of genetic susceptibility testing for occupational diseases: opinions of trainees in a high-risk job

    NARCIS (Netherlands)

    Visser, M. J.; Rhebergen, M. D. F.; Kezic, S.; van Dijk, F. J. H.; Willems, D. L.; Verberk, M. M.

    2013-01-01

    Genetic research has opened up possibilities for identification of persons with an increased susceptibility for occupational disease. However, regulations considering the ethical issues that are inevitably associated with the use of genetic tests for susceptibility for occupational diseases are

  11. Magnetic Resonance–Guided High-Intensity Focused Ultrasound Hyperthermia for Recurrent Rectal Cancer: MR Thermometry Evaluation and Preclinical Validation

    Energy Technology Data Exchange (ETDEWEB)

    Chu, William, E-mail: William.Chu@sunnybrook.ca [Department of Radiation Oncology, Sunnybrook Health Sciences Centre and the University of Toronto, Toronto, Ontario (Canada); Physical Sciences, Sunnybrook Research Institute, Toronto, Ontario (Canada); Staruch, Robert M. [Clinical Sites Research Program, Philips Research, Cambridge, Massachusetts (United States); Pichardo, Samuel [Thunder Bay Regional Research Institute, Thunder Bay, Ontario (Canada); Physics and Electrical Engineering, Lakehead University, Thunder Bay, Ontario (Canada); Tillander, Matti; Köhler, Max O. [MR Therapy, Philips Healthcare, Vantaa (Finland); Huang, Yuexi [Physical Sciences, Sunnybrook Research Institute, Toronto, Ontario (Canada); Ylihautala, Mika [MR Therapy, Philips Healthcare, Vantaa (Finland); McGuffin, Merrylee [Department of Radiation Oncology, Sunnybrook Health Sciences Centre and the University of Toronto, Toronto, Ontario (Canada); Czarnota, Gregory [Department of Radiation Oncology, Sunnybrook Health Sciences Centre and the University of Toronto, Toronto, Ontario (Canada); Physical Sciences, Sunnybrook Research Institute, Toronto, Ontario (Canada); Hynynen, Kullervo [Physical Sciences, Sunnybrook Research Institute, Toronto, Ontario (Canada)

    2016-07-15

    Purpose: To evaluate the feasibility of magnetic resonance–guided high-intensity focused ultrasound (MR-HIFU) mild hyperthermia in deep tissue targets for enhancing radiation therapy and chemotherapy in the context of recurrent rectal cancer. A preclinical study was performed to evaluate the safety and performance of MR-HIFU mild hyperthermia. A prospective imaging study was performed in volunteers with rectal cancer to evaluate MR thermometry quality near the rectum and accessibility of rectal tumors using MR-HIFU. Methods and Materials: Mild hyperthermia was performed in pig thigh (9 sonications, 6 pigs) using a clinical MR-HIFU system. Targets near the rectal wall and deep thigh were evaluated. Thermal maps obtained in 6 planes every 3.2 seconds were used to control sonications in 18-mm diameter treatment regions at temperatures of 42°C to 42.5°C for 10 to 60 minutes. Volunteer imaging-only studies to assess the quality of MR thermometry (without heating) were approved by the institutional research ethics board. Anatomic and MR thermometry images were acquired in consenting volunteers with rectal cancer. In 3 of 6 study participants, rectal filling with saline was used to reduce motion-related MR thermometry artifacts near the tumor. Results: In pigs, mean target temperature matched the desired hyperthermia temperature within 0.2°C; temporal standard deviation ≤0.5°C. With optimized control thresholds, no undesired tissue damage was observed. In human volunteers, MR temperature measurements had adequate precision and stability, especially when rectal filling was used to reduce bowel motion. Conclusions: In pigs, MR-HIFU can safely deliver mild hyperthermia (41°C-43°C) to a targeted volume for 30 minutes. In humans, careful patient selection and preparation will enable adequate targeting for recurrent rectal cancers and sufficient MR temperature mapping stability to control mild hyperthermia. These results enable human trials of MR-HIFU hyperthermia.

  12. Nutrigenomics of high fat diet induced obesity in mice suggests relationships between susceptibility to fatty liver disease and the proteasome.

    Directory of Open Access Journals (Sweden)

    Helen Waller-Evans

    Full Text Available Nutritional factors play important roles in the etiology of obesity, type 2 diabetes mellitus and their complications through genotype x environment interactions. We have characterised molecular adaptation to high fat diet (HFD feeding in inbred mouse strains widely used in genetic and physiological studies. We carried out physiological tests, plasma lipid assays, obesity measures, liver histology, hepatic lipid measurements and liver genome-wide gene transcription profiling in C57BL/6J and BALB/c mice fed either a control or a high fat diet. The two strains showed marked susceptibility (C57BL/6J and relative resistance (BALB/c to HFD-induced insulin resistance and non alcoholic fatty liver disease (NAFLD. Global gene set enrichment analysis (GSEA of transcriptome data identified consistent patterns of expression of key genes (Srebf1, Stard4, Pnpla2, Ccnd1 and molecular pathways in the two strains, which may underlie homeostatic adaptations to dietary fat. Differential regulation of pathways, including the proteasome, the ubiquitin mediated proteolysis and PPAR signalling in fat fed C57BL/6J and BALB/c suggests that altered expression of underlying diet-responsive genes may be involved in contrasting nutrigenomic predisposition and resistance to insulin resistance and NAFLD in these models. Collectively, these data, which further demonstrate the impact of gene x environment interactions on gene expression regulations, contribute to improved knowledge of natural and pathogenic adaptive genomic regulations and molecular mechanisms associated with genetically determined susceptibility and resistance to metabolic diseases.

  13. A highly selective and ratiometric fluorescent probe for cyanide by rationally altering the susceptible H-atom.

    Science.gov (United States)

    Hao, Yuanqiang; Nguyen, Khac Hong; Zhang, Yintang; Zhang, Guan; Fan, Shengnan; Li, Fen; Guo, Chao; Lu, Yuanyuan; Song, Xiaoqing; Qu, Peng; Liu, You-Nian; Xu, Maotian

    2018-01-01

    A highly selective and ratiometric fluorescent probe for cyanide was rationally designed and synthesized. The probe comprises a fluorophore unit of naphthalimide and a CN- acceptor of methylated trifluoroacetamide group. For these previous reported trifluoroacetamide derivative-based cyanide chemosensors, the H-atom of amide adjacent to trifluoroacetyl group is susceptible to be attacked by various anions (CN- itself, F-, AcO-, et al.) and even the solvent molecule, which resulted in the bewildered reaction mechanism and poor selectivity of the assay. In this work, the susceptible H-atom of trifluoroacetamide was artfully substituted by alkyl group. Thus a highly specific fluorescent probe was developed for cyanide sensing. Upon the nucleophilic addition of cyanide anion to the carbonyl of trifluoroacetamide moiety of the probe, the ICT process of the probe was significantly enhanced and leading to a remarkable red shift in both absorption and emission spectra of the probe. This fluorescent assay showed a linear range of 1.0-80.0µM and a LOD (limit of detection) of 0.23µM. All the investigated interference have no influence on the sensing behavior of the probe toward cyanide. Moreover, by coating on TLC plate, the probe can be utilized for practical detection of trace cyanide in water samples. Copyright © 2017. Published by Elsevier B.V.

  14. Nutrigenomics of high fat diet induced obesity in mice suggests relationships between susceptibility to fatty liver disease and the proteasome.

    Science.gov (United States)

    Waller-Evans, Helen; Hue, Christophe; Fearnside, Jane; Rothwell, Alice R; Lockstone, Helen E; Caldérari, Sophie; Wilder, Steven P; Cazier, Jean-Baptiste; Scott, James; Gauguier, Dominique

    2013-01-01

    Nutritional factors play important roles in the etiology of obesity, type 2 diabetes mellitus and their complications through genotype x environment interactions. We have characterised molecular adaptation to high fat diet (HFD) feeding in inbred mouse strains widely used in genetic and physiological studies. We carried out physiological tests, plasma lipid assays, obesity measures, liver histology, hepatic lipid measurements and liver genome-wide gene transcription profiling in C57BL/6J and BALB/c mice fed either a control or a high fat diet. The two strains showed marked susceptibility (C57BL/6J) and relative resistance (BALB/c) to HFD-induced insulin resistance and non alcoholic fatty liver disease (NAFLD). Global gene set enrichment analysis (GSEA) of transcriptome data identified consistent patterns of expression of key genes (Srebf1, Stard4, Pnpla2, Ccnd1) and molecular pathways in the two strains, which may underlie homeostatic adaptations to dietary fat. Differential regulation of pathways, including the proteasome, the ubiquitin mediated proteolysis and PPAR signalling in fat fed C57BL/6J and BALB/c suggests that altered expression of underlying diet-responsive genes may be involved in contrasting nutrigenomic predisposition and resistance to insulin resistance and NAFLD in these models. Collectively, these data, which further demonstrate the impact of gene x environment interactions on gene expression regulations, contribute to improved knowledge of natural and pathogenic adaptive genomic regulations and molecular mechanisms associated with genetically determined susceptibility and resistance to metabolic diseases.

  15. High susceptibility and low resistance allele frequency of Chrysodeixis includens (Lepidoptera: Noctuidae) field populations to Cry1Ac in Brazil.

    Science.gov (United States)

    Yano, Silvia Ac; Specht, Alexandre; Moscardi, Flávio; Carvalho, Renato A; Dourado, Patrick M; Martinelli, Samuel; Head, Graham P; Sosa-Gómez, Daniel R

    2016-08-01

    The soybean looper (SBL), Chrysodeixis includens (Walker), is one of the most important soybean pests in Brazil. MON 87701 × MON 89788 soybean expressing Cry1Ac has been recently deployed in Brazil, providing high levels of control against the primary lepidopteran pests. To support insect resistance management (IRM) programmes, the baseline susceptibility of SBL to Cry1Ac was assessed, and the resistance allele frequency was estimated on the basis of an F2 screen. The toxicity (LC50 ) of Cry1Ac ranged from 0.39 to 2.01 µg mL(-1) diet among all SBL field populations collected from crop seasons 2008/09 to 2012/13, which indicated approximately fivefold variation. Cry1Ac diagnostic concentrations of 5.6 and 18 µg mL(-1) diet were established for monitoring purposes, and no shift in mortality was observed. A total of 626 F2 family lines derived from SBL collected from locations across Brazil during crop season 2014/15 were screened for the presence of Cry1Ac resistance alleles. None of the 626 families survived on MON 87701 × MON 89788 soybean leaf tissue (joint frequency 0.0004). SBL showed high susceptibility and low resistance allele frequency to Cry1Ac across the main soybean-producing regions in Brazil. These findings meet important criteria for effective IRM strategy. © 2015 Society of Chemical Industry. © 2015 Society of Chemical Industry.

  16. High RBM3 expression in prostate cancer independently predicts a reduced risk of biochemical recurrence and disease progression

    Directory of Open Access Journals (Sweden)

    Bjartell Anders

    2011-09-01

    Full Text Available Abstract Background High expression of the RNA-binding protein RBM3 has previously been found to be associated with good prognosis in breast cancer, ovarian cancer, malignant melanoma and colorectal cancer. The aim of this study was to examine the prognostic impact of immunohistochemical RBM3 expression in prostate cancer. Findings Immunohistochemical RBM3 expression was examined in a tissue microarray with malignant and benign prostatic specimens from 88 patients treated with radical prostatectomy for localized disease. While rarely expressed in benign prostate gland epithelium, RBM3 was found to be up-regulated in prostate intraepithelial neoplasia and present in various fractions and intensities in invasive prostate cancer. High nuclear RBM3 expression was significantly associated with a prolonged time to biochemical recurrence (BCR (HR 0.56, 95% CI: 0.34-0.93, p = 0.024 and clinical progression (HR 0.09, 95% CI: 0.01-0.71, p = 0.021. These associations remained significant in multivariate analysis, adjusted for preoperative PSA level in blood, pathological Gleason score and presence or absence of extracapsular extension, seminal vesicle invasion and positive surgical margin (HR 0.41, 95% CI: 0.19-0.89, p = 0.024 for BCR and HR 0.06, 95% CI: 0.01-0.50, p = 0.009 for clinical progression. Conclusion Our results demonstrate that high nuclear expression of RBM3 in prostate cancer is associated with a prolonged time to disease progression and, thus, a potential biomarker of favourable prognosis. The value of RBM3 for prognostication, treatment stratification and follow-up of prostate cancer patients should be further validated in larger studies.

  17. Treatment of recurrent complicated urinary tract infections in children with vesicoureteral reflux.

    Science.gov (United States)

    Wu, Tsung-Hua; Huang, Fang-Liang; Fu, Lin-Shien; Chou, Chia-Man; Chien, Ya-Li; Huang, Chung-Ming; Lin, Chin-Fu; Chen, Po-Yen

    2016-10-01

    Urinary tract infections (UTIs) in children with vesicoureteral reflux (VUR) are often caused by uropathogens with a high rate of drug resistance and are associated with a high rate of recurrence with a single pathogen. In this study, we evaluated the incidence of recurrent UTI and the drug resistance pattern of Escherichia coli in children with VUR. We also evaluated whether combination therapy comprising fosomycin plus one other antimicrobial agent is effective for treatment of recurrent UTIs. We retrospectively reviewed the medical records of all children with VUR who developed at least one episode of UTI during the period January 1, 2003 to December 31, 2013 at a single medical center. The effectiveness of fosfomycin plus amikicin for Enterobacteriaceae or ceftazidime for Pseudomonas aeruginosa infections was prospectively studied in six children with recurrent relapsing UTIs. The study population comprised 129 children (age range, from 1month to 15 years; mean ± standard deviation, 2.37 ± 2.91 years) with VUR who developed at least one UTI during the 10-year study period; 68 (52.7%) had recurrent UTIs. The presence of an underlying urinary tract anomaly was predictive of recurrence (p = 0.028). The rates of susceptibility of E. coli to cefazolin (p < 0.001) and cefotaxime (p < 0.001) were significantly lower in patients with recurrent UTIs. Combination therapy with fosfomycin plus amikacin or ceftazidime was shown to be an effective therapeutic option for recurrent UTIs due to a single uropathogen. The rates of susceptibility of E. coli to commonly used antimicrobials were significantly lower in children who developed more than one episode of UTI. The empiric choice of cefazolin or cefotaxime was usually ineffective. Administration of fosfomycin plus amikacin or ceftazidime was an effective therapeutic and preventive strategy in children with VUR and recurrent relapsing UTI. Copyright © 2014. Published by Elsevier B.V.

  18. Individual variation in contagious yawning susceptibility is highly stable and largely unexplained by empathy or other known factors.

    Directory of Open Access Journals (Sweden)

    Alex J Bartholomew

    Full Text Available The contagious aspect of yawning is a well-known phenomenon that exhibits variation in the human population. Despite the observed variation, few studies have addressed its intra-individual reliability or the factors modulating differences in the susceptibility of healthy volunteers. Due to its obvious biological basis and impairment in diseases like autism and schizophrenia, a better understanding of this trait could lead to novel insights into these conditions and the general biological functioning of humans. We administered 328 participants a 3-minute yawning video stimulus, a cognitive battery, and a comprehensive questionnaire that included measures of empathy, emotional contagion, circadian energy rhythms, and sleepiness. Individual contagious yawning measurements were found to be highly stable across testing sessions, both in a lab setting and if administered remotely online, confirming that certain healthy individuals are less susceptible to contagious yawns than are others. Additionally, most individuals who failed to contagiously yawn in our study were not simply suppressing their reaction, as they reported not even feeling like yawning in response to the stimulus. In contrast to previous studies indicating that empathy, time of day, or intelligence may influence contagious yawning susceptibility, we found no influence of these variables once accounting for the age of the participant. Participants were less likely to show contagious yawning as their age increased, even when restricting to ages of less than 40 years. However, age was only able to explain 8% of the variability in the contagious yawn response. The vast majority of the variability in this extremely stable trait remained unexplained, suggesting that studies of its inheritance are warranted.

  19. Sorafenib or sunitinib as postoperative adjuvant therapy for Chinese patients with locally advanced clear cell renal cell carcinoma at high risk for disease recurrence.

    Science.gov (United States)

    Zhao, Juping; Zhu, Yu; Zhang, Chongyu; Wang, Xiaojing; He, Hongchao; Wang, Haofei; Wu, Yuxuan; Zhou, Wenlong; Shen, Zhoujun

    2013-11-01

    To evaluate the efficacy and safety of targeted agents (sorafenib and sunitinib) as postoperative adjuvant therapy in Chinese patients with clear cell renal cell carcinoma (CC-RCC) who are at high risk for disease recurrence. Forty-three patients treated at our center between December 2007 and December 2010 with locally advanced CC-RCC who were at a high risk for disease recurrence were enrolled into the study. The criteria for high risk of CC-RCC recurrence postoperatively were defined according to the Mayo Clinic stage, size, grade, and necrosis (SSIGN) score for CC-RCC. After radical nephrectomy, patients received either sorafenib (group A, n = 20) or sunitinib (group B, n = 23) and were followed up for at least 1 year to determine the efficacy and safety of the test products. The duration of maintenance targeted medication treatment was approximately 1 year. Group C consisted of 388 CC-RCC patients treated at our center between 1992 and 2007, who were at high risk for disease recurrence and who received no adjuvant therapy. The demography characteristics were similar among the 3 groups. The overall rate of recurrence in groups A and B was not different (15.0% and 17.4% (P > 0.05), respectively), which was lower than that of group C (38.7%, P Disease-free survival (DFS) was longer in groups A and B (18.9 ± 5.9 months and 16.9 ± 6.1 months [P > 0.05], respectively), compared with group C (13.3 ± 7.2 months, P therapy included hand-foot syndrome, fatigue, diarrhea, taste disturbance, rash, hypertension, alopecia, stomatitis, neutropenia, nausea, pruritus, hypothyroidism in groups A and B. The adverse effects were mild in both groups and the incidence was not significantly different between groups A and B. Targeted adjuvant therapy postoperatively with sorafenib or sunitinib in patients with CC-RCC who are at a high risk for disease recurrence was well tolerated and effective in reducing the rate of CC-RCC recurrence in these patients. This study is an attempt

  20. Lexical decisions in adults with low and high susceptibility to pattern-related visual stress: a preliminary investigation.

    Directory of Open Access Journals (Sweden)

    James M Gilchrist

    2015-04-01

    Full Text Available Pattern-related visual stress (PRVS is a form of sensory hypersensitivity that some people experience when viewing high contrast repeating patterns, notably alternating dark and light stripes. Those susceptible to PRVS typically have a strong aversion to such stimuli, and this is often accompanied by experiences of visual discomfort and disturbance. The patterns most likely to elicit symptoms of PRVS have a square-wave grating configuration of spatial frequency ~ 3 cycles/degree. Such stimuli are characteristic of printed text in which lines of words and the spaces between them present a high contrast grating-like stimulus. Consequently, much printed reading material has the potential to elicit PRVS that may impair reading performance, and this problem is now thought to be common in individuals with reading difficulties including dyslexia. However, the manner in which PRVS affects reading ability is unknown. One possibility is that the early sensory visual stress may interfere with the later cognitive word recognition stage of the reading process, resulting in reading performance that is slower and/or less accurate.To explore the association of PRVS with word recognition ability, lexical decision performance (speed and accuracy to words and pronounceable non-words was measured in two groups of adults, having low and high susceptibility to PRVS. Results showed that lexical decisions were generally faster but less accurate in high-PRVS, and also that high-PRVS participants made decisions significantly faster for words than for non-words, revealing a strong lexicality effect that was not present in low-PRVS. These findings are novel and, as yet, unconfirmed by other studies. We consider possible interpretation in terms of cortical activity and perceptual mechanisms.

  1. Screening for local and regional cancer recurrence in patients curatively treated for laryngeal cancer: definition of a high-risk group and estimation of the lead time.

    Science.gov (United States)

    Ritoe, Savitri C; Verbeek, André L M; Krabbe, Paul F M; Kaanders, Johannes H A M; van den Hoogen, Frank J A; Marres, Henri A M

    2007-05-01

    All patients treated for laryngeal cancer are offered the same follow-up schedule to detect asymptomatic locoregional recurrences. In this study, we evaluated the prognostic profile of patients for cancer recurrence and estimated the lead time. A cohort study was performed between 1990 and 1995. Cox proportional hazards model was used to analyze the prognostic factors. The effect of altering the follow-up for asymptomatic recurrence detection was determined after estimating the lead time. The variables cT classification, smoking, and histologic grade proved to be prognostic factors. The risk of locoregional failure was 15% in the low-risk group versus 29% in the high-risk group. The estimated lead time was 2 to 4 weeks. Risk profiles for locoregional relapse were defined. Intensifying the follow-up schedule is not advisable because the lead time is very short. An excessively high number of routine visits would have to be performed to increase the detection rate for asymptomatic recurrences. (c) 2006 Wiley Periodicals, Inc.

  2. Effects of attachment-based interventions on maternal sensitivity and infant attachment: differential susceptibility of highly reactive infants.

    Science.gov (United States)

    Velderman, Mariska Klein; Bakermans-Kranenburg, Marian J; Juffer, Femmie; van IJzendoorn, Marinus H

    2006-06-01

    The current intervention study aimed at breaking the potential intergenerational cycle of insecure attachment. The authors randomly assigned 81 first-time mothers to one of two intervention groups or a control group. The interventions involved four home visits when the infants were between 7 and 10 months old. The first intervention, VIPP, consisted of video-feedback and brochures to enhance sensitive parenting. The second intervention, VIPP-R, involved additional discussions of mothers' childhood attachment experiences in relation to their current caregiving. After the intervention, intervention mothers were more sensitive than control mothers. The interventions were most effective for highly reactive children and their mothers, providing experimental support for Belsky's (1997) hypothesis of highly reactive versus less reactive children's evolutionary based differential susceptibility to rearing influences. ((c) 2006 APA, all rights reserved).

  3. Recurrent Stroke

    DEFF Research Database (Denmark)

    Andersen, Søren Due; Gorst-Rasmussen, Anders; Lip, Gregory Y H

    2015-01-01

    Background and Purpose—The CHA2DS2VASc score and the Essen Stroke Risk Score are respectively used for risk stratification in patients with atrial fibrillation and in patients with cerebrovascular incidents. We aimed to test the ability of the 2 scores to predict stroke recurrence, death......, and cardiovascular events (stroke, transient ischemic attack, myocardial infarction, or arterial thromboembolism) in a nationwide Danish cohort study, among patients with incident ischemic stroke and no atrial fibrillation. Methods—We conducted a registry-based study in patients with incident ischemic stroke...... and no atrial fibrillation. Patients were stratified according to the CHA2DS2VASc score and the Essen Stroke Risk Score and were followed up until stroke recurrence or death. We estimated stratified incidence rates and hazard ratios and calculated the cumulative risks. Results—42 182 patients with incident...

  4. Comparison of antibiotic susceptibility in viridans group streptococci in low and high antibiotic-prescribing General Practices.

    Science.gov (United States)

    Goldsmith, C E; Hara, Y; Sato, T; Nakajima, T; Nakanishi, S; Mason, C; Moore, J E; Matsuda, M; Coulter, W A

    2015-04-01

    Antibiotic resistance has become a global public health issue. Most antibiotics are prescribed in the community, although there is less stewardship of such agents in the community compared to secondary and tertiary care. Few studies have attempted to examine the prescribing practices in General Practice and its impact on antibiotic resistance and, therefore, a study was performed in order to compare antibiotic susceptibilities of commensal viridans group streptococci (VGS) obtained from patient cohorts in General Practices (GP), who were high and low prescribers of oral antibiotics. Sixty-five patients (antibiotic susceptibility against (i) tetracyclines (doxycycline); (ii) macrolides (erythromycin); (iii) β-lactams (penicillin G); and (iv) fluoroquinolones (ofloxacin & levofloxacin). There were no significant differences in MICs between high and low GP prescribers with doxycycline (P = 0·094), erythromycin (P = 0·122), ofloxacin (P = 0·193) and levofloxacin (P = 0·058). However, there was a significant difference between high and low GP practices with regard to penicillin G (P = 0·031). This finding is important as the β-lactams are the most commonly prescribed oral antibiotic in the community. This study demonstrates that high prescribing practices may lead to an altered (higher) level of resistance to these agents in the commensal VGS population, which may be important as reservoirs of antibiotic resistance determinants in subsequent horizontal gene transfer events, particularly with newly colonizing pathogens, including pneumococci. Primary care physicians should be aware that increased prescribing of antibiotics may led to increased level of penicillin resistance. © 2015 John Wiley & Sons Ltd.

  5. Task 2 - Limits for High-Frequency Conducted Susceptibility Testing - CS114 (NRC-HQ-60-14-D-0015)

    Energy Technology Data Exchange (ETDEWEB)

    Wood, Richard Thomas [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Ewing, Paul D. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Moses, Rebecca J. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2015-09-01

    A principal focus of Task 2 under this project was for ORNL to evaluate the basis for susceptibility testing against high-frequency conducted interference and to establish recommendations to resolve concerns about the severity of test limits for the conducted susceptibility (CS) test, CS114, from MIL-STD-461. The primary concern about the test limit has been characterized by the EPRI EMI Working Group in the following terms: Demonstrating compliance with the CS114 test limits recommended in TR-102323 has proven to be problematic, even for components that have been tested to commercial standards and demonstrated proper operation in industrial applications [6]. Specifically, EPRI notes that the CS114 limits approved in regulatory documents are significantly higher than those invoked by the US military and similar commercial standards in the frequency range below 200 kHz. For this task, ORNL evaluated the original approach to establishing the test limit, EPRI technical findings from a review of the limit, and the regulatory basis through which the currently approved limits were accepted. Based on this analysis, strategies have been developed regarding changes to the CS114 limit that can resolve the technical concerns raised by the industry. Guided by the principles that reasonable assurance of safety must not be compromised but excessive conservatism should be reduced, recommendations on a suitable basis for a revised limit have been developed and can be incorporated into the planned Revision 2 of RG 1.180.

  6. Establishment of a cell line with high transfection efficiency from zebrafish Danio rerio embryos and its susceptibility to fish viruses.

    Science.gov (United States)

    Jin, Y L; Chen, L M; Le, Y; Li, Y L; Hong, Y H; Jia, K T; Yi, M S

    2017-10-01

    A cell line ZBE3 isolated from a continuous cell culture derived from zebrafish Danio rerio blastomeres by clonal growth was characterized. ZBE3 cells had been subcultured for >120 passages since the initial primary culture of the blastomeres. The ZBE3 cells grow stably at temperature from 20 to 32° C with an optimum temperature of 28° C in ESM2 or ESM4 medium with 15% foetal bovine serum (FBS). The optimum FBS concentration for ZBE3 cell growth ranged from 15 to 20%. Cytogenetical analysis indicated that the modal chromosome number of ZBE3 cells was 50, the same as the diploid chromosome number of D. rerio. Significant cytopathic effect was observed in ZBE3 cells after infection with redspotted grouper nervous necrosis virus, Singapore grouper iridovirus and grass carp reovirus, and the viral replication in the cells was confirmed by real-time quantitative PCR and transmission electron microscopy, indicating the susceptibility of ZBE3 cells to the three fish viruses. After transfected with pEGFP-N3 plasmid, ZBE3 cells showed a transfection efficiency of about 40% which was indicated by the percentage of cells expressing green fluorescence protein. The stable growth, susceptibility to fish viruses as well as high transfection efficiency make ZBE3 cells be a useful tool in transgenic manipulation, fish virus-host cell interaction and immune response in fish. © 2017 The Fisheries Society of the British Isles.

  7. {sup 18}F-FDG PET/CT-Negative Recurrent High-Grade Anaplastic Astrocytoma Detected by {sup 18}F-FDOPA PET-CT

    Energy Technology Data Exchange (ETDEWEB)

    Karunanithi, Sellam; Singh, Harmandeep; Sharma, Punit; Gupta, Deepak Kumar; Bal, Chandrasekhar [All India Institute of Medical Sciences, New Delhi (India)

    2013-12-15

    A 37-year-old woman with grade 3 anaplastic astrocytoma (AA) of the left frontal lobe, underwent surgical excision, chemotherapy and external beam radiation therapy in 2004. After being in remission for 5 years, recurrence was suspected clinically when she presented with seizures. The result of contrast-enhanced magnetic resonance imaging (MRI) was equivocal for recurrence and radiation necrosis (not available ). The patient was then referred for {sup 18}F-fluorodeoxyglucose ({sup 18}F-FDG) positron emission tomography-computed tomography (PET-CT), as the initial primary tumour was high grade in nature. {sup 18}F-FDG PET-CT was negative for recurrence and demonstrated only post-operative changes in the left frontal region (Fig. 1a, b, arrow). Due to strong clinical suspicion, 3,4-dihydroxy-6-{sup 18}F-fluoro-L-phenylalanine ({sup 18}F-FDOPA) PET-CT was done, 5 days after {sup 18}F-FDG PET-CT. The study revealed an {sup 18}F-FDOPA-avid mass lesion in the left frontal region (Fig. 1c, d, arrow), thereby confirming the presence of recurrent disease. The patient underwent surgical resection of the mass, and it was confirmed by histopathology as grade 3 AA. However, after a short asymptomatic period of 4 months the patient became symptomatic again. Follow-up MRI after 6 months of surgery revealed presence of ipsilateral and contralateral multifocal contrast enhancing recurrent mass lesions (Fig. 1e, f, arrow), suggesting the progression of disease. The patient was started on temozolamide but she died after 8 months' follow-up. Though MRI is routinely used in assessment of brain tumours, its ability to differentiate between treatment-induced changes and residual or recurrent tumour is limited. {sup 18}F-FDG PET was the first tracer used for assessment of brain tumours; however, it has a low tumour-to-background ratio in brain, limiting its utility. {sup 18}F-FDG uptake correlates with tumour grade, with high-grade gliomas (grades III and IV) showing higher uptake

  8. Endometrial stromal cells of women with recurrent miscarriage fail to discriminate between high- and low-quality human embryos.

    Directory of Open Access Journals (Sweden)

    Charlotte H E Weimar

    Full Text Available BACKGROUND: The aetiology of recurrent miscarriage (RM remains largely unexplained. Women with RM have a shorter time to pregnancy interval than normally fertile women, which may be due to more frequent implantation of non-viable embryos. We hypothesized that human endometrial stromal cells (H-EnSCs of women with RM discriminate less effectively between high-and low-quality human embryos and migrate more readily towards trophoblast spheroids than H-EnSCs of normally fertile women. METHODOLOGY/PRINCIPAL FINDINGS: Monolayers of decidualized H-EnSCs were generated from endometrial biopsies of 6 women with RM and 6 fertile controls. Cell-free migration zones were created and the effect of the presence of a high-quality (day 5 blastocyst, n = 13, a low-quality (day 5 blastocyst with three pronuclei or underdeveloped embryo, n = 12 or AC-1M88 trophoblast cell line spheroid on H-ESC migratory activity was analyzed after 18 hours. In the absence of a spheroid or embryo, migration of H-EnSCs from fertile or RM women was similar. In the presence of a low-quality embryo in the zone, the migration of H-EnSCs of control women was inhibited compared to the basal migration in the absence of an embryo (P<0.05 and compared to the migration in the presence of high-quality embryo (p<0.01. Interestingly, the migratory response H-EnSCs of women with RM did not differ between high- and low-quality embryos. Furthermore, in the presence of a spheroid their migration was enhanced compared to the H-EnSCs of controls (p<0.001. CONCLUSIONS: H-EnSCs of fertile women discriminate between high- and low-quality embryos whereas H-EnSCs of women with RM fail to do so. H-EnSCs of RM women have a higher migratory response to trophoblast spheroids. Future studies will focus on the mechanisms by which low-quality embryos inhibit the migration of H-EnSCs and how this is deregulated in women with RM.

  9. Increased susceptibility of post-weaning rats on high-fat diet to metabolic syndrome.

    Science.gov (United States)

    Cheng, Hong Sheng; Ton, So Ha; Phang, Sonia Chew Wen; Tan, Joash Ban Lee; Abdul Kadir, Khalid

    2017-11-01

    The present study aimed to examine the effects of the types of high-calorie diets (high-fat and high-fat-high-sucrose diets) and two different developmental stages (post-weaning and young adult) on the induction of metabolic syndrome. Male, post-weaning and adult (3- and 8-week old, respectively) Sprague Dawley rats were given control, high-fat (60% kcal), and high-fat-high-sucrose (60% kcal fat + 30% sucrose water) diets for eight weeks (n = 6 to 7 per group). Physical, biochemical, and transcriptional changes as well as liver histology were noted. Post-weaning rats had higher weight gain, abdominal fat mass, fasting glucose, high density lipoprotein cholesterol, faster hypertension onset, but lower circulating advanced glycation end products compared to adult rats. This is accompanied by upregulation of peroxisome proliferator-activated receptor (PPAR) α and γ in the liver and receptor for advanced glycation end products (RAGE) in the visceral adipose tissue. Post-weaning rats on high-fat diet manifested all phenotypes of metabolic syndrome and increased hepatic steatosis, which are linked to increased hepatic and adipocyte PPARγ expression. Adult rats on high-fat-high-sucrose diet merely became obese and hypertensive within the same treatment duration. Thus, it is more effective and less time-consuming to induce metabolic syndrome in male post-weaning rats with high-fat diet compared to young adult rats. As male rats were selectively included into the study, the results may not be generalisable to all post-weaning rats and further investigation on female rats is required.

  10. Genetically Modified T-cell Infusion Following Peripheral Blood Stem Cell Transplant in Treating Patients With Recurrent or High-Risk Non-Hodgkin Lymphoma

    Science.gov (United States)

    2018-01-26

    Adult Grade III Lymphomatoid Granulomatosis; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Testicular Lymphoma; Waldenström Macroglobulinemia

  11. Variants of cancer susceptibility genes in Korean BRCA1/2 mutation-negative patients with high risk for hereditary breast cancer

    OpenAIRE

    Park, Ji Soo; Lee, Seung-Tae; Nam, Eun Ji; Han, Jung Woo; Lee, Jung-Yun; Kim, Jieun; Kim, Tae Il; Park, Hyung Seok

    2018-01-01

    Background We evaluated the incidence and spectrum of pathogenic and likely pathogenic variants of cancer susceptibility genes in BRCA1/2 mutation-negative Korean patients with a high risk for hereditary breast cancer using a comprehensive multigene panel that included 35 cancer susceptibility genes. Methods Samples from 120 patients who were negative for BRCA1/2 mutations, but had been diagnosed with breast cancer that was likely hereditary, were prospectively evaluated for the prevalence of...

  12. Synthesis and magnetic hyperthermia studies on high susceptible Fe1-xMgxFe2O4 superparamagnetic nanospheres

    Science.gov (United States)

    Manohar, A.; Krishnamoorthi, C.

    2017-12-01

    Majority studies on magnetic hyperthermia properties were carried out by modifying the saturation mass magnetization (Ms) of the samples. Here efforts were made to enhance the specific heat generation rate (SHGR) of single domain superparamagnetic (SP) material by modifying its magnetic susceptibility. Well crystallined, inverse spinel structured and close to monosize Fe1-xMgxFe2O4 (x = 0, 0.1, 0.2, 0.3, 0.4, & 0.5) compounds with nanosphere geometry (diameter 10 nm) were synthesized by solvothermal reflux method at ≈ 300 °C . In the literature it is reported that magnesium ferrites synthesized at high temperatures yield mixed (normal & inverse) spinel structures. The inverse spinel structure was confirmed by X-ray powder diffraction (XRPD), lattice vibrations and magnetic characteristics of the compounds. The Ms of the compounds decrease with increase of substituent Mg2+ concentration. Under high excitation energy the inter-valance charge transfer whereas under low excitation energy the intra-valance charge transfer process were predominant. The as-synthesized nanospheres were encapsulated by hydrophobic oleic acid and were exchanged by hydrophilic poly(acrylic acid) by chemical exchange process. Estimated magnetic hyperthermia power or SHGR of the x = 0, 0.3 & 0.5 were 11, 11.4 & 22.4 W per gram of respective compounds, respectively, under 63.4 kA m-1 field amplitude and 126 kHz frequency. The SHGR enhances with Mg2+ concentration though its Ms reduces and is attributed to reduced spin-orbital coupling in the compounds with enhanced Mg2+ concentration. This may pave a new way to develop magnetic hyperthermia material by modifying magnetic susceptibility of the compounds against to the reported Ms modification approach. The obtained high SHGR of the biocompatible compounds could be used in magnetic hyperthermia applications in biomedical field.

  13. Aerobic capacity and hepatic mitochondrial lipid oxidation alters susceptibility for chronic high-fat diet-induced hepatic steatosis.

    Science.gov (United States)

    Morris, E Matthew; Meers, Grace M E; Koch, Lauren G; Britton, Steven L; Fletcher, Justin A; Fu, Xiaorong; Shankar, Kartik; Burgess, Shawn C; Ibdah, Jamal A; Rector, R Scott; Thyfault, John P

    2016-10-01

    Rats selectively bred for high capacity running (HCR) or low capacity running (LCR) display divergence for intrinsic aerobic capacity and hepatic mitochondrial oxidative capacity, both factors associated with susceptibility for nonalcoholic fatty liver disease. Here, we tested if HCR and LCR rats display differences in susceptibility for hepatic steatosis after 16 wk of high-fat diets (HFD) with either 45% or 60% of kcals from fat. HCR rats were protected against HFD-induced hepatic steatosis, whereas only the 60% HFD induced steatosis in LCR rats, as marked by a doubling of liver triglycerides. Hepatic complete fatty acid oxidation (FAO) and mitochondrial respiratory capacity were all lower in LCR compared with HCR rats. LCR rats also displayed lower hepatic complete and incomplete FAO in the presence of etomoxir, suggesting a reduced role for noncarnitine palmitoyltransferase-1-mediated lipid catabolism in LCR versus HCR rats. Hepatic complete FAO and mitochondrial respiration were largely unaffected by either chronic HFD; however, 60% HFD feeding markedly reduced 2-pyruvate oxidation, a marker of tricarboxylic acid (TCA) cycle flux, and mitochondrial complete FAO only in LCR rats. LCR rats displayed lower levels of hepatic long-chain acylcarnitines than HCR rats but maintained similar levels of hepatic acetyl-carnitine levels, further supporting lower rates of β-oxidation, and TCA cycle flux in LCR than HCR rats. Finally, only LCR rats displayed early reductions in TCA cycle genes after the acute initiation of a HFD. In conclusion, intrinsically high aerobic capacity confers protection against HFD-induced hepatic steatosis through elevated hepatic mitochondrial oxidative capacity.

  14. Liquefaction susceptibility assessment in fluvial plains using high-resolution airborne LiDAR data: the case of the 2012 Emilia earthquake sequence area (Italy)

    Science.gov (United States)

    Civico, R.; Brunori, C. A.; De Martini, P. M.; Pucci, S.; Cinti, F. R.; Pantosti, D.

    2015-07-01

    We report a case study from the Po River plain region (northern Italy), where a significant liquefaction-related land and property damage occurred during the 2012 Emilia seismic sequence. We took advantage of a 1 m pixel LiDAR Digital Terrain Model (DTM) and of the 2012 Emilia coseismic liquefaction dataset to: (a) perform a detailed geomorphological study of the Po River plain area, (b) quantitatively define the liquefaction susceptibility of the geomorphologic features that experienced different frequency of liquefaction. One main finding is that linear topographic highs of fluvial origin, together with crevasse splays and abandoned riverbeds, acted as preferential location for the occurrence of liquefaction phenomena. Moreover, we quantitatively defined a hierarchy in terms of liquefaction susceptibility for fluvial environments. We observed that a very high liquefaction susceptibility is found in coincidence with fluvial landforms, a high-to-moderate liquefaction susceptibility within a buffer distance of 100 and 200 m from mapped fluvial landforms and a low liquefaction susceptibility outside fluvial landforms and relative buffer areas. LiDAR data allowed a significant improvement in mapping with respect to conventional available topographic data and/or aerial imagery. These results have significant implications for accurate hazard and risk assessment as well as for land-use planning. We propose a potentially simpler approach for liquefaction susceptibility assessment with respect to in situ geotechnical investigations. Our findings can be applied to areas beyond Emilia, characterized by similar fluvial-dominated environments and prone to significant seismic hazard.

  15. Posttreatment human papillomavirus testing for residual or recurrent high-grade cervical intraepithelial neoplasia: a pooled analysis.

    Science.gov (United States)

    Onuki, Mamiko; Matsumoto, Koji; Sakurai, Manabu; Ochi, Hiroyuki; Minaguchi, Takeo; Satoh, Toyomi; Yoshikawa, Hiroyuki

    2016-01-01

    We conducted a pooled analysis of published studies to compare the performance of human papillomavirus (HPV) testing and cytology in detecting residual or recurrent diseases after treatment for cervical intraepithelial neoplasia grade 2 or 3 (CIN 2/3). Source articles presenting data on posttreatment HPV testing were identified from the National Library of Medicine (PubMed) database. We included 5,319 cases from 33 articles published between 1996 and 2013. The pooled sensitivity of high-risk HPV testing (0.92; 95% confidence interval [CI], 0.90 to 0.94) for detecting posttreatment CIN 2 or worse (CIN 2+) was much higher than that of cytology (0.76; 95% CI, 0.71 to 0.80). Co-testing of HPV testing and cytology maximized the sensitivity (0.93; 95% CI, 0.87 to 0.96), while HPV genotyping (detection of the same genotype between pre- and posttreatments) did not improve the sensitivity (0.89; 95% CI, 0.82 to 0.94) compared with high-risk HPV testing alone. The specificity of high-risk HPV testing (0.83; 95% CI, 0.82 to 0.84) was similar to that of cytology (0.85; 95% CI, 0.84 to 0.87) and HPV genotyping (0.83; 95% CI, 0.81 to 0.85), while co-testing had reduced specificity (0.76; 95% CI, 0.75 to 0.78). For women with positive surgical margins, high-risk HPV testing provided remarkable risk discrimination between test-positives and test-negatives (absolute risk of residual CIN 2+ 74.4% [95% CI, 64.0 to 82.6] vs. 0.8% [95% CI, 0.15 to 4.6]; phigh-risk HPV testing, either alone or in conjunction with cytology, to posttreatment surveillance strategies. HPV testing can identify populations at greatest risk of posttreatment CIN 2+ lesions, especially among women with positive section margins.

  16. Salvage high-intensity focused ultrasound ablation for prostate cancer local recurrence after external-beam radiation therapy: prognostic value of prostate MRI.

    Science.gov (United States)

    Rouvière, O; Sbihi, L; Gelet, A; Chapelon, J-Y

    2013-07-01

    To assess the prognostic value of magnetic resonance imaging (MRI) before salvage high-intensity focused ultrasound (HIFU) for locally recurrent prostate cancer after external-beam radiotherapy (EBRT). Forty-six patients who underwent prostate MRI before salvage HIFU for locally recurrent prostate cancer after EBRT were retrospectively studied. HIFU failure was defined as a prostate-specific antigen (PSA) value >nadir + 2 ng/ml (Phoenix criteria) or positive follow-up biopsy or initiation of any other salvage therapy. The following prognostic parameters were assessed: neoadjuvant hormone therapy, clinical stage and Gleason score of recurrence, PSA level and velocity at HIFU treatment, and six MRI-derived parameters (prostate volume, tumour volume, extracapsular extension, seminal vesicle invasion, tumour extension into the apex or anterior to the urethra). Two factors were significant independent predictors of salvage HIFU failure: the PSA level at HIFU treatment (p HIFU failure for locally recurrent prostate cancer after EBRT. Therefore, MRI may be useful for patient selection before post-EBRT salvage HIFU ablation. Copyright © 2013 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

  17. Direct visualization of the subthalamic nucleus and its iron distribution using high-resolution susceptibility mapping

    NARCIS (Netherlands)

    Schäfer, A.; Forstmann, B.U.; Neumann, J.; Wharton, S.; Mietke, A.; Bowtell, R.; Turner, R.

    2012-01-01

    Histological studies have shown a relatively high iron concentration in the subthalamic nucleus (STN). T2- and T2*-weighted sequences have previously been used to visualize the STN in vivo. The phase information of gradient-echo images reflects the magnetic tissue properties more directly, e.g.,

  18. Outcomes of salvage high-dose-rate brachytherapy with or without external beam radiotherapy for isolated vaginal recurrence of endometrial cancer

    Directory of Open Access Journals (Sweden)

    Shuhei Sekii

    2017-05-01

    Full Text Available Purpose: This study was designed to retrospectively analyze outcomes of high-dose-rate (HDR brachytherapy, with or without external beam radiotherapy (EBRT, in patients with vaginal recurrence of endometrial carcinoma, and to identify factors prognostic of patient outcomes. Material and methods : The medical records of all patients who underwent HDR brachytherapy for initial recurrence in the vagina of endometrial cancer after definitive surgery between 1992 and 2014 were retrospectively reviewed. All patients underwent either intracavitary brachytherapy (ICBT or interstitial brachytherapy (ISBT with or without EBRT. Late toxicity was graded using the EORTC (LENT/SOMA scale, revised in 1995. Results : Thirty-seven patients were identified. The median follow-up time was 48 months (range: 6-225 months. Of these 37 patients, 23 underwent ICBT, 14 underwent ISBT, and 26 underwent EBRT. Tumor size at first examination of initial relapse was significantly larger in the ISBT than in the ICBT group. The 4-year respective overall survival (OS, local control (LC, and progression-free survival (PFS rates in the entire cohort were 81.0%, 77.9%, and 56.8%, respectively. The interval between diagnosis of first recurrence and radiotherapy (< 3 months, ≥ 3 months was a significant predictor of LC and PFS. OS and LC rates did not differ significantly in the ICBT and ISBT groups. Two patients experienced grade 2 rectal bleeding, and four experienced grade 2 hematuria. No grade 3 or higher late complications were observed. Conclusions : Salvage HDR brachytherapy is an optimal for treating vaginal recurrence of endometrial carcinoma with acceptable morbidity. Early radiotherapy, including brachytherapy, should be considered for women who experience vaginal recurrence of endometrial cancer.

  19. Interleukin-6-deficient mice are highly susceptible to Listeria monocytogenes infection: correlation with inefficient neutrophilia.

    OpenAIRE

    Dalrymple, S A; Lucian, L A; Slattery, R; McNeil, T; Aud, D M; Fuchino, S; Lee, F; Murray, R

    1995-01-01

    We have produced interleukin-6 (IL-6)-deficient mice to examine, in vivo, the wide variety of biological activities attributed to this multifunctional cytokine. To investigate the role of IL-6 during infectious disease, IL-6-deficient mice were challenged with sublethal doses of Listeria monocytogenes, a facultative intracellular bacterium. While normal control animals were able to clear the infection, mutant animals exhibited a high mortality rate and showed uncontrolled replication of the b...

  20. Response of high-risk of recurrence/progression bladder tumours expressing sialyl-Tn and sialyl-6-T to BCG immunotherapy

    OpenAIRE

    Lima, Luís; Severino, Paulo; Silva, Mariana; Miranda, Andreia; Tavares, Ana; Pereira, Sofia; Fernandes, Elisabete; Cruz, Ricardo; Amaro, Teresina; Reis, Celso; Dall'Olio, Fabio; Amado, Francisco; Videira, Paula; Santos, Lúcio; Ferreira, José Alexandre

    2013-01-01

    Background: High risk of recurrence/progression bladder tumours is treated with Bacillus Calmette-Guérin (BCG) immunotherapy after complete resection of the tumour. Approximately 75% of these tumours express the uncommon carbohydrate antigen sialyl-Tn (Tn), a surrogate biomarker of tumour aggressiveness. Such changes in the glycosylation of cell-surface proteins influence tumour microenvironment and immune responses that may modulate treatment outcome and the course of disease. The aim of thi...

  1. Infectious Complications during Tandem High-Dose Chemotherapy and Autologous Stem Cell Transplantation for Children with High-Risk or Recurrent Solid Tumors.

    Directory of Open Access Journals (Sweden)

    Young Bae Choi

    Full Text Available We retrospectively analyzed infectious complications during tandem high-dose chemotherapy and autologous stem cell transplantation (HDCT/auto-SCT in children and adolescents with high-risk or recurrent solid tumors. A total of 324 patients underwent their first HDCT/auto-SCT between October 2004 and September 2014, and 283 of them proceeded to their second HDCT/auto-SCT (a total of 607 HDCT/auto-SCTs. During the early transplant period of 607 HDCT/auto-SCTs (from the beginning of HDCT to day 30 post-transplant, bacteremia, urinary tract infection (UTI, respiratory virus infection, and varicella zoster virus (VZV reactivation occurred in 7.1%, 2.3%, 13.0%, and 2.5% of HDCT/auto-SCTs, respectively. The early transplant period of the second HDCT/auto-SCT had infectious complications similar to the first HDCT/auto-SCT. During the late transplant period of HDCT/auto-SCT (from day 31 to 1 year post-transplant, bacteremia, UTI, and VZV reactivation occurred in 7.5%, 2.5%, and 3.9% of patients, respectively. Most infectious complications in the late transplant period occurred during the first 6 months post-transplant. There were no invasive fungal infections during the study period. Six patients died from infectious complications (4 from bacterial sepsis and 2 from respiratory virus infection. Our study suggests that infectious complications are similar following second and first HDCT/auto-SCT in children.

  2. Cold weld cracking susceptibility of high strength low alloyed (HSLA steel NIONIKRAL 70

    Directory of Open Access Journals (Sweden)

    A. S. Tawengi

    2014-10-01

    Full Text Available In view of the importance of high strength low alloy (HSLA steels, particularly for critical applications such as offshore plat forms, pipeline and pressure vessels, this paper reports on an investigation of how to weld this type of steel without cold cracking. Using manual metal arc welding process and Tekken test (Y - Grove test has been carried out both to observe the cold cracking phenome non, and to investigate the influencing factors, such as preheating temperature and energy input, as well as electrode strength and diameter. How ever the results of the experiments show that there is a risk of cold cracking.

  3. Effects of maternal high-fat diet and sedentary lifestyle on susceptibility of adult offspring to ozone exposure in rats.

    Science.gov (United States)

    Gordon, C J; Phillips, P M; Johnstone, A F M; Schmid, J; Schladweiler, M C; Ledbetter, A; Snow, S J; Kodavanti, U P

    2017-05-01

    Epidemiological and experimental data suggest that obesity exacerbates the health effects of air pollutants such as ozone (O3). Maternal inactivity and calorically rich diets lead to offspring that show signs of obesity. Exacerbated O3 susceptibility of offspring could thus be manifested by maternal obesity. Thirty-day-old female Long-Evans rats were fed a control (CD) or high-fat (HF) (60% calories) diet for 6 wks and then bred. GD1 rats were then housed with a running wheel (RW) or without a wheel (SED) until parturition, creating four groups of offspring: CD-SED, CD-RW, HF-SED and HF-RW. HF diet was terminated at PND 35 and all offspring were placed on CD. Body weight and %fat of dams were greatest in order; HF-SED > HF-RW > CD-SED > CD-RW. Adult offspring were exposed to O3 for two consecutive days (0.8 ppm, 4 h/day). Glucose tolerance tests (GTT), ventilatory parameters (plethysmography), and bronchoalveolar fluid (BALF) cell counts and protein biomarkers were performed to assess response to O3. Exercise and diet altered body weight and %fat of young offspring. GTT, ventilation and BALF cell counts were exacerbated by O3 with responses markedly exacerbated in males. HF diet and O3 led to significant exacerbation of several BALF parameters: total cell count, neutrophils and lymphocytes were increased in male HF-SED versus CD-SED. Males were hyperglycemic after O3 exposure and exhibited exacerbated GTT responses. Ventilatory dysfunction was also exacerbated in males. Maternal exercise had minimal effects on O3 response. The results of this exploratory study suggest a link between maternal obesity and susceptibility to O3 in their adult offspring in a sex-specific manner.

  4. [Strategy and practice of the healthy cosmetic management for patients with high dental caries susceptibility].

    Science.gov (United States)

    Tao, Liu; Li, Cheng; Hui, Yang; Huning, Wang; Hongzhi, Fang; Tao, Hu

    2016-10-01

    A new clinic conception, healthy cosmetic management (HCM), was innovated introduced into diagnose and treatment of patients with high caries risk. The priority of HCM should be given to aesthetic restoration of teeth, taking consideration of the conserving of tissue and pulp of teeth and the balance between health and aesthetics, which may reach to the goal of the individual clinic treatment. HCM includes five steps: 1) caries risk assessment; 2) detection of initial caries; 3) digital aesthetic design; 4) minimally invasive therapy; 5) behavior management of caries and doctor-patient communication pattern. In this article, HCM is introduced into two aspects: process management and clinical protocols, followed by the combination of the clinical practice.

  5. Seminational surveillance of fungemia in Denmark: notably high rates of fungemia and numbers of isolates with reduced azole susceptibility

    DEFF Research Database (Denmark)

    Arendrup, Maiken Cavling; Fuursted, Kurt; Gahrn-Hansen, Bente

    2005-01-01

    laboratory systems documented a continuous increase of candidemia cases since the early 1990s. For the 272 susceptibility-tested isolates, MICs of amphotericin B and caspofungin were within the limits expected for the species or genus. However, decreased azole susceptibility, defined as a fluconazole MIC...

  6. Postmastectomy radiotherapy improves disease-free survival of high risk of locoregional recurrence breast cancer patients with T1-2 and 1 to 3 positive nodes.

    Directory of Open Access Journals (Sweden)

    Zhen-Yu He

    Full Text Available The indications for post-mastectomy radiotherapy (PMRT with T1-2 breast cancer and 1-3 positive axillary lymph nodes is still controversial. The purpose of this study was to investigate the role of PMRT in T1-2 breast cancer with 1-3 positive axillary lymph node.We retrospectively reviewed the file records of 79 patients receiving PMRT and not receiving PMRT (618 patients.The median follow-up was 65 months. Multivariate analysis showed that PMRT was an independent prognostic factor of locoregional recurrence-free survival (LRFS (P = 0.010. Subgroup analysis of patients who did not undergo PMRT showed that pT stage, number of positive axillary lymph nodes, and molecular subtype were independent prognostic factors of LRFS. PMRT improved LRFS in the entire group (P = 0.005, but did not affect distant metastasis-free survival (DMFS (P = 0.494, disease-free survival (DFS (P = 0.215, and overall survival (OS (P = 0.645. For patients without PMRT, the 5-year LRFS of low-risk patients (0-1 risk factor for locoregional recurrence of 94.5% was significantly higher than that of high-risk patients (2-3 risk factors for locoregional recurrence (80.9%, P < 0.001. PMRT improved LRFS (P = 0.001 and DFS (P = 0.027 in high-risk patients, but did not improve LRFS, DMFS, DFS, and OS in low-risk patients.PMRT is beneficial in patients with high risk of locoregional recurrence breast cancer patients with T1-2 and 1 to 3 positive nodes.

  7. Treatment effect, adherence, and safety of high fluid intake for the prevention of incident and recurrent kidney stones: a systematic review and meta-analysis.

    Science.gov (United States)

    Cheungpasitporn, Wisit; Rossetti, Sandro; Friend, Keith; Erickson, Stephen B; Lieske, John C

    2016-04-01

    The objective of this systematic review and meta-analysis were to evaluate the effectiveness of high fluid intake for the prevention of incident and recurrent kidney stones, as well as its adherence and safety. A literature search was performed encompassing 1980 through July 2014. Studies that reported relative risks, odds ratios, or hazard ratios comparing the risk of kidney stone events in patients with high vs inadequate fluid intake were included. Pooled risk ratios (RRs) and 95 % confidence intervals (CIs) were calculated using a random-effect, generic inverse variance method. Nine studies [2 randomized controlled trials (RCTs) with 269 patients; 7 observational studies with 273,685 individuals] were included in the meta-analysis. Pooled RRs of kidney stones in individuals with high-fluid intake were 0.40 (95 % CI 0.20-0.79) and 0.49 (0.34-0.71) in RCTs and observational studies, respectively. High fluid intake was significantly associated with reduced risk of recurrent kidney stones: RRs 0.40 (95 % CI 0.20-0.79) and 0.20 (0.09-0.44) in RCTs and observational studies, respectively. Adherence and safety data on high fluid intake treatment were limited; 1 RCT reported no withdrawals due to adverse events. This analysis demonstrated a significantly reduced risk of incident kidney stones among individuals with high fluid consumption. High fluid consumption also reduced the risk of recurrent kidney stones. Furthermore, the magnitude of risk reduction was high. Although increased water intake appears to be safe, future studies on its safety in patients with high risk of volume overload or hyponatremia may be indicated.

  8. Miltefosine and Antimonial Drug Susceptibility of Leishmania Viannia Species and Populations in Regions of High Transmission in Colombia

    Science.gov (United States)

    Fernández, Olga Lucía; Diaz-Toro, Yira; Muvdi, Sandra; Rodríguez, Isabel; Gomez, María Adelaida; Saravia, Nancy Gore

    2014-01-01

    Background Pentavalent antimonials have been the first line treatment for dermal leishmaniasis in Colombia for over 30 years. Miltefosine is administered as second line treatment since 2005. The susceptibility of circulating populations of Leishmania to these drugs is unknown despite clinical evidence supporting the emergence of resistance. Methodology/Principal Findings In vitro susceptibility was determined for intracellular amastigotes of 245 clinical strains of the most prevalent Leishmania Viannia species in Colombia to miltefosine (HePC) and/or meglumine antimoniate (SbV); 163, (80%) were evaluated for both drugs. Additionally, susceptibility to SbV was examined in two cohorts of 85 L. V. panamensis strains isolated between 1980–1989 and 2000–2009 in the municipality of Tumaco. Susceptibility to each drug differed among strains of the same species and between species. Whereas 68% of L. V. braziliensis strains presented in vitro resistance to HePC, 69% were sensitive to SbV. Resistance to HePC and SbV occurred respectively, in 20% y 21% of L. panamensis strains. Only 3% of L. V. guyanensis were resistant to HePC, and none to SbV. Drug susceptibility differed between geographic regions and time periods. Subpopulations having disparate susceptibility to SbV were discerned among L. V. panamensis strains isolated during 1980–1990 in Tumaco where resistant strains belonged to zymodeme 2.3, and sensitive strains to zymodeme 2.2. Conclusions/Significance Large scale evaluation of clinical strains of Leishmania Viannia species demonstrated species, population, geographic, and epidemiologic differences in susceptibility to meglumine antimoniate and miltefosine, and provided baseline information for monitoring susceptibility to these drugs. Sensitive and resistant clinical strains within each species, and zymodeme as a proxy marker of antimony susceptibility for L. V. panamensis, will be useful in deciphering factors involved in susceptibility and the distribution

  9. Accelerated mapping of magnetic susceptibility using 3D planes-on-a-paddlewheel (POP) EPI at ultra-high field strength.

    Science.gov (United States)

    Stäb, Daniel; Bollmann, Steffen; Langkammer, Christian; Bredies, Kristian; Barth, Markus

    2017-04-01

    With the advent of ultra-high field MRI scanners in clinical research, susceptibility based MRI has recently gained increasing interest because of its potential to assess subtle tissue changes underlying neurological pathologies/disorders. Conventional, but rather slow, three-dimensional (3D) spoiled gradient-echo (GRE) sequences are typically employed to assess the susceptibility of tissue. 3D echo-planar imaging (EPI) represents a fast alternative but generally comes with echo-time restrictions, geometrical distortions and signal dropouts that can become severe at ultra-high fields. In this work we assess quantitative susceptibility mapping (QSM) at 7 T using non-Cartesian 3D EPI with a planes-on-a-paddlewheel (POP) trajectory, which is created by rotating a standard EPI readout train around its own phase encoding axis. We show that the threefold accelerated non-Cartesian 3D POP EPI sequence enables very fast, whole brain susceptibility mapping at an isotropic resolution of 1 mm and that the high image quality has sufficient signal-to-noise ratio in the phase data for reliable QSM processing. The susceptibility maps obtained were comparable with regard to QSM values and geometric distortions to those calculated from a conventional 4 min 3D GRE scan using the same QSM processing pipeline. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  10. VITAMIN D STATUS AND RECURRENT PRETERM BIRTH: A nested case-control study in high-risk women

    Science.gov (United States)

    Thorp, John M.; Camargo, Carlos A.; McGee, Paula L.; Harper, Margaret; Klebanoff, Mark A.; Sorokin, Yoram; Varner, Michael W.; Wapner, Ronald J.; Caritis, Steve N.; Iams, Jay D.; Carpenter, Marshall W.; Peaceman, Alan M.; Mercer, Brian M.; Sciscione, Anthony; Rouse, Dwight J.; Ramin, Susan M.; Anderson, Garland B.

    2012-01-01

    OBJECTIVE To determine if vitamin D status is associated with recurrent preterm birth, and any interactions between Vitamin D levels and fish consumption. DESIGN A nested case-control study using data from a randomized trial of omega-3 fatty acid supplementation to prevent recurrent preterm birth. SETTING 14 academic health centers in the U.S. POPULATION Women with prior spontaneous preterm birth. METHODS In 131 cases (preterm delivery less than 35 weeks) and 134 term controls, we measured serum 25-hydroxyvitamin D (25[OH]D) concentrations by liquid chromatography-tandem mass spectrometry (LC-MS) among samples collected at baseline (16–22 weeks gestation). Logistic regression models controlled for study center, maternal age, race/ethnicity, number of prior preterm deliveries, smoking status, body mass index, and treatment. MAIN OUTCOME MEASURES Recurrent preterm birth at <37, <32 weeks. RESULTS The median mid-gestation serum 25(OH)D concentration was 67 (nmol/L) and 27% had concentrations less than 50 nmol/L. Serum 25(OH)D concentration was not significantly associated with preterm birth (OR = 1.33, 95% confidence interval =0.48–3.70 for lowest vs. highest quartile). Likewise, comparing women with 25(OH)D concentrations of 50 nmol/L or higher with those with less than 50nmol/L generated an odds ratio of 0.80 (0.38, 1.69). Contrary to expected, a negative correlation was observed between fish consumption and serum 25(OH)D concentration (−0.18, P<0.01). CONCLUSION In a cohort of women with a prior preterm birth, vitamin D status at mid-pregnancy was not associated with recurrent preterm birth. PMID:23078336

  11. Long-term daily temozolomide with dose-dependent efficacy in MGMT promotor methylation negative recurrent high-grade astrocytoma.

    Science.gov (United States)

    Zhou, Zhengqiu; Howard, Tracy A; Villano, John L

    2017-11-01

    Temozolomide (TMZ) for malignant gliomas is traditionally dosed in 5 out of a 28-day cycle, however alternative regimens exist, including dose-dense. Continuous daily dosing is available, but the acceptable dose and duration of therapy is unknown. We document a 40-year-old male with recurrent anaplastic astrocytoma, IDH mutant and MGMT promotor methylation negative, who has well-tolerated continuous daily TMZ for 20 months at 100 mg per day for nearly the length of this period. A trial at 80 mg per day demonstrated disease progression with response upon return to 100 mg per day. Prior to the daily TMZ, the patient underwent three surgical resections, radiation therapy with concurrent TMZ according to the EORTC-NCIC protocol, and subsequently bevacizumab in combination with use of the Optune device. Long-term survival of patients with recurrent malignant gliomas is uncommon, and currently no standard treatment strategies exist for these patients. We present this case to demonstrate the tolerability and dose dependency of prolonged daily TMZ dosing as a therapeutic option for recurrent anaplastic astrocytomas.

  12. High rate of hepatitis C virus (HCV) recurrence in HIV-infected individuals with spontaneous HCV RNA clearance

    DEFF Research Database (Denmark)

    Peters, L; Mocroft, A; Soriano, V

    2014-01-01

    OBJECTIVES: Following resolution of hepatitis C virus (HCV) infection, recurrence has been shown to occur in some persons with repeated exposure to HCV. We aimed to investigate the rate and factors associated with HCV RNA recurrence among HIV-1-infected patients with prior spontaneous HCV RNA...... clearance in the EuroSIDA cohort. METHODS: All HIV-infected patients with documented prior spontaneous HCV clearance, and at least one subsequently collected plasma sample, were examined. The last sample was tested for HCV RNA and those with HCV RNA ≥ 615 IU/mL were defined as having HCV recurrence...... (IDUs). The median time between the first and last samples was 3.6 years (interquartile range 2.0-5.8 years). After adjustment, those on combination antiretroviral therapy [odds ratio (OR) 0.44; 95% CI 0.20-0.99; P = 0.046] and older persons (OR 0.51 per 10 years older; 95% CI 0.28-0.95; P = 0.033) were...

  13. Prothrombotic Fibrin Clot Phenotype Is Associated With Recurrent Pulmonary Embolism After Discontinuation of Anticoagulant Therapy.

    Science.gov (United States)

    Zabczyk, Michal; Plens, Krzysztof; Wojtowicz, Wioletta; Undas, Anetta

    2017-02-01

    Pulmonary embolism (PE) is a life-threatening manifestation of venous thromboembolism with a high recurrence rate after anticoagulation cessation. Recently, we have reported that prothrombotic clot phenotype in venous thromboembolism patients is associated with an increased risk of recurrent deep-vein thrombosis. We tested whether abnormal clot properties are predictive of recurrent PE. We investigated 156 consecutive white patients aged 18 to 65 years after the first-ever provoked or unprovoked PE (n=89), with or without deep-vein thrombosis. Plasma fibrin clot permeability (Ks), turbidity measurements, calibrated automated thrombography, and efficiency of fibrinolysis using clot lysis time, maximum D-dimer levels, and rate of increase in D-dimer levels were evaluated at ≥3 months of anticoagulant therapy, at least 4 weeks since the anticoagulation withdrawal. The primary end point was recurrent PE during a median follow-up of 50 months. Recurrent PE was diagnosed in 23 (14.7%; 5%/yr) patients. Recurrent PE was associated with formation of denser fibrin networks reflected by lower Ks (P=0.007) and impaired fibrinolysis, as evidenced by prolonged clot lysis time (P=0.012) and reduced maximum rate of increase in D-dimer levels in the lysis assay (P=0.004). Patients with recurrent PE had higher plasma D-dimer (P<0.001) and thrombin peak (P=0.007) compared with the remainder, whereas turbidity measurements and maximum D-dimer levels did not differ in the recurrence. Multivariate model showed that independent predictors of recurrent PE were female sex, unprovoked venous thromboembolism, higher plasma D-dimer, reduced Ks, and reduced maximum rate of increase in D-dimer levels in the lysis assay (all P<0.05). Altered fibrin clot properties including formation of more compact clots displaying impaired susceptibility to lysis may predispose to recurrent PE. © 2016 American Heart Association, Inc.

  14. Duffy-Null–Associated Low Neutrophil Counts Influence HIV-1 Susceptibility in High-Risk South African Black Women

    Science.gov (United States)

    Ramsuran, Veron; Kulkarni, Hemant; He, Weijing; Mlisana, Koleka; Wright, Edwina J.; Werner, Lise; Castiblanco, John; Dhanda, Rahul; Le, Tuan; Dolan, Matthew J.; Guan, Weihua; Weiss, Robin A.; Clark, Robert A.; Abdool Karim, Salim S.; Ndung'u, Thumbi

    2011-01-01

    Background. The Duffy-null trait and ethnic netropenia are both highly prevalent in Africa. The influence of pre-seroconversion levels of peripheral blood cell counts (PBCs) on the risk of acquiring human immunodeficiency virus (HIV)–1 infection among Africans is unknown. Methods. The triangular relationship among pre-seroconversion PBC counts, host genotypes, and risk of HIV acquisition was determined in a prospective cohort of black South African high-risk female sex workers. Twenty-seven women had seroconversion during follow-up, and 115 remained HIV negative for 2 years, despite engaging in high-risk activity. Results. Pre-seroconversion neutrophil counts in women who subsequently had seroconversion were significantly lower, whereas platelet counts were higher, compared with those who remained HIV negative. Comprising 27% of the cohort, subjects with pre-seroconversion neutrophil counts of C) was significantly associated with neutrophil counts (P = 7.9 × 10−11). DARC −46C/C results in loss of DARC expression on erthyrocytes (Duffy-null) and resistance to Plasmodium vivax malaria, and in our cohort, only subjects with this genotype had pre-seroconversion neutrophil counts of <2500 cells/mm3. The risk of acquiring HIV infection was ∼3-fold greater in those with the trait of Duffy-null–associated low neutrophil counts, compared with all other study participants. Conclusions. Pre-seroconversion neutrophil and platelet counts influence risk of HIV infection. The trait of Duffy-null–associated low neutrophil counts influences HIV susceptibility. Because of the high prevalence of this trait among persons of African ancestry, it may contribute to the dynamics of the HIV epidemic in Africa. PMID:21507922

  15. High PSA anxiety and low health literacy skills: drivers of early use of salvage ADT among men with biochemically recurrent prostate cancer after radiotherapy?

    Science.gov (United States)

    Mahal, B A; Chen, M-H; Bennett, C L; Kattan, M W; Sartor, O; Stein, K; D'Amico, A V; Nguyen, P L

    2015-07-01

    Although commonly used, early initiation of salvage androgen deprivation therapy (ADT) has not been proven to enhance survival. We evaluated whether prostate-specific antigen (PSA) anxiety or health literacy are associated with use of early salvage ADT among men with recurrent prostate cancer after radiotherapy. The prospective Comprehensive, Observational, Multicenter, Prostate Adenocarcinoma Registry was used to study 375 men with biochemically recurrent prostate cancer after external beam radiation or brachytherapy. Multivariable logistic regression was used to determine whether PSA anxiety and health literacy are associated with salvage ADT as initial management after biochemical recurrence. Sixty-eight men (18.1%) received salvage ADT as initial management for PSA recurrence. Men with high PSA anxiety were twice as likely to receive salvage ADT compared with men who did not have high PSA anxiety on both univariable [28.8% versus 13.1%; odds ratio (OR) 2.15; 95% confidence interval (CI) 1.16-4.00; P = 0.015] and multivariable analysis [adjusted OR (AOR) 2.36; 95% CI 1.21-4.62; P = 0.012]. Furthermore, men who had higher levels of health literacy were nearly half as likely to undergo salvage ADT compared with men who had lower levels of health literacy on univariable analysis (15.2% versus 26.3%; OR 0.50; 95% CI 0.29-0.88; P = 0.016), with a trend toward this association on multivariable analysis (AOR 0.58; 95% CI 0.32-1.05; P = 0.07). Among men with PSA recurrence after radiotherapy, odds of use of salvage ADT were nearly twice as great among men with high PSA anxiety or low health literacy, suggesting that these men are receiving higher rates of unproven treatment. Given that early salvage ADT is costly, worsens quality of life, and has not been shown to improve survival, quality improvement strategies are needed for these individuals. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights

  16. Predation in High CO2 Waters: Prey Fish from High-Risk Environments are Less Susceptible to Ocean Acidification.

    Science.gov (United States)

    Ferrari, Maud C O; McCormick, Mark I; Watson, Sue-Ann; Meekan, Mark G; Munday, Philip L; Chivers, Douglas P

    2017-07-01

    Most studies investigating the effects of anthropogenic environmental stressors do so in conditions that are often optimal for their test subjects, ignoring natural stressors such as competition or predation. As such, the quantitative results from such studies may often underestimate the lethality of certain toxic compounds. A well-known example of this concept is illustrated by the marked increase in the lethality of pesticides when larval amphibians are concurrently exposed to the odor of potential predators. Here, we investigated the interaction between background levels of environmental predation risk (high vs. low) and ocean acidification (ambient vs. elevated CO2) in 2 × 2 design. Wild-caught juvenile damselfish, Pomacentrus amboinensis, were exposed in the laboratory to the different risk and CO2 conditions for 4 days and released onto coral reef patches. Using a well-established field assay, we monitored the in situ behavior and mortality of the damselfish for 2 days. We predicted that juvenile fish exposed to elevated CO2 and high-risk conditions would display more severe behavioral impairments and increased mortality compared to fish exposed to elevated CO2 maintained under low-risk conditions. As expected, elevated CO2 exposure led to impaired antipredator responses and increased mortality in low-risk fish compared to ambient CO2 controls. However, we failed to find an effect of elevated CO2 on the behavior and survival of the high-risk fish. We hypothesized that the results may stem from either a behavioral compensation or a physiological response to high risk. Our results provide insights into the interactive nature of environmental and natural stressors and advance our understanding of the predicted effect of ocean acidification on aquatic ecosystems. © The Author 2017. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.

  17. The re-infection rate of high-risk HPV and the recurrence rate of vulvar intraepithelial neoplasia (VIN) usual type after surgical treatment.

    Science.gov (United States)

    Frega, Antonio; Sopracordevole, Francesco; Scirpa, Paolo; Biamonti, Alberto; Lorenzon, Laura; Scarani, Simona; De Sanctis, Luana; Pacchiarotti, Arianna; Moscarini, Massimo; French, Deborah

    2011-09-01

    VIN usual type appears to be related to the HPV's oncogenic types. The aim of this prospective multicenter study was to evaluate the re-infection rate of high-risk HPV and the recurrence rate of VIN usual type after surgical treatment. The study enrolled 103 women affected by VIN usual type. They underwent wide local excision by CO2 laser. The patients were investigated by clinical evaluation and HPV DNA test 6 months after surgical treatment, and then were followed-up at 12, 18, 24, and 36 months. The recurrences were treated with re-excision. The rate of HPV infection after surgical treatment was 34% at 6 months, 36.9% at 12 months, 40% at 18 months, 41.7% at 24 months and 44.7% at 36 months. The mean time from HPV infection to the development of VIN was 18.8 months. HPV testing in the follow-up of VIN usual type patients might be useful for identifying those patients with a higher risk of recurrence after surgical treatment, although more studies are needed. These preliminary data suggest that the test, in addition to clinical examination, can improve the efficacy of the follow-up.

  18. Immature mice are more susceptible to the detrimental effects of high fat diet on cancellous bone in the distal femur.

    Science.gov (United States)

    Inzana, Jason A; Kung, Ming; Shu, Lei; Hamada, Daisuke; Xing, Lian Ping; Zuscik, Michael J; Awad, Hani A; Mooney, Robert A

    2013-11-01

    With the increasing prevalence of obesity among children and adolescents, it is imperative to understand the implications of early diet-induced obesity on bone health. We hypothesized that cancellous bone of skeletally immature mice is more susceptible to the detrimental effects of a high fat diet (HFD) than mature mice, and that removing excess dietary fat will reverse these adverse effects. Skeletally immature (5weeks old) and mature (20weeks old) male C57BL/6J mice were fed either a HFD (60% kcal fat) or low fat diet (LFD; 10% kcal fat) for 12weeks, at which point, the trabecular bone structure in the distal femoral metaphysis and third lumbar vertebrae were evaluated by micro-computed tomography. The compressive strength of the vertebrae was also measured. In general, the HFD led to deteriorations in cancellous bone structure and compressive biomechanical properties in both age groups. The HFD-fed immature mice had a greater decrease in trabecular bone volume fraction (BVF) in the femoral metaphysis, compared to mature mice (p=0.017 by 2-way ANOVA). In the vertebrae, however, the HFD led to similar reductions in BVF and compressive strength in the two age groups. When mice on the HFD were switched to a LFD (HFD:LFD) for an additional 12weeks, the femoral metaphyseal BVF in immature mice showed no improvements, whereas the mature mice recovered their femoral metaphyseal BVF to that of age-matched lean controls. The vertebral BVF and compressive strength of HFD:LFD mouse bones, following diet correction, were equivalent to those of LFD:LFD mice in both age groups. These data suggest that femoral cancellous metaphyseal bone is more susceptible to the detrimental effects of HFD before skeletal maturity and is less able to recover after correcting the diet. Negative effects of HFD on vertebrae are less severe and can renormalize with LFD:LFD mice after diet correction, in both skeletally immature and mature animals. © 2013. Published by Elsevier Inc. All rights

  19. Establishment and characterization of GSA-1, a human cell line highly susceptible to apoptosis after free-fall.

    Science.gov (United States)

    Nomura, Jun; Himeda, Jyuni; Chen, Zheng; Sugaya, Shigeru; Takahashi, Shunji; Kita, Kazuko; Ichinose, Masaharu; Suzuki, Nobuo

    2002-12-01

    The induction of apoptosis by microgravity and/or gravity-changing stress is considered to be one of the important causes of cell death, although the molecular mechanisms of the apoptotic event remain unclarified. In this study, we established a cell line, GSA-1, from ethyl methanesulfonate-treated human RSa cells. GSA-1 cells were highly susceptible to apoptosis after a free-fall; 24.4% of these cells underwent apoptosis after free-fall, compared with only 6% of the RSa cells. The apoptosis of GSA-1 cells was augmented by ultraviolet (UV, principally 254-nm wavelength) irradiation before free-fall to a greater extents than those in RSa cells. The molecular mechanisms of apoptosis included p53 and Bax proteins; the expression of nuclear p53 and cytoplasmic Bax in GSA-1 cells increased at 4 h after free-fall irrespective of irradiation. In addition, the rate of removal of cyclobutane pyrimidine dimer (CPD) in UV-irradiated GSA-1 cells was higher in cells exposed to free-fall than in those under the 1-G condition. Our results suggested that in GSA-1 cells, free-fall accelerates apoptosis, and that this process is associated with the accumulation of p53 and Bax, as well as CPD removal. Thus, GSA-1 cells should be useful for investigating the mechanism of cellular response, including the induction of apoptosis under gravity-changing stress.

  20. Development of a nano-tesla magnetic field shielded chamber and highly precise AC-susceptibility measurement coil at μK temperatures

    Science.gov (United States)

    Kumar, Anil; Prakash, Om; Ramakrishanan, S.

    2014-04-01

    A special sample measurement chamber has been developed to perform experiments at ultralow temperatures and ultralow magnetic field. A high permeability material known as cryoperm 10 and Pb is used to shield the measurement space consisting of the signal detecting set-up and the sample. The detecting setup consists of a very sensitive susceptibility coil wound on OFHC Cu bobbin.

  1. Cis-eQTL analysis and functional validation of candidate susceptibility genes for high-grade serous ovarian cancer

    DEFF Research Database (Denmark)

    Lawrenson, Kate; Li, Qiyuan; Kar, Siddhartha

    2015-01-01

    Genome-wide association studies have reported 11 regions conferring risk of high-grade serous epithelial ovarian cancer (HGSOC). Expression quantitative trait locus (eQTL) analyses can identify candidate susceptibility genes at risk loci. Here we evaluate cis-eQTL associations at 47 regions assoc...

  2. Plasminogen Activator Inhibitor-2 Polymorphism Associates with Recurrent Coronary Event Risk in Patients with High HDL and C-Reactive Protein Levels

    Science.gov (United States)

    Corsetti, James P.; Salzman, Peter; Ryan, Dan; Moss, Arthur J.; Zareba, Wojciech; Sparks, Charles E.

    2013-01-01

    The objective of this work was to investigate whether fibrinolysis plays a role in establishing recurrent coronary event risk in a previously identified group of postinfarction patients. This group of patients was defined as having concurrently high levels of high-density lipoprotein cholesterol (HDL-C) and C-reactive protein (CRP) and was previously demonstrated to be at high-risk for recurrent coronary events. Potential risk associations of a genetic polymorphism of plasminogen activator inhibitor-2 (PAI-2) were probed as well as potential modulatory effects on such risk of a polymorphism of low-density lipoprotein receptor related protein (LRP-1), a scavenger receptor known to be involved in fibrinolysis in the context of cellular internalization of plasminogen activator/plansminogen activator inhibitor complexes. To this end, Cox multivariable modeling was performed as a function of genetic polymorphisms of PAI-2 (SERPINB, rs6095) and LRP-1 (LRP1, rs1800156) as well as a set of clinical parameters, blood biomarkers, and genetic polymorphisms previously demonstrated to be significantly and independently associated with risk in the study population including cholesteryl ester transfer protein (CETP, rs708272), p22phox (CYBA, rs4673), and thrombospondin-4 (THBS4, rs1866389). Risk association was demonstrated for the reference allele of the PAI-2 polymorphism (hazard ratio 0.41 per allele, 95% CI 0.20-0.84, p=0.014) along with continued significant risk associations for the p22phox and thrombospondin-4 polymorphisms. Additionally, further analysis revealed interaction of the LRP-1 and PAI-2 polymorphisms in generating differential risk that was illustrated using Kaplan-Meier survival analysis. We conclude from the study that fibrinolysis likely plays a role in establishing recurrent coronary risk in postinfarction patients with concurrently high levels of HDL-C and CRP as manifested by differential effects on risk by polymorphisms of several genes linked to key

  3. Modularity promotes epidemic recurrence

    CERN Document Server

    Jesan, T; Sinha, Sitabhra

    2016-01-01

    The long-term evolution of epidemic processes depends crucially on the structure of contact networks. As empirical evidence indicates that human populations exhibit strong community organization, we investigate here how such mesoscopic configurations affect the likelihood of epidemic recurrence. Through numerical simulations on real social networks and theoretical arguments using spectral methods, we demonstrate that highly contagious diseases that would have otherwise died out rapidly can persist indefinitely for an optimal range of modularity in contact networks.

  4. Genetic susceptibility to refractive error: association of vasoactive intestinal peptide receptor 2 (VIPR2 with high myopia in Chinese.

    Directory of Open Access Journals (Sweden)

    Wai Chi Yiu

    susceptibility to high myopia. EGR1, JUN, FOS and VIP are unlikely to be important in predisposing humans to high myopia.

  5. OPTIONS FOR USE OF APPROPRIATE ANTICOAGULANT THERAPY IN PATIENTS WITH THERMAL INJURY WITH A HIGH RISK OF THROMBOEMBOLIC COMPLICATIONS DEVELOPMENT ASSOCIATED WITH RECURRENT INTESTINAL BLEEDING

    Directory of Open Access Journals (Sweden)

    V. S. Borisov

    2015-01-01

    Full Text Available ABSTRACT. Patients with major thermal injury require anticoagulant therapy during almost the whole period of the burn disease, forcing the physician to balance constantly between the risk of possible bleeding associated with surgical treatment and the risk of thrombosis development in patients demonstrating a number of factors predisposing to the development of VTС. We report a clinical case of appropriate anticoagulant therapy using the new oral anticoagulants in a patient with a high risk of VTС development and recurrent bleeding from the tumor of the ascending colon. 

  6. Long-term effect of pegylated liposomal doxorubicin in recurrent platinum-resistant ovarian cancer: а clinical case

    Directory of Open Access Journals (Sweden)

    I. A. Pokataev

    2015-01-01

    Full Text Available Despite the high initial susceptibility of ovarian cancer (OC to chemotherapy, the vast majority of patients with Stages III–IV of the disease have its recurrences. Chemotherapy is a main treatment for recurrent OC. In Russia, the rate of platinum-resistant recurrences after first-line chemotherapy is more than 50 %, which may be due to the high extent of a tumor process at the moment of diagnosis, to the low rate of optimal cytoreductive interventions, and to non-optimal treatment. Many oncologists refuse to treat patients with recurrent platinum-resistant OC since the existing Russian and foreign guidelines point to the low efficiency of current chemotherapy for this type of recurrences. At the same time, whether chemotherapy should be used to treat platinum-resistant recurrences must be decided by taking into account a set of clinical factors that along with the duration of a platinum-free interval are also predictors for the efficiency of chemotherapy. These predictors should include mainly the histological pattern of a tumor; an immediate response to previous lines of chemotherapy; the number of previously used anticancer drugs; a patient’s general condition; and her existing factors that can influence the tolerability of chemotherapy. This paper describes a clinical case of a long-term survival in an OC patient who has developed a platinum-resistant recurrence just after first-line chemotherapy. Incomplete cross-resistance of the tumor to other drugs when a platinum-resistance recurrence develops, as well as its high susceptibility to the re-use of platinum-resistant derivatives possibly due to the artificial increase of a platinum-free interval should be identified among the factors that have influenced the prediction of treatment in this patient.

  7. Transoral robotic surgery for oncocytic ductal cyst of hypopharynx: a lesion with a high probability of recurrence.

    Science.gov (United States)

    Cadena, Enrique; Romero-Rojas, Alfredo; Guerra, Ricardo; Pérez-Mitchell, Carlos

    2017-11-06

    Hypopharyngeal cysts are very uncommon pathology. They are presented in adult people over 60 years. Although oncocytic cysts are benign tumors, an incomplete resection causes recurrence. The symptoms are not specific, but the more frequent are dyspnea and foreign body sensation upon swallowing. Diagnosis usually is under general anesthesia during intubation. A flexible fiberoptic laryngoscopy could be insufficient; the trumpet maneuver during this examination can reveled occult cysts. To perform a total resection, the surgeon must have a complete exposition of the operative field. We present a new case of a patient with a symptomatic hypopharyngeal cyst successfully treated with transoral robotic extirpation; our view was tridimensional magnified and the robotic instruments provided great range of movement that permitted complete and safe removal hypopharyngeal lesion.

  8. Hypoxia-Induced Intrauterine Growth Restriction Increases the Susceptibility of Rats to High-Fat Diet–Induced Metabolic Syndrome

    Science.gov (United States)

    Rueda-Clausen, Christian F.; Dolinsky, Vernon W.; Morton, Jude S.; Proctor, Spencer D.; Dyck, Jason R.B.; Davidge, Sandra T.

    2011-01-01

    OBJECTIVE It is recognized that there is a remarkable variability in the systemic response to high-fat (HF) diets that cannot be completely explained by genetic factors. In addition, pregnancy complications leading to intrauterine growth restriction (IUGR) have been associated with an increased risk of developing metabolic syndrome (MetS) later in life. Thus, we hypothesized that offspring born with IUGR exhibit permanent metabolic changes that make them more susceptible to HF diet–induced MetS. RESEARCH DESIGN AND METHODS SD rats born normal (control) or with hypoxia-induced IUGR were randomized to low-fat (10% fat) or HF (45% fat) diets. After 9 weeks of feeding, physiological and molecular pathways involved in the MetS were evaluated. RESULTS IUGR offspring exhibited decreased energy intake and physical activity relative to controls. In offspring fed a HF diet, IUGR was associated with decreased total body fat content, a relative increase in intra-abdominal fat deposition and adipocyte size, an increase in fasting plasma concentrations of leptin, triglyceride and free fatty acids, and an increased concentration of triglycerides and ceramides in both liver and skeletal muscle. These changes in lipid homeostasis were accompanied by in vivo insulin resistance and impaired glucose tolerance and associated with increased phosphorylation of protein kinase C θ, inhibition of insulin receptor substrate 1, and a decreased activation of protein kinase B (PKB; also known as Akt) in liver and skeletal muscle in response to insulin. CONCLUSIONS IUGR enhances specific deleterious metabolic responses to a HF diet. Our results suggest that offspring born with IUGR may require special attention and follow-up to prevent the early onset of MetS. PMID:21270262

  9. Recurrent partial mortality events in winter shape the dynamics of the zooxanthellate coral Oculina patagonica at high latitude in the Mediterranean

    Science.gov (United States)

    Serrano, Eduard; Ribes, Marta; Coma, Rafel

    2017-03-01

    Global warming has many biological effects on corals and plays a central role in the regression of tropical coral reefs; therefore, there is an urgent need to understand how some coral species have adapted to environmental conditions at higher latitudes. We examined the effects of temperature and light on the growth of the zooxanthellate coral Oculina patagonica (Scleractinia, Oculinidae) at the northern limit of its distribution in the eastern Iberian Peninsula (western Mediterranean) by transplanting colonies onto plates and excluding them from space competition over a 4-yr period. Each year, most of the colonies ( 70%) exhibited denuded skeletons with isolated polyps persisting on approximately half of the coral surface area. These recurrent episodes of partial coral mortality occurred in winter, and their severity appeared to be related to colony exposure to cold but not to light. Although O. patagonica exhibited high resistance to stress, coral linear extension did not resume until the coenosarc regenerated. The resumption of linear extension was related to the dissociation of the polyps from the coenosarc and the outstanding regenerative capacity of this species (10.3 mm2 d-1). These biological characteristics allow the species to survive at high latitudes. However, the recurrent and severe pattern of denuded skeletons greatly affects the dynamics of the species and may constrain population growth at high latitudes in the Mediterranean.

  10. Combined mutation and rearrangement screening by quantitative PCR high-resolution melting: is it relevant for hereditary recurrent Fever genes?

    Directory of Open Access Journals (Sweden)

    Nathalie Pallares-Ruiz

    2010-11-01

    Full Text Available The recent identification of genes implicated in hereditary recurrent fevers has allowed their specific diagnosis. So far however, only punctual mutations have been identified and a significant number of patients remain with no genetic confirmation of their disease after routine molecular approaches such as sequencing. The possible involvement of sequence rearrangements in these patients has only been examined in familial Mediterranean fever and was found to be unlikely. To assess the existence of larger genetic alterations in 3 other concerned genes, MVK (Mevalonate kinase, NLRP3 (Nod like receptor family, pyrin domain containing 3 and TNFRSF1A (TNF receptor superfamily 1A, we adapted the qPCR-HRM method to study possible intragenic deletions and duplications. This single-tube approach, combining both qualitative (mutations and quantitative (rearrangement screening, has proven effective in Lynch syndrome diagnosis. Using this approach, we studied 113 unselected (prospective group and 88 selected (retrospective group patients and identified no intragenic rearrangements in the 3 genes. Only qualitative alterations were found with a sensitivity similar to that obtained using classical molecular techniques for screening punctual mutations. Our results support that deleterious copy number alterations in MVK, NLRP3 and TNFRSF1A are rare or absent from the mutational spectrum of hereditary recurrent fevers, and demonstrate that a routine combined method such as qPCR-HRM provides no further help in genetic diagnosis. However, quantitative approaches such as qPCR or SQF-PCR did prove to be quick and effective and could still be useful after non contributory punctual mutation screening in the presence of clinically evocative signs.

  11. Clinical outcome of interstitial pulsed dose rate brachytherapy in multimodality treatment of locally advanced primary or recurrent rectal and sigmoid cancer with high risk of incomplete microscopic resection.

    Science.gov (United States)

    Nielsen, Mette Bak; Rasmussen, Peter Christian; Tanderup, Kari; Nielsen, Søren Kynde; Fokdal, Lars; Laurberg, Søren; Lindegaard, Jacob Christian

    2016-12-01

    To evaluate the role of interstitial pulsed dose rate brachytherapy (PDR-BT) in multimodality treatment of locally advanced primary or recurrent rectal and sigmoid cancer with high risk of microscopic incomplete resection (R1). A total of 73 consecutive patients (recurrent/primary: 40/33) were treated with PDR-BT between 2001 and 2010. Patients received preoperative external beam radiotherapy (EBRT) and concomitant chemotherapy. Following resection of the tumor and the involved pelvic organs, a median of four (3-8) catheters were sutured to the tumor bed with a distance of approximately 1 cm between the catheters. A target respecting the catheters with a margin of 5 mm was contoured on computed tomography (CT) and three-dimensional (3D) dose planning with a planning aim for BT of D90 > 30 Gy, (0.6 Gy/pulse, 1 pulse/h) was performed. Previously irradiated patients (27%) underwent surgery that was directly followed by PDR-BT. Postoperative EBRT was then applied to the tumor bed 3-5 weeks after PDR-BT. A total of 23 patients (31%) received a radical resection (R0) and 45 patients (62%) received an R1 resection. Five patients (7%) received a macroscopic incomplete resection (R2). The five-year overall survival was 33%. Local control at five years was 67% for patients who received a R0 resection and 32% for patients who received an R1 resection. The five-year actuarial risk of a grade 3-4 BT-related complication was 5%. Meaningful disease control and survival can be obtained at an acceptable rate of late morbidity in selected patients with locally advanced primary and recurrent rectal or sigmoid cancer using (chemo) RT, extensive surgery and PDR-BT when a high risk of an R1 resection is expected.

  12. Severe Obesity Impacts Recurrence-Free Survival of Women with High-Risk Endometrial Cancer: Results of a French Multicenter Study

    National Research Council Canada - National Science Library

    Canlorbe, Geoffroy; Bendifallah, Sofiane; Raimond, Emilie; Graesslin, Olivier; Hudry, Delphine; Coutant, Charles; Touboul, Cyril; Bleu, Géraldine; Collinet, Pierre; Darai, Emile; Ballester, Marcos

    2015-01-01

    Studies focusing on the impact of obesity on survival in endometrial cancer (EC) have reported controversial results and few data exist on the impact of obesity on recurrence rate and recurrence-free survival (RFS...

  13. High rate of non-susceptibility to metronidazole and clindamycin in anaerobic isolates: Data from a clinical laboratory from Karachi, Pakistan.

    Science.gov (United States)

    Sheikh, Sadia Omer; Jabeen, Kauser; Qaiser, Saba; Ahsan, Syed Tanwir; Khan, Erum; Zafar, Afia

    2015-06-01

    Due to increasing resistance amongst anaerobic pathogens periodic surveillance of resistance has been recommended in regional/local settings. Anaerobic antimicrobial susceptibility testing is not routinely performed in many laboratories in Pakistan, hence absence of local data may lead to inappropriate empirical therapy in serious cases. 121 clinically significant anaerobic strains (26/121; 21% bacteremic isolates) were isolated and saved from 2010 to 2011. Susceptibility testing against metronidazole, clindamycin, co-amoxiclav, meropenem, piperacillin/tazobactam, linezolid and gatifloxacin was performed by determining minimum inhibitory concentrations (MICs). A high proportion of non-susceptible strains to metronidazole (10% of 121 isolates) and clindamycin (12% of 121 isolates) was seen, most noticeable in Bacteroides fragilis. Three Bacteroides species strains were non-susceptible to both metronidazole and clindamycin. One strain of Clostridium species was fully resistant to metronidazole and had intermediate resistance to clindamycin. No resistance to any of the other tested antibiotics was seen. Resistance to metronidazole was higher in bacteremic vs. non bacteremic isolates (p = value 0.07). In our setting where there is a high usage of empirical metronidazole and clindamycin for the treatment of serious anaerobic infections clinicians should be aware of increased resistance to these agents. Periodic surveillance of resistance to anti-anaerobic drugs especially metronidazole and clindamycin should be performed to generate antibiogram and guide appropriate empiric therapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Increased iron accumulation occurs in the earliest stages of demyelinating disease: an ultra-high field susceptibility mapping study in Clinically Isolated Syndrome.

    Science.gov (United States)

    Al-Radaideh, Ali M; Wharton, Samuel J; Lim, Su-Yin; Tench, Christopher R; Morgan, Paul S; Bowtell, Richard W; Constantinescu, Cris S; Gowland, Penny A

    2013-06-01

    To determine, using ultra-high field magnetic resonance imaging (MRI), whether changes in iron content occur in the earliest phases of demyelinating disease, by quantifying the magnetic susceptibility of deep grey matter structures in patients with Clinically Isolated Syndrome (CIS) that is suggestive of multiple sclerosis (MS), as compared with age-matched healthy subjects. We compared 19 CIS patients to 20 age-matched, healthy controls. Scanning of the study subjects was performed on a 7T Philips Achieva system, using a 3-dimensional, T2*-weighted gradient echo acquisition. Phase data were first high-pass filtered, using a dipole fitting method, and then inverted to produce magnetic susceptibility maps. Region of interest (ROI) analysis was used to estimate magnetic susceptibility values for deep grey matter structures (caudate nucleus, putamen, globus pallidus, the thalamus and its pulvinar). Significantly increased relative susceptibilities were found in the CIS group, compared with controls, for the caudate nucleus (p = 0.05). In CIS patients, the time elapsed since the clinical event and the Expanded Disability Status Scale (EDSS) scores were not correlated with iron levels in any ROI (r(2) 0.05); however, a moderate correlation (r(2) = 0.3; p disease.

  15. Gender-specific increase in susceptibility to metabolic syndrome of offspring rats after prenatal caffeine exposure with post-weaning high-fat diet

    Energy Technology Data Exchange (ETDEWEB)

    Li, Jing [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Luo, Hanwen [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Wu, Yimeng; He, Zheng; Zhang, Li; Guo, Yu [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Ma, Lu [Department of Epidemiology & Health Statistics, Public Health School of Wuhan University, Wuhan 430071 (China); Magdalou, Jacques [UMR 7561 CNRS-NancyUniversité, Faculté de Médicine, Vandoeuvre-lès-Nancy (France); Chen, Liaobin [Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan 430071 (China); Wang, Hui, E-mail: wanghui19@whu.edu.cn [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan 430071 (China)

    2015-05-01

    Prenatal caffeine exposure (PCE) alters the hypothalamic–pituitary–adrenocortical (HPA) axis-associated neuroendocrine metabolic programming and induces an increased susceptibility to metabolic syndrome (MS) in intrauterine growth retardation (IUGR) offspring rats. High-fat diet (HFD) is one of the main environmental factors accounting for the incidence of MS. In this study, we aimed to clarify the gender-specific increase in susceptibility to MS in offspring rats after PCE with post-weaning HFD. Maternal Wistar rats were administered with caffeine (120 mg/kg·d) from gestational day 11 until delivery. The offspring rats with normal diet or HFD were euthanized at postnatal week 24, and blood samples were collected. Results showed that PCE not only reduced serum adrenocorticotropic hormone (ACTH) and corticosterone levels, but also enhanced serum glucose, triglyceride and total cholesterol (TCH) concentrations in the offspring rats. Moreover, several interactions among PCE, HFD and gender were observed by a three-way ANOVA analysis. In PCE offspring, HFD could aggravate the degree of increased serum triglyceride level. Meanwhile, serum corticosterone levels of females were decreased more obviously than those of males in PCE offspring. The results also revealed interactions between HFD and gender in the levels of serum ACTH, triglyceride and TCH, which were changed more evidently in female HFD offspring. These results indicate that HFD could exacerbate the dysfunction of lipid metabolism and the susceptibility to MS induced by PCE, and the female offspring are more sensitive to HFD-induced neuroendocrine metabolic dysfunction than their male counterparts. - Highlights: • Caffeine induced HPA axis dysfunction in offspring rats fed by high-fat diet (HFD). • Caffeine induced an increased susceptibility to metabolic syndrome. • HFD aggravated susceptibility to metabolic syndrome induced by caffeine. • Female was more sensitive to HFD-induced neuroendocrine

  16. Recurrences after intensity modulated radiotherapy for head and neck squamous cell carcinoma more likely to originate from regions with high baseline [18F]-FDG uptake

    DEFF Research Database (Denmark)

    Due, Anne K.; Vogelius, Ivan R.; Aznar, Marianne C.

    2014-01-01

    received radiotherapy for HNSCC from 2005 to 2009. Among 100 patients achieving complete clinical response and a later recurrence, 39 patients with 48 loco-regional failures had a recurrence CT scan before any salvage therapy. The estimated point of origin of each recurrence was transferred to the planning...

  17. The multidimensional cube recurrence

    NARCIS (Netherlands)

    Henriques, A.G.|info:eu-repo/dai/nl/314131132; Speyer, D.E.

    2010-01-01

    We introduce a recurrence which we term the multidimensional cube recurrence, generalizing the octahedron recurrence studied by Propp, Fomin and Zelevinsky, Speyer, and Fock and Goncharov and the three-dimensional cube recurrence studied by Fomin and Zelevinsky, and Carroll and Speyer. The states of

  18. Salvage prostate re-irradiation using high-dose-rate brachytherapy or focal stereotactic body radiotherapy for local recurrence after definitive radiation therapy.

    Science.gov (United States)

    Mbeutcha, Aurélie; Chauveinc, Laurent; Bondiau, Pierre-Yves; Chand, Marie-Eve; Durand, Matthieu; Chevallier, Daniel; Amiel, Jean; Kee, Daniel Lam Cham; Hannoun-Lévi, Jean-Michel

    2017-03-09

    Optimal management of locally recurrent prostate cancer after definitive radiation therapy is still challenging. With the development of highly accurate radiotherapy devices, prostate salvage re-irradiation might generate lower toxicity rates than classical salvage therapies. We retrospectively evaluated the toxicity and the feasibility of a prostate re-irradiation after definitive radiation therapy failure. Two modalities were investigated: high-dose-rate brachytherapy (HDRB) on whole prostate gland and focal stereotactic radiotherapy (SBRT) using CyberKnife® linac. Between 2011 and 2015, 28 patients with imaged and/or biopsy-proven intra-prostatic recurrence of cancer after definitive radiation therapy underwent a salvage re-irradiation using HDRB (n = 10) or focal SBRT (n = 18). The schedule of re-irradiation was 35 Gy in 5 fractions. Biological response (defined as post-salvage radiation PSA variation) and biochemical no-evidence of disease (bNED) were evaluated in the whole cohort. For patients who had a positive biological response after salvage radiation, biochemical recurrence (BCR) and survival after salvage radiotherapy were evaluated. Post-salvage toxicities were assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) v4.03 and were compared to baseline status. Within a median follow-up of 22.5 months (IQR = 8-42), 9 (90%) patients experienced a positive biological response after salvage HDRB and 5 (50%) remained bNED at the end of the follow-up. Among patients who initially responded to salvage HDRB, the BCR rate was 44.4% after a median interval of 19.5 months (IQR = 11.5-26). Only one patient experienced a transient grade 3 urinary complication. In the SBRT group, the median follow-up was 14.5 months (IQR = 7-23) and 10 (55.6%) out of the 18 patients remained bNED. Among the 15 patients who initially responded to salvage SBRT, 5 (33.3%) experienced a BCR. One patient experienced a transient grade 4

  19. Clinical Evaluation of High and Low-Level Laser Treatment (CO2vsInGaAlP Diode Laser) for Recurrent Aphthous Stomatitis.

    Science.gov (United States)

    Zeini Jahromi, Nasim; Ghapanchi, Janan; Pourshahidi, Sara; Zahed, Maryam; Ebrahimi, Hooman

    2017-03-01

    Recurrent aphthous stomatitis (RAS) is one of the most common lesions in the oral cavity. Due to its multifactorial nature, there is no definitive treatment for RAS. Laser therapy is one of the suggested treatments to reduce patient's discomfort. The purpose of the present clinical trial is to assess the effect of low and high level laser therapy on pain control and wound healing of RAS. Thirty six patients with minor RAS were divided into three groups. Group 1 (n=14) received CO2 laser, group 2 (n=12) were treated with InGaAlP Diode laser and group 3 (n=10) received sham laser as placebo. All patients were evaluated daily up to 15 days after receiving one session of laser therapy. Pain severity before and after treatment, wound healing, patient's satisfaction, and functional disturbance before and after treatment were recorded for each patient. According to statistical analysis, pain reduction after treatment in group 1 was 7.00±2.41, in group 2 was 2.08±2.31, and in group 3 was 1.40±1.77. In addition, a significant difference was observed in the reduction of functional complications in CO2 laser treated patients compared to the other two groups. High-level laser treatment showed analgesic effects on RAS, but no healing was observed. Low-level laser therapy demonstrated no positive effect on recurrent aphthous ulcers.

  20. Severe Obesity Impacts Recurrence-Free Survival of Women with High-Risk Endometrial Cancer: Results of a French Multicenter Study.

    Science.gov (United States)

    Canlorbe, Geoffroy; Bendifallah, Sofiane; Raimond, Emilie; Graesslin, Olivier; Hudry, Delphine; Coutant, Charles; Touboul, Cyril; Bleu, Géraldine; Collinet, Pierre; Darai, Emile; Ballester, Marcos

    2015-08-01

    Studies focusing on the impact of obesity on survival in endometrial cancer (EC) have reported controversial results and few data exist on the impact of obesity on recurrence rate and recurrence-free survival (RFS). The aim of this study was to assess the impact of obesity on surgical staging and RFS in EC according to the European Society of Medical Oncology (ESMO) risk groups. Data of 729 women with EC who received primary surgical treatment between January 2000 and December 2012 were abstracted from a multicenter database. RFS distributions according to body mass index (BMI) in each ESMO risk group were estimated using the Kaplan-Meier method. Survival was evaluated using the log-rank test, and the Cox proportional hazards model was used to determine influence of multiple variables. Distribution of the 729 women with EC according to BMI was BMI obese women in the low-/intermediate-risk groups, but a BMI ≥ 35 was independently correlated to a poorer RFS (hazard ratio 12.5; 95 % confidence interval 3.1-51.3) for women in the high-risk group. Severe obesity negatively impacts RFS in women with high-risk EC, underlining the importance of complete surgical staging and adapted adjuvant therapies in this subgroup of women.

  1. EFFECTS OF MATERNAL HIGH FAT DIET AND SEDENTARY LIFESTYLE ON SUSCEPTIBILITY OF ADULT OFFSPRING TO OZONE EXPOSURE IN RATS

    Science.gov (United States)

    Epidemiological and experimental data suggest that obesity exacerbates the health effects of air pollutants such as ozone (O3). Maternal inactivity and calorically rich diets lead to offspring that show signs of obesity. Exacerbated O3 susceptibility of offspring could thus be m...

  2. Seminational surveillance of fungemia in Denmark: notably high rates of fungemia and numbers of isolates with reduced azole susceptibility

    DEFF Research Database (Denmark)

    Arendrup, Maiken Cavling; Fuursted, Kurt; Gahrn-Hansen, Bente

    2005-01-01

    The aim of this study was to present the first set of comprehensive data on fungemia in Denmark including the distribution of species and range of susceptibility to major antifungal compounds based on a seminational surveillance study initiated in 2003. The catchment area of the participating hos...

  3. Genome-wide high-density SNP linkage search for glioma susceptibility loci: results from the Gliogene Consortium

    DEFF Research Database (Denmark)

    Shete, Sanjay; Lau, Ching C; Houlston, Richard S

    2011-01-01

    Gliomas, which generally have a poor prognosis, are the most common primary malignant brain tumors in adults. Recent genome-wide association studies have shown that inherited susceptibility plays a role in the development of glioma. Although first-degree relatives of patients exhibit a two-fold i...

  4. Assessment of the Relationship between Recurrent High-risk Pregnancy and Mothers’ Previous Experience of Having an Infant Admitted to a Neonatal Intensive Care Unit

    Directory of Open Access Journals (Sweden)

    Sedigheh Hantoosh Zadeh

    2015-01-01

    Full Text Available Background & aim:  High-risk pregnancies increase the risk of Intensive Care Unit (ICU and Neonatal Intensive Care Unit (NICU admission in mothers and their newborns. In this study, we aimed to identify the association between the recurrence of high-risk pregnancy and mothers’ previous experience of having an infant admitted to NICU. Methods:We performed a cohort, retrospective study to compare subsequent pregnancy outcomes among 232 control subjects and 200 female cases with a previous experience of having a newborn requiring NICU admission due to intrauterine growth retardation, preeclampsia, preterm birth, premature rupture of membranes, and asphyxia. The information about the prevalence of subsequent high-risk pregnancies was gathered via phone calls. Results: As the results indicated, heparin, progesterone, and aspirin were more frequently administered in the case group during subsequent pregnancies, compared to the control group (P

  5. High-dose-rate brachytherapy with or without intensity modulated radiation therapy as salvage treatment for an isolated, gross local recurrence of prostate cancer post-prostatectomy.

    Science.gov (United States)

    Strom, Tobin J; Wilder, Richard B; Fernandez, Daniel C; Mellon, Eric A; Saini, Amarjit S; Hunt, Dylan C; Biagioli, Matthew C

    2014-01-01

    To evaluate the use of high-dose-rate (HDR) brachytherapy ± intensity modulated radiation therapy (IMRT) as salvage therapy for patients with an isolated, gross local recurrence of prostate cancer after radical prostatectomy. Between October 2009 and May 2013, the authors treated six patients with salvage iridium-192 HDR brachytherapy ± IMRT for biopsy-proven, recurrent prostate cancer post-prostatectomy. In each patient, a pelvic MRI scan or CT scan demonstrated a nodule (range 1.6, 4.7 cm) in the prostate bed. Although prostate-specific antigen values were 0.2-9.5 ng/mL at the time of salvage brachytherapy, there was no pelvic adenopathy on CT or MRI scan, and a bone scan was negative in all cases. Five patients were treated with IMRT to 4500-5040 cGy in 25-28 fractions to the prostate bed followed by two 950 cGy HDR brachytherapy fractions separated by 1-2 weeks. A sixth patient underwent HDR brachytherapy monotherapy consisting of 3800 cGy in four fractions over 3 days. Toxicities were graded according to the Common Terminology Criteria for Adverse Events, version 4.0. Median followup was 9 months (range 3, 40 months). All six patients have been free of androgen deprivation therapy and have an undetectable prostate-specific antigen. One patient developed late Grade 2 urinary incontinence. There was no late grade ≥2 gastrointestinal toxicity. HDR brachytherapy ± IMRT is a safe and effective salvage therapy option for an isolated, gross local recurrence of prostate cancer after radical prostatectomy and merits further study. Copyright © 2014. Published by Elsevier Inc.

  6. Reirradiation of head and neck cancer with high-dose-rate brachytherapy: a customizable intraluminal solution for postoperative treatment of tracheal mucosa recurrence.

    Science.gov (United States)

    Doyle, Laura A; Harrison, Amy S; Cognetti, David; Xiao, Ying; Yu, Yan; Liu, Haisong; Ahn, Peter H; Anné, P Rani; Showalter, Timothy N

    2011-01-01

    Delivering adequate dose to tracheal mucosa recurrence after multiple prior courses of surgery and radiation presented a challenge for radiation delivery. Tumor bed location and size, combined with previous doses to surrounding areas, complicated the use of external beam therapy with either photons or electrons. High-dose-rate (HDR) brachytherapy was explored to provide sufficient dose coverage. A 45-year-old gentleman presented with recurrent head and neck cancer. After undergoing additional excision of gross tumor in the tracheal region, radiation was recommended to improve local control. The region of residual tumor was confined to a small superficial lesion at the posterior-superior aspect of the trachea, involving mucosa located along the bend of the trachea, immediately deep to the stoma. External beam treatment was discussed but was not recommended based on recurrence location in the prior radiation field and patient's flexed chin position. HDR technique with a custom applicator was preferred. A three-dimensional HDR plan based on computed tomography used a single catheter optimized to cover gross tumor volume as delineated by physician. Prescribed dose was 5 Gy/fraction for six fractions (two fractions/wk). The applicator position was verified daily with computed tomography and physician setup approval before treatment. The patient was positioned on a wing board to allow access to the stoma. HDR brachytherapy was well tolerated. Intraluminal HDR brachytherapy is a viable option for providing dose to region inside tracheal stoma. Advantages over photon and electron beam therapy include reduced dose to surrounding tissues previously irradiated, skin dose, and reproducibility of treatment delivery. Copyright © 2011 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

  7. Biphasic {sup 68}Ga-PSMA-HBED-CC-PET/CT in patients with recurrent and high-risk prostate carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Sahlmann, Carsten-Oliver; Meller, Birgit; Bouter, Caroline; Meller, Johannes [University Medical Center Goettingen, Department of Nuclear Medicine, Goettingen (Germany); Ritter, Christian Oliver; Lotz, Joachim [University Medical Center Goettingen, Department of Diagnostic and Interventional Radiology, Goettingen (Germany); Stroebel, Philipp [University Medical Center Goettingen, Department of Pathology, Goettingen (Germany); Trojan, Lutz; Hijazi, Sameh [University Medical Center Goettingen, Department of Urology, Goettingen (Germany)

    2016-05-15

    Binding of {sup 68}Ga-PSMA-HBED-CC ({sup 68}Ga-PSMA) at prostate cancer (PC) cells increases over time. A biphasic protocol may help separating benign from tumor lesions. The aim of this study was the retrospective evaluation of a diagnostic incremental value of a dual-time point (biphasic) {sup 68}Ga-PSMA-PET/CT in patients with prostate cancer. Retrospective analysis of 35 consecutive patients (49-78 years, median 71) with newly diagnosed PC (12/35) or recurrence of PC (23/35). PET/CT (Gemini TF16, Philips) was acquired 1 h and 3 h p. i. of 140-392 MBq (300 MBq median) {sup 68}Ga-PSMA, followed by a diagnostic contrast CT. PET findings were correlated with histology or unequivocal CT findings. Semiquantitative PET data (SUVmax, SUV mean) were acquired and target-to-background-ratios (T/B-ratio) were calculated for benign and malign lesions for both time points. Size of lymph nodes (LN) on diagnostic CT was recorded. Statistical analysis was performed for assessment of significant changes of semiquantitative PET-parameters over time and for correlation of size and uptake of lymph nodes. One hundred and four lesions were evaluated. Sixty lesions were referenced by histology or unequivocal CT findings, including eight (13.3 %) histopathologically benign lymph nodes, 12 (20 %) histopathologically lymph node metastases, 12 (20 %) primary tumors, three (5 %) local recurrences, and 25 (41.7 %) bone metastases. Forty-four lesions were axillary LN with normal CT-appearance. Benign lesions had significantly lower SUVmax and T/B-ratios compared with malignant findings. Malign lesions showed a significant increase of both parameters over time compared to benign findings. There was no correlation between LN size and SUVmax. The sensitivity, specificity, the positive predictive value and negative predictive value of PET/CT regarding pelvic LN was 94 %, 99 %, 89 %, and 99.5 %, respectively. In contrast to benign tissues, the uptake of proven tumor lesions increases on {sup 68

  8. Multiplex Recurrence Networks

    Science.gov (United States)

    Eroglu, Deniz; Marwan, Norbert

    2017-04-01

    The complex nature of a variety of phenomena in physical, biological, or earth sciences is driven by a large number of degrees of freedom which are strongly interconnected. Although the evolution of such systems is described by multivariate time series (MTS), so far research mostly focuses on analyzing these components one by one. Recurrence based analyses are powerful methods to understand the underlying dynamics of a dynamical system and have been used for many successful applications including examples from earth science, economics, or chemical reactions. The backbone of these techniques is creating the phase space of the system. However, increasing the dimension of a system requires increasing the length of the time series in order get significant and reliable results. This requirement is one of the challenges in many disciplines, in particular in palaeoclimate, thus, it is not easy to create a phase space from measured MTS due to the limited number of available obervations (samples). To overcome this problem, we suggest to create recurrence networks from each component of the system and combine them into a multiplex network structure, the multiplex recurrence network (MRN). We test the MRN by using prototypical mathematical models and demonstrate its use by studying high-dimensional palaeoclimate dynamics derived from pollen data from the Bear Lake (Utah, US). By using the MRN, we can distinguish typical climate transition events, e.g., such between Marine Isotope Stages.

  9. Preventing Relapse/Recurrence in Recurrent Depression With Cognitive Therapy: A Randomized Controlled Trial

    Science.gov (United States)

    Bockting, Claudi L. H.; Schene, Aart H.; Spinhoven, Philip; Koeter, Maarten W. J.; Wouters, Luuk F.; Huyser, Jochanan; Kamphuis, Jan H.

    2005-01-01

    This article reports on the outcome of a randomized controlled trial of cognitive group therapy (CT) to prevent relapse/recurrence in a group of high-risk patients diagnosed with recurrent depression. Recurrently depressed patients (N = 187) currently in remission following various types of treatment were randomized to treatment as usual,…

  10. High association of angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism with recurrent aphthous stomatitis.

    Science.gov (United States)

    Karakus, Nevin; Yigit, Serbulent; Kalkan, Goknur; Sezer, Saime

    2013-08-01

    Recurrent aphthous stomatitis (RAS) is a common ulcerative disease of the oral mucosa. Oral ulcers are also the most common feature of Behçet's disease (BD). Association of angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism with BD has been reported in Turkish population. The aim of the present study was to investigate the possible association between ACE gene I/D polymorphism and RAS, and evaluate if there was an association with clinical features in a relatively large cohort of Turkish patients. The study included 198 patients affected by RAS and 214 healthy controls. ACE gene I/D polymorphism genotypes were determined using polymerase chain reaction with I and D allele-specific primers. The genotype and allele frequencies of I/D polymorphism showed statistically significant differences between RAS patients and controls (p < 0.0001 and p < 0.0001, respectively). After stratifying RAS patients according to clinical and demographical characteristics, no significant association was observed. In conclusion, the results of this study suggest that I/D polymorphism of the ACE gene was positively associated with predisposition to develop RAS in Turkish population. Further studies with larger populations are recommended.

  11. Recurrent Omental Hemangiopericytoma: A Therapeutic Challenge

    Directory of Open Access Journals (Sweden)

    Sara Jaber

    2016-01-01

    Full Text Available Hemangiopericytomas are vascular tumors with a susceptibility to arise anywhere in the human body. We present a case of a 68-year-old female with primary omental hemangiopericytoma and a two-time recurrence managed with surgery and close follow-up. The first recurrence was at 52 months and the second at 37 months following the prior presentation. No adjuvant chemotherapy or radiation therapy was administered. Given the widespread nature of the cell of origin, routine follow-up postoperatively with interval imaging in order to detect recurrences is imperative. Pathologic tumor characteristics may determine potential for recurrence and may also assist in determining whether adjuvant treatment modalities should be included in the management plan. Review of the English literature reveals a total of 24 cases of omental hemangiopericytomas inclusive of the current report.

  12. Variants of cancer susceptibility genes in Korean BRCA1/2 mutation-negative patients with high risk for hereditary breast cancer.

    Science.gov (United States)

    Park, Ji Soo; Lee, Seung-Tae; Nam, Eun Ji; Han, Jung Woo; Lee, Jung-Yun; Kim, Jieun; Kim, Tae Il; Park, Hyung Seok

    2018-01-16

    We evaluated the incidence and spectrum of pathogenic and likely pathogenic variants of cancer susceptibility genes in BRCA1/2 mutation-negative Korean patients with a high risk for hereditary breast cancer using a comprehensive multigene panel that included 35 cancer susceptibility genes. Samples from 120 patients who were negative for BRCA1/2 mutations, but had been diagnosed with breast cancer that was likely hereditary, were prospectively evaluated for the prevalence of high-penetrance and moderate-penetrance germline mutations. Nine patients (7.5%) had at least one pathogenic or likely pathogenic variant. Ten variants were identified in these patients: TP53 in two patients, PALB2 in three patients, BARD1 in two patients, BRIP1 in two patients, and MRE11A in one patient. We also identified 30 types of 139 variants of unknown significance (VUS). High-penetrance germline mutations, including TP53 and PALB2, tended to occur with high frequency in young (cancer patients (4/19, 21.1%) than in those diagnosed with breast cancer at ≥35 years of age (1/101, 1.0%; p = 0.003). These combined results demonstrate that multigene panels offer an alternative strategy for identifying veiled pathogenic and likely pathogenic mutations in breast cancer susceptibility genes.

  13. Diamagnetic susceptibility obtained from the six-vertex model and its implications for the high-temperature diamagnetic state of cuprate superconductors.

    Science.gov (United States)

    Sau, Jay D; Tewari, Sumanta

    2011-10-21

    We study the diamagnetism of the six-vertex model with the arrows as directed bond currents. To our knowledge, this is the first study of the diamagnetism of this model. A special version of this model, called the F model, describes the thermal disordering transition of an orbital antiferromagnet, known as d-density wave, a proposed state for the pseudogap phase of the high-T(c) cuprates. We find that the F model is strongly diamagnetic and the susceptibility may diverge in the high-temperature critical phase with power-law arrow correlations. These results may explain the surprising recent observation of a diverging low-field diamagnetic susceptibility seen in some optimally doped cuprates within the d-density wave model of the pseudogap phase. © 2011 American Physical Society

  14. Predictive factors of late biochemical recurrence after radical prostatectomy.

    Science.gov (United States)

    Negishi, Takahito; Kuroiwa, Kentarou; Hori, Yoshifumi; Tomoda, Toshihisa; Uchino, Hiroshi; Tokuda, Noriaki; Furubayashi, Nobuki; Nagase, Kei; Iwai, Hidenori; Nakamura, Motonobu

    2017-03-01

    To assess the characteristics of biochemical recurrence in the late period (>5 years after radical prostatectomy) and the differences in the predictors of biochemical recurrence in different periods, we conducted a multicenter retrospective study. We reviewed 478 men who underwent radical prostatectomy for clinically localized prostate cancer. All of the patients were followed up for at least 5 years. The cohort was then divided into three groups; no recurrence group, recurrence biochemical recurrence in each period. Biochemical recurrence occurred in 135 men. In 113 (84%) of the patients, biochemical recurrence occurred at biochemical recurrence at biochemical recurrence at ≥5 years after surgery (hazard ratio: 3.03); however, a high preoperative prostate-specific antigen level was not. Biochemical recurrence occurred at ≥5 years after surgery in 16% of the patients. A positive surgical margin predicted biochemical recurrence in both the early and late periods.

  15. Discriminant Analysis of 18F-Fluoro-Thymidine Kinetic Parameters to Predict Survival in Patients with Recurrent High-Grade Glioma

    Science.gov (United States)

    Wardak, Mirwais; Schiepers, Christiaan; Dahlbom, Magnus; Cloughesy, Timothy; Chen, Wei; Satyamurthy, Nagichettiar; Czernin, Johannes; Phelps, Michael E.; Huang, Sung-Cheng

    2011-01-01

    Purpose The primary objective of this study was to investigate if changes in 18F-FLT kinetic parameters, taken at an early stage after start of therapy, could predict overall survival (OS) and progression-free survival (PFS) in patients with recurrent malignant glioma undergoing treatment with bevacizumab and irinotecan. Experimental Design High-grade recurrent brain tumors were investigated in 18 patients (8M, 10F), 26-76 yr. Each had 3 dynamic PET studies: at baseline, and after 2 weeks, and 6 weeks from the start of treatment. 2.0 MBq/kg of 18F-FLT was injected intravenously and dynamic PET images acquired for 1 hr. Factor analysis generated factor images from which blood and tumor uptake curves were derived. A 3-compartment, 2-tissue model was applied to estimate the tumor 18F-FLT kinetic rate constants using a metabolite and partial volume corrected input function. Different combinations of predictor variables were exhaustively searched in a discriminant function to accurately classify patients into their known OS and PFS groups. A leave-one-out cross-validation technique was used to assess the generalizability of the model predictions. Results In this study population, changes in single parameters such as standardized uptake value or influx rate constant did not accurately classify patients into their respective OS groups (Discriminant analysis using changes in 18F-FLT kinetic parameters early during treatment appears to be a powerful method for evaluating the efficacy of therapeutic regimens. PMID:21868765

  16. Genome-Based Analysis of Enterococcus faecium Bacteremia Associated with Recurrent and Mixed-Strain Infection.

    Science.gov (United States)

    Raven, Kathy E; Gouliouris, Theodore; Parkhill, Julian; Peacock, Sharon J

    2018-03-01

    Vancomycin-resistant Enterococcus faecium (VREfm) bloodstream infections are associated with high recurrence rates. This study used genome sequencing to accurately distinguish the frequency of relapse and reinfection in patients with recurrent E. faecium bacteremia and to investigate strain relatedness in patients with apparent VREfm and vancomycin-susceptible E. faecium (VSEfm) mixed infection. A retrospective study was performed at the Cambridge University Hospitals NHS Foundation Trust (CUH) between November 2006 and December 2012. We analyzed the genomes of 44 E. faecium isolates from 21 patients (26 VREfm isolates from 12 patients with recurrent bacteremia and 18 isolates from 9 patients with putative VREfm/VSEfm mixed infection). Phenotypic antibiotic susceptibility was determined using a Vitek2 instrument. Genomes were compared with those of a further 263 E. faecium isolates associated with bacteremia in patients at CUH over the same time period. Pairwise comparison of core genomes indicated that 10 (71%) episodes of recurrent VREfm bacteremia were due to reinfection with a new strain, with reinfection being more likely with increasing time between the two positive cultures. The majority (78%) of patients with a mixed VREfm and VSEfm infection had unrelated strains. More than half (59%) of study isolates were closely related to another isolate associated with bacteremia from CUH. This included 60% of isolates associated with reinfection, indicating acquisition in the hospital. This study provides the first high-resolution insights into recurrence and mixed infection by E. faecium and demonstrates that reinfection with a new strain, often acquired from the hospital, is a driver of recurrence. Copyright © 2018 Raven et al.

  17. High-fat/fructose feeding during prenatal and postnatal development in female rats increases susceptibility to renal and metabolic injury later in life

    OpenAIRE

    Flynn, Elizabeth R.; Alexander, Barbara T.; Lee, Jonathan; Hutchens, Zachary M.; Maric-Bilkan, Christine

    2012-01-01

    Accumulating evidence suggests that both an adverse prenatal and early postnatal environment increase susceptibility to renal and metabolic dysfunction later in life; however, whether exposure to adverse conditions during both prenatal and postnatal development act synergistically to potentiate the severity of renal and metabolic injury remains unknown. Sprague-Dawley rats were fed either a standard diet or a diet high in fat/fructose throughout pregnancy and lactation. After being weaned, fe...

  18. Enhanced Metastatic Recurrence Via Lymphatic Trafficking of a High-Metastatic Variant of Human Triple-Negative Breast Cancer After Surgical Resection in Orthotopic Nude Mouse Models.

    Science.gov (United States)

    Yano, Shuya; Takehara, Kiyoto; Tazawa, Hiroshi; Kishimoto, Hiroyuki; Kagawa, Shunsuke; Bouvet, Michael; Fujiwara, Toshiyoshi; Hoffman, Robert M

    2017-03-01

    We previously developed and characterized a highly invasive and metastatic triple-negative breast cancer (TNBC) variant by serial orthotopic implantation of MDA-MB-231 human breast cancer cells in nude mice. Eventually, a highly invasive and metastatic variant of human TNBC was isolated after lymph node metastases was harvested and orthotopically re-implanted into the mammary gland of nude mice for two cycles. The variant thereby isolated is highly invasive in the mammary gland and metastasized to lymph nodes in 10 of 12 mice compared to 2 of 12 of the parental cell line. In the present report, we observed that high-metastatic MDA-MB-231H-RFP cells produced significantly larger subcutaneous tumors compared with parental MDA-MB-231 cells in nude mice. Extensive lymphatic trafficking by high-metastatic MDA-MB-231 cells was also observed. High-metastatic MDA-MB-231 developed larger recurrent tumors 2 weeks after tumor resection compared with tumors that were not resected in orthotopic models. Surgical resection of the MDA-MB-231 high-metastatic variant primary tumor in orthotopic models also resulted in rapid and enhanced lymphatic trafficking of residual cancer cells and extensive lymph node and lung metastasis that did not occur in the non-surgical mice. These results suggest that surgical resection of high metastatic TNBC can greatly increase the malignancy of residual cancer. J. Cell. Biochem. 118: 559-569, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  19. Stress corrosion cracking susceptibility of a high strength Mg-7%Gd-5%Y-1%Nd-0.5%Zr alloy

    Directory of Open Access Journals (Sweden)

    S.D. Wang

    2014-12-01

    Full Text Available Through performing the tensile tests with different strain rates in 3.5 wt.% NaCl solution, the stress corrosion cracking (SCC behavior and the effect of strain rate on the SCC susceptibility of an extruded Mg-7%Gd-5%Y-1%Nd-0.5%Zr (EW75 alloy have been investigated. Results demonstrate that the alloy is susceptible to SCC when the strain rate is lower than 5 × 10−6 s−1. At the strain rate of 1 × 10−6 s−1, the SCC susceptibility index (ISCC is 0.96 and the elongation-to-failure (εf is only 0.11%. Fractography indicates that the brittle quasi-cleavage feature is very obvious and become more pronounced with decreasing the strain rate. Further analysis confirms that the cracking mode is predominantly transgranular, but the partial intergranular cracking at some localized area can also occur. Meanwhile, it seems that the crack propagation path is unrelated to the existing phase particles.

  20. Detection and Characterization of Infections and Infection Susceptibility

    Science.gov (United States)

    2017-12-13

    Immune Disorders; Chronic Granulomatous Disease; Genetic Immunological Deficiencies; Hyperimmunoglobulin-E Recurrent Infection Syndrome; Recurrent Infections; Unknown Immune Deficiency; GATA2 Deficiency (MonoMAC); Nontuberculous Mycobacterial Infections; Hyper IgE (Job s) Syndrome; Leukocyte Adhesion Deficiency; Susceptibility to Disseminated Infections; Primary Immune Deficiency Disease (PIDD)

  1. Double oral esomeprazole after a 3-day intravenous esomeprazole infusion reduces recurrent peptic ulcer bleeding in high-risk patients: a randomised controlled study.

    Science.gov (United States)

    Cheng, Hsiu-Chi; Wu, Chung-Tai; Chang, Wei-Lun; Cheng, Wei-Chun; Chen, Wei-Ying; Sheu, Bor-Shyang

    2014-12-01

    Patients with high Rockall scores have increased risk of ulcer rebleeding after 3-day esomeprazole infusions. To investigate whether double oral esomeprazole given after a 3-day esomeprazole infusion decreases ulcer rebleeding for patients with high Rockall scores. We prospectively enrolled 293 patients with peptic ulcer bleeding who had achieved endoscopic haemostasis. After a 3-day esomeprazole infusion, patients with Rockall scores ≥6 were randomised into the oral double-dose group (n=93) or the oral standard-dose group (n=94) to receive 11 days of oral esomeprazole 40 mg twice daily or once daily, respectively. The patients with Rockall scores esomeprazole 40 mg once daily. Thereafter, all patients received oral esomeprazole 40 mg once daily for two more weeks until the end of the 28-day study period. The primary end point was peptic ulcer rebleeding. Among patients with Rockall scores ≥6, the oral double-dose group had a higher cumulative rebleeding-free proportion than the oral standard-dose group (p=0.02, log-rank test). The proportion of patients free from recurrent bleeding during the 4th-28th day in the oral double-dose group remained lower than that of the group with Rockall scores esomeprazole at 40 mg twice daily after esomeprazole infusion reduced recurrent peptic ulcer bleeding in high-risk patients with Rockall scores ≥6. NCT01591083. 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.

  2. Genetic diagnosis of high-penetrance susceptibility for colorectal cancer (CRC) is achievable for a high proportion of familial CRC by exome sequencing.

    Science.gov (United States)

    Chubb, Daniel; Broderick, Peter; Frampton, Matthew; Kinnersley, Ben; Sherborne, Amy; Penegar, Steven; Lloyd, Amy; Ma, Yussanne P; Dobbins, Sara E; Houlston, Richard S

    2015-02-10

    Knowledge of the contribution of high-penetrance susceptibility to familial colorectal cancer (CRC) is relevant to the counseling, treatment, and surveillance of CRC patients and families. To quantify the impact of germline mutation to familial CRC, we sequenced the mismatch repair genes (MMR) APC, MUTYH, and SMAD4/BMPR1A in 626 early-onset familial CRC cases ascertained through a population-based United Kingdom national registry. In addition, we evaluated the contribution of mutations in the exonuclease domain (exodom) of POLE and POLD1 genes that have recently been reported to confer CRC risk. Overall mutations (pathogenic, likely pathogenic) in MMR genes make the highest contribution to familial CRC (10.9%). Mutations in the other established CRC genes account for 3.3% of cases. POLE/POLD1 exodom mutations were identified in three patients with family histories consistent with dominant transmission of CRC. Collectively, mutations in the known genes account for 14.2% of familial CRC (89 of 626 cases; 95% CI = 11.5, 17.2). A genetic diagnosis is feasible in a high proportion of familial CRC. Mainstreaming such analysis in clinical practice should enable the medical management of patients and their families to be optimized. Findings suggest CRC screening of POLE and POLD1 mutation carriers should be comparable to that afforded to those at risk of HNPCC. Although the risk of CRC associated with unexplained familial CRC is in general moderate, in some families the risk is substantive and likely to be the consequence of unidentified genes, as exemplified by POLE and POLD1. Our findings have utility in the design of genetic analyses to identify such novel CRC risk genes. © 2015 by American Society of Clinical Oncology.

  3. Biofilm production and antibiotic susceptibility profiles of ...

    African Journals Online (AJOL)

    Staphylococcus aureus is a common pathogen associated with nosocomial as well as community acquired infections. Despite multiple reports on the severity and recurrent nature of S. aureus infection, the pathogenesis as well as antibiotic susceptibility profiles of S. aureus infecting HIV and AIDS patients has not been well ...

  4. Graphene susceptibility in Holstein model

    Energy Technology Data Exchange (ETDEWEB)

    Mousavi, Hamze, E-mail: hamze.mousavi@gmail.co [Department of Physics, Razi University, Kermanshah (Iran, Islamic Republic of); Nano Science and Nano Technology Research Center, Razi University, Kermanshah (Iran, Islamic Republic of)

    2011-06-15

    We study the effects of the electron-phonon interaction on the temperature dependence of the orbital magnetic susceptibility of monolayer graphene. We use the linear response theory and Green's function formalism within the Holstein Hamiltonian model. The results show that the effects of the electron-phonon interaction on the susceptibility of graphene sheet have different behaviors in two temperature regions. In the low temperature region, susceptibility increases when the electron-phonon coupling strength increases. On the other hand, the susceptibility reduces with increasing the electron-phonon coupling strength in the high temperature region. - Highlights: Effect of electron-phonon interaction on the susceptibility of graphene is studied. Linear response theory and Green's function technique in Holstein model are used. Effect of electron-phonon on susceptibility has different behaviors in two temperature regions.

  5. Image-guided, whole-pelvic, intensity-modulated radiotherapy for biochemical recurrence following radical prostatectomy in high-risk prostate cancer patients.

    Science.gov (United States)

    Byun, Sang Jun; Kim, Young Seok; Ahn, Hanjong; Kim, Choung-Soo

    2018-01-01

    The optimal field size of salvage radiotherapy (SRT) for biochemical recurrence, particularly for patients with high-risk prostate cancer, remains undefined. This retrospective analysis was performed to investigate oncological outcomes as well as treatment-related toxicity following salvage intensity-modulated radiotherapy (IMRT) to the whole pelvis and to compare the results with other studies implementing a small field size of the prostate bed. The medical records of 170 patients with high-risk prostate cancer who received SRT for biochemical recurrence following prostatectomy were reviewed. Whole-pelvic IMRT was administered with a median dose of 66 Gy in 30 fractions. To improve treatment accuracy, an endorectal balloon device and daily cone-beam computed tomography were utilized. Androgen-deprivation therapy combined with SRT was administered to 97 (57.1%) patients. Eventually, 68 (40.0%) patients showed biochemical progression (BCP) after SRT. With a median follow-up period of 56 months, the 5-year BCP-free survival was 38.6%. The overall and cause-specific survival rates were 90.9% and 96.7%, respectively. Regarding BCP-free survival analysis, pathological T stage, persistent prostate-specific antigen (PSA) elevation after prostatectomy, and preSRT PSA level were significant prognostic factors on univariate analysis. On multivariate analysis, pathological T stage and preSRT PSA value retained their significance. Acute and late grade-3 genitourinary toxicities were observed in one (0.6%) and five (2.9%) patients, respectively. One patient each developed acute and late grade-3 gastrointestinal toxicity. SRT to whole pelvis using IMRT and image guidance is as safe as SRT to the prostate bed, but its efficacy should be confirmed in ongoing randomized trials. PreSRT PSA was the only controllable prognostic factor, suggesting the benefit of early SRT.

  6. Image-guided, whole-pelvic, intensity-modulated radiotherapy for biochemical recurrence following radical prostatectomy in high-risk prostate cancer patients.

    Directory of Open Access Journals (Sweden)

    Sang Jun Byun

    Full Text Available The optimal field size of salvage radiotherapy (SRT for biochemical recurrence, particularly for patients with high-risk prostate cancer, remains undefined. This retrospective analysis was performed to investigate oncological outcomes as well as treatment-related toxicity following salvage intensity-modulated radiotherapy (IMRT to the whole pelvis and to compare the results with other studies implementing a small field size of the prostate bed.The medical records of 170 patients with high-risk prostate cancer who received SRT for biochemical recurrence following prostatectomy were reviewed. Whole-pelvic IMRT was administered with a median dose of 66 Gy in 30 fractions. To improve treatment accuracy, an endorectal balloon device and daily cone-beam computed tomography were utilized. Androgen-deprivation therapy combined with SRT was administered to 97 (57.1% patients.Eventually, 68 (40.0% patients showed biochemical progression (BCP after SRT. With a median follow-up period of 56 months, the 5-year BCP-free survival was 38.6%. The overall and cause-specific survival rates were 90.9% and 96.7%, respectively. Regarding BCP-free survival analysis, pathological T stage, persistent prostate-specific antigen (PSA elevation after prostatectomy, and preSRT PSA level were significant prognostic factors on univariate analysis. On multivariate analysis, pathological T stage and preSRT PSA value retained their significance. Acute and late grade-3 genitourinary toxicities were observed in one (0.6% and five (2.9% patients, respectively. One patient each developed acute and late grade-3 gastrointestinal toxicity.SRT to whole pelvis using IMRT and image guidance is as safe as SRT to the prostate bed, but its efficacy should be confirmed in ongoing randomized trials. PreSRT PSA was the only controllable prognostic factor, suggesting the benefit of early SRT.

  7. High-risk human papillomavirus E7 expression reduces cell-surface MHC class I molecules and increases susceptibility to natural killer cells

    DEFF Research Database (Denmark)

    Bottley, G; Watherston, O G; Hiew, Y-L

    2007-01-01

    High-risk human papillomavirus (HPV) is a major causative agent of cervical cancer and the E6 and E7 genes encode the major HPV oncoproteins. The E7 protein from high-risk HPV types alters cell cycle progression and represses genes encoding components of the antigen-presentation pathway, suggesting...... a role for E7 in tumour immune evasion. We show that knockdown of E7 expression in HPV16- and HPV18-transformed cervical carcinoma cells by RNA interference increased expression of major histocompatibility complex (MHC) class I at the cell surface and reduced susceptibility of these cells to natural...

  8. High-Dose Viscum album Extract Treatment in the Prevention of Recurrent Bladder Cancer: A Retrospective Case Series

    OpenAIRE

    von Schoen-Angerer, Tido; Wilkens, Johannes; Kienle, Gunver S; Kiene, Helmut; Vagedes, Jan

    2015-01-01

    Viscum album extract (European mistletoe), containing immune-active compounds with dose-dependent cytotoxic activity, is being used as an adjuvant cancer treatment in Europe. Few studies have been done with high-dose, fever-inducing Viscum album treatment. The authors retrospectively analyzed the case notes of patients with resectable bladder cancer who underwent initiation of high-dose Viscum album treatment at their clinic between January 2006 to December 2012. High-dose Viscum album showed...

  9. Diagnostic instability of recurrence and the impact on recurrence rates in depressive and anxiety disorders.

    Science.gov (United States)

    Scholten, Willemijn D; Batelaan, Neeltje M; Penninx, Brenda W J H; van Balkom, Anton J L M; Smit, Johannes H; Schoevers, Robert A; van Oppen, Patricia

    2016-05-01

    Despite increasing evidence for the diagnostic instability between and within depressive and anxiety disorders, most studies report solely on the recurrence rates of the specific index disorders. Neglecting this evidence has an inherent risk of underestimating recurrence rates of depressive and anxiety disorders. This study investigates the impact of diagnostic instability of recurrence rates in depression and anxiety. Data were derived from the Netherlands Study of Depression and Anxiety (NESDA). The sample of 656 participants had a panic disorder with or without agoraphobia, agoraphobia, social phobia, generalized anxiety disorder, major depressive disorder or dysthymia, and a subsequent remission. Recurrence rates of index disorders (diagnostically stable recurrence) and newly arisen anxiety or depressive disorders (diagnostically unstable recurrence), were calculated over a 4-year follow-up period. In anxiety disorders (n=281), the recurrence rate is more than doubled, from 23.8% with a stable recurrence, to 54.8%, when diagnostically unstable recurrences are included. In depressive disorders (N=173) the recurrence rate increases from 37.6% to 49.7%, and in comorbid anxiety and depressive disorders (N=202) the diagnostically unstable recurrences increase from 54.0% to 66.3%. Attrition during follow up may have biased the results; remission was defined as absence of symptoms for 1 month; very short-term remission and recurrence patterns were not assessed. Diagnostically unstable recurrences have a significant impact on recurrence rates, with the greatest instability for anxiety disorders. When only diagnostically stable recurrences are assessed, recurrence rates are highly underrated and provide biased estimates of the true course of these disorders. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Recurrent renal giant leiomyosarcoma.

    Science.gov (United States)

    Öziş, Salih Erpulat; Gülpınar, Kamil; Şahlı, Zafer; Konak, Baha Burak; Keskin, Mete; Özdemir, Süleyman; Ataoğlu, Ömür

    2016-01-01

    Primary renal leiomyosarcomas are rare, aggressive tumors. They constitute 1-2% of adult malignant renal tumors. Although leiomyosarcomas are the most common histological type (50-60%) of renal sarcomas, information on renal leiomyosarcoma is limited. Local or systemic recurrences are common. The radiological appearance of renal leiomyosarcomas is not specific, therefore renal leiomyosarcoma cannot be distinguished from renal cell carcinoma by imaging methods in all patients. A 74-year-old female patient presented to our clinic complaining of a palpable mass on the right side of her abdomen in November 2012. The abdominal magnetic resonance imaging revealed a mass, 25 × 24 × 23 cm in size. Her past medical history revealed that she has undergone right radical nephrectomy in 2007, due to a 11 × 12 × 13 cm renal mass that was then reported as renal cell carcinoma on abdominal magnetic resonance imaging, but the pathological diagnosis was low-grade renal leiomyosarcoma. The most recent follow-up of the patient was in 2011, with no signs of local recurrence or distant metastases within this four-year period. The patient underwent laparotomy on November 2012, and a 35 cm retroperitoneal mass was excised. The pathological examination of the mass was reported as high-grade leiomyosarcoma. The formation of this giant retroperitoneal mass in 1 year can be explained by the transformation of the lesion's pathology from low-grade to a high-grade tumor.

  11. High frequency of methicillin-susceptible and methicillin-resistant Staphylococcus aureus in children under 1 year old with skin and soft tissue infections.

    Science.gov (United States)

    Salazar-Ospina, Lorena; Jiménez, Judy Natalia

    2017-09-21

    Staphylococcus aureus is responsible for a large number of infections in pediatric population; however, information about the behavior of such infections in this population is limited. The aim of the study was to describe the clinical, epidemiological, and molecular characteristics of infections caused by methicillin-susceptible and resistant S. aureus (MSSA-MRSA) in a pediatric population. A cross-sectional descriptive study in patients from birth to 14 years of age from three high-complexity institutions was conducted (2008-2010). All patients infected with methicillin-resistant S. aureus and a representative sample of patients infected with methicillin-susceptible S. aureus were included. Clinical and epidemiological information was obtained from medical records and molecular characterization included spa typing, pulsed-field gel electrophoresis (PFGE), and multilocus sequence typing (MLST). In addition, staphylococcal cassette chromosome mec (SCCmec) and virulence factor genes were detected. A total of 182 patients, 65 with methicillin-susceptible S. aureus infections and 117 with methicillin-resistant S. aureus infections, were included in the study; 41.4% of the patients being under 1 year. The most frequent infections were of the skin and soft tissues. Backgrounds such as having stayed in day care centers and previous use of antibiotics were more common in patients with methicillin-resistant S. aureus infections (p≤0.05). Sixteen clonal complexes were identified and methicillin-susceptible S. aureus strains were more diverse. The most common cassette was staphylococcal cassette chromosomemec IVc (70.8%), which was linked to Panton-Valentine leukocidin (pvl). In contrast with other locations, a prevalence of infections in children under 1 year of age in the city could be observed; this emphasizes the importance of epidemiological knowledge at the local level. Copyright © 2017 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights

  12. Recurrent pregnancy loss: current perspectives

    Directory of Open Access Journals (Sweden)

    El Hachem H

    2017-05-01

    Full Text Available Hady El Hachem,1,2 Vincent Crepaux,3 Pascale May-Panloup,4 Philippe Descamps,3 Guillaume Legendre,3 Pierre-Emmanuel Bouet3 1Department of Reproductive Medicine, Ovo Clinic, Montréal, QC, Canada; 2Department of Obstetrics and Gynecology, University of Montreal, Montréal, QC, Canada; 3Department of Obstetrics and Gynecology, Angers University Hopsital, Angers, France; 4Department of Reproductive Biology, Angers University Hospital, Angers, France Abstract: Recurrent pregnancy loss is an important reproductive health issue, affecting 2%–5% of couples. Common established causes include uterine anomalies, antiphospholipid syndrome, hormonal and metabolic disorders, and cytogenetic abnormalities. Other etiologies have been proposed but are still considered controversial, such as chronic endometritis, inherited thrombophilias, luteal phase deficiency, and high sperm DNA fragmentation levels. Over the years, evidence-based treatments such as surgical correction of uterine anomalies or aspirin and heparin for antiphospholipid syndrome have improved the outcomes for couples with recurrent pregnancy loss. However, almost half of the cases remain unexplained and are empirically treated using progesterone supplementation, anticoagulation, and/or immunomodulatory treatments. Regardless of the cause, the long-term prognosis of couples with recurrent pregnancy loss is good, and most eventually achieve a healthy live birth. However, multiple pregnancy losses can have a significant psychological toll on affected couples, and many efforts are being made to improve treatments and decrease the time needed to achieve a successful pregnancy. This article reviews the established and controversial etiologies, and the recommended therapeutic strategies, with a special focus on unexplained recurrent pregnancy losses and the empiric treatments used nowadays. It also discusses the current role of preimplantation genetic testing in the management of recurrent pregnancy

  13. AN EVALUATION OF HYDROGEN INDUCED CRACKING SUSCEPTIBILITY OF TITANIUM ALLOYS IN US HIGH-LEVEL NUCLEAR WASTE REPOSITORY ENVIRONMENTS

    Energy Technology Data Exchange (ETDEWEB)

    G. De; K. Mon; G. Gordon; D. Shoesmith; F. Hua

    2006-02-21

    This paper evaluates hydrogen-induced cracking (HIC) susceptibility of titanium alloys in environments anticipated in the Yucca Mountain nuclear waste repository with particular emphasis on the. effect of the oxide passive film on the hydrogen absorption process of titanium alloys being evaluated. The titanium alloys considered in this review include Ti 2, 5 , 7, 9, 11, 12, 16, 17, 18, 24 and 29. In general, the concentration of hydrogen in a titanium alloy can increase due to absorption of atomic hydrogen produced from passive general corrosion of that alloy or galvanic coupling of it to a less noble metal. It is concluded that under the exposure conditions anticipated in the Yucca Mountain repository, the HIC of titanium drip shield will not occur because there will not be sufficient hydrogen in the metal even after 10,000 years of emplacement. Due to the conservatisms adopted in the current evaluation, this assessment is considered very conservative.

  14. Assessment of Risk for Recurrent Diverticulitis

    Science.gov (United States)

    Sallinen, Ville; Mali, Juha; Leppäniemi, Ari; Mentula, Panu

    2015-01-01

    Abstract Recurrence of acute diverticulitis is common, and—especially complicated recurrence—causes significant morbidity. To prevent recurrence, selected patients have been offered prophylactic sigmoid resection. However, as there is no tool to predict whose diverticulitis will recur and, in particular, who will have complicated recurrence, the indications for sigmoid resections have been variable. The objective of this study was to identify risk factors predicting recurrence of acute diverticulitis. This is a retrospective cohort study of patients presenting with computed tomography–confirmed acute diverticulitis and treated nonresectionally during 2006 to 2010. Risk factors for recurrence were identified using uni- and multivariate Cox regression. A total of 512 patients were included. History of diverticulitis was an independent risk factor predicting uncomplicated recurrence of diverticulitis (1–2 earlier diverticulitis HR 1.6, 3 or more—HR 3.2). History of diverticulitis (HR 3.3), abscess (HR 6.2), and corticosteroid medication (HR 16.1) were independent risk factors for complicated recurrence. Based on regression coefficients, risk scoring was created: 1 point for history of diverticulitis, 2 points for abscess, and 3 points for corticosteroid medication. The risk score was unable to predict uncomplicated recurrence (AUC 0.48), but was able to predict complicated recurrence (AUC 0.80). Patients were further divided into low-risk (0–2 points) and high-risk (>2 points) groups. Low-risk and high-risk groups had 3% and 43% 5-year complicated recurrence rates, respectively. Risk for complicated recurrence of acute diverticulitis can be assessed using risk scoring. The risk for uncomplicated recurrence increases along with increasing number of previous diverticulitis. PMID:25715253

  15. High Glasgow Blatchford Score at admission is associated with recurrent bleeding after discharge for patients hospitalized with upper gastrointestinal bleeding.

    Science.gov (United States)

    Sengupta, Neil; Tapper, Elliot B; Patwardhan, Vilas R; Ketwaroo, Gyanprakash A; Thaker, Adarsh M; Leffler, Daniel A; Feuerstein, Joseph D

    2016-01-01

    Upper gastrointestinal bleeding (UGIB) is associated with significant morbidity. The Glasgow Blatchford Score (GBS) can predict endoscopic intervention and in-hospital death, but the ability to predict post-discharge outcomes is unknown. The aims of the study were to determine whether the admission GBS is associated with post-discharge rebleeding and 30-day readmission following hospitalization for UGIB. In this prospective, observational, cohort study, consecutive patients who were hospitalized with UGIB were enrolled. Admission GBS scores were calculated, and patients with GBS > 7 were classified as high risk. Patients were contacted 30 days following discharge to determine: 1) rate of hospital readmission due to rebleeding, 2) all-cause readmissions, and 3) mortality. Multivariable Cox regression was used to determine associations between GBS, rebleeding, and readmission. A total of 336 patients with UGIB were identified. Patients with high risk GBS were older (68 vs. 62 years; P = 0.01), and were more likely to receive blood (85 % vs. 39 %; P  7) should be monitored following discharge as they have a high risk of rebleeding. © Georg Thieme Verlag KG Stuttgart · New York.

  16. Hypoxia-inducible factor 1α predicts recurrence in high-grade soft tissue sarcoma of extremities and trunk wall

    DEFF Research Database (Denmark)

    Nyström, Harriet; Jönsson, M; Werner-Hartman, L

    2017-01-01

    BACKGROUND AND AIM: Sarcomas are of mesenchymal origin and typically show abundant tumour stroma and presence of necrosis. In search for novel biomarkers for personalised therapy, we determined the prognostic impact of stromal markers, hypoxia and neovascularity in high-grade soft tissue leiomyos......BACKGROUND AND AIM: Sarcomas are of mesenchymal origin and typically show abundant tumour stroma and presence of necrosis. In search for novel biomarkers for personalised therapy, we determined the prognostic impact of stromal markers, hypoxia and neovascularity in high-grade soft tissue...... leiomyosarcoma and pleomorphic undifferentiated sarcoma. METHOD: We evaluated CD163, colony-stimulating factor (CSF)-1, CD16 and hypoxia-inducible factor 1 (HIF-1)α using immunohistochemical staining and assessed microvessel density using CD31 in 73 high-grade leiomyosarcomas and undifferentiated pleomorphic...... sarcomas of the extremities and the trunk wall. The results were correlated to metastasis-free and overall survival. RESULTS: Expression of HIF-1α was associated with the presence of necrosis and independently predicted shorter metastasis-free survival (HR 3.2, CI 1.4 to 7.0, p=0.004), whereas neither...

  17. Recurrent Novae — A Review

    Directory of Open Access Journals (Sweden)

    K. Mukai

    2015-02-01

    Full Text Available In recent years, recurrent nova eruptions are often observed very intensely in wide range of wavelengths from radio to optical to X-rays. Here I present selected highlights from recent multi-wavelength observations. The enigma of T Pyx is at the heart of this paper. While our current understanding of CV and symbiotic star evolution can explain why certain subset of recurrent novae have high accretion rate, that of T Pyx must be greatly elevated compared to the evolutionary mean. At the same time, we have extensive data to be able to estimate how the nova envelope was ejected in T Pyx, and it turns to be a rather complex tale. One suspects that envelope ejection in recurrent and classical novae in general is more complicated than the textbook descriptions. At the end of the review, I will speculate that these two may be connected.

  18. High-fat/fructose feeding during prenatal and postnatal development in female rats increases susceptibility to renal and metabolic injury later in life.

    Science.gov (United States)

    Flynn, Elizabeth R; Alexander, Barbara T; Lee, Jonathan; Hutchens, Zachary M; Maric-Bilkan, Christine

    2013-02-15

    Accumulating evidence suggests that both an adverse prenatal and early postnatal environment increase susceptibility to renal and metabolic dysfunction later in life; however, whether exposure to adverse conditions during both prenatal and postnatal development act synergistically to potentiate the severity of renal and metabolic injury remains unknown. Sprague-Dawley rats were fed either a standard diet or a diet high in fat/fructose throughout pregnancy and lactation. After being weaned, female offspring were randomized to either standard diet or the high-fat/high-fructose diet, resulting in the following treatment groups: NF-NF, offspring of mothers fed a standard diet and fed a standard diet postnatally; NF-HF, offspring of mothers fed a standard diet and fed a high-fat/fructose diet postnatally; HF-NF, offspring of mothers fed a high-fat/fructose diet and fed a standard diet postnatally; HF-HF, offspring of mothers fed a high-fat/fructose diet and fed a high-fat/fructose diet postnatally. At the time of euthanasia (17 wk of age), HF-HF offspring weighed 30% more and had 110% more visceral fat than NF-NF offspring. The HF-HF offspring also had elevated blood glucose levels, glucose intolerance, 286% increase in urine albumin excretion, and 60% increase in glomerulosclerosis compared with NF-NF. In addition, HF-HF offspring exhibited a 100% increase in transforming growth factor-β protein expression and 116% increase in the abundance of infiltrated macrophages compared with the NF-NF offspring. These observations suggest that high-fat/fructose feeding during prenatal and throughout postnatal life increases the susceptibility to renal and metabolic injury later in life.

  19. High serum YKL-40 levels in patients with primary breast cancer is related to short recurrence free survival

    DEFF Research Database (Denmark)

    Johansen, Julia S; Christensen, Ib Jarle; Riisbro, Rikke

    2003-01-01

    YKL-40 is a growth factor for connective tissue cells and stimulates migration of endothelial cells. YKL-40 is secreted by cancer cells, and elevated serum YKL-40 in patients with metastatic breast cancer and colorectal cancer is associated with a poorer prognosis as compared to patients with nor......YKL-40 is a growth factor for connective tissue cells and stimulates migration of endothelial cells. YKL-40 is secreted by cancer cells, and elevated serum YKL-40 in patients with metastatic breast cancer and colorectal cancer is associated with a poorer prognosis as compared to patients...... YKL-40 concentration in the patients was 57 microg/l (range 22-688 microg/l) and significantly elevated (p compared to serum YKL-40 in healthy females. Nineteen percent of the patients had high serum YKL-40 (i.e., >95 percentile of healthy females). Patients with high serum YKL-40 had...... shorter relapse-free interval (hazard ratio (HR) = 1.77, 95% confidence interval (CI): 1.06-2.95, p = 0.028) and overall survival (HR = 1.78, 95% CI: 1.04-3.05, p = 0.036) than patients with normal serum YKL-40. Serum YKL-40 was higher (p = 0.005) in lymph node positive patients as compared to lymph node...

  20. Genetic variants near TIMP3 and high-density lipoprotein–associated loci influence susceptibility to age-related macular degeneration

    Science.gov (United States)

    Chen, Wei; Stambolian, Dwight; Edwards, Albert O.; Branham, Kari E.; Othman, Mohammad; Jakobsdottir, Johanna; Tosakulwong, Nirubol; Pericak-Vance, Margaret A.; Campochiaro, Peter A.; Klein, Michael L.; Tan, Perciliz L.; Conley, Yvette P.; Kanda, Atsuhiro; Kopplin, Laura; Li, Yanming; Augustaitis, Katherine J.; Karoukis, Athanasios J.; Scott, William K.; Agarwal, Anita; Kovach, Jaclyn L.; Schwartz, Stephen G.; Postel, Eric A.; Brooks, Matthew; Baratz, Keith H.; Brown, William L.; Brucker, Alexander J.; Orlin, Anton; Brown, Gary; Ho, Allen; Regillo, Carl; Donoso, Larry; Tian, Lifeng; Kaderli, Brian; Hadley, Dexter; Hagstrom, Stephanie A.; Peachey, Neal S.; Klein, Ronald; Klein, Barbara E. K.; Gotoh, Norimoto; Yamashiro, Kenji; Ferris, Frederick; Fagerness, Jesen A.; Reynolds, Robyn; Farrer, Lindsay A.; Kim, Ivana K.; Miller, Joan W.; Cortón, Marta; Carracedo, Angel; Sanchez-Salorio, Manuel; Pugh, Elizabeth W.; Doheny, Kimberly F.; Brion, Maria; DeAngelis, Margaret M.; Weeks, Daniel E.; Zack, Donald J.; Chew, Emily Y.; Heckenlively, John R.; Yoshimura, Nagahisa; Iyengar, Sudha K.; Francis, Peter J.; Katsanis, Nicholas; Seddon, Johanna M.; Haines, Jonathan L.; Gorin, Michael B.; Abecasis, Gonçalo R.; Swaroop, Anand; Johnson, Robert N.; Ai, Everett; McDonald, H. Richard; Stolarczuk, Margaret; Pavan, Peter Reed; Billiris, Karina K.; Iyer, Mohan; Menosky, Matthew M.; Pautler, Scott E.; Millard, Sharon M.; Hubbard, Baker; Aaberg, Thomas; DuBois, Lindy; Lyon, Alice; Anderson-Nelson, Susan; Jampol, Lee M.; Weinberg, David V.; Muñana, Annie; Rozenbajgier, Zuzanna; Orth, David; Cohen, Jack; MacCumber, Matthew; MacCumber, Matthew; Figliulo, Celeste; Porcz, Liz; Folk, James; Boldt, H. Culver; Russell, Stephen R.; Ivins, Rachel; Hinz, Connie J.; Barr, Charles C.; Bloom, Steve; Jaegers, Ken; Kritchman, Brian; Whittington, Greg; Heier, Jeffrey; Frederick, Albert R.; Morley, Michael G.; Topping, Trexler; Davis, Heather L.; Bressler, Susan B.; Bressler, Neil M.; Doll, Warren; Trese, Michael; Capone, Antonio; Garretson, Bruce R.; Hassan, Tarek S.; Ruby, Alan J.; Osentoski, Tammy; McCannel, Colin A.; Ruszczyk, Margaret J.; Grand, Gilbert; Blinder, Kevin; Holekamp, Nancy M.; Joseph, Daniel P.; Shah, Gaurav; Nobel, Ginny S.; Antoszyk, Andrew N.; Browning, David J.; Stallings, Alison H; Singerman, Lawrence J.; Miller, David; Novak, Michael; Pendergast, Scott; Zegarra, Hernando; Schura, Stephanie A.; Smith-Brewer, Sheila; Davidorf, Frederick H.; Chambers, Robert; Chorich, Louis; Salerno, Jill; Dreyer, Richard F.; Ma, Colin; Kopfer, Marcia R.; Klein, Michael L.; Wilson, David J.; Nolte, Susan K.; Grunwald, Juan E.; Brucker, Alexander J.; Dunaief, Josh; Fine, Stuart L.; Maguire, Albert M.; Stoltz, Robert A.; McRay, Monique N.; Fish, Gary Edd; Anand, Rajiv; Spencer, Rand; Arnwine, Jean; Chandra, Suresh R.; Altaweel, Michael; Blodi, Barbara; Gottlieb, Justin; Ip, Michael; Nork, T. Michael; Perry-Raymond, Jennie; Fine, Stuart L.; Maguire, Maureen G.; Brightwell-Arnold, Mary; Harkins, Sandra; Peskin, Ellen; Ying, Gui-Shuang; Kurinij, Natalie

    2010-01-01

    We executed a genome-wide association scan for age-related macular degeneration (AMD) in 2,157 cases and 1,150 controls. Our results validate AMD susceptibility loci near CFH (P < 10−75), ARMS2 (P < 10−59), C2/CFB (P < 10−20), C3 (P < 10−9), and CFI (P < 10−6). We compared our top findings with the Tufts/Massachusetts General Hospital genome-wide association study of advanced AMD (821 cases, 1,709 controls) and genotyped 30 promising markers in additional individuals (up to 7,749 cases and 4,625 controls). With these data, we identified a susceptibility locus near TIMP3 (overall P = 1.1 × 10−11), a metalloproteinase involved in degradation of the extracellular matrix and previously implicated in early-onset maculopathy. In addition, our data revealed strong association signals with alleles at two loci (LIPC, P = 1.3 × 10−7; CETP, P = 7.4 × 10−7) that were previously associated with high-density lipoprotein cholesterol (HDL-c) levels in blood. Consistent with the hypothesis that HDL metabolism is associated with AMD pathogenesis, we also observed association with AMD of HDL-c—associated alleles near LPL (P = 3.0 × 10−3) and ABCA1 (P = 5.6 × 10−4). Multilocus analysis including all susceptibility loci showed that 329 of 331 individuals (99%) with the highest-risk genotypes were cases, and 85% of these had advanced AMD. Our studies extend the catalog of AMD associated loci, help identify individuals at high risk of disease, and provide clues about underlying cellular pathways that should eventually lead to new therapies. PMID:20385819

  1. Neither high-dose nor low-dose brachytherapy increases flap morbidity in salvage treatment of recurrent head and neck cancer

    Directory of Open Access Journals (Sweden)

    Peter W. Henderson

    2016-08-01

    Full Text Available Purpose: While brachytherapy is often used concurrently with flap reconstruction following surgical ablation for head and neck cancer, it remains unclear whether it increases morbidity in the particularly high risk subset of patients undergoing salvage treatment for recurrent head and neck cancer (RH&NC. Material and methods : A retrospective chart review was undertaken that evaluated patients with RH&NC who underwent flap coverage after surgical re-resection and concomitant brachytherapy. The primary endpoint was flap viability, and the secondary endpoints were flap and recipient site complications. Results : In the 23 subjects included in series, flap viability and skin graft take was 100%. Overall recipient site complication rate was 34.8%, high-dose radiation (HDR group 50%, and low-dose radiation (LDR group 29.4%. There was no statistically significant difference between these groups. Conclusions : In patients who undergo flap reconstruction and immediate postoperative radiotherapy following salvage procedures for RH&NC, flap coverage of defects in combination with brachytherapy remains a safe and effective means of providing stable soft tissue coverage.

  2. S100P expression is a novel prognostic factor in hepatocellular carcinoma and predicts survival in patients with high tumor stage or early recurrent tumors.

    Science.gov (United States)

    Yuan, Ray-Hwang; Chang, Ko-Tung; Chen, Yu-Ling; Hsu, Hey-Chi; Lee, Po-Huang; Lai, Po-Lin; Jeng, Yung-Ming

    2013-01-01

    The calcium-binding protein S100P is expressed in a variety of human cancer cells and is important in cancer cell growth and invasion. Using differential display, we found S100P is overexpressed in human hepatocellular carcinoma (HCC). We examined the expression of 305 unifocal, primary HCC tumors using immunohistochemistry. The S100P protein was expressed in 173 of the 305 (56.7%) HCC tumors. The expression of S100P correlated with female sex (P = 0.0162), high serum α-fetoprotein level (P = 0.0001), high tumor grade (P = 0.0029), high tumor stage (P = 0.0319), the presence of the p53 mutation (P = 0.0032), and the absence of the β-catenin mutation (P = 0.0489). Patients with HCC tumors that expressed S100P were more likely to have early tumor recurrence (ETR) (P = 0.0189) and lower 5-year survival (P = 0.0023). The multivariate analysis confirmed that S100P expression was an independent prognostic factor in HCC. The combinatorial analysis showed an additive unfavorable prognostic interaction between S100P expression and the p53 mutation. In contrast, the β-catenin mutation was associated with better prognosis in both S100P-positive and -negative HCCs. Furthermore, S100P expression was a predictor of survival in HCC patients with high tumor stage or ETR (P = 0.0026 and P = 0.0002, respectively). Our study indicates the expression of the S100P protein is a novel independent predictor for poor prognosis in HCC, and it is also an unfavorable prognostic predictor in HCC patients with high tumor stage or ETR.

  3. Recurrence of anxiety disorders and its predictors.

    Science.gov (United States)

    Scholten, Willemijn D; Batelaan, Neeltje M; van Balkom, Anton Jlm; Wjh Penninx, Brenda; Smit, Johannes H; van Oppen, Patricia

    2013-05-01

    The chronic course of anxiety disorders and its high burden of disease are partly due to the recurrence of anxiety disorders after remission. However, knowledge about recurrence rates and predictors of recurrence is scarce. This article reports on recurrence rates of anxiety disorders and investigates predictors of recurrence from a broad range of socio-demographic characteristics, illness-related and psychosocial putative predictors. Baseline and 2-year follow-up data were derived from the Netherlands Study of Depression and Anxiety (NESDA). Participants who had at least one lifetime anxiety disorder (panic disorder with or without agoraphobia, agoraphobia alone, social phobia or generalized anxiety disorder), but were remitted at baseline (N=429) were included. Recurrence of anxiety disorders during the 2-year follow-up period was assessed using the Composite International Diagnostic Interview, version 2.1. Recurrence rates among pure and multiple anxiety disorders did not differ significantly and the overall recurrence rate of anxiety disorders was 23.5%. In those recurring, the incidence of a new anxiety disorder was common (32.7%). Disability and anxiety sensitivity remained predictive of recurrence of anxiety disorders in multivariable regression analysis. The included participants had more severe symptoms at baseline than the non-response group and lifetime anxiety diagnoses were assessed, retrospectively. Recurrence of anxiety disorders is common and clinicians should be aware of the diagnostic instability within anxiety disorders. Disability and anxiety sensitivity are independent predictors of recurrence of anxiety disorders. Altering these predictors in regular cognitive behavioural therapy could contribute to the reduction of recurrence. Copyright © 2012 Elsevier B.V. All rights reserved.

  4. High-Dose Busulfan and High-Dose Cyclophosphamide Followed By Donor Bone Marrow Transplant in Treating Patients With Leukemia, Myelodysplastic Syndrome, Multiple Myeloma, or Recurrent Hodgkin or Non-Hodgkin Lymphoma

    Science.gov (United States)

    2010-08-05

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With T(15;17)(q22;q12); Adult Acute Myeloid Leukemia With T(16;16)(p13;q22); Adult Acute Myeloid Leukemia With T(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Acute Promyelocytic Leukemia (M3); Adult Erythroleukemia (M6a); Adult Nasal Type Extranodal NK/T-cell Lymphoma; Adult Pure Erythroid Leukemia (M6b); Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Burkitt Lymphoma; Childhood Acute Erythroleukemia (M6); Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myeloid Leukemia in Remission; Childhood Acute Myelomonocytic Leukemia (M4); Childhood Acute Promyelocytic Leukemia (M3); Childhood Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Chronic Phase Chronic Myelogenous Leukemia; Cutaneous B-cell Non-Hodgkin Lymphoma; De Novo Myelodysplastic Syndromes; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Peripheral T-Cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent

  5. Lymphotropism and host responses during acute wild-type canine distemper virus infections in a highly susceptible natural host

    DEFF Research Database (Denmark)

    Nielsen, Line; Søgaard, Mette; Jensen, Trine Hammer

    2009-01-01

    The mechanisms behind the in vivo virulence of immunosuppressive wild-type Morbillivirus infections are still not fully understood. To investigate lymphotropism and host responses we have selected the natural host model of canine distemper virus (CDV) infection in mink. This model displays multis...... in PBMCs was investigated throughout the acute infections. We observed Th1- and Th2-type cytokine responses beginning in the prodromal phase, and late inflammatory responses were shared between the wild-type infections.......The mechanisms behind the in vivo virulence of immunosuppressive wild-type Morbillivirus infections are still not fully understood. To investigate lymphotropism and host responses we have selected the natural host model of canine distemper virus (CDV) infection in mink. This model displays...... multisystemic infection similar to measles virus (MV) and rinderpest virus (RPV) infections in their susceptible natural hosts. The wild-type CDVs investigated provoked marked virulence differences inducing mild versus marked to severe acute disease. The mildly virulent wild-type induced transient lymphopenia...

  6. Anterior perirectal fat tissue thickness is a strong predictor of recurrence after high-intensity focused ultrasound for prostate cancer.

    Science.gov (United States)

    Sumitomo, Makoto; Asakuma, Junichi; Yoshii, Hidehiko; Sato, Akinori; Horiguchi, Akio; Ito, Keiichi; Nagakura, Kazuhiko; Asano, Tomohiko

    2010-09-01

    To evaluate if and why obesity affects the clinical outcome in patients undergoing high-intensity focused ultrasound (HIFU) treatment for prostate cancer (CaP). 115 patients who underwent HIFU treatment for localized CaP were categorized as obese, overweight or normal according to body mass index (BMI). The thickness of the anterior perirectal fat tissue (APFT) was measured by transrectal ultrasonography. Treatment was considered to have failed in the case of biochemical failure according to the Phoenix definition, positive follow-up biopsy or initiation of salvage therapy. Cox proportional hazards analyses were used to identify possible predictors for disease free survival (DFS), and an experimental fat tissue model was made to evaluate the ablation effect at the target tissue. According to the classification by the Western Pacific Regional Office of WHO, 43 patients were of normal weight, 24 were overweight and 48 were obese. The BMI groups did not differ in Gleason score, prostate-specific antigen level at diagnosis or clinical stage. There were, however, significant correlations between BMI and prostate-specific antigen nadir (P APFT thickness (P APFT (P APFT thickness, for which obesity could be a useful surrogate, might represent the causative factor for poor clinical outcome after transrectal HIFU treatment for CaP.

  7. A high response rate to liposomal doxorubicin is seen among women with BRCA mutations treated for recurrent epithelial ovarian cancer.

    Science.gov (United States)

    Adams, Sarah F; Marsh, Evelyn B; Elmasri, Wafic; Halberstadt, Steffanie; Vandecker, Stephanie; Sammel, Mary D; Bradbury, Angela R; Daly, Mary; Karlan, Beth; Rubin, Stephen C

    2011-12-01

    Ten percent of ovarian cancer is attributed to hereditary syndromes, most commonly to mutations in the BRCA1 or BRCA2 genes. These cancers are characterized by a prolonged sensitivity to platinum agents in spite of presentation at advanced stages. We hypothesized that women with BRCA-associated ovarian cancer would also show a high response rate to pegylated liposomal doxorubicin (Doxil). A retrospective cohort study was conducted to compare the response rate, progression-free, and overall survival among women with BRCA-associated or sporadic ovarian cancer who were treated with Doxil. A response to Doxil was seen in 13 of 23 patients with BRCA mutations (56.5%; 3 by RECIST criteria and 10 by CA125 levels) compared with only 8 of 41 women with non-hereditary cancers (19.5%; 2 by RECIST criteria and 6 by CA125 levels; p=0.004). This was associated with an improved progression-free and overall survival as measured from the time of Doxil administration. Notably, platinum sensitivity did not directly correlate with a response to Doxil. Women with BRCA-associated ovarian tumors demonstrate a greater sensitivity to cytotoxic therapy with Doxil than has previously been reported in unselected cases. Copyright © 2011 Elsevier Inc. All rights reserved.

  8. Emergence of a daptomycin-non-susceptible Enterococcus faecium strain that encodes mutations in DNA repair genes after high-dose daptomycin therapy.

    Science.gov (United States)

    Matono, Takashi; Hayakawa, Kayoko; Hirai, Risen; Tanimura, Akira; Yamamoto, Kei; Fujiya, Yoshihiro; Mawatari, Momoko; Kutsuna, Satoshi; Takeshita, Nozomi; Mezaki, Kazuhisa; Ohmagari, Norio; Miyoshi-Akiyama, Tohru

    2016-04-01

    An increasing number of reports have documented the emergence of daptomycin-nonsusceptible Enterococcus in patients during daptomycin therapy. Even though several mechanisms for daptomycin-nonsusceptibility have been suggested, the potential genetic mutations which might contribute to the daptomycin-nonsusceptibility are not fully understood. We isolated a vancomycin-susceptible, daptomycin nonsusceptible Enterococcus faecium strain from a patient with acute lymphocytic leukemia who received high-dose daptomycin therapy for E. faecium endocarditis. Whole-genome sequencing analysis revealed mutations within genes encoding DNA repair proteins MutL and RecJ of the daptomycin-nonsusceptible Enterococcus strain which might have facilitated its emergence. We identified the mutations of DNA mismatch repair genes in a clinical isolate of daptomycin nonsusceptible E. faecium which emerged in spite of high-dose daptomycin therapy. The finding implicates the possible association of DNA repair mechanism and daptomycin resistance. Careful monitoring is necessary to avoid the emergence of daptomycin non-susceptible isolates of E. faecium and particularly in cases of long-term daptomycin use or in immunocompromised patients.

  9. Long-term functional outcome and risk factors for recurrence after surgical treatment for low and high perianal fistulas of cryptoglandular origin

    NARCIS (Netherlands)

    van Koperen, Paul J.; Wind, Jan; Bemelman, Willem A.; Bakx, Roel; Reitsma, Johannes B.; Slors, J. Frederik M.

    2008-01-01

    PURPOSE: This study assessed long-term functional outcome and explored risk factors for fistula recurrence in patients surgically treated for cryptoglandular fistulas. METHODS: Three hundred ten consecutive patients were surgically treated for perianal fistulas. After exclusion of patients with

  10. High recurrence of device-related adverse events following transvenous lead extraction procedure in patients with cardiac resynchronization devices.

    Science.gov (United States)

    Regoli, François; Bongiorni, Maria Grazia; Rordorf, Roberto; Santamaria, Matteo; Klersy, Caterine; Segreti, Luca; De Regibus, Valentina; Moccetti, Tiziano; Conte, Giulio; Caputo, Maria Luce; Auricchio, Angelo

    2016-10-01

    Little is known about the clinical outcome and recurring system-related adverse events (SAE) in cardiac resynchronization therapy (CRT) patients after transvenous lead extraction (TLE). From January 2009 to June 2014, 256 consecutive CRT patients (mean age 68.3 ± 11.6 years, 216 male, 88% in New York Heart Association class II-IV, ejection fraction 35.1 ± 10.8%) were treated at four European institutions with TLE. Indications for TLE included systemic (18%) or local (45%) infection, system malfunction (34%), or other (3%). Demographic, clinical, TLE procedural, and follow-up data were collected retrospectively. Adverse events (AE) were considered as death from any cause, cardiovascular hospitalization, and SAE (SAE included pocket and/or systemic infection, lead malfunction, or pocket haematoma requiring revision). Complete removal was achieved for 609 out of 614 leads (99.2%) by using either manual traction (28%), mechanical (52%) or laser (20%) sheaths. Over a median follow-up of 21 (interquartile range 12-29) months, cumulative incidences of any AE and SAE were 53.9% and 21.1%, respectively. Recurring system malfunction occurred in 23 patients (9.0%), infection in 16 patients (6.2%), and pocket haematoma requiring revision in 15 patients (5.9%). Oral anticoagulation therapy was an independent predictor of both any AE [hazard ratio (HR) 2.09, 95% confidence interval (CI) 1.35-3.22, P = 0.001] and SAE (HR 2.38, 95% CI 1.21-4.68, P = 0.012) after TLE. Even though TLE is safe and effective to treat CRT patients, a high burden of recurring SAE after TLE was observed at mid-term follow-up. Careful evaluation of both patient characteristics as well as implantation strategy is suggested when indicating TLE in a CRT patient, particularly in patients receiving oral anticoagulation therapy. © 2016 The Authors. European Journal of Heart Failure © 2016 European Society of Cardiology.

  11. Planning with intensity-modulated radiotherapy and tomotherapy to modulate dose across breast to reflect recurrence risk (IMPORT High trial).

    Science.gov (United States)

    Donovan, Ellen M; Ciurlionis, Laura; Fairfoul, Jamie; James, Hayley; Mayles, Helen; Manktelow, Sophie; Raj, Sanjay; Tsang, Yat; Tywman, Nicola; Yarnold, John; Coles, Charlotte

    2011-03-15

    To establish planning solutions for a concomitant three-level radiation dose distribution to the breast using linear accelerator- or tomotherapy-based intensity-modulated radiotherapy (IMRT), for the U.K. Intensity Modulated and Partial Organ (IMPORT) High trial. Computed tomography data sets for 9 patients undergoing breast conservation surgery with implanted tumor bed gold markers were used to prepare three-level dose distributions encompassing the whole breast (36 Gy), partial breast (40 Gy), and tumor bed boost (48 or 53 Gy) treated concomitantly in 15 fractions within 3 weeks. Forward and inverse planned IMRT and tomotherapy were investigated as solutions. A standard electron field was compared with a photon field arrangement encompassing the tumor bed boost volume. The out-of-field doses were measured for all methods. Dose-volume constraints of volume >90% receiving 32.4 Gy and volume >95% receiving 50.4 Gy for the whole breast and tumor bed were achieved. The constraint of volume >90% receiving 36 Gy for the partial breast was fulfilled in the inverse IMRT and tomotherapy plans and in 7 of 9 cases of a forward planned IMRT distribution. An electron boost to the tumor bed was inadequate in 8 of 9 cases. The IMRT methods delivered a greater whole body dose than the standard breast tangents. A contralateral lung volume >2.5 Gy was increased in the inverse IMRT and tomotherapy plans, although it did not exceed the constraint. We have demonstrated a set of widely applicable solutions that fulfilled the stringent clinical trial requirements for the delivery of a concomitant three-level dose distribution to the breast. Copyright © 2011 Elsevier Inc. All rights reserved.

  12. Acute recurrent polyhydramnios

    DEFF Research Database (Denmark)

    Rode, Line; Bundgaard, Anne; Skibsted, Lillian

    2007-01-01

    Acute recurrent polyhydramnios is a rare occurrence characterized by a poor fetal outcome. This is a case report describing a 34-year-old woman presenting with acute recurrent polyhydramnios. Treatment with non-steroidal anti-inflammatory drugs (NSAID) and therapeutic amniocenteses was initiated...... an enzyme-linked immunosorbent assay. As in normal pregnancies, amniotic prolactin levels decreased by 80% from highest to lowest value in this case of resolving acute recurrent polyhydramnios....

  13. Recurrent fever in children

    OpenAIRE

    Sofia Torreggiani; Giovanni Filocamo; Susanna Esposito

    2016-01-01

    Children presenting with recurrent fever may represent a diagnostic challenge. After excluding the most common etiologies, which include the consecutive occurrence of independent uncomplicated infections, a wide range of possible causes are considered. This article summarizes infectious and noninfectious causes of recurrent fever in pediatric patients. We highlight that, when investigating recurrent fever, it is important to consider age at onset, family history, duration of febrile episodes,...

  14. Recurrent pregnancy loss and obesity.

    Science.gov (United States)

    Sugiura-Ogasawara, Mayumi

    2015-05-01

    Recurrent pregnancy loss (RPL) was defined as two or more miscarriages. Antiphospholipid syndrome, uterine anomalies, and parental chromosomal abnormalities, particularly translocation and abnormal embryonic karyotype, are identifiable causes of RPL. Obesity may increase the risk of sporadic miscarriage in pregnancies conceived spontaneously. Obesity with body mass index (BMI)>30 kg/m2 is an independent risk factor for further miscarriage with odds ratio 1.7-3.5 in patients with early RPL. Obesity is associated with euploid miscarriage. Unexplained RPL with euploid embryo might be a common disease caused by both polymorphisms of multiple susceptibility genes and lifestyle factors such as women's age, obesity, and smoking. Patients with a history of RPL were found to have a higher risk of cardiovascular disease, celiac disease, gastric ulcer, gastritis, and atopic dermatitis. No study has examined the effect of weight loss on the prevention of further miscarriage in patients with RPL. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Clinical Trial Results of the HER-2/neu (E75) Vaccine to Prevent Breast Cancer Recurrence in High-Risk Patients

    Science.gov (United States)

    Mittendorf, Elizabeth A.; Clifton, Guy T.; Holmes, Jarrod P.; Clive, Kevin S.; Patil, Ritesh; Benavides, Linda C.; Gates, Jeremy D.; Sears, Alan K.; Stojadinovic, Alexander; Ponniah, Sathibalan; Peoples, George E.

    2012-01-01

    BACKGROUND The authors conducted exploratory phase 1–2 clinical trials vaccinating breast cancer patients with E75, a human leukocyte antigen (HLA) A2/A3–restricted HER-2/neu (HER2) peptide, and granulocyte-macrophage colony-stimulating factor. The vaccine is given as adjuvant therapy to prevent disease recurrence. They previously reported that the vaccine is safe and effective in stimulating expansion of E75-specific cytotoxic T cells. Here, they report 24-month landmark analyses of disease-free survival (DFS). METHODS These dose escalation/schedule optimization trials enrolled lymph node-positive and high-risk lymph node-negative patients with HER2 (immunohistochemistry [IHC] 1-3+) expressing tumors. HLA-A2/A3+ patients were vaccinated; others were followed prospectively as controls for recurrence. DFS was analyzed by Kaplan-Meier curves; groups were compared using log-rank tests. RESULTS Of 195 enrolled patients, 182 were evaluable: 106 (58.2%) in the vaccinated group and 76 (41.8%) in the control group. The 24-month landmark analysis DFS was 94.3% in the vaccinated group and 86.8% in the control group (P = .08). Importantly, because of trial design, 65% of patients received a lower than optimal vaccine dose. In subset analyses, patients who benefited most from vaccination (vaccinated group vs control group) had lymph node-positive (DFS, 90.2% vs 79.1%; P = .13), HER2 IHC 1+-2+ (DFS, 94.0% vs 79.4%; P = .04), or grade 1 or 2 (DFS, 98.4% vs 86.0%; P = .01) tumors and were optimally dosed (DFS, 97.3% vs 86.8%; P = .08). A booster program has been initiated; no patients receiving booster inoculations have recurred. CONCLUSIONS The E75 vaccine has clinical efficacy that is more prominent in certain patients. A phase 3 trial enrolling lymph node-positive patients with HER2 low-expressing tumors is warranted. PMID:21989902

  16. Sulfhydryl reagent susceptibility in proteins with high sequence similarity--triosephosphate isomerase from Trypanosoma brucei, Trypanosoma cruzi and Leishmania mexicana.

    Science.gov (United States)

    Garza-Ramos, G; Cabrera, N; Saavedra-Lira, E; Tuena de Gómez-Puyou, M; Ostoa-Saloma, P; Pérez-Montfort, R; Gómez-Puyou, A

    1998-05-01

    The amino acid sequence of triosephosphate isomerase from Trypanosoma brucei, Trypanosoma cruzi, and Leishmania mexicana have an identity of 68%. Using the numbering system for the T. brucei enzyme, in their aligned sequences, the T. cruzi and leishmanial enzymes have cysteine residues at positions 14, 40, 117 and 126. T. brucei triosephosphate isomerase has cysteine residues at positions 14, 40 and 126, and a valine residue at position 117. Dithionitrobenzoic acid and methylmethane thiosulfonate inhibited the three enzymes, but T. cruzi triosephosphate isomerase was more than 100-fold more sensitive. The sensitivity of wild type triosephosphate isomerase from T. cruzi and T. brucei to the reagents was equal to that of the Cys117Val and Val117Cys mutant enzymes, respectively. Triosephosphate isomerases that have cysteine residues at positions 40 and 126, but lack a cysteine residue at position 14 are insensitive to methylmethane thiosulfonate. Thus, sulfhydryl reagents act on Cys14. At stoichiometric concentrations, the reagents inhibited the three enzymes as a consequence of structural alterations as measured by binding of 8-anilino-1-napthalenesulfonic acid to previously buried hydrophobic regions. However, the times for half-maximal alterations were 10 min, 15 hours and over 30 hours for T. cruzi, T. brucei and L. mexicana triosephosphate isomerase, respectively. The effect of pH on the action of the sulfhydryl reagents and molecular modeling showed no differences in the solvent accessibility of Cys14. As Cys14 forms part of the dimer interface, the data indicate that, in the three enzymes, barriers of different magnitude hinder the interaction between the sulfhydryl reagents and Cys14. The barrier is lower in T. cruzi triosephosphate isomerase which makes its dimer interface more susceptible for perturbation.

  17. High-throughput behavioral phenotyping of drug and alcohol susceptibility traits in the expanded panel of BXD recombinant inbred strains

    Energy Technology Data Exchange (ETDEWEB)

    Philip, Vivek M [ORNL; Ansah, T [University of Tennessee Health Science Center, Memphis; Blaha, C, [University of Tennessee Health Science Center, Memphis; Cook, Melloni N. [University of Memphis; Hamre, Kristin M. [University of Tennessee Health Science Center, Memphis; Lariviere, William R [University of Pittsburgh; Matthews, Douglas B [Baylor University; Goldowitz, Daniel [University of British Columbia, Vancouver; Chesler, Elissa J [ORNL

    2010-01-01

    Genetic reference populations, particularly the BXD recombinant inbred strains, are a valuable resource for the discovery of the bio-molecular substrates and genetic drivers responsible for trait variation and co- ariation. This approach can be profitably applied in the analysis of susceptibility and mechanisms of drug and alcohol use disorders for which many predisposing behaviors may predict occurrence and manifestation of increased preference for these substances. Many of these traits are modeled by common mouse behavioral assays, facilitating the detection of patterns and sources of genetic co-regulation of predisposing phenotypes and substance consumption. Members of the Tennessee Mouse Genome Consortium have obtained behavioral phenotype data from 260 measures related to multiple behavioral assays across several domains: self-administration, response to, and withdrawal from cocaine, MDMA, morphine and alcohol; novelty seeking; behavioral despair and related neurological phenomena; pain sensitivity; stress sensitivity; anxiety; hyperactivity; and sleep/wake cycles. All traits have been measured in both sexes and the recently expanded panel of 69 additional BXD recombinant inbred strains (N=69). Sex differences and heritability estimates were obtained for each trait, and a comparison of early (N = 32) and recent BXD RI lines was performed. Primary data is publicly available for heritability, sex difference and genetic analyses using www.GeneNetwork.org. These analyses include QTL detection and genetic analysis of gene expression. Stored results from these analyses are available at http://ontologicaldiscovery.org for comparison to other genomic analysis results. Together with the results of related studies, these data form a public resource for integrative systems genetic analysis of neurobehavioral traits.

  18. Association analysis of a highly polymorphic CAG Repeat in the human potassium channel gene KCNN3 and migraine susceptibility

    Directory of Open Access Journals (Sweden)

    Ovcaric Mick

    2005-09-01

    Full Text Available Abstract Background Migraine is a polygenic multifactorial disease, possessing environmental and genetic causative factors with multiple involved genes. Mutations in various ion channel genes are responsible for a number of neurological disorders. KCNN3 is a neuronal small conductance calcium-activated potassium channel gene that contains two polyglutamine tracts, encoded by polymorphic CAG repeats in the gene. This gene plays a critical role in determining the firing pattern of neurons and acts to regulate intracellular calcium channels. Methods The present association study tested whether length variations in the second (more 3' polymorphic CAG repeat in exon 1 of the KCNN3 gene, are involved in susceptibility to migraine with and without aura (MA and MO. In total 423 DNA samples from unrelated individuals, of which 202 consisted of migraine patients and 221 non-migraine controls, were genotyped and analysed using a fluorescence labelled primer set on an ABI310 Genetic Analyzer. Allele frequencies were calculated from observed genotype counts for the KCNN3 polymorphism. Analysis was performed using standard contingency table analysis, incorporating the chi-squared test of independence and CLUMP analysis. Results Overall, there was no convincing evidence that KCNN3 CAG lengths differ between Caucasian migraineurs and controls, with no significant difference in the allelic length distribution of CAG repeats between the population groups (P = 0.090. Also the MA and MO subtypes did not differ significantly between control allelic distributions (P > 0.05. The prevalence of the long CAG repeat (>19 repeats did not reach statistical significance in migraineurs (P = 0.15, nor was there a significant difference between the MA and MO subgroups observed compared to controls (P = 0.46 and P = 0.09, respectively, or between MA vs MO (P = 0.40. Conclusion This association study provides no evidence that length variations of the second polyglutamine array in

  19. Can pre- and postoperative magnetic resonance imaging predict recurrence-free survival after whole-gland high-intensity focused ablation for prostate cancer?

    Energy Technology Data Exchange (ETDEWEB)

    Rosset, Remy; Bratan, Flavie [Hopital Edouard Herriot, Hospices Civils de Lyon, Department of Urinary and Vascular Radiology, Lyon (France); Crouzet, Sebastien [Hopital Edouard Herriot, Hospices Civils de Lyon, Department of Urology, Lyon (France); Universite de Lyon, Lyon (France); Faculte de Medecine Lyon Est, Universite Lyon 1, Lyon (France); Inserm, U1032, LabTau, Lyon (France); Tonoli-Catez, Helene [Hopital Edouard Herriot, Hospices Civils de Lyon, Department of Urology, Lyon (France); Mege-Lechevallier, Florence [Hopital Edouard Herriot, Hospices Civils de Lyon, Department of Pathology, Lyon (France); Gelet, Albert [Hopital Edouard Herriot, Hospices Civils de Lyon, Department of Urology, Lyon (France); Inserm, U1032, LabTau, Lyon (France); Rouviere, Olivier [Hopital Edouard Herriot, Hospices Civils de Lyon, Department of Urinary and Vascular Radiology, Lyon (France); Universite de Lyon, Lyon (France); Faculte de Medecine Lyon Est, Universite Lyon 1, Lyon (France); Inserm, U1032, LabTau, Lyon (France)

    2017-04-15

    Our aim was to assess whether magnetic resonance imaging (MRI) features predict recurrence-free survival (RFS) after prostate cancer high-intensity focused ultrasound (HIFU) ablation. We retrospectively selected 81 patients who underwent (i) whole-gland HIFU ablation between 2007 and 2011 as first-line therapy or salvage treatment after radiotherapy or brachytherapy, and (ii) pre- and postoperative MRI. On preoperative imaging, two senior (R1, R2) and one junior (R3) readers assessed the number of sectors invaded by the lesion with the highest Likert score (dominant lesion) using a 27-sector diagram. On postoperative imaging, readers assessed destruction of the dominant lesion using a three-level score. Multivariate analysis included the number of sectors invaded by the dominant lesion, its Likert and destruction scores, the pre-HIFU prostate-specific antigen (PSA) level, Gleason score, and the clinical setting (primary/salvage). The most significant predictor was the number of prostate sectors invaded by the dominant lesion for R2 and R3 (p≤0.001) and the destruction score of the dominant lesion for R1 (p = 0.011). The pre-HIFU PSA level was an independent predictor for R2 (p = 0.014), but with only marginal significance for R1 (p = 0.059) and R3 (p = 0.053). The dominant lesion's size and destruction assessed by MRI provide independent prognostic information compared with usual predictors. (orig.)

  20. Are there patients with T1 to T2, lymph node-negative breast cancer who are "high-risk" for locoregional disease recurrence?

    Science.gov (United States)

    Mamtani, Anita; Patil, Sujata; Stempel, Michelle M; Morrow, Monica

    2017-07-15

    Indications for postmastectomy radiotherapy (PMRT) in patients with T1 to T2, lymph node-negative (N0) breast cancer with "high-risk" features are controversial. The European Organization for Research and Treatment of Cancer (EORTC) 22922 and National Cancer Institute of Canada Clinical Trials Group MA20 trials reporting improved 10-year disease-free survival with lymph node irradiation included patients with high-risk N0 disease, but, to the authors' knowledge, benefits in patients receiving modern systemic therapy are uncertain. The authors retrospectively identified patients with T1 to T2N0 disease who were treated with mastectomy from January 2006 through December 2011. High-risk features included age patients, only 15 received PMRT and were excluded. Of the remaining 657 patients, 187 (28%) had 1 high-risk feature and 449 patients (68%) had ≥ 2 high-risk features. A total of 36 patients with unknown tumor grade were excluded from risk analysis. Approximately 98% of patients underwent sentinel lymph node biopsy alone and 86% received adjuvant systemic therapy. At a median of 5.6 years of follow-up, the locoregional disease recurrence (LRR) rate was 4.7% (31 patients). Increasing tumor size was found to be associated with LRR (hazard ratio, 1.70; P = .006), whereas other high-risk features were not (all P > .05). Receipt of systemic therapy decreased the LRR rate (hazard ratio, 0.40; P = .03). Although crude LRR rates increased from 3.8% to 9.4% with 1 versus ≥ 4 high-risk features, the number of risk factors was not found to be significantly associated with LRR (P = .54). In the current study, a low crude LRR rate (4.7%) was observed in a large unselected cohort of patients with T1 to T2N0 breast cancer with high-risk features who were treated with mastectomy and systemic therapy without PMRT. Although increasing tumor size and the omission of systemic therapy were found to be predictive, other features did not confer a higher LRR

  1. MRI of recurrent rectosigmoid carcinoma.

    Science.gov (United States)

    Markus, J; Morrissey, B; deGara, C; Tarulli, G

    1997-01-01

    A prospective study was performed to determine the most reliable MRI criteria to distinguish recurrent rectosigmoid carcinoma from benign postoperative fibrosis. Twenty-two consecutive patients who were suspected to have recurrent rectosigmoid carcinoma were examined by T2 and precontrast and contrast enhanced T1 weighted images. The prospective interpretations, the presence of high signal on T2 weighted images, the shape of the margins of a mass and the degree of contrast enhancement were correlated with histology and follow up to determine their respective accuracies, sensitivities and specificities. The best criteria for recurrent tumor was the combination of high signal on T2 weighted images, round margins and > 40% contrast enhancement, which had an accuracy of 92%, sensitivity of 100% and specificity of 85%. In patients who were more than one year postoperative the specificity was 100%. The most reliable MRI criteria for distinguishing recurrent rectosigmoid carcinoma from benign postoperative fibrosis are the combination of the signal intensity on T2 weighed images, the shape of the margins of a mass and the presence of greater than 40% contrast enhancement.

  2. Recurrent processing during object recognition

    Directory of Open Access Journals (Sweden)

    Randall C. O'Reilly

    2013-04-01

    Full Text Available How does the brain learn to recognize objects visually, and perform this difficult feat robustly in the face of many sources of ambiguity and variability? We present a computational model based on the biology of the relevant visual pathways that learns to reliably recognize 100 different object categories in the face of of naturally-occurring variability in location, rotation, size, and lighting. The model exhibits robustness to highly ambiguous, partially occluded inputs. Both the unified, biologically plausible learning mechanism and the robustness to occlusion derive from the role that recurrent connectivity and recurrent processing mechanisms play in the model. Furthermore, this interaction of recurrent connectivity and learning predicts that high-level visual representations should be shaped by error signals from nearby, associated brain areas over the course of visual learning. Consistent with this prediction, we show how semantic knowledge about object categories changes the nature of their learned visual representations, as well as how this representational shift supports the mapping between perceptual and conceptual knowledge. Altogether, these findings support the potential importance of ongoing recurrent processing throughout the brain's visual system and suggest ways in which object recognition can be understood in terms of interactions within and between processes over time.

  3. Significant association of deficiencies of hemoglobin, iron, vitamin B12, and folic acid and high homocysteine level with recurrent aphthous stomatitis.

    Science.gov (United States)

    Sun, Andy; Chen, Hsin-Ming; Cheng, Shih-Jung; Wang, Yi-Ping; Chang, Julia Yu-Fong; Wu, Yang-Che; Chiang, Chun-Pin

    2015-04-01

    A portion of patients with recurrent aphthous stomatitis (RAS) may have nutritional deficiency. This study evaluated whether there was an intimate association of the deficiencies of hemoglobin, iron, vitamin B12, and folic acid and high blood homocysteine level with RAS. The blood hemoglobin, iron, vitamin B12, folic acid, and homocysteine concentrations in 273 RAS patients were measured and compared with the corresponding levels in 273 age- and sex-matched healthy control subjects. We found that 57 (20.9%), 55 (20.1%), 13 (4.8%), and 7 (2.6%) RAS patients had deficiencies of hemoglobin (Men < 13 g/dl, Women < 12 g/dl), iron (<60 μg/dl), vitamin B12 (<200 pg/ml), and folic acid (<4 ng/ml), respectively. Moreover, 21 (7.7%) RAS patients had abnormally high blood homocysteine level. RAS patients had a significantly higher frequency of hemoglobin, iron, vitamin B12, or folic acid deficiency and of abnormally elevated blood homocysteine level than healthy control subjects (all P-values = 0.000 except for folic acid P = 0.022). If 273 RAS patients were further divided into 32 patients with major-typed RAS (MjRAS) and 241 patients with minor-typed RAS (MiRAS), we found that male MjRAS patients had a significantly lower mean hemoglobin concentration than MiRAS patients (P = 0.021), but MjRAS patients had a significantly higher mean homocysteine level than MiRAS patients (P = 0.000). We conclude that there is a significant association of deficiencies of hemoglobin, iron, vitamin B12, and folic acid and abnormally high blood homocysteine level with RAS. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. Lack of bladder carcinogenicity of dietary sodium saccharin in analbuminaemic rats, which are highly susceptible to N-nitroso-n-butyl-(4-hydroxybutyl)amine.

    Science.gov (United States)

    Homma, Y; Kondo, Y; Kakizoe, T; Aso, Y; Nagase, S

    1991-06-01

    A previous 1-wk study measuring the agglutinability of bladder epithelial cells by concanavalin A had suggested a high susceptibility of analbuminaemic rats to bladder carcinogenesis by sodium saccharin (Honma et al., Cancer Letters 1983, 19, 7). A long-term study was conducted to confirm the results of this short-term assay. Sodium saccharin was administered at 5% in the diet to groups of 35 male analbuminaemic rats and 36 male rats of the Sprague-Dawley strain. No bladder carcinomas nor precancerous lesions were observed in any of the rats exposed to sodium saccharin. The discrepancy between the results of the agglutination assay and the long-term experiment might be attributable to a sharp increase in urine volume in analbuminaemic rats during the first week of treatment. The resultant distension of the bladder wall might make the epithelial cells more susceptible to concanavalin A agglutination. The results indicated no demonstrable bladder carcinogenicity of sodium saccharin in analbuminaemic rats and excluded the possibility that these particular mutant rats could be useful animals for shorter-duration screening for bladder carcinogens.

  5. Differential diagnosis of recurrent bronchitis in children

    Directory of Open Access Journals (Sweden)

    I. I. Zakirov

    2016-01-01

    Full Text Available The interest of the doctors — pediatricians to recurrent bronchitis is caused by its high specific weight in the structure of bronchopulmonary pathology in children, the complexity and the need to search the differential selection of an individual regimen and prevention. Recurrent bronchitis with bronchoobstructive syndromes patient is regarded as a predictor of asthma, however, erroneously consider these nosological forms as the stages of a single pathophysiological chain as congenital and acquired diseases of respiratory system, pathology of gastro-intestinal tract, cardio-vascular system can masquerade as recurrent bronchitis. The aim of this work — to analyze the current medical literature on the problem of differential search causes leading recurrent respiratory syndrome in children. Materials and methods. The review publications domestic and foreign authors studied data from clinical and epidemiological studies. Results and its discussion. Anatomical physiological characteristics of the respiratory tract, complicated premorbid background, the re-infection of the child respiratory infection contribute to the recurrent course of bronchitis. The most common recurrent bronchitis is transient, recurrent bronchitis episodes completely stoped with the age of the child. Recurrent respiratory infections can fix bronchial hyperreactivity and with the presence of aggravated allergic history lead to the development of asthma. Severe bronchitis, resistance to standard scheme of therapy, the frequent recurrence of respiratory syndrome dictate the need to expand the diagnostic research to clarify the leading cause of recurrent bronchitis. Conclusion. Recurrent bronchitis is considered as a separate nosological form. At the same time, by repeated episodes of respiratory infection may be masked by malformations, hereditary diseases of respiratory system, bronchus foreign body microaspiration syndrome, pathology of the cardio-vascular system. 

  6. Risk factors for idiopathic optic neuritis recurrence.

    Directory of Open Access Journals (Sweden)

    Yi Du

    Full Text Available Approximately 30-50% of idiopathic optic neuritis (ION patients experience one or multiple episodes of recurrence. The aim of this study was to search for risk factors for ION recurrence.Clinical data on hospitalized patients diagnosed with ION between January 2003 and January 2011 at the First Affiliated Hospital of Guangxi Medical University were retrospectively collected. Univariate and multivariate analyses were performed on factors that might cause ION recurrence. In total, 115 ION cases (32 recurrent and 83 non-recurrent cases with complete data were analyzed. The length of the follow-up period ranged from 12 to 108 months (median: 42 months.The univariate analysis showed that the recurrence rate for unilateral ION was higher than that for bilateral ION (40% vs. 12%, p=0.001. Underlying diseases had a significant impact on recurrence (p<0.001: the recurrence rates due to neuromyelitis optica (NMO, multiple sclerosis (MS, demyelinating lesions alone of the central nervous system, and unknown causes were 89%, 70%, 41%, and 8.7%, respectively. The multivariate analysis showed that the factors causing relatively high recurrence rates included NMO (odds ratio [OR], 73.5; 95% confidence interval [CI], 7.3 to 740.9, MS (OR, 33.9; 95% CI, 5.2 to 222.2, and demyelinating lesions alone (OR, 8.9; 95% CI, 2.3 to 34.4, unilateral involvement (OR, 5.7; 95% CI, 1.5 to 21.3, relatively low initial glucocorticoid dosage (equivalent to ≤ 100 mg prednisone/day (OR, 4.3; 95% CI, 1.0 to 17.9.Underlying diseases, laterality (unilateral or bilateral, and initial glucocorticoid dosage are important risk factors of ION recurrence. Clinical physicians are advised to treat ION patients with a sufficient dose of glucocorticoid in the initial treatment stage to reduce the recurrence risk.

  7. High expression of Y-box-binding protein 1 correlates with poor prognosis and early recurrence in patients with small invasive lung adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Zhao S

    2016-05-01

    Full Text Available Shilei Zhao,1,* Wei Guo,1,* Jinxiu Li,1 Wendan Yu,1 Tao Guo,1 Wuguo Deng,2,3 Chundong Gu1 1The First Affiliated Hospital, Institute of Cancer Stem Cell, Lung Cancer Diagnosis and Treatment Center, Dalian Medical University, Dalian, 2Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-Sen University, Guangzhou, 3State Key Laboratory of Targeted Drug for Tumors of Guangdong Province, Guangzhou Double Bioproduct Inc., Guangzhou, People’s Republic of China *These authors contributed equally to this work Background: Prognosis of small (≤2 cm invasive lung adenocarcinoma remains poor, and identification of high-risk individuals from the patients after complete surgical resection of lung adenocarcinoma has become an urgent problem. YBX1 has been reported to be able to predict prognosis in many cancers (except lung adenocarcinoma that are independent of TNM (tumor, nodes, metastases staging, especially small invasive lung adenocarcinoma. Therefore, we examined the significance of YBX1 expression on prognosis and recurrence in patients with small invasive lung adenocarcinoma. Material and methods: A total of 75 patients with small invasive lung adenocarcinoma after complete resection were enrolled from January 2008 to December 2010. Immunohistochemical staining was used to detect the expression of YBX1, and receiver operating characteristic curve analysis was performed to precisely assess the overall expression of YBX1. Meanwhile, primary lesions were identified based on the International Association for the Study of Lung Cancer, the American Thoracic Society, and the European Respiratory Society’s classification of lung adenocarcinoma. The effect of different clinicopathological factors on patients’ survival was examined. Furthermore, Western blot analysis was used to show the expression of YBX1 in vitro. Results: Sensitivity and specificity of YBX1 for detecting small

  8. Efficacy of Blended Cognitive Behavior Therapy for High Fear of Recurrence in Breast, Prostate, and Colorectal Cancer Survivors: The SWORD Study, a Randomized Controlled Trial.

    Science.gov (United States)

    van de Wal, Marieke; Thewes, Belinda; Gielissen, Marieke; Speckens, Anne; Prins, Judith

    2017-07-01

    Purpose Fear of cancer recurrence (FCR) is a common problem experienced by cancer survivors. Approximately one third of survivors report high FCR. This study aimed to evaluate whether blended cognitive behavior therapy (bCBT) can reduce the severity of FCR in cancer survivors curatively treated for breast, prostate, or colorectal cancer. Patients and Methods This randomized controlled trial included 88 cancer survivors with high FCR (Cancer Worry Scale score ≥ 14) from 6 months to 5 years after cancer treatment. Participants were randomly allocated (ratio 1:1, stratified by cancer type) to receive bCBT, including five face-to face and three online sessions (n = 45) or care as usual (CAU; n = 43). Participants completed questionnaires at baseline (T0) and 3 months later (T1). The intervention group completed bCBT between T0 and T1. The primary outcome was FCR severity assessed with the Cancer Worry Scale. Secondary outcomes included other distress-related measures. Statistical (one-way between-group analyses of covariance) and clinical effects (clinically significant improvement) were analyzed by intention to treat. Results Participants who received bCBT reported significantly less FCR than those who received CAU (mean difference, -3.48; 95% CI, -4.69 to -2.28; P < .001) with a moderate-to-large effect size ( d = 0.76). Clinically significant improvement in FCR was significantly higher in the bCBT group than in the CAU group (13 [29%] of 45 compared with 0 [0%] of 43; P < .001); self-rated improvement was also higher in the bCBT group (30 [71%] of 42 compared with 12 [32%] of 38 in the CAU group; P < .001). Conclusion bCBT has a statistically and clinically significant effect on the severity of FCR in cancer survivors and is a promising new treatment approach.

  9. SU-G-TeP2-10: Feasibility of Newly Designed Applicator for High Dose Rate Brachytherapy Treatment of Patients with Vaginal Vault Recurrence

    Energy Technology Data Exchange (ETDEWEB)

    Lee, V; Wong, M; Chan, M; Cheung, S; Leung, R; Lee, K; Law, G; Tung, S [Tuen Mun Hospital (Hong Kong); Huang, X; Chui, E; Leung, K [The Chinese University of Hong Kong (Hong Kong); Kwong, D [The University of Hong Kong (Hong Kong)

    2016-06-15

    Purpose: To compare the dose of an in-house 3D-printed gynecology applicator (TMHGA) for vaginal vault recurrence of corpus cancer patients after operation for high dose rate brachytherapy treatment with commercially available applicators. Methods: A newly designed applicator is made from 3D-printing methods using ABSM30i. The isodose of the applicator is compared with Elekta multi-channel (MC) applicator and titanium Rotterdam applicator with coupling central tube and vaginal cylinder (RC). Three plans are created using three applicators in a CT set of water phantom. The applicators are anchored using the applicator library and implant library in the Elekta Oncentra treatment planning system (ver.4.5). The rectum is mimicked by creating a 2cm diameter cylinder, with a distance 1mm posteriorly away from the high risk CTV (HR-CTV). Similarly, the bladder is replicated by a 6cm diameter cylinder with distance 1mm anteriorly from the HR-CTV. Three plans are all normalized 1.5cm superior, 0.5cm anterior and 0.5cm posterior of the applicator surface. By fixing D90 of HR-CTV to 6Gy, the D2cc of rectum and bladder of three plans are compared. Results: The D2cc of the bladder for using TMHGA is lower than MC and RC by 14.0% and 11.9% respectively. While the D2cc of the rectum for using TMHGA is lower than MC and RC by 18.9% and 12.4% respectively. The total treatment time of TMHGA plan is shorter than MC and RC by 11.2% and 12.9%. Conclusion: The applicator created via 3D printing delivers a lower dose to the bladder and the rectum while keeping the same coverage to HR-CTV as other commercially available applicators. Additionally, the new applicator resulted in a reduction of treatment time, which is always welcome.

  10. Exposure to lard-based high-fat diet during fetal and lactation periods modifies breast cancer susceptibility in adulthood in rats.

    Science.gov (United States)

    de Oliveira Andrade, Fábia; Fontelles, Camile Castilho; Rosim, Mariana Papaléo; de Oliveira, Tiago Franco; de Melo Loureiro, Ana Paula; Mancini-Filho, Jorge; Rogero, Marcelo Macedo; Moreno, Fernando Salvador; de Assis, Sonia; Barbisan, Luiz Fernando; Hilakivi-Clarke, Leena; Ong, Thomas Prates

    2014-06-01

    The present study investigated whether early life exposure to high levels of animal fat increases breast cancer risk in adulthood in rats. Dams consumed a lard-based high-fat (HF) diet (60% fat-derived energy) or an AIN93G control diet (16% fat-derived energy) during gestation or gestation and lactation. Their 7-week-old female offspring were exposed to 7,12-dimethyl-benzo[a]anthracene to induce mammary tumors. Pregnant dams consuming an HF diet had higher circulating leptin levels than pregnant control dams. However, compared to the control offspring, significantly lower susceptibility to mammary cancer development was observed in the offspring of dams fed an HF diet during pregnancy (lower tumor incidence, multiplicity and weight), or pregnancy and lactation (lower tumor multiplicity only). Mammary epithelial elongation, cell proliferation (Ki67) and expression of NFκB p65 were significantly lower and p21 expression and global H3K9me3 levels were higher in the mammary glands of rats exposed to an HF lard diet in utero. They also tended to have lower Rank/Rankl ratios (P=.09) and serum progesterone levels (P=.07) than control offspring. In the mammary glands of offspring of dams consuming an HF diet during both pregnancy and lactation, the number of terminal end buds, epithelial elongation and the BCL-2/BAX ratio were significantly lower and serum leptin levels were higher than in the controls. Our data confirm that the breast cancer risk of offspring can be programmed by maternal dietary intake. However, contrary to our expectation, exposure to high levels of lard during early life decreased later susceptibility to breast cancer. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Secondary variants in individuals undergoing exome sequencing: screening of 572 individuals identifies high-penetrance mutations in cancer-susceptibility genes.

    Science.gov (United States)

    Johnston, Jennifer J; Rubinstein, Wendy S; Facio, Flavia M; Ng, David; Singh, Larry N; Teer, Jamie K; Mullikin, James C; Biesecker, Leslie G

    2012-07-13

    Genome- and exome-sequencing costs are continuing to fall, and many individuals are undergoing these assessments as research participants and patients. The issue of secondary (so-called incidental) findings in exome analysis is controversial, and data are needed on methods of detection and their frequency. We piloted secondary variant detection by analyzing exomes for mutations in cancer-susceptibility syndromes in subjects ascertained for atherosclerosis phenotypes. We performed exome sequencing on 572 ClinSeq participants, and in 37 genes, we interpreted variants that cause high-penetrance cancer syndromes by using an algorithm that filtered results on the basis of mutation type, quality, and frequency and that filtered mutation-database entries on the basis of defined categories of causation. We identified 454 sequence variants that differed from the human reference. Exclusions were made on the basis of sequence quality (26 variants) and high frequency in the cohort (77 variants) or dbSNP (17 variants), leaving 334 variants of potential clinical importance. These were further filtered on the basis of curation of literature reports. Seven participants, four of whom were of Ashkenazi Jewish descent and three of whom did not meet family-history-based referral criteria, had deleterious BRCA1 or BRCA2 mutations. One participant had a deleterious SDHC mutation, which causes paragangliomas. Exome sequencing, coupled with multidisciplinary interpretation, detected clinically important mutations in cancer-susceptibility genes; four of such mutations were in individuals without a significant family history of disease. We conclude that secondary variants of high clinical importance will be detected at an appreciable frequency in exomes, and we suggest that priority be given to the development of more efficient modes of interpretation with trials in larger patient groups. Copyright © 2012 The American Society of Human Genetics. Published by Elsevier Inc. All rights

  12. qPCR-High resolution melt analysis for drug susceptibility testing of Mycobacterium leprae directly from clinical specimens of leprosy patients.

    Directory of Open Access Journals (Sweden)

    Sergio Araujo

    2017-06-01

    Full Text Available Real-Time PCR-High Resolution Melting (qPCR-HRM analysis has been recently described for rapid drug susceptibility testing (DST of Mycobacterium leprae. The purpose of the current study was to further evaluate the validity, reliability, and accuracy of this assay for M. leprae DST in clinical specimens.The specificity and sensitivity for determining the presence and susceptibility of M. leprae to dapsone based on the folP1 drug resistance determining region (DRDR, rifampin (rpoB DRDR and ofloxacin (gyrA DRDR was evaluated using 211 clinical specimens from leprosy patients, including 156 multibacillary (MB and 55 paucibacillary (PB cases. When comparing the results of qPCR-HRM DST and PCR/direct DNA sequencing, 100% concordance was obtained. The effects of in-house phenol/chloroform extraction versus column-based DNA purification protocols, and that of storage and fixation protocols of specimens for qPCR-HRM DST, were also evaluated. qPCR-HRM results for all DRDR gene assays (folP1, rpoB, and gyrA were obtained from both MB (154/156; 98.7% and PB (35/55; 63.3% patients. All PCR negative specimens were from patients with low numbers of bacilli enumerated by an M. leprae-specific qPCR. We observed that frozen and formalin-fixed paraffin embedded (FFPE tissues or archival Fite's stained slides were suitable for HRM analysis. Among 20 mycobacterial and other skin bacterial species tested, only M. lepromatosis, highly related to M. leprae, generated amplicons in the qPCR-HRM DST assay for folP1 and rpoB DRDR targets. Both DNA purification protocols tested were efficient in recovering DNA suitable for HRM analysis. However, 3% of clinical specimens purified using the phenol/chloroform DNA purification protocol gave false drug resistant data. DNA obtained from freshly frozen (n = 172, formalin-fixed paraffin embedded (FFPE tissues (n = 36 or archival Fite's stained slides (n = 3 were suitable for qPCR-HRM DST analysis. The HRM-based assay was also able

  13. Percentage of high-grade tumour volume does not meaningfully improve prediction of early biochemical recurrence after radical prostatectomy compared with Gleason score.

    Science.gov (United States)

    Hansen, Jens; Bianchi, Marco; Sun, Maxine; Rink, Michael; Castiglione, Fabio; Abdollah, Firas; Steuber, Thomas; Ahyai, Sascha A; Steurer, Stefan; Göbel, Cosima; Freschi, Massimo; Montorsi, Francesco; Shariat, Shahrokh F; Fisch, Margit; Graefen, Markus; Karakiewicz, Pierre I; Briganti, Alberto; Chun, Felix K-H

    2014-03-01

    To examine whether percentage of tumour volume (%TV) and percentage of high-grade tumour volume (%HGTV) help to better identify men at higher risk of early biochemical recurrence (BCR) after radical prostatectomy (RP) for non-metastatic high-risk prostate cancer, as early BCR after RP might be associated with higher risk of metastases and cancer-specific mortality. We examined the data of 595 men treated with RP for non-metastatic high-risk prostate cancer between 1992 and 2011 at two European tertiary care centres. Kaplan-Meier analyses were used to graphically depict 2-year BCR-free survival. Multivariable Cox regression models addressed early BCR. We tested whether addition of %TV and %HGTV to a multivariable Cox regression model helps to increase a model's predictive accuracy (PA) for prediction of early BCR. In all, 32 men (10%) with specimen-confined prostate cancer (pT2-pT3a, negative surgical margin, pN0) and 67 men (24%) with non-specimen-confined prostate cancer had early BCR. After stratification according to %HGTV (%HGTV threshold: ≤33.33 vs >33.33%), the 2-year BCR-free survival rates were respectively 93 vs 60% (log-rank P 0.05). However, adding %HGTV (regardless of its coding) to other covariates in multivariable Cox regression analysis did not increase the model's PA in a meaningful fashion compared with the use of the detailed Gleason grading system (6 vs 7a vs 7b vs 8 vs 9-10). In a large cohort of patients with high-risk prostate cancer, %HGTV and %TV did not improve prediction of early BCR after RP substantially, although %HGTV was an independent predictor of early BCR. Therefore, sophisticated TV/HGTV measurements do not seem to have additional benefit for early BCR prediction relative to the use of Gleason grading. However, these results need to be confirmed in larger, prospective studies. © 2013 The Authors. BJU International © 2013 BJU International.

  14. Recurrent Infections May Signal Immunodeficiencies

    Science.gov (United States)

    ... Recurrent Infections May Signal Immunodeficiencies Share | Recurrent Infections May Signal Immunodeficiencies This article has been reviewed by ... common bacterial infections? If so, these recurrent infections may be a sign of an immunodeficiency disorder. The ...

  15. Progestagen therapy for recurrent miscarriage

    National Research Council Canada - National Science Library

    Szekeres-Bartho, Julia; Balasch, Juan

    .... METHODS We searched PubMed and the Cochrane database covering the period of 1968-2007. The search terms progestogens and recurrent miscarriage, NK cells and recurrent miscarriage as well as cytokines and recurrent miscarriage were used...

  16. Homologous prime-boost strategy with TgPI-1 improves the immune response and protects highly susceptible mice against chronic Toxoplasma gondii infection.

    Science.gov (United States)

    Sánchez, Vanesa R; Fenoy, Ignacio M; Picchio, Mariano S; Soto, Ariadna S; Arcon, Nadia; Goldman, Alejandra; Martin, Valentina

    2015-10-01

    Subunit-based vaccines are safer than live or attenuated pathogen vaccines, although they are generally weak immunogens. Thus, proper combination of immunization strategies and adjuvants are needed to increase their efficacy. We have previously protected C3H/HeN mice from Toxoplasma gondii infection by immunization with the serine protease inhibitor-1 (TgPI-1) in combination with alum. In this work, we explore an original vaccination protocol that combines administration of recombinant TgPI-1 by intradermal and intranasal routes in order to enhance protection in the highly susceptible C57BL/6 strain. Mice primed intradermally with rTgPI-1 plus alum and boosted intranasally with rTgPI-1 plus CpG-ODN elicited a strong specific Th1/Th2 humoral response, along with a mucosal immune response characterized by specific-IgA in intestinal lavages. A positive cellular response of mesentheric lymph node cells and Th1/Th2 cytokine secretion in the ileon were also detected. When immunized mice were challenged with the cystogenic Me49 T. gondii strain, they displayed up to 62% reduction in brain parasite burden. Moreover, adoptive transfer of mesenteric lymph node cells from vaccinated to naïve mice induced significant protection against infection. These results demonstrate that this strategy that combines the administration of TgPI-1 by two different routes, intradermal priming and intranasal boost, improves protective immunity against T. gondii chronic infection in highly susceptible mice. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Overcoming recurrent spontaneous abortions in women suffering from IgG subclass deficiency: high efficiency of low dose intravenous immunoglobulins treatment.

    Science.gov (United States)

    Manfredi, G; Dell'Aera, L; Liguori, R

    2015-05-01

    It's well known that iv. immunoglobulins may be useful to overcome habitual abortions, but the mechanisms at the base of a successful outcome and the likelihoods are still unknown. In one hundred and sixty women with habitual abortions and one hundred and sixty healthy mothers, we evaluated blood IgG subclasses; among the patients, sixteen merely showed IgG subclass deficiency, after leaving out any autoimmunity and/or coagulation disorders. All the patients (100%) showed IgG3, twelve (75%) IgG1, eight (50%) IgG4 and six (37,5%) IgG2 deficiency; healthy control people's IgG subclasses fell in normal range in 156 women, but just four women showed IgG2 and IgG4 deficiency with neither immune deficiency's clinical marks nor increased vulnerability to infections. All the patients were treated with whole immunoglobulins iv. infusion (200 mg/kg/monthly) all over the pregnancy. The successful pregnancy rate is very high (>90%): 100% out of women showing IgG1 (12/12), 87,5% of IgG3 (14/16), 75% of IgG4 (6/8) and 66% of IgG2 deficiency (4/6) had successful pregnancies. The Odd's Ratio between IgG subclass deficiency and recurrent abortions is 4,33 with confidence interval of 95%; chi square value is 7.68 (pIgG subclass deficiency without autoimmunity and/or coagulation disorders, likely restoring idiotype-antiidiotype network; showing evidence of IgG subclasses deficiency (mostly IgG1 and IgG3) may help identify patients who can benefit from iv. immunoglobulin treatment.

  18. [CZECANCA: CZEch CAncer paNel for Clinical Application-- Design and Optimization of the Targeted Sequencing Panel for the Identification of Cancer Susceptibility in High-risk Individuals from the Czech Republic].

    Science.gov (United States)

    Soukupová, J; Zemánková, P; Kleiblová, P; Janatová, M; Kleibl, Z

    2016-01-01

    Individuals with hereditary cancer syndromes form a minor but clinically important subgroup of oncology patients, comprising several thousand cases in the Czech Republic annually. In these patients, the identification of pathogenic mutations in cancer susceptibility genes has an important predictive and, in some cases, prognostic value. It also enables rational preventive strategies in asymptomatic carriers from affected families. More than 150 cancer susceptibility genes have been described so far; however, mutations in most of them are very rare, occurring with substantial population variability, and hence their clinical interpretation is very complicated. Diagnostics of mutations in cancer susceptibility genes have benefited from the broad availability of next-generation sequencing analyses using targeted gene panels. In order to rationalize the diagnostics of hereditary cancer syndromes in the Czech Republic, we have prepared the sequence capture panel "CZECANCA", targeting 219 cancer susceptibility genes. Besides more than 50 clinically important high- and moderate-penetrance susceptibility genes, the panel also targets less common candidate genes with uncertain clinical relevance. Alongside the panel design, we have optimized the analytical and bioinformatics pipeline, which will facilitate establishing a collective nationwide database of genotypes and clinical data from the analyzed individuals. The key objective of this project is to provide diagnostic laboratories in the Czech Republic with a reliable procedure and collective database improving the clinical utility of next-generation sequencing analyses in high-risk patients, which would help improve the interpretation of rare or population-specific variants in cancer susceptibility genes.

  19. Influence of maternal immunity on vaccine efficacy and susceptibility of commercial broilers against highly pathogenic avian influenza virus

    Science.gov (United States)

    Maternal antibodies provide early protection from disease, but may interfere with the vaccination efficacy in short-lived broilers. This study seeks to assess how maternal immunity can interfere with vaccine efficacy against clade 2.3.4.4 H5N2 highly pathogenic avian influenza virus (HPAIV) and how ...

  20. High-Resolution Genome-Wide Linkage Mapping Identifies Susceptibility Loci for BMI in the Chinese Population

    DEFF Research Database (Denmark)

    Zhang, Dong Feng; Pang, Zengchang; Li, Shuxia

    2012-01-01

    linkage could exist in different ethnic populations. BMI was measured from 126 dizygotic twins in Qingdao municipality who were genotyped using high-resolution Affymetrix Genome-Wide Human SNP arrays containing about 1 million single-nucleotide polymorphisms (SNPs). Nonparametric linkage analysis...

  1. The absence of GH signaling affects the susceptibility to high-fat diet-induced hypothalamic inflammation in male mice

    DEFF Research Database (Denmark)

    Baquedano, Eva; Ruiz-Lopez, Ana M; Sustarsic, Elahu G

    2014-01-01

    GH is important in metabolic control, and mice with disruption of the gene encoding the GH receptor (GHR) and GH binding protein (GHR-/- mice) are dwarf with low serum IGF-1 and insulin levels, high GH levels, and increased longevity, despite their obesity and altered lipid and metabolic profiles...

  2. RECURRENT CROUP IN CHILDREN

    Directory of Open Access Journals (Sweden)

    S. L. Piskunova

    2014-01-01

    Full Text Available The article presents the results of examination of 1849 children, entering children's infectioushospitalofVladivostokwith the clinical picture of croup of viral etiology. The clinical features of primary and recurrent croup are described. Frequency of recurrent croup inVladivostokis 8%. Children with a recurrent croup had the burdened premorbid background, and also persistent herpetic infections (cytomegalic infection in 42,9% cases, cytomegalic infection in combination with the herpes simplex virus -1. Frequency of croups substantially rose in the period of epidemic of influenza.

  3. Recurrent Respiratory Infections in Children

    Directory of Open Access Journals (Sweden)

    F. Yurochko

    2012-02-01

    Full Text Available The paper covers a problem of recurrent respiratory infections (RRI in children. Their description, risk factors, diagnostic algorithm have been dwelt. A special attention is paid to the treatment. An optimal antibiotic in RRI of bacterial genesis is a high-dose amoxicillin/clavulanate (registered as Augmentin™ ES in Ukraine, the efficacy of which is 94.6–96.3 % according to different data.

  4. The Polyp Prevention Trial–Continued Follow-up Study: No Effect of a Low-Fat, High-Fiber, High-Fruit, and -Vegetable Diet on Adenoma Recurrence Eight Years after Randomization

    National Research Council Canada - National Science Library

    Elaine Lanza; Binbing Yu; Gwen Murphy; Paul S. Albert; Bette Caan; James R. Marshall; Peter Lance; Electra D. Paskett; Joel Weissfeld; Marty Slattery; Randall Burt; Frank Iber; Moshe Shike; James W. Kikendall; Brenda K. Brewer; Arthur Schatzkin

    2007-01-01

    .... Although intervention participants reported a significantly reduced intake of dietary fat, and increased fiber, fruit, and vegetable intakes, their risk of recurrent adenomas was not significantly...

  5. Exceptionally high organic nitrogen concentrations in a semi-arid South Texas estuary susceptible to brown tide blooms

    Science.gov (United States)

    Wetz, Michael S.; Cira, Emily K.; Sterba-Boatwright, Blair; Montagna, Paul A.; Palmer, Terence A.; Hayes, Kenneth C.

    2017-03-01

    Studies of estuarine eutrophication have tended to focus on systems with continually flowing rivers, while little is known about estuaries from semi-arid/arid regions. Here we report results from an assessment of water quality conditions in Baffin Bay, Texas, a shallow (2 fold higher than in three other Texas estuaries. In contrast, inorganic nitrogen (ammonium, nitrate) and phosphate concentrations were relatively low. Statistically significant long-term annual increases in chlorophyll a and salinity were observed in Baffin Bay, while long-term seasonal increases were observed for water temperature and TKN. Overall, Baffin Bay is displaying multiple symptoms of eutrophication, namely very high organic carbon, organic nitrogen and chlorophyll concentrations, as well as symptoms not quantified here such as fish kills and episodic hypoxia. Much of the increase in chlorophyll in Baffin Bay, at least since ∼1990, have coincided with blooms of the mixotrophic phytoplankton species, Aureoumbra lagunensis, which is thought to be favored under high proportions of organic to inorganic nitrogen. Thus the high and possibly increasing organic nitrogen concentrations, coupled with a long-term annual increase in salinity and a long-term seasonal increase in water temperature are likely to promote additional brown tide blooms in this system in the future.

  6. High long-term absolute risk of recurrent venous thromboembolism in patients with hereditary deficiencies of protein S, protein C or antithrombin

    NARCIS (Netherlands)

    Brouwer, Jan-Leendert P.; Lijfering, Willem M.; ten Kate, Min Ki; Kluin-Nelemans, Hanneke C.; Veeger, Nic J. G. M.; van der Meer, Jan

    Hereditary deficiencies of protein S, protein C and antithrombin are known risk factors for first venous thromboembolism. We assessed the absolute risk of recurrence, and the contribution of concomitant thrombophilic defects in a large cohort of families with these deficiencies. Annual incidence of

  7. Local recurrence after breast-conserving therapy for invasive breast cancer: high incidence in young patients and association with poor survival

    NARCIS (Netherlands)

    Elkhuizen, P. H.; van de Vijver, M. J.; Hermans, J.; Zonderland, H. M.; van de Velde, C. J.; Leer, J. W.

    1998-01-01

    PURPOSE: To study risk factors for local recurrence (LR) after breast-conserving therapy (BCT) for invasive breast cancer and, for patients with an LR, the mode of detection, location, treatment, influence of radiation therapy, and impact on survival. METHODS AND MATERIALS: 1360 patients (median age

  8. Clinical outcome of interstitial pulsed dose rate brachytherapy in multimodality treatment of locally advanced primary or recurrent rectal and sigmoid cancer with high risk of incomplete microscopic resection

    DEFF Research Database (Denmark)

    Nielsen, Mette Bak; Rasmussen, Peter Chr.; Tanderup, Kari

    2016-01-01

    (recurrent/primary: 40/33) were treated with PDR-BT between 2001 and 2010. Patients received preoperative external beam radiotherapy (EBRT) and concomitant chemotherapy. Following resection of the tumor and the involved pelvic organs, a median of four (3-8) catheters were sutured to the tumor bed...

  9. Combined pegylated liposomal doxorubicin and bortezomib is highly effective in patients with recurrent or refractory multiple myeloma who received prior thalidomide/lenalidomide therapy

    NARCIS (Netherlands)

    P. Sonneveld (Pieter); R. Hajek (Roman); A. Nagler (Arnon); A. Spencer (Andrew); J. Bladé (Joan); T. Robak (Tadeusz); S.H. Zhuang (Sen); J-L. Harousseau (Jean-Luc); R.Z. Orlowski (Robert)

    2008-01-01

    textabstractBACKGROUND. Recently, the authors reported improved time to disease progression (TTP) with a combination of pegylated liposomal doxorubicin (PLD) and bortezomib compared with bortezomib alone in a phase 3 randomized trial in patients with recurrent/refractory multiple myeloma (MM). In

  10. Combined pegylated liposomal doxorubicin and bortezomib is highly effective in patients with recurrent or refractory multiple myeloma who received prior thalidomide/lenalidomide therapy.

    NARCIS (Netherlands)

    Sonneveld, P.; Hajek, R.; Nagler, A.; Spencer, A.; Blade, J.; Robak, T.; Zhuang, S.H.; Harousseau, J.L.; Orlowski, R.Z.

    2008-01-01

    BACKGROUND: Recently, the authors reported improved time to disease progression (TTP) with a combination of pegylated liposomal doxorubicin (PLD) and bortezomib compared with bortezomib alone in a phase 3 randomized trial in patients with recurrent/refractory multiple myeloma (MM). In the current

  11. Colistin Dosage without Loading Dose Is Efficacious when Treating Carbapenem-Resistant Acinetobacter baumannii Ventilator-Associated Pneumonia Caused by Strains with High Susceptibility to Colistin.

    Science.gov (United States)

    Álvarez-Marín, Rocío; López-Rojas, Rafael; Márquez, Juan Antonio; Gómez, María José; Molina, José; Cisneros, José Miguel; Ortiz-Leyba, Carlos; Aznar, Javier; Garnacho-Montero, José; Pachón, Jerónimo

    2016-01-01

    This study aims to analyze the mortality and the length of ICU stay (LOS) of A. baumannii VAP compared to respiratory colonization in patients with mechanical ventilation (MV). A prospective cohort study was performed in an ICU of adult patients (February 2010-June 2011). One hundred patients on MV with A. baumannii in lower respiratory airways were recruited, and classified as VAP or airways colonization according to CPIS criteria, with a punctuation ≥6. LOS, 30-days mortality, A. baumannii bacteremia, and clinical features including antibiotic therapy were recorded. Multivariate analysis (linear and Cox regression) and survival analysis (Kaplan-Meier curves) were performed. Fifty-seven VAP and 43 colonized A. baumannii patients were analyzed. Among the A. baumannii strains, 99% were non-susceptible to carbapenems and the MIC90 of colistin was 0.12 mg/l. Therapy was appropriate in 94.6% of VAP patients, most of them with colistin 6 MIU/day, although in 13 (23.6%) cases colistin was started 48 hours after the onset of VAP. Mortality was similar in both groups (VAP 24.6% vs. colonized 27.9%, p = 0.7). Bacteremia and acute kidney insufficiency were associated with decreased survival (p = 0.02 and p = 0.04, respectively) in VAP patients. LOS was 21.5 (11.5-42.75) vs. 9 (6-22) days for VAP and colonized patients (p = 0.004). VAP (p = 0.003) and age (p = 0.01) were independently related to a longer LOS. Multidrug-resistant A. baumannii VAP treated with colistin does not have a different mortality compared to lower airways colonization, among patients on mechanical-ventilation, in a setting of high susceptibility to colistin of A. baumannii.

  12. Expression of cry2Ah1 and two domain II mutants in transgenic tobacco confers high resistance to susceptible and Cry1Ac-resistant cotton bollworm.

    Science.gov (United States)

    Li, Shengyan; Wang, Zeyu; Zhou, Yiyao; Li, Changhui; Wang, Guiping; Wang, Hai; Zhang, Jie; Liang, Gemei; Lang, Zhihong

    2018-01-11

    To improve the novel Bacillus thuringiensis insecticidal gene cry2Ah1 toxicity, two mutants cry2Ah1-vp (V354VP) and cry2Ah1-sp (V354SP) were performed. SWISS-MODEL analysis showed two mutants had a longer loop located between β-4 and β-5 of domain II, resulting in higher binding affinity with brush border membrane vesicles (BBMV) of Helicoverpa armigera comparing with Cry2Ah1. The cry2Ah1, cry2Ah1-vp, and cry2Ah1-sp were optimized codon usage according to plant codon bias, and named mcry2Ah1, mcry2Ah1-vp, and mcry2Ah1-sp. They were transformed into tobacco via Agrobacterium-mediated transformation and a total of 4, 8, and 24 transgenic tobacco plants were obtained, respectively. The molecular detection showed the exogenous gene was integrated into tobacco genome, and successfully expressed at the transcript and translation levels. Cry2Ah1 protein in transgenic tobacco plants varied from 4.41 to 40.28 μg g -1 fresh weight. Insect bioassays indicated that all transgenic tobacco plants were highly toxic to both susceptible and Cry1Ac-resistant cotton bollworm larvae, and the insect resistance efficiency to Cry1Ac-resistant cotton bollworm was highest in mcry2Ah1-sp transgenic tobacco plants. The results demonstrated that cry2Ah1 was a useful Bt insecticidal gene to susceptible and Cry1Ac-resistant cotton bollworm and had potential application for insect biocontrol and as a candidate for pyramid strategy in Bt crops.

  13. Recurrent Intracerebral Hemorrhage

    DEFF Research Database (Denmark)

    Schmidt, Linnea Boegeskov; Goertz, Sanne; Wohlfahrt, Jan

    2016-01-01

    treatment and renal insufficiency were associated with increased recurrence risks (RR 1.64, 95% CI 1.39-1.93 and RR 1.72, 95% CI 1.34-2.17, respectively), whereas anti-hypertensive treatment was associated with a reduced risk (RR 0.82, 95% CI 0.74-0.91). We observed non-significant associations between...... reuptake inhibitors (SSRI's), and nonsteroidal anti-inflammatory drugs (NSAID's) with recurrent ICH. METHODS: The cohort consisted of all individuals diagnosed with a primary ICH in Denmark 1996-2011. Information on comorbidities, surgical treatment for the primary ICH, and the use of ATT, SSRI's and NSAID...... the use of any of the investigated medicines with antithrombotic effect (ATT, SSRI's, NSAID's) and recurrent ICH. CONCLUSIONS: The substantial short-and long-term recurrence risks warrant aggressive management of hypertension following a primary ICH, particularly in patients treated surgically...

  14. Immunomodulation in Recurrent Miscarriage

    National Research Council Canada - National Science Library

    Kumar, Ashok

    2014-01-01

    ... % of women with recurrent miscarriage (RM). Several studies demonstrated that successful pregnancy is dependant on shifting of maternal immune response from (proinflammatory) Th1 toward (anti-inflammatory) Th2 phenotypes...

  15. High ECT2 expression is an independent prognostic factor for poor overall survival and recurrence-free survival in non-small cell lung adenocarcinoma.

    Directory of Open Access Journals (Sweden)

    Shijie Zhou

    Full Text Available Different subtypes of non-small cell lung cancer (NSCLC have distinct sites of origin, histologies, genetic and epigenetic changes. In this study, we explored the mechanisms of ECT2 dysregulation and compared its prognostic value in lung adenocarcinoma (LUAD and lung squamous cell carcinoma (LUSC. In addition, we also investigated the enrichment of ECT2 co-expressed genes in KEGG pathways in LUAD and LUSC. Bioinformatic analysis was performed based on data from the Cancer Genome Atlas (TCGA-LUAD and TCGA-LUSC. Results showed that ECT2 expression was significantly upregulated in both LUAD and LUSC compared with normal lung tissues. ECT2 expression was considerably higher in LUSC than in LUAD. The level of ECT2 DNA methylation was significantly lower in LUSC than in LUAD. ECT2 mutation was observed in 5% of LUAD and in 51% of LUSC cases. Amplification was the predominant alteration. LUAD patients with ECT2 amplification had significantly worse disease-free survival (p = 0.022. High ECT2 expression was associated with unfavorable overall survival (OS (p<0.0001 and recurrence-free survival (RFS (p = 0.001 in LUAD patients. Nevertheless, these associations were not observed in patients with LUSC. The following univariate and multivariate analysis showed that the high ECT2 expression was an independent prognostic factor for poor OS (HR: 2.039, 95%CI: 1.457-2.852, p<0.001 and RFS (HR: 1.715, 95%CI: 1.210-2.432, p = 0.002 in LUAD patients, but not in LUSC patients. Among 518 genes co-expressed with ECT2 in LUAD and 386 genes co-expressed with ECT2 in LUSC, there were only 98 genes in the overlapping cluster. Some of the genes related KEGG pathways in LUAD were not observed in LUSC. These differences might help to explain the different prognostic value of ECT2 in LUAD and LUSC, which are also worthy of further studies.

  16. Multifocal recurrent periostitis

    Energy Technology Data Exchange (ETDEWEB)

    Kozlowski, K.; Anderson, R.; Tink, A.

    1981-11-01

    Two case reports of recurrent multifocal periostitis in two girls aged 15 and 16 are added to the eight cases already reported in the literature. The disease is characterised clinically by recurrent mesomelic swelling of the extremities and radiologically by periosteal thickening and sclerosis of underlying bone. Hyperglobulinaemia is the most constant biochemical finding. The bone biopsy shows no typical features. The possibility of a viral etiology is discussed.

  17. Fetal gender ratio in recurrent miscarriages

    Directory of Open Access Journals (Sweden)

    Del Fabro A

    2011-07-01

    Full Text Available Anna Del Fabro1, Lorenza Driul1, Omar Anis1, Ambrogio P Londero1, Serena Bertozzi2, Livio Bortotto3, Diego Marchesoni11Clinic of Obstetrics and Gynecology, 2Clinic of Surgery, 3Unit of Genetics, University Hospital of Udine, Udine, ItalyBackground: The purpose of this study was to evaluate the gender ratio and incidence of chromosomal anomalies in the products of conception (POC from recurrent miscarriages.Methods: We determined the karyotypes of POC from patients with recurrent spontaneous miscarriages between 1999 and 2009.Results: In total, 313 specimens were successfully karyotyped, with a median gestational age of 10 weeks at miscarriage (interquartile range 8–13; 199 (64% were females and 114 (36% were males. In total, 121 (39% had abnormal karyotypes, the most prevalent of which were chromosome 21 and 16 trisomies, triploidy, and monosomy X.Conclusion: Our findings suggest that female POC might be more susceptible to recurrent miscarriages than male ones during embryogenesis, implantation, and initial fetal development.Keywords: fetal gender, recurrent miscarriages, karyotype anomalies

  18. Streptococcus pyogenes Sortase Mutants Are Highly Susceptible to Killing by Host Factors Due to Aberrant Envelope Physiology

    Science.gov (United States)

    Raz, Assaf; Tanasescu, Ana-Maria; Zhao, Anna M.; Serrano, Anna; Alston, Tricia; Sol, Asaf; Bachrach, Gilad; Fischetti, Vincent A.

    2015-01-01

    Cell wall anchored virulence factors are critical for infection and colonization of the host by Gram-positive bacteria. Such proteins have an N-terminal leader sequence and a C-terminal sorting signal, composed of an LPXTG motif, a hydrophobic stretch, and a few positively charged amino acids. The sorting signal halts translocation across the membrane, allowing sortase to cleave the LPXTG motif, leading to surface anchoring. Deletion of sortase prevents the anchoring of virulence factors to the wall; the effects on bacterial physiology however, have not been thoroughly characterized. Here we show that deletion of Streptococcus pyogenes sortase A leads to accumulation of sorting intermediates, particularly at the septum, altering cellular morphology and physiology, and compromising membrane integrity. Such cells are highly sensitive to cathelicidin, and are rapidly killed in blood and plasma. These phenomena are not a loss-of-function effect caused by the absence of anchored surface proteins, but specifically result from the accumulation of sorting intermediates. Reduction in the level of sorting intermediates leads to a return of the sortase mutant to normal morphology, while expression of M protein with an altered LPXTG motif in wild type cells leads to toxicity in the host environment, similar to that observed in the sortase mutant. These unanticipated effects suggest that inhibition of sortase by small-molecule inhibitors could similarly lead to the rapid elimination of pathogens from an infected host, making such inhibitors much better anti-bacterial agents than previously believed. PMID:26484774

  19. Threatened and endangered subspecies with vulnerable ecological traits Also have high susceptibility to sea level rise and habitat fragmentation

    Science.gov (United States)

    Benscoter, Allison M.; Reece, Joshua S.; Noss, Reed F.; Brandt, Laura B.; Mazzotti, Frank J.; Romañach, Stephanie S.; Watling, James I.

    2013-01-01

    The presence of multiple interacting threats to biodiversity and the increasing rate of species extinction make it critical to prioritize management efforts on species and communities that maximize conservation success. We implemented a multi-step approach that coupled vulnerability assessments evaluating threats to Florida taxa such as climate change, sea-level rise, and habitat fragmentation with in-depth literature surveys of taxon-specific ecological traits. The vulnerability, adaptive capacity, and ecological traits of 12 threatened and endangered subspecies were compared to non-listed subspecies of the same parent species. Overall, the threatened and endangered subspecies showed high vulnerability and low adaptive capacity, in particular to sea level rise and habitat fragmentation. They also exhibited larger home ranges and greater dispersal limitation compared to non-endangered subspecies, which may inhibit their ability to track changing climate in fragmented landscapes. There was evidence for lower reproductive capacity in some of the threatened or endangered taxa, but not for most. Taxa located in the Florida Keys or in other low coastal areas were most vulnerable to sea level rise, and also showed low levels of adaptive capacity, indicating they may have a lower probability of conservation success. Our analysis of at-risk subspecies and closely related non-endangered subspecies demonstrates that ecological traits help to explain observed differences in vulnerability and adaptive capacity. This study points to the importance of assessing the relative contributions of multiple threats and evaluating conservation value at the species (or subspecies) level when resources are limited and several factors affect conservation success.

  20. Inguinal hernia recurrence: Classification and approach

    Directory of Open Access Journals (Sweden)

    Campanelli Giampiero

    2006-01-01

    Full Text Available The authors reviewed the records of 2,468 operations of groin hernia in 2,350 patients, including 277 recurrent hernias updated to January 2005. The data obtained - evaluating technique, results and complications - were used to propose a simple anatomo-clinical classification into three types which could be used to plan the surgical strategy:Type R1: first recurrencehigh,′ oblique external, reducible hernia with small (< 2 cm defect in non-obese patients, after pure tissue or mesh repairType R2: first recurrence ′low,′ direct, reducible hernia with small (< 2 cm defect in non-obese patients, after pure tissue or mesh repairType R3: all the other recurrences - including femoral recurrences; recurrent groin hernia with big defect (inguinal eventration; multirecurrent hernias; nonreducible, linked with a controlateral primitive or recurrent hernia; and situations compromised from aggravating factors (for example obesity or anyway not easily included in R1 or R2, after pure tissue or mesh repair.

  1. Psychoeducational Intervention to Reduce Fear of Cancer Recurrence in People at High Risk of Developing Another Primary Melanoma: Results of a Randomized Controlled Trial.

    Science.gov (United States)

    Dieng, Mbathio; Butow, Phyllis N; Costa, Daniel S J; Morton, Rachael L; Menzies, Scott W; Mireskandari, Shab; Tesson, Stephanie; Mann, Graham J; Cust, Anne E; Kasparian, Nadine A

    2016-12-20

    Purpose People with a history of melanoma commonly report a fear of cancer recurrence (FCR), yet psychologic support is not routinely offered as part of ongoing melanoma care. This randomized controlled trial examined the efficacy of a psychoeducational intervention to reduce FCR and improve psychologic adjustment in this patient group compared with usual care. Methods The intervention comprised a newly developed psychoeducational resource and three telephone-based psychotherapeutic sessions over a 1-month period timed in accordance with dermatologic appointments. Participants were randomly assigned to intervention (n = 80) or usual care (n = 84). Assessments were completed at baseline, 1 month, and 6 months after dermatologic appointments. Linear mixed models were used to examine differences between treatment and control groups for patient-reported outcomes, including FCR, anxiety, stress, depression, melanoma-related knowledge, health behaviors, satisfaction with melanoma care, unmet needs, and health-related quality of life. Results At 6 months, the intervention group reported lower FCR severity, trigger, and distress scores than the control group in the baseline-adjusted models; the between-group mean difference was -1.9 for FCR severity (95% CI, -3.1 to -0.7; P = .002), -2.0 for FCR triggers (95% CI, -3.3 to -0.7; P = .003), and -0.7 for FCR distress (95% CI, -1.3 to -0.1; P = .03). The decrease in FCR severity (but not triggers or distress) remained statistically significant after adjustment for other covariates ( P = .04). At 6 months, the intervention group also reported lower stress (-1.6; 95% CI, -3.1 to -0.2; P = .03) and improved melanoma-related knowledge (1.7; 95% CI, 0.8 to 2.6; P < .001) compared with the control group. No differences were found between groups for other secondary outcomes. Conclusion This newly developed evidence-based psychoeducational intervention was effective in reducing FCR and stress and increasing melanoma-related knowledge

  2. Subsets of Women With Close or Positive Margins After Breast-Conserving Surgery With High Local Recurrence Risk Despite Breast Plus Boost Radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Lupe, Krystine [British Columbia Cancer Agency, Department of Radiation Oncology, Victoria and Vancouver, British Columbia (Canada); Truong, Pauline T., E-mail: ptruong@bccancer.bc.ca [British Columbia Cancer Agency, Department of Radiation Oncology, Victoria and Vancouver, British Columbia (Canada); Breast Cancer Outcomes Unit, British Columbia Cancer Agency, Vancouver, British Columbia (Canada); University of British Columbia, Vancouver, British Columbia (Canada); Alexander, Cheryl [Breast Cancer Outcomes Unit, British Columbia Cancer Agency, Vancouver, British Columbia (Canada); Lesperance, Mary [Department of Mathematics and Statistics, University of Victoria, Victoria, Vancouver, British Columbia (Canada); Speers, Caroline [Breast Cancer Outcomes Unit, British Columbia Cancer Agency, Vancouver, British Columbia (Canada); Tyldesley, Scott [British Columbia Cancer Agency, Department of Radiation Oncology, Victoria and Vancouver, British Columbia (Canada); Breast Cancer Outcomes Unit, British Columbia Cancer Agency, Vancouver, British Columbia (Canada); University of British Columbia, Vancouver, British Columbia (Canada)

    2011-11-15

    Purpose: (1) To examine the effect of surgical margin status on local recurrence (LR) and survival following breast-conserving therapy; (2) To identify subsets with close or positive margins with high LR risk despite whole breast radiotherapy (RT) plus boost. Methods and Materials: Subjects were 2,264 women with pT1-3, any N, M0 invasive breast cancer, treated with breast-conserving surgery and whole breast {+-} boost RT. Five-year Kaplan-Meier (KM) LR, breast cancer-specific and overall survival (BCSS and OS) were compared between cohorts with negative (n = 1,980), close (n = 222), and positive (n = 62) margins. LR rates were analyzed according to clinicopathologic characteristics. Multivariable Cox regression modeling and matched analysis of close/positive margin cases and negative margin controls were performed. Results: Median follow-up was 5.2 years. Boost RT was used in 92% of patients with close or positive margins. Five-year KM LR rates in the negative, close and positive margin cohorts were 1.3%, 4.0%, and 5.2%, respectively (p = 0.001). BCSS and OS were similar in the three margin subgroups. In the close/positive margin cohort, LR rates were 10.2% with age <45 years, 11.8% with Grade III, 11.3% with lymphovascular invasion (LVI), and 26.3% with {>=}4 positive nodes. Corresponding rates in the negative margin cohort were 2.3%, 2.4%, 1.0%, and 2.4%, respectively. On Cox regression analysis of the entire cohort, close or positive margin, Grade III histology, {>=}4 positive nodes, and lack of systemic therapy were significantly associated with higher LR risk. When close/positive margin cases were matched to negative margin controls, the difference in 5-year LR remained significant (4.25% vs. 0.7%, p < 0.001). Conclusions: On univariable analysis, subsets with close or positive margins, in combination with age <45 years, Grade III, LVI, and {>=}4 positive nodes, have 5-year LR >10% despite whole breast plus boost RT. These patients should be considered for

  3. Validation of High-Risk Computed Tomography Features for Detection of Local Recurrence After Stereotactic Body Radiation Therapy for Early-Stage Non-Small Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Peulen, Heike [Department of Radiation Oncology, Netherlands Cancer Institute, Amsterdam (Netherlands); Mantel, Frederick [Department of Radiation Oncology, University of Wuerzburg, Wuerzburg (Germany); Department of Radiation Oncology, University Hospital Zurich, Zurich (Switzerland); Guckenberger, Matthias [Department of Radiation Oncology, University of Wuerzburg, Wuerzburg (Germany); Belderbos, José [Department of Radiation Oncology, Netherlands Cancer Institute, Amsterdam (Netherlands); Werner-Wasik, Maria [Department of Radiation Oncology, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania (United States); Hope, Andrew; Giuliani, Meredith [Department of Radiation Oncology University of Toronto and Princess Margaret Cancer Center, Toronto, Ontario (Canada); Grills, Inga [Department of Radiation Oncology Beaumont Hospital, Royal Oak, Michigan (United States); Sonke, Jan-Jakob, E-mail: j.sonke@nki.nl [Department of Radiation Oncology, Netherlands Cancer Institute, Amsterdam (Netherlands)

    2016-09-01

    Purpose: Fibrotic changes after stereotactic body radiation therapy (SBRT) for stage I non-small cell lung cancer (NSCLC) are difficult to distinguish from local recurrences (LR), hampering proper patient selection for salvage therapy. This study validates previously reported high-risk computed tomography (CT) features (HRFs) for detection of LR in an independent patient cohort. Methods and Materials: From a multicenter database, 13 patients with biopsy-proven LR were matched 1:2 to 26 non-LR control patients based on dose, planning target volume (PTV), follow-up time, and lung lobe. Tested HRFs were enlarging opacity, sequential enlarging opacity, enlarging opacity after 12 months, bulging margin, linear margin disappearance, loss of air bronchogram, and craniocaudal growth. Additionally, 2 new features were analyzed: the occurrence of new unilateral pleural effusion, and growth based on relative volume, assessed by manual delineation. Results: All HRFs were significantly associated with LR except for loss of air bronchogram. The best performing HRFs were bulging margin, linear margin disappearance, and craniocaudal growth. Receiver operating characteristic analysis of the number of HRFs to detect LR had an area under the curve (AUC) of 0.97 (95% confidence interval [CI] 0.9-1.0), which was identical to the performance described in the original report. The best compromise (closest to 100% sensitivity and specificity) was found at ≥4 HRFs, with a sensitivity of 92% and a specificity of 85%. A model consisting of only 2 HRFs, bulging margin and craniocaudal growth, resulted in a sensitivity of 85% and a specificity of 100%, with an AUC of 0.96 (95% CI 0.9-1.0) (HRFs ≥2). Pleural effusion and relative growth did not significantly improve the model. Conclusion: We successfully validated CT-based HRFs for detection of LR after SBRT for early-stage NSCLC. As an alternative to number of HRFs, we propose a simplified model with the combination of the 2 best HRFs

  4. Recurrent BRCA1 and BRCA2 mutations in breast cancer patients of African ancestry.

    Science.gov (United States)

    Zhang, Jing; Fackenthal, James D; Zheng, Yonglan; Huo, Dezheng; Hou, Ningqi; Niu, Qun; Zvosec, Cecilia; Ogundiran, Temidayo O; Hennis, Anselm J; Leske, Maria Cristina; Nemesure, Barbara; Wu, Suh-Yuh; Olopade, Olufunmilayo I

    2012-07-01

    Recurrent mutations constituted nearly three quarters of all BRCA1 mutations and almost half of all BRCA2 mutations identified in the first cohort of the Nigerian Breast Cancer Study. To further characterize breast/ovarian cancer risks associated with BRCA1/BRCA2 mutations in the African diaspora, we genotyped recurrent mutations among Nigerian, African American, and Barbadian breast cancer patients. A replication cohort of 356 Nigerian breast cancer patients was genotyped for 12 recurrent BRCA1/2 mutant alleles (Y101X, 1742insG, 4241delTG, M1775R, 4359insC, C64Y, 1623delTTAAA, Q1090X, and 943ins10 from BRCA1, and 1538delAAGA, 2630del11, and 9045delGAAA from BRCA2) by means of SNaPshot followed by direct sequencing or by direct sequencing alone. In addition, 260 African Americans and 118 Barbadians were genotyped for six of the recurrent BRCA1 mutations by SNaPshot assay. Of all the BRCA1/2 recurrent mutations we identified in the first cohort, six were identified in 11 patients in the replication study. These mutation carriers constitute 3.1 % [95 % Confidence Interval (CI) 1.6-5.5 %] of the replication cohort. By comparison, 6.9 % (95 % CI 4.7-9.7 %) of the discovery cohort carried BRCA1/2 recurrent mutations. For the subset of recurrent mutations we tested in breast cancer cases from Barbados or the United States, only two 943ins10 carriers were identified in African Americans. Nigerian breast cancer patients from Ibadan carry a broad and unique spectrum of BRCA1/2 mutations. Our data suggest that BRCA1/2 mutation testing limited to recurrent mutations is not sufficient to understand the BRCA1/2-associated breast cancer risk in African populations in the diaspora. As the cost of Sanger sequencing is considerably reduced, deploying innovative technologies such as high throughput DNA sequencing of BRCA1/2 and other cancer susceptibility genes will be essential for identifying high-risk individuals and families to reduce the burden of aggressive early onset breast

  5. Candidate high myopia loci on chromosomes 18p and 12q do not play a major role in susceptibility to common myopia

    Science.gov (United States)

    Ibay, Grace; Doan, Betty; Reider, Lauren; Dana, Debra; Schlifka, Melissa; Hu, Heping; Holmes, Taura; O'Neill, Jennifer; Owens, Robert; Ciner, Elise; Bailey–Wilson, Joan E; Stambolian, Dwight

    2004-01-01

    Background To determine whether previously reported loci predisposing to nonsyndromic high myopia show linkage to common myopia in pedigrees from two ethnic groups: Ashkenazi Jewish and Amish. We hypothesized that these high myopia loci might exhibit allelic heterogeneity and be responsible for moderate /mild or common myopia. Methods Cycloplegic and manifest refraction were performed on 38 Jewish and 40 Amish families. Individuals with at least -1.00 D in each meridian of both eyes were classified as myopic. Genomic DNA was genotyped with 12 markers on chromosomes 12q21-23 and 18p11.3. Parametric and nonparametric linkage analyses were conducted to determine whether susceptibility alleles at these loci are important in families with less severe, clinical forms of myopia. Results There was no strong evidence of linkage of common myopia to these candidate regions: all two-point and multipoint heterogeneity LOD scores were .0 and non-parametric linkage p-values were > 0.01. However, one Amish family showed slight evidence of linkage (LOD>1.0) on 12q; another 3 Amish families each gave LOD >1.0 on 18p; and 3 Jewish families each gave LOD >1.0 on 12q. Conclusions Significant evidence of linkage (LOD> 3) of myopia was not found on chromosome 18p or 12q loci in these families. These results suggest that these loci do not play a major role in the causation of common myopia in our families studied. PMID:15291966

  6. Virulence Factors and Antibiotic Susceptibility of Staphylococcus aureus Isolates in Ready-to-Eat Foods: Detection of S. aureus Contamination and a High Prevalence of Virulence Genes

    Directory of Open Access Journals (Sweden)

    Suat Moi Puah

    2016-02-01

    Full Text Available Staphylococcus aureus is one of the leading causes of food poisoning. Its pathogenicity results from the possession of virulence genes that produce different toxins which result in self-limiting to severe illness often requiring hospitalization. In this study of 200 sushi and sashimi samples, S. aureus contamination was confirmed in 26% of the food samples. The S. aureus isolates were further characterized for virulence genes and antibiotic susceptibility. A high incidence of virulence genes was identified in 96.2% of the isolates and 20 different virulence gene profiles were confirmed. DNA amplification showed that 30.8% (16/52 of the S. aureus carried at least one SE gene which causes staphylococcal food poisoning. The most common enterotoxin gene was seg (11.5% and the egc cluster was detected in 5.8% of the isolates. A combination of hla and hld was the most prevalent coexistence virulence genes and accounted for 59.6% of all isolates. Antibiotic resistance studies showed tetracycline resistance to be the most common at 28.8% while multi-drug resistance was found to be low at 3.8%. In conclusion, the high rate of S. aureus in the sampled sushi and sashimi indicates the need for food safety guidelines.

  7. Candidate high myopia loci on chromosomes 18p and 12q do not play a major role in susceptibility to common myopia

    Directory of Open Access Journals (Sweden)

    Ciner Elise

    2004-08-01

    Full Text Available Abstract Background To determine whether previously reported loci predisposing to nonsyndromic high myopia show linkage to common myopia in pedigrees from two ethnic groups: Ashkenazi Jewish and Amish. We hypothesized that these high myopia loci might exhibit allelic heterogeneity and be responsible for moderate /mild or common myopia. Methods Cycloplegic and manifest refraction were performed on 38 Jewish and 40 Amish families. Individuals with at least -1.00 D in each meridian of both eyes were classified as myopic. Genomic DNA was genotyped with 12 markers on chromosomes 12q21-23 and 18p11.3. Parametric and nonparametric linkage analyses were conducted to determine whether susceptibility alleles at these loci are important in families with less severe, clinical forms of myopia. Results There was no strong evidence of linkage of common myopia to these candidate regions: all two-point and multipoint heterogeneity LOD scores were 0.01. However, one Amish family showed slight evidence of linkage (LOD>1.0 on 12q; another 3 Amish families each gave LOD >1.0 on 18p; and 3 Jewish families each gave LOD >1.0 on 12q. Conclusions Significant evidence of linkage (LOD> 3 of myopia was not found on chromosome 18p or 12q loci in these families. These results suggest that these loci do not play a major role in the causation of common myopia in our families studied.

  8. Infiltrative Hepatocellular Carcinoma With Portal Vein Tumor Thrombosis Treated With a Single High-Dose Y90 Radioembolization and Subsequent Liver Transplantation Without a Recurrence.

    Science.gov (United States)

    Dendy, Meaghan S; Camacho, Juan C; Ludwig, Johannes M; Krasinskas, Alyssa M; Knechtle, Stuart J; Kim, Hyun S

    2017-09-01

    Infiltrative hepatocellular carcinoma with macrovascular invasion is a relatively rare presentation and usually fatal disease. Both patients exceeded Milan and University of California-San Francisco (UCSF) criteria, and per Barcelona Clinic Liver Cancer group guidelines, they were enrolled in a prospective open-label radioembolization phase II trial that gave them optimized lobar doses of Yttrium-90 as solely the first-line therapy without concomitant or additional pharmacological or locoregional therapies. Three months after radioembolization, the patients demonstrated no residual viable disease on surveillance imaging. The patients were then followed up with serial imaging for 2 years in 3-month intervals, without documenting recurrence or extrahepatic disease. Finally, both patients underwent transplantation and after more than 20 months of imaging surveillance, no locoregional or systemic recurrence have been observed. We present, to our knowledge, the first 2 reports of transplantation after successfully downstaging infiltrative disease with portal vein tumoral thrombosis, which traditionally poses as a relative contraindication for resection or transplantation.

  9. Prospective Evaluation of Intraprostatic Inflammation and Focal Atrophy as a Predictor of Risk of High-Grade Prostate Cancer and Recurrence after Prostatectomy

    Science.gov (United States)

    2016-09-01

    Chief results from Aim 3: Here we report on the exciting finding for mast cells, a component of the innate immune system. We quantified mast cells...findings for prognosis were more nuanced: mast cells (a type of tissue resident immune cell) within the tumor at the time of prostatectomy appeared to...cancer, risk, incidence, recurrence, inflammation, focal atrophy, mast cells, immune cells, tissue microarray, biopsy, image analysis, odds ratio. 3

  10. Data in support of a central role of plasminogen activator inhibitor-2 polymorphism in recurrent cardiovascular disease risk in the setting of high HDL cholesterol and C-reactive protein using Bayesian network modeling.

    Science.gov (United States)

    Corsetti, James P; Salzman, Peter; Ryan, Dan; Moss, Arthur J; Zareba, Wojciech; Sparks, Charles E

    2016-09-01

    Data is presented that was utilized as the basis for Bayesian network modeling of influence pathways focusing on the central role of a polymorphism of plasminogen activator inhibitor-2 (PAI-2) on recurrent cardiovascular disease risk in patients with high levels of HDL cholesterol and C-reactive protein (CRP) as a marker of inflammation, "Influences on Plasminogen Activator Inhibitor-2 Polymorphism-Associated Recurrent Cardiovascular Disease Risk in Patients with High HDL Cholesterol and Inflammation" (Corsetti et al., 2016; [1]). The data consist of occurrence of recurrent coronary events in 166 post myocardial infarction patients along with 1. clinical data on gender, race, age, and body mass index; 2. blood level data on 17 biomarkers; and 3. genotype data on 53 presumptive CVD-related single nucleotide polymorphisms. Additionally, a flow diagram of the Bayesian modeling procedure is presented along with Bayesian network subgraphs (root nodes to outcome events) utilized as the data from which PAI-2 associated influence pathways were derived (Corsetti et al., 2016; [1]).

  11. Paramagnetic susceptibility of the Zr{sub 62}Cu{sub 22}Al{sub 10}Fe{sub 5}Dy{sub 1} metallic glass subjected to high-pressure torsion deformation

    Energy Technology Data Exchange (ETDEWEB)

    Korolev, A.V., E-mail: korolyov@imp.uran.ru [Institute of Metal Physics of the Ural Branch RAS, Ekaterinburg (Russian Federation); Ural Federal University, Ekaterinburg (Russian Federation); Kourov, N.I. [Institute of Metal Physics of the Ural Branch RAS, Ekaterinburg (Russian Federation); Pushin, V.G. [Institute of Metal Physics of the Ural Branch RAS, Ekaterinburg (Russian Federation); Ural Federal University, Ekaterinburg (Russian Federation); Gunderov, D.V. [Saint-Petersburg State University, Saint-Petersburg (Russian Federation); Ufa State Aviation Technical University, Ufa (Russian Federation); Boltynjuk, E.V.; Ubyivovk, E.V. [Saint-Petersburg State University, Saint-Petersburg (Russian Federation); Valiev, R.Z. [Saint-Petersburg State University, Saint-Petersburg (Russian Federation); Ufa State Aviation Technical University, Ufa (Russian Federation)

    2017-09-01

    Highlights: • Zr-based BMG was subjected to HPT at temperatures of 20 °C and 150 °C. • Magnetic measurements reveal well recordable changes in paramagnetic susceptibility. • Paramagnetic susceptibility may be an indicator of a change in the structural state. - Abstract: The Zr{sub 62}Cu{sub 22}Al{sub 10}Fe{sub 5}Dy{sub 1} bulk metallic glass is studied in the as-cast state and in the state after processing by high-pressure torsion at temperatures of 20 °C and 150 °C. According to the data from X-ray diffraction and transmission electron microscopy, the structural state of the samples depends weakly on the conducted processing. At the same time, magnetic measurements reveal well recordable changes in paramagnetic susceptibility induced by the processing of the samples. It is assumed that, because of high-pressure torsion deformation, there occurs a noticeable change in the material electronic structure, which leads to a change in the full susceptibility of the samples. The performed studies demonstrate that paramagnetic susceptibility may be an indicator of a change in the structural state of paramagnetic amorphous metallic substances.

  12. ER-positive breast cancer patients with more than three positive nodes or grade 3 tumors are at high risk of late recurrence after 5-year adjuvant endocrine therapy.

    Science.gov (United States)

    Song, Fangbin; Zhang, Jianbing; Li, Shanbao; Wu, Junyi; Jin, Tao; Qin, Jun; Wang, Ye; Wang, Min; Xu, Junming

    2017-01-01

    Currently, although several clinical trials available give strong suggestions that extension of endocrine therapy has benefits, the risk level at which patients may benefit from extended endocrine therapy remains uncertain. This study aimed to identify the proportion of patients at a substantial risk of late recurrence after 5-year adjuvant endocrine therapy. We reviewed 1,056 female patients with primary breast cancer who underwent curative resection between January 2006 and December 2011. Univariate and multivariate analyses were performed using the Cox proportional hazards regression model to identify prognostic factors. A total of 327 eligible patients were eventually enrolled in this study. Among them, 42 (12.8%) patients suffered from distant metastasis and 34 (10.4%) patients experienced locoregional recurrence after 5-year adjuvant endocrine therapy. In multivariate analysis, patients with more than three positive nodes (hazard ratio [HR] =2.176, 95% CI=1.071-4.421; P =0.032) and histologic grade 3 disease (HR=2.098, 95% CI=1.300-3.385; P =0.002) were significantly associated with high risk of late recurrence. However, only histologic grade 3 (HR=2.212, 95% CI=1.166-4.194; P =0.015) was significantly associated with high risk of distant metastasis. Late relapse after completion of 5-year adjuvant endocrine therapy was still common, and grade 3 and more than three positive nodes were the risk factors of late recurrence, while grade 3 was the only risk factor of late distant metastasis. These patients might benefit from extended endocrine therapy.

  13. Search for new breast cancer susceptibility genes

    NARCIS (Netherlands)

    Oldenburg, Rogier Abel

    2008-01-01

    This thesis describes the search for new high-risk breast cancer susceptibility genes by linkage analysis. To date 20-25% of familial breast cancer is explained by mutations in the high-risk BRCA1 and BRCA2 breast cancer susceptibility genes. For the remaining families the genetic etiology is

  14. Recurrent Fever in Children

    Directory of Open Access Journals (Sweden)

    Sofia Torreggiani

    2016-03-01

    Full Text Available Children presenting with recurrent fever may represent a diagnostic challenge. After excluding the most common etiologies, which include the consecutive occurrence of independent uncomplicated infections, a wide range of possible causes are considered. This article summarizes infectious and noninfectious causes of recurrent fever in pediatric patients. We highlight that, when investigating recurrent fever, it is important to consider age at onset, family history, duration of febrile episodes, length of interval between episodes, associated symptoms and response to treatment. Additionally, information regarding travel history and exposure to animals is helpful, especially with regard to infections. With the exclusion of repeated independent uncomplicated infections, many infective causes of recurrent fever are relatively rare in Western countries; therefore, clinicians should be attuned to suggestive case history data. It is important to rule out the possibility of an infectious process or a malignancy, in particular, if steroid therapy is being considered. After excluding an infectious or neoplastic etiology, immune-mediated and autoinflammatory diseases should be taken into consideration. Together with case history data, a careful physical exam during and between febrile episodes may give useful clues and guide laboratory investigations. However, despite a thorough evaluation, a recurrent fever may remain unexplained. A watchful follow-up is thus mandatory because new signs and symptoms may appear over time.

  15. Differentiation of Primary Central Nervous System Lymphoma and High-Grade Glioma with Dynamic Susceptibility Contrast-Enhanced Perfusion Magnetic Resonance Imaging

    Energy Technology Data Exchange (ETDEWEB)

    Weihua Liao; Yunhai Liu; Xiaoyi Wang; Xinya Jiang; Beisha Tang; Jiasheng Fang; Changqing Chen; Zhongliang Hu (Dept.s of Radiology, Neurology, Neurosurgery, and Pathology, Xiangya Hospital, Central South Univ., Changsha, Hunan (China))

    2009-02-15

    Background: Preoperative differentiation of primary central nervous system lymphomas (PCNSLs) from other tumors is important for presurgical staging, intraoperative management, and postoperative treatment. Dynamic susceptibility contrast-enhanced perfusion magnetic resonance imaging (DSC perfusion MRI) can provide in vivo assessment of the microvasculature in intracranial mass lesions. Purpose: To determine the utility of DSC perfusion MRI in the differentiation of PCNSLs and high-grade gliomas, as well as their pathological and physiological differences. Material and Methods: Nine patients with pathologically proven PCNSLs and 11 patients with high-grade gliomas were examined using a 1.5T MRI scanner. DSC perfusion MRI was performed by gradient-echo echo-planar imaging (GE-EPI). The maximum rCBV ratio, the signal intensity-time curves, and the percentage of signal intensity recovery were obtained. The maximum relative cerebral blood volume (rCBV) ratio and the percentage of signal intensity recovery of PCNSLs were compared with those of high-grade gliomas by using Student's t test. Microvessel density (MVD) was evaluated using immunohistochemical staining of surgical specimens with anti-CD34, and MVDs of the two tumor groups were compared by using Student's t test. Results: The maximum rCBV ratio of primary intracranial lymphomas was 1.72+-0.59, while that of high-grade gliomas was 4.86+-2.18. PCNSLs tended to have relatively low perfusion compared to high-grade gliomas (P=0.001), and the MVD labeled by anti-CD34 of PCNSLs was much lower than that of gliomas (P<0.001). The signal intensity-time curve of primary intracranial lymphomas was different from that of high-grade gliomas. The percentage of signal intensity recovery was significantly greater in PCNSLs compared with that of high-grade gliomas (P<0.001). Conclusion: The difference in DSC perfusion MRI characteristics between PCNSLs and high-grade gliomas is determined by their different

  16. Uncomplicated Urinary Tract Infections in Women in a Sao Paulo Quaternary Care Hospital: Bacterial Spectrum and Susceptibility Patterns

    Directory of Open Access Journals (Sweden)

    Marcelo Hisano

    2014-03-01

    Full Text Available Uncomplicated urinary tract infections (UTI in women are very common. Regular analysis of bacterial flora is important to formulate updated guidelines. The objective of this study is to determine and compare the microbiology of UTIs and their susceptibility patterns in a quaternary care hospital. In a seven-year review, the urine culture results of 480 female patients with uncomplicated UTIs were analyzed. Patients were divided into three groups according to their diagnosis and treatment characteristics: Group 1, cystitis at outpatient basis; group 2, cystitis at the Emergency Unit; and group 3, pyelonephritis. Group 1 included older patients, with a higher incidence of concomitant diabetes mellitus and recurrent UTIs. E. coli was the most common pathogen, responsible for 75.1% of cases, mainly for pyelonephritis (87.3%. Of the oral antimicrobials tested for cystitis, amoxicillin/clavulanate and nitrofurantoin had the highest susceptibility profiles (84.4% and 87.3%, respectively. For E. coli only, their susceptibility profiles were as high as 90.8% and 97.4%, respectively. For pyelonephritis treatment, fluoroquinoles had a susceptibility profile <90%, while ceftriaxone and gentamicin had susceptibility >90%. Uncomplicated UTI treatment is becoming more challenging because the susceptibility profiles of oral antimicrobials are increasingly resistant. In our environment, cystitis can still be managed with nitrofurantoin. Uncomplicated pyelonephritis should be managed with ceftriaxone or gentamicin.

  17. Recurrence Risk of Hyperemesis Gravidarum

    Science.gov (United States)

    2011-01-01

    The purpose of this study is to describe the recurrence risk for hyperemesis gravidarum (HG). Women who registered on a website sponsored by the Hyperemesis Education and Research Foundation as having had one HG-complicated pregnancy were contacted to follow-up on a subsequent pregnancy. One hundred women responded. Fifty-seven had become pregnant again, 2 were trying to conceive, 37 were not willing to get pregnant again due to HG, and 4 did not have a 2nd pregnancy for other reasons. Among the 57 women who responded that they had become pregnant again, 81% reported having severe nausea and vomiting in their second pregnancy. Among the women reporting recurrent HG, 98% reported losing weight and taking prescribed medication for HG, 83% reported treatment with IV fluids, 20% reported treatment with TPN or NG tube feeding, and 48% reported hospitalization for HG. This study demonstrates both a high recurrence rate and a large percentage of women who change reproductive plans due to their experience with hyperemesis gravidarum. PMID:21429077

  18. Multiple Genetic Analysis System-Based Antibiotic Susceptibility Testing in Helicobacter pylori and High Eradication Rate With Phenotypic Resistance-Guided Quadruple Therapy.

    Science.gov (United States)

    Dong, Fangyuan; Ji, Danian; Huang, Renxiang; Zhang, Fan; Huang, Yiqin; Xiang, Ping; Kong, Mimi; Nan, Li; Zeng, Xianping; Wu, Yong; Bao, Zhijun

    2015-11-01

    /18), whereas in detecting LVX resistance were 100% (25/25) and 83.3% (15/18), respectively. Finally, the eradication rate in test group was significantly higher than that in control group as demonstrated by intention-to-treat analysis and per-protocol analysis.MGAS is a promising assay for H. pylori identification and antibiotic susceptibility testing. Phenotypic resistance-guided quadruple therapy showed a high efficacy in treating patients with H. pylori infection.

  19. Distinct high resolution genome profiles of early onset and late onset colorectal cancer integrated with gene expression data identify candidate susceptibility loci

    Directory of Open Access Journals (Sweden)

    Merok Marianne A

    2010-05-01

    Full Text Available Abstract Background Estimates suggest that up to 30% of colorectal cancers (CRC may develop due to an increased genetic risk. The mean age at diagnosis for CRC is about 70 years. Time of disease onset 20 years younger than the mean age is assumed to be indicative of genetic susceptibility. We have compared high resolution tumor genome copy number variation (CNV (Roche NimbleGen, 385 000 oligo CGH array in microsatellite stable (MSS tumors from two age groups, including 23 young at onset patients without known hereditary syndromes and with a median age of 44 years (range: 28-53 and 17 elderly patients with median age 79 years (range: 69-87. Our aim was to identify differences in the tumor genomes between these groups and pinpoint potential susceptibility loci. Integration analysis of CNV and genome wide mRNA expression data, available for the same tumors, was performed to identify a restricted candidate gene list. Results The total fraction of the genome with aberrant copy number, the overall genomic profile and the TP53 mutation spectrum were similar between the two age groups. However, both the number of chromosomal aberrations and the number of breakpoints differed significantly between the groups. Gains of 2q35, 10q21.3-22.1, 10q22.3 and 19q13.2-13.31 and losses from 1p31.3, 1q21.1, 2q21.2, 4p16.1-q28.3, 10p11.1 and 19p12, positions that in total contain more than 500 genes, were found significantly more often in the early onset group as compared to the late onset group. Integration analysis revealed a covariation of DNA copy number at these sites and mRNA expression for 107 of the genes. Seven of these genes, CLC, EIF4E, LTBP4, PLA2G12A, PPAT, RG9MTD2, and ZNF574, had significantly different mRNA expression comparing median expression levels across the transcriptome between the two groups. Conclusions Ten genomic loci, containing more than 500 protein coding genes, are identified as more often altered in tumors from early onset versus late

  20. Effect of dietary high-oleic acid sunflower seed, palm oil and vitamin E supplementation on broiler performance, fatty acid composition and oxidation susceptibility of meat.

    Science.gov (United States)

    Rebolé, A; Rodríguez, M L; Ortiz, L T; Alzueta, C; Centeno, C; Viveros, A; Brenes, A; Arija, I

    2006-10-01

    1. A study was conducted to evaluate the effect of inclusion of two fat sources: high-oleic acid sunflower seed (HOASS; 0, 50, 100, 150 and 200 g/kg diet) and palm oil (PO), and dietary supplementation of vitamin E (alpha-tocopheryl acetate, 200 mg/kg diet) on performance, fatty acid composition and susceptibility to oxidation of white and dark chicken meat during refrigerated storage. Female chicks (3 to 6 weeks) were given one of 5 diets containing 90 g/kg of added fat with increasing monounsaturated fatty acid (MUFA) content, adjusted by progressively replacing PO by HOASS. 2. Body weight gain and gain:food ratio of birds were depressed in diets containing the highest proportions of HOASS (150 and 200 g/kg). Relative abdominal fat was reduced in birds fed diets including HOASS, except in the diet containing 100 g HOASS/kg. The inclusion of alpha-tocopheryl acetate improved body weight gain and gain:food ratio. 3. According to the fatty acid profile of the diets, saturated and polyunsaturated fatty acid (SFA and PUFA, respectively) contents were significantly reduced and MUFA content was significantly increased in white and dark chicken meats when the saturated oil, PO, was replaced progressively by HOASS in the diet. The inclusion of alpha-tocopheryl acetate increased PUFA content in both meats. 4. After 4 and 7 d of refrigerated storage, white and dark meat samples obtained from birds fed on diets containing HOASS had significantly lower thiobarbituric acid reacting substance (TBARS) values than those derived from the PO diet. The addition of alpha-tocopheryl acetate significantly reduced the lipid oxidation in white and dark meat. 5. Overall, the results showed that increasing MUFA content of chicken meat by replacing dietary PO with HOASS (up to 100 g/kg) did not adversely affect broiler performance and reduced the susceptibility of meat to oxidation during refrigerated storage. Dietary alpha-tocopherol supplementation improved chicken performance and was

  1. Aging Increases Susceptibility to High Fat Diet-Induced Metabolic Syndrome in C57BL/6 Mice: Improvement in Glycemic and Lipid Profile after Antioxidant Therapy

    Directory of Open Access Journals (Sweden)

    Valéria Nunes-Souza

    2016-01-01

    Full Text Available Nonalcoholic fatty liver disease (NAFLD has been considered a novel component of the metabolic syndrome (MetS, with the oxidative stress participating in its progression. This study aimed to evaluate the metabolic profile in young and old mice with MetS, and the effects of apocynin and tempol on glycemic and lipid parameters. Young and old C57BL/6 mice with high fat diet- (HFD- induced MetS received apocynin and tempol 50 mg·kg−1/day in their drinking water for 10 weeks. After HFD, the young group showed elevated fasting glucose, worsened lipid profile in plasma, steatosis, and hepatic lipid peroxidation. Nevertheless, the old group presented significant increase in fasting insulin levels, insulin resistance, plasma and hepatic lipid peroxidation, and pronounced steatosis. The hepatic superoxide dismutase and catalase activity did not differ between the groups. Tempol and apocynin seemed to prevent hepatic lipid deposition in both groups. Furthermore, apocynin improved glucose tolerance and insulin sensitivity in old mice. In summary, old mice are more susceptible to HFD-induced metabolic changes than their young counterparts. Also, the antioxidant therapy improved insulin sensitivity and glucose tolerance, and in addition, apocynin seemed to prevent the HFD-induced hepatic fat deposition, suggesting an important role of oxidative stress in the induction of NAFLD.

  2. Aging Increases Susceptibility to High Fat Diet-Induced Metabolic Syndrome in C57BL/6 Mice: Improvement in Glycemic and Lipid Profile after Antioxidant Therapy.

    Science.gov (United States)

    Nunes-Souza, Valéria; César-Gomes, Cheila Juliana; Da Fonseca, Lucas José Sá; Guedes, Glaucevane Da Silva; Smaniotto, Salete; Rabelo, Luíza Antas

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD) has been considered a novel component of the metabolic syndrome (MetS), with the oxidative stress participating in its progression. This study aimed to evaluate the metabolic profile in young and old mice with MetS, and the effects of apocynin and tempol on glycemic and lipid parameters. Young and old C57BL/6 mice with high fat diet- (HFD-) induced MetS received apocynin and tempol 50 mg·kg(-1)/day in their drinking water for 10 weeks. After HFD, the young group showed elevated fasting glucose, worsened lipid profile in plasma, steatosis, and hepatic lipid peroxidation. Nevertheless, the old group presented significant increase in fasting insulin levels, insulin resistance, plasma and hepatic lipid peroxidation, and pronounced steatosis. The hepatic superoxide dismutase and catalase activity did not differ between the groups. Tempol and apocynin seemed to prevent hepatic lipid deposition in both groups. Furthermore, apocynin improved glucose tolerance and insulin sensitivity in old mice. In summary, old mice are more susceptible to HFD-induced metabolic changes than their young counterparts. Also, the antioxidant therapy improved insulin sensitivity and glucose tolerance, and in addition, apocynin seemed to prevent the HFD-induced hepatic fat deposition, suggesting an important role of oxidative stress in the induction of NAFLD.

  3. Paradoxical perfusion metrics of high-grade gliomas with an oligodendroglioma component: quantitative analysis of dynamic susceptibility contrast perfusion MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Sunwoo, Leonard; Park, Sun-Won [Seoul National University College of Medicine, Department of Radiology, Seoul (Korea, Republic of); Seoul Metropolitan Government - Seoul National University Boramae Medical Center, Department of Radiology, Seoul (Korea, Republic of); Choi, Seung Hong [Seoul National University Hospital, Department of Radiology, Seoul (Korea, Republic of); Seoul National University, Center for Nanoparticle Research, Institute for Basic Science, and School of Chemical and Biological Engineering, Seoul (Korea, Republic of); Yoo, Roh-Eul; Kang, Koung Mi; Yun, Tae Jin; Kim, Ji-hoon; Sohn, Chul-Ho [Seoul National University College of Medicine, Department of Radiology, Seoul (Korea, Republic of); Seoul National University Hospital, Department of Radiology, Seoul (Korea, Republic of); Kim, Tae Min; Lee, Se-Hoon [Seoul National University Hospital, Department of Internal Medicine, Seoul (Korea, Republic of); Park, Chul-Kee [Seoul National University Hospital, Department of Neurosurgery, Seoul (Korea, Republic of); Won, Jae-Kyung; Park, Sung-Hye [Seoul National University Hospital, Department of Pathology, Seoul (Korea, Republic of); Kim, Il Han [Seoul National University Hospital, Department of Radiation Oncology, Seoul (Korea, Republic of)

    2015-11-15

    The aim of this study is to investigate perfusion characteristics of glioblastoma with an oligodendroglioma component (GBMO) compared with conventional glioblastoma (GBM) using dynamic susceptibility contrast (DSC) perfusion magnetic resonance (MR) imaging and microvessel density (MVD). The study was approved by the institutional review board. Newly diagnosed high-grade glioma patients were enrolled (n = 72; 20 GBMs, 14 GBMOs, 19 anaplastic astrocytomas (AAs), 13 anaplastic oligodendrogliomas (AOs), and six anaplastic oligoastrocytomas (AOAs)). All participants underwent preoperative MR imaging including DSC perfusion MR imaging. Normalized cerebral blood volume (nCBV) values were analyzed using a histogram approach. Histogram parameters were subsequently compared across each tumor subtype and grade. MVD was quantified by immunohistochemistry staining and correlated with perfusion parameters. Progression-free survival (PFS) was assessed according to the tumor subtype. GBMO displayed significantly reduced nCBV values compared with GBM, whereas grade III tumors with oligodendroglial components (AO and AOA) exhibited significantly increased nCBV values compared with AA (p < 0.001). MVD analyses revealed the same pattern as nCBV results. In addition, a positive correlation between MVD and nCBV values was noted (r = 0.633, p < 0.001). Patients with oligodendroglial tumors exhibited significantly increased PFS compared with patients with pure astrocytomas in each grade. In contrast to grade III tumors, the presence of oligodendroglial components in grade IV tumors resulted in paradoxically reduced perfusion metrics and MVD. In addition, patients with GBMO exhibited a better clinical outcome compared with patients with GBM. (orig.)

  4. Superconducting FeSe{sub 0.5}Te{sub 0.5} under high pressure: Susceptibility, XRD and Moessbauer studies.

    Energy Technology Data Exchange (ETDEWEB)

    Ksenofontov, Vadim; Schoop, Leslie; Felser, Claudia [Institute of Inorganic and Analytical Chemistry, Johannes Gutenberg University, Mainz (Germany); Medvedev, Sergey; Eremets, Michail [Max-Planck-Institute for Chemistry, Mainz (Germany); Tsurkan, Vladimir; Deisenhofer, Joachim; Loidl, Alois [Institute of Physics, University of Augsburg, Augsburg (Germany); Wortmann, Gerhard [Department of Physics, University of Paderborn, Paderborn (Germany)

    2011-07-01

    High-pressure magnetic, structural and Moessbauer studies were performed on single-crystalline samples of superconducting (sc) FeSe{sub 0.5}Te{sub 0.5} with T{sub c} = 14.5 K. Susceptibility data up to 1.5 GPa revealed a strong increase of Tc up to 25 K, followed by a plateau in T{sub c} up to 6.0 GPa. Further increase of pressure leads to a disappearance of sc state around 7.0 GPa. Structural and Moessbauer studies explain this fact by a structural phase transition of the sc PbO to the non-sc NiAs structure. We discuss the fact of an almost pressure-independent T{sub c}, between 1.5 and 6.0 GPa by the respective variation of the lattice constants and hyperfine parameters in FeSe. We conclude that the strong increase of T{sub c} in FeSe{sub 0.5}Te{sub 0.5} with pressure up to 1.5 GPa can not be attributed to a change in the phonon-DOS.

  5. Assessment of climatic and seismic cycles in southern chile from high resolution XRF and magnetic susceptibility measurements of historic lake sediments.

    Science.gov (United States)

    Boes, X.; Hubert-Ferrari, A.; Fagel, N.

    2006-12-01

    The high-resolution sedimentological studies performed on the sediment cores collected in the oceans or in the lakes constitutes the basis for inter-comparison of past climate variability. Among the new high-resolution approaches, the X-Ray Fluorescence (XRF) analysis of varved marine and lacustrine cores represents some of the best resolution. These data are particularly useful for tracking short-term climate changes expressed with calibrated time scales. However, the XRF results obtain on the fresh cores surface may be of low resolution because the core material is wet and unconsolidated. One particularly attractive method to solve this problem consists of impregnating the sediment cores with polymers in order to polish the core surface for XRF analyses. This step is essential for being able to get significant XRF and Magnetic Susceptibility (MS) results in the muddy cores. Since the 1960s, the evolution of sediment impregnation methods has been strongly linked to the development of innovative techniques (e.g., sampling devices, cryogenic and vacuum technologies, polymers, etc.). In this communication, we first propose a revised method that may be applied to prepare sediment cores for high-resolution XRF and MS data acquisition. Then we show an example of XRF and MS results obtain on laminated lake sediments from South America (Lago Puyehue, 40°S). As this area is very sensitive in terms of precipitation change (i.e., Southern Westerlies); the XRF data are compared with the regional instrumental precipitation database. The results are discussed in terms of climate and sismo- tectonic impacts over historic times. Our results shows that, in order to better interpret XRF tool over long sequences, the measurements should be first "calibrated" according to instrumental data such as precipitation, temperatures, and earthquake magnitudes.

  6. Nivolumab or Expectant Observation Following Ipilimumab, Nivolumab, and Surgery in Treating Patients With High Risk Localized, Locoregionally Advanced, or Recurrent Mucosal Melanoma

    Science.gov (United States)

    2017-10-16

    Cervical Carcinoma; Esophageal Carcinoma; Mucosal Melanoma; Mucosal Melanoma of the Head and Neck; Oral Cavity Mucosal Melanoma; Recurrent Melanoma; Stage II Vulvar Cancer AJCC v7; Stage III Vulvar Cancer AJCC v7; Stage IIIA Vulvar Cancer AJCC v7; Stage IIIB Vulvar Cancer AJCC v7; Stage IIIC Vulvar Cancer AJCC v7; Stage IV Oral Cavity Cancer AJCC v6 and v7; Stage IV Vulvar Cancer AJCC v7; Stage IVA Oral Cavity Cancer AJCC v6 and v7; Stage IVB Oral Cavity Cancer AJCC v6 and v7; Stage IVC Oral Cavity Cancer AJCC v6 and v7; Vaginal Carcinoma

  7. On Solving Linear Recurrences

    Science.gov (United States)

    Dobbs, David E.

    2013-01-01

    A direct method is given for solving first-order linear recurrences with constant coefficients. The limiting value of that solution is studied as "n to infinity." This classroom note could serve as enrichment material for the typical introductory course on discrete mathematics that follows a calculus course.

  8. Recurrences of strange attractors

    Indian Academy of Sciences (India)

    order to detect the transitions from or to SNAs too. The outline of this paper is as follows: in §2, we present the recurrence approach to detect the different transitions. This approach is applied in §3 to detect transi- tions to SNAs in the quasiperiodically forced logistic map. Section 4 examines the transition from SNAs to chaos.

  9. Recurrent diabetic ketoacidosis

    DEFF Research Database (Denmark)

    Skinner, T. Chas

    2002-01-01

    Longitudinal studies indicate that 20% of paediatric patients account for 80% of all admissions for diabetic ketoacidosis (DKA). The frequency of DKA peaks during adolescence and, although individuals generally go into remission, they may continue to have bouts of recurrent DKA in adulthood. The ...

  10. Training Recurrent Networks

    DEFF Research Database (Denmark)

    Pedersen, Morten With

    1997-01-01

    Training recurrent networks is generally believed to be a difficult task. Excessive training times and lack of convergence to an acceptable solution are frequently reported. In this paper we seek to explain the reason for this from a numerical point of view and show how to avoid problems when...

  11. Recurrent Spatial Transformer Networks

    DEFF Research Database (Denmark)

    Sønderby, Søren Kaae; Sønderby, Casper Kaae; Maaløe, Lars

    2015-01-01

    We integrate the recently proposed spatial transformer network (SPN) [Jaderberg et. al 2015] into a recurrent neural network (RNN) to form an RNN-SPN model. We use the RNN-SPN to classify digits in cluttered MNIST sequences. The proposed model achieves a single digit error of 1.5% compared to 2...

  12. Chronic recurrent multifocal osteomyelitis

    NARCIS (Netherlands)

    Wedman, Jan; van Weissenbruch, Ranny

    We report what is, to our best knowledge, the first case of chronic recurrent multifocal osteomyelitis (CRMO) in which the frontal and sphenoid bones were involved. Characterized by a prolonged and fluctuating course of osteomyelitis at different sites, CRMO is self-limited, although sequelae can

  13. Lung Cancer Indicators Recurrence

    Science.gov (United States)

    This study describes prognostic factors for lung cancer spread and recurrence, as well as subsequent risk of death from the disease. The investigators observed that regardless of cancer stage, grade, or type of lung cancer, patients in the study were more

  14. [Prophylaxis of Recurrent Venous Leg Ulcer].

    Science.gov (United States)

    Kroeger, K; Storck, M; Kujath, P; Rabe, E; Dissemond, J

    2017-06-01

    Venous leg ulcer (VLU) counts among the most common chronic wounds in Europe. Treatment is lengthy, cumbersome and costly, and there is a high rate of recurrence. This review shows the measures that should be offered to every patient with healed VLU to permanently prevent recurrence. To prevent VLU in case of varicose veins, the progression of chronic venous insufficiency (CVI) has to be stopped. There is convincing evidence that the effective treatment of varicose veins reduces the recurrence rate in patients with VLU. In patients with post-thrombotic syndrome (PTS), further thrombosis should be prevented through targeted prophylaxis of new thromboembolic events. The benefit of endovascular revascularization on the VLU recurrence rate in patients with post-thrombotic damage in the pelvic veins has not been proven in clinical studies. On the other hand, it has been clearly demonstrated in several studies that compression therapy is the basic procedure for the prevention of recurrent VLU in patients with varicose veins or PTS, regardless of whether other measures have been implemented or not. Good adherence in patients with compression therapy is more important than choosing the highest possible compression class. Future efforts for patients with VLU must aim to provide therapists with tools and treatment strategies to guide their patients and to increase patients' acceptance and understanding of the importance of self-management, in particular regarding compression therapy for the prevention of recurrent VLU. Georg Thieme Verlag KG Stuttgart · New York.

  15. Recurrent Shoulder Instability After Primary Bankart Repair.

    Science.gov (United States)

    Donohue, Michael A; Mauntel, Timothy C; Dickens, Jonathan F

    2017-09-01

    The glenohumeral joint is one of the most frequently dislocated joints and occurs with increasing frequency in collision and contact athletes, especially those in sports that repeatedly place the glenohumeral joint in a position of vulnerability. Nonoperative management of shoulder instability especially in young contact athletes results in unacceptably high recurrence rates; thus, early surgical stabilization has become commonplace. Surgical stabilization typically yields acceptable outcomes. However, recurrent anterior instability may occur following a previous stabilization procedure at rates of 7% to 12%. Recurrent glenohumeral instability represents a treatment challenge for orthopedic surgeons as it not only has the potential to result in subsequent surgery, therapy, and missed activity time, but also has been associated with long-term degenerative joint changes. Thus, recurrent instability requires close examination to determine underlying pathology leading to failure. Evaluation of underlying pathology requires consideration of patient activity-related factors, hyperlaxity and multidirectional instability, glenoid bone loss, glenoid track lesions, and other pathologic lesions. Revision surgical stabilization approaches include arthroscopic and open stabilization, as well as glenoid osseous augmentation procedures. Postoperative rehabilitation and release to sports and activity must be tailored to protect the shoulder from continued instability. Understanding that risk of recurrent glenohumeral instability and the risk factors associated with it are essential so that these factors may be mitigated and recurrent instability prevented.

  16. Laboratory constraints on models of earthquake recurrence

    Science.gov (United States)

    Beeler, Nicholas M.; Tullis, Terry; Junger, Jenni; Kilgore, Brian D.; Goldsby, David L.

    2014-01-01

    In this study, rock friction ‘stick-slip’ experiments are used to develop constraints on models of earthquake recurrence. Constant-rate loading of bare rock surfaces in high quality experiments produces stick-slip recurrence that is periodic at least to second order. When the loading rate is varied, recurrence is approximately inversely proportional to loading rate. These laboratory events initiate due to a slip rate-dependent process that also determines the size of the stress drop [Dieterich, 1979; Ruina, 1983] and as a consequence, stress drop varies weakly but systematically with loading rate [e.g., Gu and Wong, 1991; Karner and Marone, 2000; McLaskey et al., 2012]. This is especially evident in experiments where the loading rate is changed by orders of magnitude, as is thought to be the loading condition of naturally occurring, small repeating earthquakes driven by afterslip, or low-frequency earthquakes loaded by episodic slip. As follows from the previous studies referred to above, experimentally observed stress drops are well described by a logarithmic dependence on recurrence interval that can be cast as a non-linear slip-predictable model. The fault’s rate dependence of strength is the key physical parameter. Additionally, even at constant loading rate the most reproducible laboratory recurrence is not exactly periodic, unlike existing friction recurrence models. We present example laboratory catalogs that document the variance and show that in large catalogs, even at constant loading rate, stress drop and recurrence co-vary systematically. The origin of this covariance is largely consistent with variability of the dependence of fault strength on slip rate. Laboratory catalogs show aspects of both slip and time predictability and successive stress drops are strongly correlated indicating a ‘memory’ of prior slip history that extends over at least one recurrence cycle.

  17. Recurrence risk of ictal asystole in epilepsy.

    Science.gov (United States)

    Hampel, Kevin G; Thijs, Roland D; Elger, Christian E; Surges, Rainer

    2017-08-22

    To determine the recurrence risk of ictal asystole (IA) and its determining factors in people with epilepsy. We performed a systematic review of published cases with IA in 3 databases and additionally searched our local database for patients with multiple seizures simultaneously recorded with ECG and EEG and at least one IA. IA recurrence risk was estimated by including all seizures without knowledge of the chronological order. Various clinical features were assessed by an individual patient data meta-analysis. A random mixed effect logistic regression model was applied to estimate the average recurrence risk of IA. Plausibility of the calculated IA recurrence risk was checked by analyzing the local dataset with available information in chronological order. Eighty patients with 182 IA in 537 seizures were included. Recurrence risk of IA amounted to 40% (95% confidence interval [CI] 32%-50%). None of the clinical factors (age, sex, type and duration of epilepsy, hemispheric lateralization, duration of IA per patient) appeared to have a significant effect on the short-term recurrence risk of IA. When considering the local dataset only, IA recurrence risk was estimated to 30% (95% CI 14%-53%). Information whether IA coincided with symptoms (i.e., syncope) or not was given in 60 patients: 100 out of 142 IAs were symptomatic. Our data suggest that in case of clinically suspected IA, the recording of 1 or 2 seizures is not sufficient to rule out IA. Furthermore, the high short-term recurrence risk favors aggressive treatment, including pacemaker implantation if seizure freedom cannot be achieved. Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

  18. Laboratory constraints on models of earthquake recurrence

    Science.gov (United States)

    Beeler, N. M.; Tullis, Terry; Junger, Jenni; Kilgore, Brian; Goldsby, David

    2014-12-01

    In this study, rock friction "stick-slip" experiments are used to develop constraints on models of earthquake recurrence. Constant rate loading of bare rock surfaces in high-quality experiments produces stick-slip recurrence that is periodic at least to second order. When the loading rate is varied, recurrence is approximately inversely proportional to loading rate. These laboratory events initiate due to a slip-rate-dependent process that also determines the size of the stress drop and, as a consequence, stress drop varies weakly but systematically with loading rate. This is especially evident in experiments where the loading rate is changed by orders of magnitude, as is thought to be the loading condition of naturally occurring, small repeating earthquakes driven by afterslip, or low-frequency earthquakes loaded by episodic slip. The experimentally observed stress drops are well described by a logarithmic dependence on recurrence interval that can be cast as a nonlinear slip predictable model. The fault's rate dependence of strength is the key physical parameter. Additionally, even at constant loading rate the most reproducible laboratory recurrence is not exactly periodic, unlike existing friction recurrence models. We present example laboratory catalogs that document the variance and show that in large catalogs, even at constant loading rate, stress drop and recurrence covary systematically. The origin of this covariance is largely consistent with variability of the dependence of fault strength on slip rate. Laboratory catalogs show aspects of both slip and time predictability, and successive stress drops are strongly correlated indicating a "memory" of prior slip history that extends over at least one recurrence cycle.

  19. The production of Regge recurrences

    CERN Document Server

    Michael, C

    1973-01-01

    For resonance states lying on a given Regge trajectory, the two-body production mechanism as a function of the excitation of the recurrence state is discussed. A dual resonance model suggests general features for the Regge-Regge-particle coupling involved in such production. An application is made to the high energy production in pi N to pi pi N of rho , f/sub 0/ and g mesons with emphasis on the relative production cross sections, the relative t-dependences, the ratio of natural to unnatural parity exchange and the helicity dependence. (18 refs).

  20. Medical Therapy and Recurrent Ischemic Events in High Risk Patients Surviving their Myocardial Infarction for at Least 12 Months: Comparison of Patients with ST Elevation Versus Non-ST Elevation Myocardial Infarction.

    Science.gov (United States)

    Zeymer, Uwe; Riedel, Katrin; Hahn, Michael

    2017-12-01

    Data about treatments and recurrent ischemic events in patients surviving their most recent myocardial infarction event-free for at least 12 months are scarce. In a retrospective data analysis, charts of patients who had a myocardial infarction 1-3 years ago with an event-free period of at least 12 months after the index event and at least one high risk factor were centrally collected and analyzed. Here we compare patients with ST elevation myocardial infarction (STEMI) versus non-ST elevation myocardial infarction (NSTEMI). A total of 666 patients, 342 with STEMI and 324 with NSTEMI, were included. Revascularization procedures for the index event were performed in 89% of patients with STEMI and 72% of patients with NSTEMI. About 62% of patients were still on dual antiplatelet therapy after 12 months, predominantly with aspirin and clopidogrel. This rate declined to 30% after 18 months. Patients with STEMI had a higher mortality (19% versus 13%, p = 0.04) and major adverse cardiovascular and cerebrovascular event rate (MACCE; 33% versus 23%, p = 0.03) during follow-up up to 36 months, while there were no significant differences with respect to recurrent myocardial infarction or stroke. The number of high risk factors was closely linked to the rate of MACCE at follow up. Patients surviving their myocardial infarction without any further event during the first 12 months have a high rate of recurrent ischemic events in both STEMI and NSTEMI cases during subsequent follow-up. Therefore, secondary prevention therapies should be continued even one year after myocardial infarction, which might improve outcomes.

  1. Highly diverse and antimicrobial susceptible Escherichia coli display a naïve bacterial population in fruit bats from the Republic of Congo

    Science.gov (United States)

    Nowak, Kathrin; Fahr, Jakob; Weber, Natalie; Lübke-Becker, Antina; Semmler, Torsten; Weiss, Sabrina; Mombouli, Jean-Vivien; Wieler, Lothar H.; Guenther, Sebastian

    2017-01-01

    Bats are suspected to be a reservoir of several bacterial and viral pathogens relevant to animal and human health, but studies on Escherichia coli in these animals are sparse. We investigated the presence of E. coli in tissue samples (liver, lung and intestines) collected from 50 fruit bats of five different species (Eidolon helvum, Epomops franqueti, Hypsignathus monstrosus, Myonycteris torquata, Rousettus aegyptiacus) of two different areas in the Republic of Congo between 2009 and 2010. To assess E. coli pathotypes and phylogenetic relationships, we determined the presence of 59 virulence associated genes and multilocus sequence types (STs). Isolates were further tested for their susceptibility to several antimicrobial substances by agar disk diffusion test and for the presence of an Extended-Spectrum Beta-Lactamase phenotype. E. coli was detected in 60% of the bats analysed. The diversity of E. coli strains was very high, with 37 different STs within 40 isolates. Occasionally, we detected sequence types (e.g. ST69, ST127, and ST131) and pathotypes (e.g. ExPEC, EPEC and atypical EPEC), which are known pathogens in human and/or animal infections. Although the majority of strains were assigned to phylogenetic group B2 (46.2%), which is linked with the ExPEC pathovar, occurrence of virulence-associated genes in these strains were unexpectedly low. Due to this, and as only few of the E. coli isolates showed intermediate resistance to certain antimicrobial substances, we assume a rather naïve E. coli population, lacking contact to humans or domestic animals. Future studies featuring in depth comparative whole genome sequence analyses will provide insights into the microevolution of this interesting strain collection. PMID:28700648

  2. First evaluation after implementation of a quality control system for the second line drug susceptibility testing of Mycobacterium tuberculosis joint efforts in low and high incidence countries.

    Directory of Open Access Journals (Sweden)

    Doris Hillemann

    Full Text Available Three networks/projects involving 27 European countries were established to investigate the quality of second-line drug (SLD susceptibility testing with conventional and molecular methods. 1. The "Baltic-Nordic TB-Laboratory Network" comprised 11 reference laboratories in the Baltic-Nordic States. They performed SLD testing in the first phase with a panel of 20 Mycobacterium tuberculosis strains. After several laboratories made technical changes a second panel of 10 strains with a higher proportion of resistant strains were tested. Although the concordance for Ofloxacin, Kanamycin, and Capreomycin was consistently high, the largest improvements in performance were achieved for the analysis of Ofloxacin resistant (from 88.9 to 95.0%, and Capreomycin resistant (from 71.0 to 88.9% strains. 2. Within the FP7 TB PAN-NET project (EU Grant agreement 223681 a quality control panel to standardize the EQA (External Quality Assurance for first-line drugs (FLD and SLD testing for phenotypic and molecular methods was established. The strains were characterized by their robustness, unambiguous results when tested, and low proportion of secondary drug resistances. 3. The (European Reference Laboratory Network-TB ERLN-TB network analyzed four different panels for drug resistance testing using phenotypic and molecular methods; in two rounds in 2010 the 31 participating laboratories began with 5 strains, followed by 10 strains and 6 additional crude DNA extracts in 2011 and 2012 were examined by conventional DST and molecular methods. Overall, we demonstrated the importance of developing inter-laboratory networks to establish quality assurance and improvement of SLD testing of M. tuberculosis.

  3. Interleukin-17A-Deficient Mice Are Highly Susceptible to Toxoplasma gondii Infection Due to Excessively Induced T. gondii HSP70 and Interferon Gamma Production.

    Science.gov (United States)

    Moroda, Masataka; Takamoto, Masaya; Iwakura, Yoichiro; Nakayama, Jun; Aosai, Fumie

    2017-12-01

    Interleukin17A (IL-17A) is known to be involved in the host defense against pathogens and the pathogenesis of autoimmune diseases. Previously, we showed that excessive amounts of interferon gamma (IFN-γ) play an important role in the pathogenesis of the lethal effects of Toxoplasma gondii by inducing anaphylactic responses. In the study described in this report, we examined the effects of IL-17A deficiency on murine host defense against oral T. gondii infection. IL-17A-deficient C57BL/6 (B6) mice exhibited higher rates of mortality than wild-type (WT) mice during the acute phase of T. gondii infection. CD4+ T cells in the mesenteric lymph nodes (mLNs) and ileum of T. gondii-infected IL-17A-deficient mice produced higher levels of IFN-γ than did those of WT mice. In addition, the level of T. gondii HSP70 (T.gHSP70) expression was also significantly increased in the ileum, mLNs, liver, and spleen of infected IL-17A-deficient mice compared with that in WT mice. These elevated levels of expression of T.gHSP70 and IFN-γ in infected IL-17A-deficient mice were presumably linked to the IL-17A defect since they decreased to WT levels after treatment with recombinant IL-17A. Furthermore, IL-17A-deficient mice were highly susceptible to the anaphylactic effect of T.gHSP70, and the survival of IL-17A-deficient mice during the acute phase was improved by treatment with an anti-T.gHSP70 monoclonal antibody. These results suggest that IL-17A plays an important role in host survival against T. gondii infection by protecting the host from an anaphylactic reaction via the downregulation of T.gHSP70 and IFN-γ production. Copyright © 2017 American Society for Microbiology.

  4. Coping with Fear of Recurrence

    Science.gov (United States)

    ... What Comes Next After Finishing Treatment Coping With Fear of Recurrence Having a Baby After Cancer: Pregnancy ... treatment and preparing for the future. Coping With Fear of Recurrence Learn ways to manage the fear ...

  5. Recurrent Acute Pancreatitis and Therapy for Ulcerative Colitis

    Directory of Open Access Journals (Sweden)

    Jean Louis Frossard

    2010-09-01

    Full Text Available Drugs are a rare cause of pancreatitis. Whereas some drugs are well known to induce an attack of pancreatitis, some people may be more prone to develop pancreatitis because of personal susceptibility. We describe a recurrent case of acute pancreatitis after administration of several drugs in a patient with intestinal inflammatory bowel disease that needed to be treated with subsequent antiinflammatory agents. Genetic mutation in the CFTR gene was found in the patient that led us to postulate that CFTR was a trigger for drug-induced acute pancreatitis. In conclusion, genetic analysis should be advised in case of recurrent pancreatitis in patient with intestinal inflammatory bowel disease.

  6. Antimicrobial susceptibility of Brazilian Clostridium difficile strains determined by agar dilution and disk diffusion

    Directory of Open Access Journals (Sweden)

    Edmir Geraldo Fraga

    2016-09-01

    Full Text Available Clostridium difficile is a leading cause of diarrhea in hospitalized patients worldwide. While metronidazole and vancomycin are the most prescribed antibiotics for the treatment of this infection, teicoplanin, tigecycline and nitazoxanide are alternatives drugs. Knowledge on the antibiotic susceptibility profiles is a basic step to differentiate recurrence from treatment failure due to antimicrobial resistance. Because C. difficile antimicrobial susceptibility is largely unknown in Brazil, we aimed to determine the profile of C. difficile strains cultivated from stool samples of inpatients with diarrhea and a positive toxin A/B test using both agar dilution and disk diffusion methods. All 50 strains tested were sensitive to metronidazole according to CLSI and EUCAST breakpoints with an MIC90 value of 2 μg/mL. Nitazoxanide and tigecycline were highly active in vitro against these strains with an MIC90 value of 0.125 μg/mL for both antimicrobials. The MIC90 were 4 μg/mL and 2 μg/mL for vancomycin and teicoplanin, respectively. A resistance rate of 8% was observed for moxifloxacin. Disk diffusion can be used as an alternative to screen for moxifloxacin resistance, nitazoxanide, tigecycline and metronidazole susceptibility, but it cannot be used for testing glycopeptides. Our results suggest that C. difficile strains from São Paulo city, Brazil, are susceptible to metronidazole and have low MIC90 values for most of the current therapeutic options available in Brazil.

  7. Antimicrobial susceptibility of Brazilian Clostridium difficile strains determined by agar dilution and disk diffusion

    Directory of Open Access Journals (Sweden)

    Edmir Geraldo Fraga

    Full Text Available Abstract Clostridium difficile is a leading cause of diarrhea in hospitalized patients worldwide. While metronidazole and vancomycin are the most prescribed antibiotics for the treatment of this infection, teicoplanin, tigecycline and nitazoxanide are alternatives drugs. Knowledge on the antibiotic susceptibility profiles is a basic step to differentiate recurrence from treatment failure due to antimicrobial resistance. Because C. difficile antimicrobial susceptibility is largely unknown in Brazil, we aimed to determine the profile of C. difficile strains cultivated from stool samples of inpatients with diarrhea and a positive toxin A/B test using both agar dilution and disk diffusion methods. All 50 strains tested were sensitive to metronidazole according to CLSI and EUCAST breakpoints with an MIC90 value of 2 μg/mL. Nitazoxanide and tigecycline were highly active in vitro against these strains with an MIC90 value of 0.125 μg/mL for both antimicrobials. The MIC90 were 4 μg/mL and 2 μg/mL for vancomycin and teicoplanin, respectively. A resistance rate of 8% was observed for moxifloxacin. Disk diffusion can be used as an alternative to screen for moxifloxacin resistance, nitazoxanide, tigecycline and metronidazole susceptibility, but it cannot be used for testing glycopeptides. Our results suggest that C. difficile strains from São Paulo city, Brazil, are susceptible to metronidazole and have low MIC90 values for most of the current therapeutic options available in Brazil.

  8. Recurrent Aphthous Stomatitis: A Review

    OpenAIRE

    Edgar, Natalie Rose; Saleh, Dahlia; Miller, Richard A.

    2017-01-01

    Aphthous stomatitis is a painful and often recurrent inflammatory process of the oral mucosa that can appear secondary to various well-defined disease processes. Idiopathic recurrent aphthous stomatitis is referred to as recurrent aphthous stomatitis. The differential diagnosis for recurrent aphthous ulcerations is extensive and ranges from idiopathic benign causes to inherited fever syndromes, to connective tissue disease, or even inflammatory bowel diseases. A thorough history and review of...

  9. Hypnotic Induction is followed by State-like changes in the organization of EEG Functional Connectivity in the Theta and Beta Frequency bands in high-hypnotically susceptible individuals

    Directory of Open Access Journals (Sweden)

    Graham eJamieson

    2014-07-01

    Full Text Available Altered state theories of hypnosis posit that a qualitatively distinct state of mental processing, which emerges in those with high hypnotic susceptibility following a hypnotic induction, enables the generation of anomalous experiences in response to specific hypnotic suggestions. If so then such a state should be observable as a discrete pattern of changes to functional connectivity (shared information between brain regions following a hypnotic induction in high but not low hypnotically susceptible participants. Twenty-eight channel EEG was recorded from 12 high susceptible (highs and 11 low susceptible (lows participants with their eyes closed prior to and following a standard hypnotic induction. The EEG was used to provide a measure of functional connectivity using both coherence (COH and the imaginary component of coherence (iCOH, which is insensitive to the effects of volume conduction. COH and iCOH were calculated between all electrode pairs for the frequency bands: delta (0.1–3.9Hz, theta (4–7.9Hz alpha (8–12.9Hz, beta1 (13–19.9Hz, beta2 (20–29.9Hz and gamma (30–45Hz. The results showed that there was an increase in theta iCOH from the pre-hypnosis to hypnosis condition in highs but not lows with a large proportion of significant links being focused on a central-parietal hub. There was also a decrease in beta1 iCOH from the pre-hypnosis to hypnosis condition with a focus on a fronto-central and an occipital hub that was greater in high compared to low susceptibles. There were no significant differences for COH or for spectral band amplitude in any frequency band. The results are interpreted as indicating that the hypnotic induction elicited a qualitative change in the organization of specific control systems within the brain for high as compared to low susceptible participants. This change in the functional organization of neural networks is a plausible indicator of the much theorized hypnotic-state.

  10. Hypnotic induction is followed by state-like changes in the organization of EEG functional connectivity in the theta and beta frequency bands in high-hypnotically susceptible individuals

    Science.gov (United States)

    Jamieson, Graham A.; Burgess, Adrian P.

    2014-01-01

    Altered state theories of hypnosis posit that a qualitatively distinct state of mental processing, which emerges in those with high hypnotic susceptibility following a hypnotic induction, enables the generation of anomalous experiences in response to specific hypnotic suggestions. If so then such a state should be observable as a discrete pattern of changes to functional connectivity (shared information) between brain regions following a hypnotic induction in high but not low hypnotically susceptible participants. Twenty-eight channel EEG was recorded from 12 high susceptible (highs) and 11 low susceptible (lows) participants with their eyes closed prior to and following a standard hypnotic induction. The EEG was used to provide a measure of functional connectivity using both coherence (COH) and the imaginary component of coherence (iCOH), which is insensitive to the effects of volume conduction. COH and iCOH were calculated between all electrode pairs for the frequency bands: delta (0.1–3.9 Hz), theta (4–7.9 Hz) alpha (8–12.9 Hz), beta1 (13–19.9 Hz), beta2 (20–29.9 Hz) and gamma (30–45 Hz). The results showed that there was an increase in theta iCOH from the pre-hypnosis to hypnosis condition in highs but not lows with a large proportion of significant links being focused on a central-parietal hub. There was also a decrease in beta1 iCOH from the pre-hypnosis to hypnosis condition with a focus on a fronto-central and an occipital hub that was greater in high compared to low susceptibles. There were no significant differences for COH or for spectral band amplitude in any frequency band. The results are interpreted as indicating that the hypnotic induction elicited a qualitative change in the organization of specific control systems within the brain for high as compared to low susceptible participants. This change in the functional organization of neural networks is a plausible indicator of the much theorized “hypnotic-state.” PMID:25104928

  11. Immunomodulators to treat recurrent miscarriage

    NARCIS (Netherlands)

    Prins, Jelmer R.; Kieffer, Tom E.C.; Scherjon, Sicco A.

    2014-01-01

    Recurrent miscarriage is a reproductive disorder affecting many couples. Although several factors are associated with recurrent miscarriage, in more than 50% of the cases the cause is unknown. Maladaptation of the maternal immune system is associated with recurrent miscarriage and could explain part

  12. Inherited susceptibility and radiation exposure

    Energy Technology Data Exchange (ETDEWEB)

    Little, J.B. [Harvard School of Public Health, Boston, MA (United States)

    1997-03-01

    There is continuing concern that some people in the general population may have genetic makeups that place them at particularly high risk for radiation-induced cancer. The existence of such a susceptible subpopulation would have obvious implications for the estimation of risks of radiation exposure. Although it has been long known that familial aggregations of cancer do sometimes occur, recent evidence suggests that a general genetic predisposition to cancer does not exist; most cancers occur sporadically. On the other hand, nearly 10% of the known Mendelian genetic disorders are associated with cancer. A number of these involve a familial predisposition to cancer, and some are characterized by an enhanced susceptibility to the induction of cancer by various physical and chemical carcinogens, including ionizing radiation. Such increased susceptibility will depend on several factors including the frequency of the susceptibility gene in the population and its penetrance, the strength of the predisposition, and the degree to which the cancer incidence in susceptible individuals may be increased by the carcinogen. It is now known that these cancer-predisposing genes may be responsible not only for rare familial cancer syndromes, but also for a proportion of the common cancers. Although the currently known disorders can account for only a small fraction of all cancers, they serve as models for genetic predisposition to carcinogen-induced cancer in the general population. In the present report, the author describes current knowledge of those specific disorders that are associated with an enhanced predisposition to radiation-induced cancer, and discusses how this knowledge may bear on the susceptibility to radiation-induced cancer in the general population and estimates of the risk of radiation exposure.

  13. Chemoradiation in patients with unresectable extrahepatic and hilar cholangiocarcinoma or at high risk for disease recurrence after resection.. Analysis of treatment efficacy and failure in patients receiving postoperative or primary chemoradiation

    Energy Technology Data Exchange (ETDEWEB)

    Habermehl, D.; Lindel, K.; Rieken, S.; Haase, K.; Welzel, T.; Debus, J.; Combs, S.E. [University Hospital of Heidelberg (Germany). Dept. of Radiation Oncology; Goeppert, B.; Schirmacher, P. [Heidelberg Univ. (Germany). Inst. of Pathology; Buechler, M.W. [University Hospital of Heidelberg (Germany). Dept. of Visceral Surgery

    2012-09-15

    Background: The purpose of this work was to determine efficacy, toxicity, and patterns of recurrence after concurrent chemoradiation (CRT) in patients with extrahepatic bile duct cancer (EHBDC) and hilar cholangiocarcinoma (Klatskin tumours) in case of incomplete resection or unresectable disease. Patients and methods: From 2003-2010, 25 patients with nonmetastasized EHBDC and hilar cholangiocarcinoma were treated with radiotherapy and CRT at our institution in an postoperative setting (10 patients, 9 patients with R1 resections) or in case of unresectable disease (15 patients). Median age was 63 years (range 38-80 years) and there were 20 men and 5 women. Median applied dose was 45 Gy in both patient groups. Results: Patients at high risk (9 times R1 resection, 1 pathologically confirmed lymphangiosis) for tumour recurrence after curative surgery had a median time to disease progression of 8.7 months and an estimated mean overall survival of 23.2 months (6 of 10 patients are still under observation). Patients undergoing combined chemoradiation in case of unresectable primary tumours are still having a poor prognosis with a progression-free survival of 7.1 months and a median overall survival of 12.0 months. The main site of progression was systemic (liver, peritoneum) in both patient groups. Conclusion: Chemoradiation with gemcitabine is safe and can be applied safely in either patients with EHBDC or Klatskin tumours at high risk for tumour recurrence after resection and patients with unresectable tumours. Escalation of systemic and local treatment should be investigated in future clinical trials. (orig.)

  14. Recurrent giant juvenile fibroadenoma

    Directory of Open Access Journals (Sweden)

    Kathryn S. King

    2017-11-01

    Full Text Available Breast masses in children, though rare, present a difficult clinical challenge as they can represent a wide variety of entities from benign fibroadenomas to phyllodes tumors. Rapidly growing or recurrent masses can be particularly concerning to patients, families and physicians alike. Clinical examination and conventional imaging modalities are not efficacious in distinguishing between different tumor types and surgical excision is often recommended for both final diagnosis and for treatment of large or rapidly growing masses. While surgical excision can result in significant long-term deformity of the breast there are some surgical techniques that can be used to limit deformity and/or aid in future reconstruction. Here we present a case of recurrent giant juvenile fibroadenoma with a review of the clinical presentation, diagnostic tools and treatment options.

  15. Recurrent Takotsubo Cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Erkan Yıldırım

    2016-09-01

    Full Text Available Stress-induced cardiomyopathy or takotsubo syndrome is a transient cardiac dysfunction which is precipitated by intense emotional or physical stress. It mimics acute coronary syndrome clinically (chest pain and dyspnea and has specific echocardiographic findings in the absence of significant coronary stenosis. The underlying pathophysiologic mechanism is mostly due to stress-induced catecholamine release. This syndrome is more commonly seen in females especially in the postmenopausal period. The prognosis of stress-induced cardiomyopathy is usually favorable with a prevalence of in-hospital mortality of less than 2%. Reports of a single episode of stress-induced cardiomyopathy are common in the literature, but recurrence of stress-induced cardiomyopathy is rare. Herein, we present an uncommon case of recurrent stress-induced cardiomyopathy in order to provide an explanation of the pathophysiology of this unique syndrome.

  16. Recurrent amiodarone pulmonary toxicity.

    Science.gov (United States)

    Chendrasekhar, A; Barke, R A; Druck, P

    1996-01-01

    Amiodarone, a widely used antiarrhythmic drug, is associated with pulmonary toxicity, with an estimated mortality of 1% to 33%. Standard treatment for amiodarone pulmonary toxicity (APT) has been discontinuance of the drug and steroid therapy. We report a case of APT that recurred after withdrawal of steroids and failed to respond to reinstatement of steroid therapy. Recurrent APT is a rare clinical entity that has been reported only twice in recent literature.

  17. Recurrent aphthous stomatitis.

    Science.gov (United States)

    Akintoye, Sunday O; Greenberg, Martin S

    2005-01-01

    The cause of recurrent aphthous stomatitis (RAS) remains unknown despite considerable research. This article reviews the evidence for current theories regarding this disorder, including possible suspected relationships with microbial and immunologic factors, and presents medical diseases that mimic RAS lesions in certain patients. Topical management of the common form of minor RAS is described along with systemic therapy currently available to patients with severe forms of this disease.

  18. Recurrent cutaneous leishmaniasis

    OpenAIRE

    Gomes,Ciro Martins; Damasco,Fabiana dos Santos; Morais,Orlando Oliveira de; Paula,Carmen Dea Ribeiro de; Sampaio,Raimunda Nonata Ribeiro

    2013-01-01

    We present a case of an 18-year-old male patient who, after two years of inappropriate treatment for cutaneous leishmaniasis, began to show nodules arising at the edges of the former healing scar. He was immune competent and denied any trauma. The diagnosis of recurrent cutaneous leishmaniasis was made following positive culture of aspirate samples. The patient was treated with N-methylglucamine associated with pentoxifylline for 30 days. Similar cases require special attention mainly because...

  19. Clinicopathologic factors associated with recurrence in parotid carcinoma.

    Science.gov (United States)

    Lee, Dong Hoon; Yoon, Tae Mi; Lee, Joon Kyoo; Lim, Sang Chul

    2017-08-25

    Parotid carcinomas have varying histological types and diverse biologic behaviors. Establishing an adequate treatment plan and predicting recurrence is important. To analyze the risk factors associated with recurrence in our 5 year experience with 30 cases of primary parotid carcinoma undergoing surgery at a single institute. From January 2009 to December 2013, 30 patients with surgical treatment of parotid carcinoma were identified based on their medical records. The 30 patients were comprised of 17 males and 13 females. Among 11 patients with T4 tumors, seven patients had recurrence. Among seven patients with cervical nodal metastasis, all patient except one had recurrence. Clinically late stages (stage III and IV) showed more common recurrence than early stage (stage I and II) lesions. Lymphovascular invasion was seen in 5 patients, and all patients had recurrence. Among 11 patients with extracapsular spread, 7 patients had recurrence. In 17 patients with high grade carcinomas, ten patients had recurrence. In 13 patients with low grade carcinomas, no patients experienced recurrence. T- and N-stage, clinical stage, lymphovascular invasion, extracapsular spread, and histopathologic grade correlate significantly with recurrence in parotid carcinoma. Copyright © 2017 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

  20. Software-aided approach to investigate peptide structure and metabolic susceptibility of amide bonds in peptide drugs based on high resolution mass spectrometry

    Science.gov (United States)

    Fontaine, Fabien; Morettoni, Luca; Zamora, Ismael

    2017-01-01

    Interest in using peptide molecules as therapeutic agents due to high selectivity and efficacy is increasing within the pharmaceutical industry. However, most peptide-derived drugs cannot be administered orally because of low bioavailability and instability in the gastrointestinal tract due to protease activity. Therefore, structural modifications peptides are required to improve their stability. For this purpose, several in-silico software tools have been developed such as PeptideCutter or PoPS, which aim to predict peptide cleavage sites for different proteases. Moreover, several databases exist where this information is collected and stored from public sources such as MEROPS and ExPASy ENZYME databases. These tools can help design a peptide drug with increased stability against proteolysis, though they are limited to natural amino acids or cannot process cyclic peptides, for example. We worked to develop a new methodology to analyze peptide structure and amide bond metabolic stability based on the peptide structure (linear/cyclic, natural/unnatural amino acids). This approach used liquid chromatography / high resolution, mass spectrometry to obtain the analytical data from in vitro incubations. We collected experimental data for a set (linear/cyclic, natural/unnatural amino acids) of fourteen peptide drugs and four substrate peptides incubated with different proteolytic media: trypsin, chymotrypsin, pepsin, pancreatic elastase, dipeptidyl peptidase-4 and neprilysin. Mass spectrometry data was analyzed to find metabolites and determine their structures, then all the results were stored in a chemically aware manner, which allows us to compute the peptide bond susceptibility by using a frequency analysis of the metabolic-liable bonds. In total 132 metabolites were found from the various in vitro conditions tested resulting in 77 distinct cleavage sites. The most frequent observed cleavage sites agreed with those reported in the literature. The main advantages of

  1. Software-aided approach to investigate peptide structure and metabolic susceptibility of amide bonds in peptide drugs based on high resolution mass spectrometry.

    Directory of Open Access Journals (Sweden)

    Tatiana Radchenko

    Full Text Available Interest in using peptide molecules as therapeutic agents due to high selectivity and efficacy is increasing within the pharmaceutical industry. However, most peptide-derived drugs cannot be administered orally because of low bioavailability and instability in the gastrointestinal tract due to protease activity. Therefore, structural modifications peptides are required to improve their stability. For this purpose, several in-silico software tools have been developed such as PeptideCutter or PoPS, which aim to predict peptide cleavage sites for different proteases. Moreover, several databases exist where this information is collected and stored from public sources such as MEROPS and ExPASy ENZYME databases. These tools can help design a peptide drug with increased stability against proteolysis, though they are limited to natural amino acids or cannot process cyclic peptides, for example. We worked to develop a new methodology to analyze peptide structure and amide bond metabolic stability based on the peptide structure (linear/cyclic, natural/unnatural amino acids. This approach used liquid chromatography / high resolution, mass spectrometry to obtain the analytical data from in vitro incubations. We collected experimental data for a set (linear/cyclic, natural/unnatural amino acids of fourteen peptide drugs and four substrate peptides incubated with different proteolytic media: trypsin, chymotrypsin, pepsin, pancreatic elastase, dipeptidyl peptidase-4 and neprilysin. Mass spectrometry data was analyzed to find metabolites and determine their structures, then all the results were stored in a chemically aware manner, which allows us to compute the peptide bond susceptibility by using a frequency analysis of the metabolic-liable bonds. In total 132 metabolites were found from the various in vitro conditions tested resulting in 77 distinct cleavage sites. The most frequent observed cleavage sites agreed with those reported in the literature. The

  2. Software-aided approach to investigate peptide structure and metabolic susceptibility of amide bonds in peptide drugs based on high resolution mass spectrometry.

    Science.gov (United States)

    Radchenko, Tatiana; Brink, Andreas; Siegrist, Yves; Kochansky, Christopher; Bateman, Alison; Fontaine, Fabien; Morettoni, Luca; Zamora, Ismael

    2017-01-01

    Interest in using peptide molecules as therapeutic agents due to high selectivity and efficacy is increasing within the pharmaceutical industry. However, most peptide-derived drugs cannot be administered orally because of low bioavailability and instability in the gastrointestinal tract due to protease activity. Therefore, structural modifications peptides are required to improve their stability. For this purpose, several in-silico software tools have been developed such as PeptideCutter or PoPS, which aim to predict peptide cleavage sites for different proteases. Moreover, several databases exist where this information is collected and stored from public sources such as MEROPS and ExPASy ENZYME databases. These tools can help design a peptide drug with increased stability against proteolysis, though they are limited to natural amino acids or cannot process cyclic peptides, for example. We worked to develop a new methodology to analyze peptide structure and amide bond metabolic stability based on the peptide structure (linear/cyclic, natural/unnatural amino acids). This approach used liquid chromatography / high resolution, mass spectrometry to obtain the analytical data from in vitro incubations. We collected experimental data for a set (linear/cyclic, natural/unnatural amino acids) of fourteen peptide drugs and four substrate peptides incubated with different proteolytic media: trypsin, chymotrypsin, pepsin, pancreatic elastase, dipeptidyl peptidase-4 and neprilysin. Mass spectrometry data was analyzed to find metabolites and determine their structures, then all the results were stored in a chemically aware manner, which allows us to compute the peptide bond susceptibility by using a frequency analysis of the metabolic-liable bonds. In total 132 metabolites were found from the various in vitro conditions tested resulting in 77 distinct cleavage sites. The most frequent observed cleavage sites agreed with those reported in the literature. The main advantages of

  3. Compression for preventing recurrence of venous ulcers.

    Science.gov (United States)

    Nelson, E Andrea; Bell-Syer, Sally E M

    2014-09-09

    Up to 1% of adults will have a leg ulcer at some time. The majority of leg ulcers are venous in origin and are caused by high pressure in the veins due to blockage or weakness of the valves in the veins of the leg. Prevention and treatment of venous ulcers is aimed at reducing the pressure either by removing/repairing the veins, or by applying compression bandages/stockings to reduce the pressure in the veins.The majority of venous ulcers heal with compression bandages, however ulcers frequently recur. Clinical guidelines therefore recommend that people continue to wear compression, usually in the form of hosiery (tights, stockings, socks) after their ulcer heals, to prevent recurrence. To assess the effects of compression (socks, stockings, tights, bandages) in preventing the recurrence of venous ulcers. If compression does prevent ulceration compared with no compression, then to identify whether there is evidence to recommend particular levels of compression (high, medium or low, for example), types of compression, or brands of compression to prevent ulcer recurrence after healing. For this second update we searched The Cochrane Wounds Group Specialised Register (searched 4 September 2014) which includes the results of regular searches of MEDLINE, EMBASE and CINAHL; The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2014, Issue 8). Randomised controlled trials (RCTs)evaluating compression bandages or hosiery for preventing the recurrence of venous ulcers. Two review authors undertook data extraction and risk of bias assessment independently. Four trials (979 participants) were eligible for inclusion in this review. One trial in patients with recently healed venous ulcers (n = 153) compared recurrence rates with and without compression and found that compression significantly reduced ulcer recurrence at six months (Risk ratio (RR) 0.46, 95% CI 0.27 to 0.76).Two trials compared high-compression hosiery (equivalent to UK class 3) with

  4. Genetic Susceptibility to Triple Negative Breast Cancer

    OpenAIRE

    Stevens, Kristen N.; Vachon, Celine M.; Couch, Fergus J.

    2013-01-01

    Triple negative breast cancers (TNBC), defined by the absence of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor-2 expression, account for 12-24% of all breast cancers. TNBC is associated with early recurrence of disease and poor outcome. Germline mutations in the BRCA1 and BRCA2 breast cancer susceptibility genes have been associated with up to 15% of TNBC, and TNBC accounts for 70% of breast tumors arising in BRCA1 mutation carriers and 16-23% of breast ...

  5. Susceptibility to malignant hyperthermia

    NARCIS (Netherlands)

    Snoeck, Marcus Matheus Johannes

    2004-01-01

    In this thesis the author studied the diagnostic procedures for susceptibility to malignant hyperthermia (MH), with special emphasis upon refining the biological diagnostic test and improving protocols and guidelines for investigation of MH susceptibility. MH is a pharmacogenetic disease of skeletal

  6. ER-positive breast cancer patients with more than three positive nodes or grade 3 tumors are at high risk of late recurrence after 5-year adjuvant endocrine therapy

    Directory of Open Access Journals (Sweden)

    Song F

    2017-10-01

    Full Text Available Fangbin Song,1 Jianbing Zhang,2 Shanbao Li,1 Junyi Wu,1 Tao Jin,1 Jun Qin,1 Ye Wang,1 Min Wang,1 Junming Xu1 1Department of General Surgery, 2Department of Pathology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China Purpose: Currently, although several clinical trials available give strong suggestions that extension of endocrine therapy has benefits, the risk level at which patients may benefit from extended endocrine therapy remains uncertain. This study aimed to identify the proportion of patients at a substantial risk of late recurrence after 5-year adjuvant endocrine therapy.Patients and methods: We reviewed 1,056 female patients with primary breast cancer who underwent curative resection between January 2006 and December 2011. Univariate and multivariate analyses were performed using the Cox proportional hazards regression model to identify prognostic factors.Results: A total of 327 eligible patients were eventually enrolled in this study. Among them, 42 (12.8% patients suffered from distant metastasis and 34 (10.4% patients experienced locoregional recurrence after 5-year adjuvant endocrine therapy. In multivariate analysis, patients with more than three positive nodes (hazard ratio [HR] =2.176, 95% CI=1.071–4.421; P=0.032 and histologic grade 3 disease (HR=2.098, 95% CI=1.300–3.385; P=0.002 were significantly associated with high risk of late recurrence. However, only histologic grade 3 (HR=2.212, 95% CI=1.166–4.194; P=0.015 was significantly associated with high risk of distant metastasis.Conclusion: Late relapse after completion of 5-year adjuvant endocrine therapy was still common, and grade 3 and more than three positive nodes were the risk factors of late recurrence, while grade 3 was the only risk factor of late distant metastasis. These patients might benefit from extended endocrine therapy. Keywords: Ki-67, breast neoplasms, prognosis, extended endocrine

  7. Multidimensional Genetic Analysis of Repeated Seizures in the Hybrid Mouse Diversity Panel Reveals a Novel Epileptogenesis Susceptibility Locus

    Directory of Open Access Journals (Sweden)

    Russell J. Ferland

    2017-08-01

    Full Text Available Epilepsy has many causes and comorbidities affecting as many as 4% of people in their lifetime. Both idiopathic and symptomatic epilepsies are highly heritable, but genetic factors are difficult to characterize among humans due to complex disease etiologies. Rodent genetic studies have been critical to the discovery of seizure susceptibility loci, including Kcnj10 mutations identified in both mouse and human cohorts. However, genetic analyses of epilepsy phenotypes in mice to date have been carried out as acute studies in seizure-naive animals or in Mendelian models of epilepsy, while humans with epilepsy have a history of recurrent seizures that also modify brain physiology. We have applied a repeated seizure model to a genetic reference population, following seizure susceptibility over a 36-d period. Initial differences in generalized seizure threshold among the Hybrid Mouse Diversity Panel (HMDP were associated with a well-characterized seizure susceptibility locus found in mice: Seizure susceptibility 1. Remarkably, Szs1 influence diminished as subsequent induced seizures had diminishing latencies in certain HMDP strains. Administration of eight seizures, followed by an incubation period and an induced retest seizure, revealed novel associations within the calmodulin-binding transcription activator 1, Camta1. Using systems genetics, we have identified four candidate genes that are differentially expressed between seizure-sensitive and -resistant strains close to our novel Epileptogenesis susceptibility factor 1 (Esf1 locus that may act individually or as a coordinated response to the neuronal stress of seizures.

  8. Recurrent Clostridium difficile infections: the importance of the intestinal microbiota.

    Science.gov (United States)

    Zanella Terrier, Marie Céline; Simonet, Martine Louis; Bichard, Philippe; Frossard, Jean Louis

    2014-06-21

    Clostridium difficile infections (CDI) are a leading cause of antibiotic-associated and nosocomial diarrhea. Despite effective antibiotic treatments, recurrent infections are common. With the recent emergence of hypervirulent isolates of C. difficile, CDI is a growing epidemic with higher rates of recurrence, increasing severity and mortality. Fecal microbiota transplantation (FMT) is an alternative treatment for recurrent CDI. A better understanding of intestinal microbiota and its role in CDI has opened the door to this promising therapeutic approach. FMT is thought to resolve dysbiosis by restoring gut microbiota diversity thereby breaking the cycle of recurrent CDI. Since the first reported use of FMT for recurrent CDI in 1958, systematic reviews of case series and case report have shown its effectiveness with high resolution rates compared to standard antibiotic treatment. This article focuses on current guidelines for CDI treatment, the role of intestinal microbiota in CDI recurrence and current evidence about FMT efficacy, adverse effects and acceptability.

  9. Recurrent Clostridium difficile infections: The importance of the intestinal microbiota

    Science.gov (United States)

    Zanella Terrier, Marie Céline; Simonet, Martine Louis; Bichard, Philippe; Frossard, Jean Louis

    2014-01-01

    Clostridium difficile infections (CDI) are a leading cause of antibiotic-associated and nosocomial diarrhea. Despite effective antibiotic treatments, recurrent infections are common. With the recent emergence of hypervirulent isolates of C. difficile, CDI is a growing epidemic with higher rates of recurrence, increasing severity and mortality. Fecal microbiota transplantation (FMT) is an alternative treatment for recurrent CDI. A better understanding of intestinal microbiota and its role in CDI has opened the door to this promising therapeutic approach. FMT is thought to resolve dysbiosis by restoring gut microbiota diversity thereby breaking the cycle of recurrent CDI. Since the first reported use of FMT for recurrent CDI in 1958, systematic reviews of case series and case report have shown its effectiveness with high resolution rates compared to standard antibiotic treatment. This article focuses on current guidelines for CDI treatment, the role of intestinal microbiota in CDI recurrence and current evidence about FMT efficacy, adverse effects and acceptability. PMID:24966611

  10. Recurrence and Treatment after Renal Transplantation in Children with FSGS

    Directory of Open Access Journals (Sweden)

    Hee Gyung Kang

    2016-01-01

    Full Text Available Focal segmental glomerulosclerosis (FSGS is a common cause of end-stage renal disease and a common pathologic diagnosis of idiopathic nephrotic syndrome (NS, especially in steroid-resistant cases. FSGS is known to recur after kidney transplantation, frequently followed by graft loss. However, not all patients with FSGS suffer from recurrence after kidney transplantation, and genetic and secondary FSGS have a negligible risk of recurrence. Furthermore, many cases of recurrence achieve remission with the current management of recurrence (intensive plasmapheresis/immunosuppression, including rituximab, and other promising agents are being evaluated. Therefore, a pathologic diagnosis of FSGS itself should not cause postponement of allograft kidney transplantation. For patients with a high risk of recurrence who presented with classical symptoms of NS, that is, severe edema, proteinuria, and hypoalbuminemia, close monitoring of proteinuria is necessary, followed by immediate, intensive treatment for recurrence.

  11. Standard fractionation external beam radiotherapy with and without intraoperative radiotherapy for locally recurrent rectal cancer: the role of local therapy in patients with a high competing risk of death from distant disease.

    Science.gov (United States)

    Kishan, Amar U; Voog, Justin C; Wiseman, Jonathan; Cook, Ryan R; Ancukiewicz, Marek; Lee, Percy; Ryan, David P; Clark, Jeffrey W; Berger, David L; Cusack, James C; Wo, Jennifer Y; Hong, Theodore S

    2017-08-01

    We sought to evaluate the effectiveness and safety of utilizing radiotherapy (RT) with standard fractionation, with or without intraoperative RT (IORT), to treat locally recurrent rectal cancer (LRRC). Retrospective review of 25 patients with LRRC treated with standard fractionation RT from 2005 to 2011. 15 patients (60%) had prior pelvic RT and 10 (40%) had synchronous metastases. The median equivalent dose in 2-Gy fractions was 30 and 49.6 Gy in patients with and without prior RT, respectively. 23 patients (92%) received concurrent chemotherapy and 16 (64%) underwent surgical resection. Eight patients (33.3%, four with and four without prior RT) received IORT. A competing risks model was developed to estimate the cumulative incidence of local failure with death treated as a competing event. Median follow-up was 36.9 months after the date of local recurrence. 3-year rates of overall survival (OS), local control (LC) and death with LC were 51.6%, 73.3% and 69.2%, respectively. On multivariable analysis, surgical resection was significantly predictive of improved OS (p history of prior RT. Advances in knowledge: The utility of RT with standard fractionation, generally with chemotherapy, in the treatment of LRRC is demonstrated. In this high-risk cohort of patients with a 40% incidence of synchronous metastatic disease, surgical resection of the recurrence was the major predictor of OS, though a benefit to IORT was also suggested. No patients had grade ≥3 acute or late toxicity, though 40% had undergone prior RT, underscoring the tolerability of standard fractionation RT in this setting.

  12. Treatment with sofosbuvir and ledipasvir without ribavirin for 12 weeks is highly effective for recurrent hepatitis C virus genotype 1b infection after living donor liver transplantation: a Japanese multicenter experience.

    Science.gov (United States)

    Ueda, Yoshihide; Ikegami, Toru; Akamatsu, Nobuhisa; Soyama, Akihiko; Shinoda, Masahiro; Goto, Ryoichi; Okajima, Hideaki; Yoshizumi, Tomoharu; Taketomi, Akinobu; Kitagawa, Yuko; Eguchi, Susumu; Kokudo, Norihiro; Uemoto, Shinji; Maehara, Yoshihiko

    2017-08-01

    The optimal therapy for recurrent hepatitis C virus (HCV) infection after liver transplantation has not yet been established. This study aimed to clarify the efficacy and safety of interferon-free therapy with sofosbuvir and ledipasvir without ribavirin for 12 weeks in Japanese patients with HCV genotype 1b infection after living donor liver transplantation. A cohort study of living donor liver transplant recipients with recurrent HCV genotype 1b infection treated with sofosbuvir (400 mg/day) and ledipasvir (90 mg/day) was performed at six liver transplant centers in Japan. Fifty-four patients were treated with sofosbuvir and ledipasvir. Thirty-eight patients (70%) were treatment experienced, including 17 patients who had undergone prior direct-acting-antiviral-based triple therapy. Ten patients had resistance-associated substitutions at L31 or Y93 in the NS5A region of the HCV genome. Fifty-three patients completed the 12-week treatment protocol; treatment was discontinued in one patient who developed pneumonia at 4 weeks and died thereafter. All 53 patients who completed the treatment regimen achieved a sustained virological response 12 weeks after completion of treatment. Treatment was well tolerated in most patients, but seven patients developed serious adverse events, including hemorrhagic duodenal ulcers (n = 3), infection (n = 2), pleural effusion (n = 1), and alveolar hemorrhage (n = 1). Sofosbuvir and ledipasvir treatment without ribavirin for 12 weeks was highly effective in achieving a sustained virological response in Japanese patients who developed recurrent HCV genotype 1b infection after living donor liver transplantation.

  13. pH-induced change in cell susceptibility to butanol in a high butanol-tolerant bacterium, Enterococcus faecalis strain CM4A.

    Science.gov (United States)

    Kanno, Manabu; Tamaki, Hideyuki; Mitani, Yasuo; Kimura, Nobutada; Hanada, Satoshi; Kamagata, Yoichi

    2015-01-01

    Though butanol is considered as a potential biofuel, its toxicity toward microorganisms is the main bottleneck for the biological butanol production. Recently, butanol-tolerant bacteria have been proposed as alternative butanol production hosts overcoming the end product inhibition. One remaining key issue to be addressed is how physicochemical properties such as pH and temperature affect microbial butanol tolerance during cultivation and fermentation. We investigated the pH effect on butanol tolerance of a high butanol-tolerant bacterium, Enterococcus faecalis strain CM4A. The strain grew over a broad pH range (pH 4.0 to 12.0) and preferred alkaline pH (pH 8.0 and 10.0) in the absence of butanol. However, in the presence of butanol, strain CM4A grew better under acidic and neutral pH conditions (pH 6.0 and 6.8). Membrane fatty acid analysis revealed that the cells exposed to butanol exhibited increased cyclopropane and saturated fatty acids, which contribute to butanol tolerance of the strain by decreasing membrane fluidity, more evidently at acidic and neutral pH than at alkaline pH. Meanwhile, the strain grown under alkaline pH without butanol increased short chain fatty acids, which is involved in increasing membrane fluidity for alkaline adaptation. Such a change was not observed in the cells grown under alkaline pH with butanol. These results suggested that strain CM4A simultaneously exposed to butanol and alkali stresses was not likely able to properly adjust membrane fluidity due to the opposite response to each stress and thereby showed low butanol tolerance under alkaline pH. Indeed, the cells exposed to butanol at alkaline pH showed an irregular shape with disrupted membrane structure under transmission electron microscopy observation, which also indicated the impact of butanol and alkali stresses on functioning of cellular membrane. The study clearly demonstrated the alkaline pH-induced increase of cell susceptibility to butanol in the tested strain

  14. Predictors and Outcomes of Recurrent Venous Thromboembolism in Elderly Patients.

    Science.gov (United States)

    Lauber, Sandro; Limacher, Andreas; Tritschler, Tobias; Stalder, Odile; Méan, Marie; Righini, Marc; Aschwanden, Markus; Beer, Jürg Hans; Frauchiger, Beat; Osterwalder, Josef; Kucher, Nils; Lämmle, Bernhard; Cornuz, Jacques; Angelillo-Scherrer, Anne; Matter, Christian M; Husmann, Marc; Banyai, Martin; Staub, Daniel; Mazzolai, Lucia; Hugli, Olivier; Rodondi, Nicolas; Aujesky, Drahomir

    2018-01-04

    Little is known about predictors and outcomes of recurrent venous thromboembolism in elderly patients. We prospectively followed up 991 patients aged ≥65 years with acute venous thromboembolism in a multicenter Swiss cohort study. The primary outcome was symptomatic recurrent venous thromboembolism. We explored the association between baseline characteristics and treatments and recurrent venous thromboembolism using competing risk regression, adjusting for periods of anticoagulation as a time-varying co-variate. We also assessed the clinical consequences (case-fatality, localization) of recurrent venous thromboembolism. During a median follow-up period of 30 months, 122 patients developed recurrent venous thromboembolism, corresponding to a 3-year cumulative incidence of 14.8%. The case-fatality of recurrence was high (20.5%), particularly in patients with unprovoked (23%) and cancer-related venous thromboembolism (29%). After adjustment, only unprovoked venous thromboembolism (sub-hazard ratio [SHR] 1.67 compared to provoked venous thromboembolism; 95% confidence interval [CI] 1.00-2.77) and proximal deep vein thrombosis (SHR 2.41 compared to isolated distal deep vein thrombosis; 95% CI 1.07-5.38) were significantly associated with recurrence. Patients with initial pulmonary embolism were more likely to have another pulmonary embolism as a recurrent event than patients with deep vein thrombosis. Elderly patients with acute venous thromboembolism have a substantial long-term risk of recurrent venous thromboembolism and recurrence carries a high case-fatality rate. Only two factors, unprovoked venous thromboembolism and proximal deep vein thrombosis, were independently associated with recurrent venous thromboembolism, indicating that traditional risk factors for venous thromboembolism recurrence (e.g., cancer) may be less relevant in the elderly. Copyright © 2018. Published by Elsevier Inc.

  15. Postoperative radiotherapy appeared to improve the disease free survival rate of patients with extrahepatic bile duct cancer at high risk of loco-regional recurrence

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Mi Young; Kim, Jin Hee; Kim, Yong Hoon [Keimyung University Dongsan Medical Center, Keimyung University School of Medicine, Daegu (Korea, Republic of); Byun, Sang Jun [Dept. of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of)

    2016-12-15

    To investigate the outcomes of postoperative radiotherapy (RT), in patients with extrahepatic bile duct (EHBD) cancer by comparing the survival rate between patients undergoing surgery alone or surgery plus postoperative RT, and to identify the prognostic factors affecting survival. Between 2000 and 2013, 52 patients with EHBD cancer underwent surgical resection. Of these, 33 patients did not receive postoperative RT (group I), and 19 patients did (group II). R1 resection was significantly more frequent in group II. The median radiation dose was 5,040 cGy. The 3-year overall survival (OS) rate for group I and group II was 38% and 56%, respectively (p = 0.274). The 3-year disease free survival (DFS) rate for group I and group II was 20% and 31%, respectively (p = 0.049), and the 3-year loco-regional recurrence free survival (LRFS) rates were 19% and 58%, respectively (p = 0.002). Multivariate analyses showed that postoperative RT and lymphovascular invasion were independent prognostic factors for DFS and LRFS. Overall, 42 patients (80%) experienced treatment failure. Distant metastasis was the predominant pattern of failure in group II. Postoperative RT after surgical resection appeared to improve the loco-regional control and DFS rate. More effort is needed to reduce distant metastasis, the major pattern of failure, in patients who receive postoperative RT.

  16. Postoperative radiotherapy appeared to improve the disease free survival rate of patients with extrahepatic bile duct cancer at high risk of loco-regional recurrence.

    Science.gov (United States)

    Kim, Mi Young; Kim, Jin Hee; Kim, Yonghoon; Byun, Sang Jun

    2016-12-01

    To investigate the outcomes of postoperative radiotherapy (RT), in patients with extrahepatic bile duct (EHBD) cancer by comparing the survival rate between patients undergoing surgery alone or surgery plus postoperative RT, and to identify the prognostic factors affecting survival. Between 2000 and 2013, 52 patients with EHBD cancer underwent surgical resection. Of these, 33 patients did not receive postoperative RT (group I), and 19 patients did (group II). R1 resection was significantly more frequent in group II. The median radiation dose was 5,040 cGy. The 3-year overall survival (OS) rate for group I and group II was 38% and 56%, respectively (p = 0.274). The 3-year disease free survival (DFS) rate for group I and group II was 20% and 31%, respectively (p = 0.049), and the 3-year loco-regional recurrence free survival (LRFS) rates were 19% and 58%, respectively (p = 0.002). Multivariate analyses showed that postoperative RT and lymphovascular invasion were independent prognostic factors for DFS and LRFS. Overall, 42 patients (80%) experienced treatment failure. Distant metastasis was the predominant pattern of failure in group II. Postoperative RT after surgical resection appeared to improve the loco-regional control and DFS rate. More effort is needed to reduce distant metastasis, the major pattern of failure, in patients who receive postoperative RT.

  17. Definitive Reirradiation for Locoregionally Recurrent Non-Small Cell Lung Cancer With Proton Beam Therapy or Intensity Modulated Radiation Therapy: Predictors of High-Grade Toxicity and Survival Outcomes

    Energy Technology Data Exchange (ETDEWEB)

    McAvoy, Sarah; Ciura, Katherine; Wei, Caimiao; Rineer, Justin; Liao, Zhongxing; Chang, Joe Y.; Palmer, Matthew B.; Cox, James D.; Komaki, Ritsuko; Gomez, Daniel R., E-mail: DGomez@mdanderson.org

    2014-11-15

    locoregional recurrence and distant metastasis are high, and patients should be selected carefully to maximize the benefit of additional aggressive local therapy while minimizing the risk of adverse side effects.

  18. Braquiterapia intersticial de alta tasa de rescate en cáncer cabeza cuello previamente radiado High-dose-rate (HDR brachytherapy in previously irradiated recurrent head and neck cancer

    Directory of Open Access Journals (Sweden)

    Lucía Gutiérrez-Bayard

    2011-09-01

    Full Text Available A pesar de los avances en el tratamiento de cáncer de cabeza y cuello (CCC, el 15-50% de los pacientes presentan recurrencia locorregional. Para los pacientes que presentan enfermedad localmente recurrente o un segundo tumor primario en un campo previamente irradiado, las opciones terapéuticas de rescate son limitadas, siendo la resección quirúrgica con intención curativa la opción de elección para los pacientes con enfermedad limitada. Reirradiación con o sin la adición de quimioterapia puede ser una buena opción, obteniendo en pacientes seleccionados supervivencia a largo plazo. La braquiterapia de alta tasa de dosis (HDRBT puede jugar un papel importante en el tratamiento de rescate en tumores de cabeza y cuello recurrentes. Presentamos un paciente de 56 años diagnosticado de cáncer de lengua sometido a cirugía y radioterapia externa adyuvante, y recurrencia metastásica ganglionar cervical contralateral a los 18 meses. Recibió tratamiento multidisciplinar con quimioterapia, cirugía y braquiterapia intersticial.Despite advances in the treatment of head and neck cancer (HNC, 15-50% of patients present locoregional disease recurrence. The therapeutic options are limited for patients who present locally recurrent disease or a second primary tumor in a previously irradiated field. Surgical salvage with curative intent is the preferred option for patients with limited-volume disease. Re-irradiation with or without the addition of chemotherapy may hold promise for long-term survival for selected patients. High-dose-rate (HDR brachytherapy can play an important role in the salvage treatment of previously irradiated recurrent head and neck cancer. The case reported was a 56-year old man diagnosed of tongue cancer who presented recurrent metastatic contralateral cervical node 1.5 years after radical treatment with surgery and adjuvant external radiotherapy. He received multidisciplinary treatment with chemotherapy, surgery and HDR

  19. Multiscale recurrence quantification analysis of order recurrence plots

    Science.gov (United States)

    Xu, Mengjia; Shang, Pengjian; Lin, Aijing

    2017-03-01

    In this paper, we propose a new method of multiscale recurrence quantification analysis (MSRQA) to analyze the structure of order recurrence plots. The MSRQA is based on order patterns over a range of time scales. Compared with conventional recurrence quantification analysis (RQA), the MSRQA can show richer and more recognizable information on the local characteristics of diverse systems which successfully describes their recurrence properties. Both synthetic series and stock market indexes exhibit their properties of recurrence at large time scales that quite differ from those at a single time scale. Some systems present more accurate recurrence patterns under large time scales. It demonstrates that the new approach is effective for distinguishing three similar stock market systems and showing some inherent differences.

  20. [Recurrent left atrial myxoma].

    Science.gov (United States)

    Moreno Martínez, Francisco L; Lagomasino Hidalgo, Alvaro; Mirabal Rodríguez, Roger; López Bermúdez, Félix H; López Bernal, Omaida J

    2003-01-01

    Primary cardiac tumors are rare. Mixomas are the most common among them; 75% are located in the left atrium, 20% in the right atrium, and the rest in the ventricles. The seldom appear in atrio-ventricular valves. Recidivant mixoma are also rare, appearing in 1-5% of all patients that have undergone surgical treatment of a mixoma. In this paper we present our experience with a female patient, who 8 years after having been operated of a left atrial mixoma, began with symptoms of mild heart failure. Transthoracic echocardiography revealed recurrence of the tumor, and was therefore subjected to a second open-heart surgery from which she recovered without complications.

  1. Recurrent Pregnancy Loss

    Directory of Open Access Journals (Sweden)

    Véronique Piroux

    1997-01-01

    Full Text Available Antiphospholipid antibodies (APA are associated with thrombosis, thrombocytopenia and fetal loss but they occur in a variety of diseases. Despite many efforts, a correlation between the specificity of particular subgroups of APA and particular clinical situations remains to be established. The antigens at the origin of APA remain to be identified. We discuss here the possible links between cell apoptosis or necrosis, leading to plasma membrane alterations, and the occurrence of APA in response to sustained stimulation. The pathogenic potential of APA is also considered with respect to recurrent pregnancy loss.

  2. Recurrent Miller Fisher syndrome.

    Science.gov (United States)

    Madhavan, S; Geetha; Bhargavan, P V

    2004-07-01

    Miller Fisher syndrome (MFS) is a variant of Guillan Barre syndrome characterized by the triad of ophthalmoplegia, ataxia and areflexia. Recurrences are exceptional with Miller Fisher syndrome. We are reporting a case with two episodes of MFS within two years. Initially he presented with partial ophthalmoplegia, ataxia. Second episode was characterized by full-blown presentation characterized by ataxia, areflexia and ophthalmoplegia. CSF analysis was typical during both episodes. Nerve conduction velocity study was fairly within normal limits. MRI of brain was within normal limits. He responded to symptomatic measures initially, then to steroids in the second episode. We are reporting the case due to its rarity.

  3. Cognitive, physiological, and personality correlates of recurrence of depression

    NARCIS (Netherlands)

    Bos, EH; Bouhuys, AL; Geerts, E; Van Os, TWDP; Van der Spoel, ID; Brouwer, WH; Ormel, J

    Background: The risk of recurrence in depressive disorder is high and increases with the number of episodes. We investigated whether individuals with a history of recurrent depression deviate from individuals with a single episode, as regards risk-related variables in 3 different domains of

  4. Sellar recurrent hemangiopericytoma without metastasis: a case report

    African Journals Online (AJOL)

    Radical surgery is the treatment of choice, but must be supplemented with postoperative radiotherapy. Hemangiopericytomas have a high potential for recurrence and metastasis. Sellar location is very rare and can simulate a pituitary adenoma.We report a case of a 24 year-old woman diagnosed with sellar recurrent HPC ...

  5. Continuation and maintenance use of antidepressants in recurrent depression

    NARCIS (Netherlands)

    Bockting, Claudi L H; ten Doesschate, Mascha C; Spijker, Jan; Spinhoven, Philip; Koeter, Maarten W J; Schene, Aart H

    2008-01-01

    Background: Maintenance antidepressant (AD) medication is the most commonly used preventive strategy in a highly recurrent disease, i. e. depression. Little is known about the discontinuation of maintenance AD use and the association with recurrence in daily clinical practice. The purpose was to

  6. Electrochemotherapy for large cutaneous recurrence of breast cancer

    DEFF Research Database (Denmark)

    Matthiessen, Louise Wichmann; Johannesen, Helle Hjorth; Hendel, Helle Westergren

    2012-01-01

    Cutaneous recurrences of breast cancer may cause considerable discomfort due to ulceration, oozing, and pain and can also be difficult to treat. Electrochemotherapy is a localised anticancer treatment using electric pulses to make cell membranes permeable, augmenting uptake of chemotherapeutic...... drugs, and thus enabling highly efficient tumour cell kill. This is the first systematic investigation of electrochemotherapy for larger cutaneous recurrences of breast cancer....

  7. Recurrence and Mortality after Surgical Treatment of Soft Tissue ...

    African Journals Online (AJOL)

    Fibrosarcoma was the most common histological type (36.0%) and the mean tumour size was 13.0 +7.36 cm. Most (44.7%) patients presented with high grade tumours and 78.0 % of the patients presented with a recurrence. Most of the recurrences (71.7%) occurred within the first year of treatment. Failure to get adjuvant ...

  8. Duodenal infusion of donor feces for recurrent Clostridium difficile

    NARCIS (Netherlands)

    van Nood, Els; Vrieze, Anne; Nieuwdorp, Max; Fuentes, Susana; Zoetendal, Erwin G.; de Vos, Willem M.; Visser, Caroline E.; Kuijper, Ed J.; Bartelsman, Joep F. W. M.; Tijssen, Jan G. P.; Speelman, Peter; Dijkgraaf, Marcel G. W.; Keller, Josbert J.

    2013-01-01

    Recurrent Clostridium difficile infection is difficult to treat, and failure rates for antibiotic therapy are high. We studied the effect of duodenal infusion of donor feces in patients with recurrent C. difficile infection. We randomly assigned patients to receive one of three therapies: an initial

  9. Duodenal Infusion of Donor Feces for Recurrent Clostridium difficile

    NARCIS (Netherlands)

    Nood, van E.; Vrieze, A.; Nieuwdorp, M.; Fuentes Enriquez de Salamanca, S.; Zoetendal, E.G.; Vos, de W.M.; Visser, C.E.; Kuijper, E.J.; Bartelsman, J.F.; Tijssen, J.G.; Speelman, P.; Dijkgraaf, M.G.; Keller, J.J.

    2013-01-01

    Background Recurrent Clostridium difficile infection is difficult to treat, and failure rates for antibiotic therapy are high. We studied the effect of duodenal infusion of donor feces in patients with recurrent C. difficile infection. Methods We randomly assigned patients to receive one of three

  10. Lactoferrin gene polymorphisms in Italian patients with recurrent tonsillitis.

    Science.gov (United States)

    Zupin, Luisa; Angelelli, Francesco; Grasso, Domenico Leonardo; Crovella, Sergio

    2016-09-01

    Recurrent tonsillitis is an oral pathology characterized by inflammation of tonsils. The disease susceptibility depends upon environmental and host factors, specifically the innate immune response, the first line of host defence could play an important role. Among innate immunity members, lactoferrin, known for its antimicrobial properties, was previously correlated with the risk of oral pathology as periodontitis and dental caries. 89 Italian children presenting recurrent tonsillitis and 95 healthy children were genotyped for two LTF non-synonymous polymorphisms, called Thr29Ala and Arg47Lys, in order to investigate their potential role in recurrent tonsillitis susceptibility. no different allele, genotype and haplotype frequency distributions were detected comparing patients and controls. data from the current study indicate that LTF polymorphisms might not be involved in recurrent tonsillitis development in our Italian population. However, since the importance of lactoferrin in oral immunity has been previously assessed, further studies should be necessary to unravel the potential role of LTF genetic variants in oral cavity. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  11. Etiology and antibiotic susceptibility pattern of community-acquired ...

    African Journals Online (AJOL)

    Streptomycin showed the highest susceptibility to bacteria isolates while the least susceptibility was observed with augmentin. Rational use of antibiotics with regular antibiotics susceptibility surveillance studies is recommended to maintain high antibiotic therapeutic profile. Keywords: Community-acquired urinary tract ...

  12. Susceptibility Status of Anopheles gambiae s.l. (Diptera: Culicidae ...

    African Journals Online (AJOL)

    komla

    susceptible 'Kisumu' strain, both Korle-Bu and Airport populations were highly resistant to DDT and gave resistance levels which were over nine-fold for permethrin and over 2.5-fold for deltamethrin. Both wild and susceptible populations showed full susceptibility to malathion. The S and M forms of A. gambiae s.s. were ...

  13. Susceptibility status of Anopheles gambiae s.l. (Diptera: Culicidae ...

    African Journals Online (AJOL)

    susceptible 'Kisumu' strain, both Korle-Bu and Airport populations were highly resistant to DDT and gave resistance levels which were over nine-fold for permethrin and over 2.5-fold for deltamethrin. Both wild and susceptible populations showed full susceptibility to malathion. The S and M forms of A. gambiae s.s. were ...

  14. Microwave susceptibility experiments

    Energy Technology Data Exchange (ETDEWEB)

    McConaghy, C.

    1984-05-29

    In certain experimental environments, systems can be affected or damaged by microwave pulses. I have conducted tests at LLNL to understand the phenomenology of microwave susceptibility of system components and subsystem components. To date, my experiments have concentrated on bipolar transistors, similar to what might be used in discrete analog circuits, and on CMOS RAM chips, which might be used in a computer memory system. I observed a decrease in failure energies for both the transistor and the integrated curcuit as I shortened the microwave pulse width. An S band (2.86 GHz) transmit/receive (T/R) tube has also been tested both at S band and at X band (8.16 GHz). The S band pulse had limitations in rise-time from zero power, which had an effect on the amount of power that could be transmitted through the T/R tube, as much as 0.7% of the incident power passed through the tube. All tests were conducted in closed-waveguide or coax test-fixtures, in contrast to the anechoic chambers utilized by other experimenters. I have used both S band and X band Klystron generators. For very high power (greater than 1 MW), I used an additional pulse-compression cavity at S band. Other subsystem components such as an X band mixer and an X band T/R tube will be tested in the future. 8 references.

  15. 18F-FDOPA PET/CT or PET/MRI in Measuring Tumors in Patients With Newly-Diagnosed or Recurrent Gliomas

    Science.gov (United States)

    2017-01-30

    Adult Anaplastic Ependymoma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Diffuse Astrocytoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Mixed Glioma; Adult Oligodendroglioma; Adult Pilocytic Astrocytoma; Adult Pineal Gland Astrocytoma; Adult Subependymal Giant Cell Astrocytoma; Childhood High-grade Cerebellar Astrocytoma; Childhood High-grade Cerebral Astrocytoma; Childhood Low-grade Cerebellar Astrocytoma; Childhood Low-grade Cerebral Astrocytoma; Recurrent Adult Brain Tumor; Recurrent Childhood Anaplastic Astrocytoma; Recurrent Childhood Anaplastic Oligoastrocytoma; Recurrent Childhood Anaplastic Oligodendroglioma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Diffuse Astrocytoma; Recurrent Childhood Fibrillary Astrocytoma; Recurrent Childhood Gemistocytic Astrocytoma; Recurrent Childhood Giant Cell Glioblastoma; Recurrent Childhood Glioblastoma; Recurrent Childhood Gliomatosis Cerebri; Recurrent Childhood Gliosarcoma; Recurrent Childhood Oligoastrocytoma; Recurrent Childhood Oligodendroglioma; Recurrent Childhood Pilomyxoid Astrocytoma; Recurrent Childhood Protoplasmic Astrocytoma; Recurrent Childhood Subependymal Giant Cell Astrocytoma; Recurrent Childhood Visual Pathway and Hypothalamic Glioma; Recurrent Childhood Visual Pathway Glioma; Untreated Childhood Anaplastic Astrocytoma; Untreated Childhood Anaplastic Oligoastrocytoma; Untreated Childhood Anaplastic Oligodendroglioma; Untreated Childhood Brain Stem Glioma; Untreated Childhood Cerebellar Astrocytoma; Untreated Childhood Cerebral Astrocytoma; Untreated Childhood Diffuse Astrocytoma; Untreated Childhood Fibrillary Astrocytoma; Untreated Childhood Gemistocytic Astrocytoma; Untreated Childhood Giant Cell Glioblastoma; Untreated Childhood Glioblastoma; Untreated Childhood Gliomatosis Cerebri; Untreated Childhood Gliosarcoma; Untreated Childhood

  16. Recurrent oral angioleiomyoma

    Directory of Open Access Journals (Sweden)

    V G Mahima

    2011-01-01

    Full Text Available Angioleiomyomas are vascular variant of leiomyomas which are benign tumors of smooth muscle. They are exceedingly rare in the oral cavity. Malignant transformation of these tumors has also been reported occasionally which warrants knowledge of this soft tissue tumor. A 57 year old male patient reported with a 15 day history of an asymptomatic growth that had started insidiously in his lower left back tooth region. Clinical examination revealed a solitary, oval, sessile growth in the mandibular left retro molar region. Excisional biopsy was suggestive of Angioleiomyoma. A recurrence of the same was noted two months later which was also histopathologically reported as Angioleiomyoma. The same was confirmed using special stains. This case reports an unusual presentation of Angioleiomyoma with regards to both recurrence as well as rapid growth. It is important to be well aware of this uncommon entity as these tumors often can mimic or transform into malignancy. Precise clinicopathological examinations are therefore invaluable in establishing an accurate diagnosis and delivering suitable treatment.

  17. Recurrent polymorphic mating type variation in MadagascanBulbophyllumspecies (Orchidaceae) exemplifies a high incidence of auto-pollination in tropical orchids.

    Science.gov (United States)

    Gamisch, Alexander; Fischer, Gunter A; Comes, Hans Peter

    2014-06-01

    The transition from outcrossing to self-fertilization is one of the most common evolutionary changes in angiosperms. The orchid family exemplifies this evolutionary trend but, because of a general lack of large-scale surveys on auto-pollination in orchid taxa, the incidence and modes of auto-pollination among (sub)tropical orchids remain poorly known. In the present study, we assessed the frequency and mode of auto-pollination within and among species of a largely monophyletic group of Madagascan Bulbophyllum . The capacity for autonomous fruit set was investigated by bagging experiments in the greenhouse and the field, complemented with detailed floral micromorphological studies of the gynostemium. Our survey comprises 393 accessions, representing at least 78 species, and thus approximately 37% of the species diversity of the genus in the Madagascan region. Our studies revealed that mating type is directly related to gynostemium structure, most often involving the presence or absence of a physical barrier termed 'rostellum'. As a novel and unexpected finding, we identified eight species of a single lineage of Madagascan Bulbophyllum (termed 'clade C'), in which auto-pollinating morphs (selfers), either lacking a rostellum or (rarely) possessing a stigmatic rostellum, co-exist with their pollinator-dependent conspecifics (outcrossers). We hypothesize that auto-pollination via rostellum abortion has a simple genetic basis, and probably evolved rapidly and recurrently by subtle changes in the timing of rostellum development (heterochrony). Thus, species of clade C may have an intrinsic genetic and developmental lability toward auto-pollination, allowing rapid evolutionary response under environmental, perhaps human-disturbed conditions favouring reproductive assurance. Overall, these findings should stimulate further research on the incidence, evolution, and maintenance of mating type variation in tropical orchids, as well as how they adapt(ed) to changing

  18. Endoscopic cubital tunnel recurrence rates.

    Science.gov (United States)

    Cobb, Tyson K; Sterbank, Patrick T; Lemke, Jon H

    2010-06-01

    Cubital tunnel syndrome is the second most common nerve entrapment in the upper extremity. There are no current publications concerning the recurrence rates after endoscopic cubital tunnel release. The purpose of this study is to evaluate the recurrence rate of endoscopic cubital tunnel release compared to published reports of recurrence following open cubital tunnel procedures. We reviewed 134 consecutive cases of endoscopic cubital tunnel release in 117 patients. There were 104 cases in 94 patients with greater than 3 months follow-up. The mean follow-up time was 736 days. They were grouped using Dellon's classification. Two literature control groups were used from published reports of recurrence rate following open cubital tunnel release. A recurrence was identified if the patient was symptom-free following surgery but had symptoms reappear 3 months or more after surgery as defined in the literature. Of the 104 cases, 92.31% had more than a 4-month follow-up. One case (0.96%) met the criteria for recurrence at 4 months postprocedure. Data were then compared to the literature control groups used from published reports of recurrence rates following open cubital tunnel release. Pooled, the combined controls had 22 of 180 cases (12.22%) with recurrences. The percentage of procedure recurrence varied significantly with p value equal to 0.0004. It is recognized that there is a lack of common classification and comparative analysis of these studies, but they do classify preoperative grading and recurrence similarly. We are 95% confident that our true recurrence rate is between 0.02% and 5.24% and that endoscopic cubital tunnel release has a recurrence rate, which is not higher than open cubital tunnel release literature controls.

  19. Clinical performance of hybrid capture 2 human papillomavirus testing for recurrent high-grade cervical/vaginal intraepithelial neoplasm in patients with an ASC-US Papanicolaou test result during long-term posttherapy follow-up monitoring.

    Science.gov (United States)

    De Vivar, Andrea Diaz; Dawlett, Marilyn; Wang, Jian-Ping; Jack, Annie; Gong, Yun; Staerkel, Gregg; Guo, Ming

    2015-02-01

    Women who have been treated for high-grade cervical or vaginal intraepithelial neoplasia (CIN or VAIN) or invasive carcinoma are at risk for recurrent/persistent disease and require long-term monitoring. The role of human papillomavirus (HPV) testing in this setting is unclear. To evaluate the clinical performance of the Hybrid Capture 2 (HC2) HPV test for recurrent/residual high-grade CIN or VAIN in patients with a posttherapy abnormal squamous cells of undetermined significance (ASC-US) Papanicolaou test result. We reviewed the follow-up data on 100 patients who had an ASC-US Papanicolaou test and HC2 HPV results after treatment for high-grade CIN/VAIN or carcinoma. Human papillomavirus genotyping was performed for women with a negative HC2 result whose follow-up biopsy revealed CIN/VAIN 2+. The patients' mean age was 47 years. The HC2 test result was positive in 33% of the patients. Follow-up biopsy was available for 17 of these patients (52%) and for 25 of the 67 patients (37%) with a negative HC2 result. A total of 5 of the patients (29%) with a positive HC2 result and 2 of the patients (8%) with a negative HC2 result had CIN/VAIN 3 on follow-up biopsy, a statistically insignificant difference (P = .10). Human papillomavirus 16/18 genotypes were detected in the CIN/VAIN 2+ lesions of 5 patients with a negative HC2 result. HC2 yielded a false-negative rate of 8% for CIN 3. HC2 testing therefore may not be sufficient for triage of patients with an ASC-US Papanicolaou test result. Patients with ASC-US during long-term posttherapy follow-up need close monitoring, with colposcopic evaluation if clinically indicated.

  20. Prospective Multicenter Study of Carbapenemase-Producing Enterobacteriaceae from 83 Hospitals in Spain Reveals High In Vitro Susceptibility to Colistin and Meropenem

    Science.gov (United States)

    Ortega, Adriana; Bartolomé, Rosa; Bou, Germán; Conejo, Carmen; Fernández-Martínez, Marta; González-López, Juan José; Martínez-García, Laura; Martínez-Martínez, Luis; Merino, María; Miró, Elisenda; Mora, Marta; Oliver, Antonio; Pascual, Álvaro; Rodríguez-Baño, Jesús; Ruiz-Carrascoso, Guillermo; Ruiz-Garbajosa, Patricia; Zamorano, Laura; Bautista, Verónica; Pérez-Vázquez, María; Campos, José

    2015-01-01

    The aim of this study was to determine the impact of carbapenemase-producing Enterobacteriaceae (CPE) in Spain in 2013 by describing the prevalence, dissemination, and geographic distribution of CPE clones, and their population structure and antibiotic susceptibility. From February 2013 to May 2013, 83 hospitals (about 40,000 hospital beds) prospectively collected nonduplicate Enterobacteriaceae using the screening cutoff recommended by EUCAST. Carbapenemase characterization was performed by phenotypic methods and confirmed by PCR and sequencing. Multilocus sequencing types (MLST) were determined for Klebsiella pneumoniae and Escherichia coli. A total of 702 Enterobacteriaceae isolates met the inclusion criteria; 379 (54%) were CPE. OXA-48 (71.5%) and VIM-1 (25.3%) were the most frequent carbapenemases, and K. pneumoniae (74.4%), Enterobacter cloacae (10.3%), and E. coli (8.4%) were the species most affected. Susceptibility to colistin, amikacin, and meropenem was 95.5%, 81.3%, and 74.7%, respectively. The most prevalent sequence types (STs) were ST11 and ST405 for K. pneumoniae and ST131 for E. coli. Forty-five (54.1%) of the hospitals had at least one CPE case. For K. pneumoniae, ST11/OXA-48, ST15/OXA-48, ST405/OXA-48, and ST11/VIM-1 were detected in two or more Spanish provinces. ST11 isolates carried four carbapenemases (VIM-1, OXA-48, KPC-2, and OXA-245), but ST405 isolates carried OXA-48 only. A wide interregional spread of CPE in Spain was observed, mainly due to a few successful clones of OXA-48-producing K. pneumoniae (e.g., ST11 and ST405). The dissemination of OXA-48-producing E. coli is a new finding of public health concern. According to the susceptibilities determined in vitro, most of the CPE (94.5%) had three or more options for antibiotic treatment. PMID:25824224

  1. The highly conserved serine threonine kinase StkP of Streptococcus pneumoniae contributes to penicillin susceptibility independently from genes encoding penicillin-binding proteins

    Directory of Open Access Journals (Sweden)

    Dias Ricardo

    2009-06-01

    Full Text Available Abstract Background The serine/threonine kinase StkP of Streptococcus pneumoniae is a major virulence factor in the mouse model of infection. StkP is a modular protein with a N-terminal kinase domain a C-terminal PASTA domain carrying the signature of penicillin-binding protein (PBP and prokaryotic serine threonine kinase. In laboratory cultures, one target of StkP is the phosphoglucosamine mutase GlmM involved in the first steps of peptidoglycan biosynthesis. In order to further elucidate the importance of StkP in S. pneumoniae, its role in resistance to β-lactams has been assessed by mutational analysis in laboratory cultures and its genetic conservation has been investigated in isolates from infected sites (virulent, asymptomatic carriers, susceptible and non-susceptible to β-lactams. Results Deletion replacement mutation in stkP conferred hypersensitivity to penicillin G and was epistatic on mutations in PBP2X, PBP2B and PBP1A from the resistant 9V clinical isolate URA1258. Genetic analysis of 55 clinical isolates identified 11 StkP alleles differing from the reference R6 allele. None relevant mutation in the kinase or the PASTA domains were found to account for susceptibility of the isolates. Rather the minimal inhibitory concentration (MIC values of the strains appeared to be determined by their PBP alleles. Conclusion The results of genetic dissection analysis in lab strain Cp1015 reveal that StkP is involved in the bacterial response to penicillin and is epistatic on mutations PBP 2B, 2X and 1A. However analysis of the clinical isolates did not allow us to find the StkP alleles putatively involved in determining the virulence or the resistance level of a given strain, suggesting a strong conservation of StkP in clinical isolates.

  2. Antibiotic susceptibility of Atopobium vaginae

    Directory of Open Access Journals (Sweden)

    Verschraegen Gerda

    2006-03-01

    Full Text Available Abstract Background Previous studies have indicated that a recently described anaerobic bacterium, Atopobium vaginae is associated with bacterial vaginosis (BV. Thus far the four isolates of this fastidious micro-organism were found to be highly resistant to metronidazole and susceptible for clindamycin, two antibiotics preferred for the treatment of BV. Methods Nine strains of Atopobium vaginae, four strains of Gardnerella vaginalis, two strains of Lactobacillus iners and one strain each of Bifidobacterium breve, B. longum, L. crispatus, L. gasseri and L. jensenii were tested against 15 antimicrobial agents using the Etest. Results All nine strains of A. vaginae were highly resistant to nalidixic acid and colistin while being inhibited by low concentrations of clindamycin (range: G. vaginalis strains were also susceptible for clindamycin ( 256 μg/ml but susceptible to clindamycin (0.023 – 0.125 μg/ml. Conclusion Clindamycin has higher activity against G. vaginalis and A. vaginae than metronidazole, but not all A. vaginae isolates are metronidazole resistant, as seemed to be a straightforward conclusion from previous studies on a more limited number of strains.

  3. Genome wide high density SNP-based linkage analysis of childhood absence epilepsy identifies a susceptibility locus on chromosome 3p23-p14

    DEFF Research Database (Denmark)

    Chioza, Barry A; Aicardi, Jean; Aschauer, Harald

    2009-01-01

    Childhood absence epilepsy (CAE) is an idiopathic generalised epilepsy (IGE) characterised by typical absence seizures manifested by transitory loss of awareness with 2.5-4 Hz spike-wave complexes on ictal EEG. A genetic component to the aetiology is well recognised but the mechanism of inheritance.......1.1 and a susceptibility locus was identified on chromosome 3p23-p14 (Z(mean)=3.9, palpha=0.7). The linked region harbours the functional candidate genes TRAK1 and CACNA2D2. Fine-mapping using a tagSNP approach demonstrated disease association with variants in TRAK1....

  4. Differential susceptibility in steelhead trout populations to an emergent MD strain of infectious hematopoietic necrosis virus

    Science.gov (United States)

    Breyta, R.; Jones, Amelia; Kurath, Gael

    2014-01-01

    A significant emergence of trout-adapted MD subgroup infectious hematopoietic necrosis virus (IHNV) began in the coastal region of Washington State, USA, in 2007. This emergence event lasted until 2011 and caused both asymptomatic adult fish infection and symptomatic epidemic disease and mortality in juvenile fish. Incidence of virus during this emergence demonstrated a heterogeneous distribution among rivers of the coastal region, leaving fish populations of some rivers apparently untouched while others suffered significant and recurrent infection and mortality (Breyta et. al. 2013; Dis Aquat Org 104:179-195). In this study, we examined the possible contribution of variations in susceptibility of fish populations, age-related resistance, and virus virulence to the observed landscape heterogeneity. We found that the most significant variable was host susceptibility: by controlled experimental challenge studies steelhead trout populations with no history of IHNV infection were 1 to 3 orders of magnitude more sensitive than a fish population with a long history of IHNV infection. In addition, 2 fish populations from the same river, which descended relatively recently from a common ancestral population, demonstrated 1 to 2 orders of magnitude difference in susceptibility. Fish age-related development of resistance was most evident in the more susceptible of 2 related fish populations. Finally, the strain of virus involved in the 2007 coastal Washington emergence had high virulence but was within the range of other known M group viruses tested. These results suggest that one major driver of landscape heterogeneity in the 2007 coastal Washington IHNV emergence was variation in fish population susceptibility and that this trait may have a heritable component.

  5. Recurrent pregnancy loss

    DEFF Research Database (Denmark)

    Egerup, Pia; Kolte, A M; Larsen, E C

    2016-01-01

    STUDY QUESTION: Is there a different prognostic impact for consecutive and non-consecutive early pregnancy losses in women with secondary recurrent pregnancy loss (RPL)? SUMMARY ANSWER: Only consecutive early pregnancy losses after the last birth have a statistically significant negative prognostic...... impact in women with secondary RPL. WHAT IS KNOWN ALREADY: The risk of a new pregnancy loss increases with the number of previous pregnancy losses in patients with RPL. Second trimester losses seem to exhibit a stronger negative impact than early losses. It is unknown whether the sequence of pregnancy...... losses plays a role for the prognosis in patients with a prior birth. STUDY DESIGN, SIZE, DURATION: This retrospective cohort study of pregnancy outcome in patients with unexplained secondary RPL included in three previously published, Danish double-blinded placebo-controlled trials of intravenous...

  6. Analysis of Brain Recurrence

    Science.gov (United States)

    Frilot, Clifton; Kim, Paul Y.; Carrubba, Simona; McCarty, David E.; Chesson, Andrew L.; Marino, Andrew A.

    Analysis of Brain Recurrence (ABR) is a method for extracting physiologically significant information from the electroencephalogram (EEG), a non-stationary electrical output of the brain, the ultimate complex dynamical system. ABR permits quantification of temporal patterns in the EEG produced by the non-autonomous differential laws that govern brain metabolism. In the context of appropriate experimental and statistical designs, ABR is ideally suited to the task of interpreting the EEG. Present applications of ABR include discovery of a human magnetic sense, increased mechanistic understanding of neuronal membrane processes, diagnosis of degenerative neurological disease, detection of changes in brain metabolism caused by weak environmental electromagnetic fields, objective characterization of the quality of human sleep, and evaluation of sleep disorders. ABR has important beneficial implications for the development of clinical and experimental neuroscience.

  7. Real-Time Optical Antimicrobial Susceptibility Testing

    DEFF Research Database (Denmark)

    Fredborg, Marlene; Andersen, Klaus R; Jørgensen, Erik

    2013-01-01

    Rapid antibiotic susceptibility testing is in highly demand in health-care fields as antimicrobial resistant bacterial strains emerge and spread. Here we describe an optical screening system (oCelloScope), which based on time-lapse imaging of 96 bacteria-antibiotic combinations at a time, introdu......Rapid antibiotic susceptibility testing is in highly demand in health-care fields as antimicrobial resistant bacterial strains emerge and spread. Here we describe an optical screening system (oCelloScope), which based on time-lapse imaging of 96 bacteria-antibiotic combinations at a time......, introduces real-time detection of bacterial growth and antimicrobial susceptibility, with imaging material to support the automatically generated graphs. Automated antibiotic susceptibility tests of a monoculture showed statistically significant antibiotic effect within 6 minutes and within 30 minutes...

  8. Recurrent uncomplicated urinary tract infections in women: a review.

    Science.gov (United States)

    Nosseir, Sandy B; Lind, Lawrence R; Winkler, Harvey A

    2012-03-01

    Recurrent urinary tract infections most often present with symptoms of irritative voiding. In most cases, they are caused by reinfection with a previously isolated organism. Patients with one or more symptoms of uncomplicated recurrent urinary tract infection should undergo thorough examination and screening for underlying comorbidities that increase susceptibility. When frequent reinfections, empiric treatment relapse, persistent infections, or risk factors for complicated infections are encountered, patients may benefit from urodynamics, cystoscopy, renal ultrasound, intravenous urogram, or voiding cystourethrogram to evaluate for anatomic, functional, or metabolic abnormalities affecting the urinary tract (e.g., stones, stricture, obstruction, vesicoureteral reflux, lesions, detrusor underactivity). These patients may benefit from culture-guided empiric treatment and further evaluation by urology, nephrology, or infectious disease specialists. In patients with a history of uncomplicated urinary tract infections, empiric treatment guided by local antimicrobial resistance may efficiently treat a suspected recurrence. After successful treatment of the acute infection, postcoital prophylaxis, continuous prophylaxis, or self-start empiric treatment may be selected based on frequency of recurrent infections, temporal relation to intercourse, and patient characteristics. Ancillary measures such as probiotics, cranberry products, or local estrogen replacement may also be considered. This article will review the current definition, epidemiology, pathogenesis, diagnosis, work-up, treatment, treatment side effects, and prevention of recurrent urinary tract infections in women. A suggested algorithm for evaluation and treatment based on current literature is provided.

  9. Recurrent parent genome recovery analysis in a marker-assisted backcrossing program of rice (Oryza sativa L.).

    Science.gov (United States)

    Miah, Gous; Rafii, Mohd Y; Ismail, Mohd R; Puteh, Adam B; Rahim, Harun A; Latif, Mohammad A

    2015-02-01

    Backcross breeding is the most commonly used method for incorporating a blast resistance gene into a rice cultivar. Linkage between the resistance gene and undesirable units can persist for many generations of backcrossing. Marker-assisted backcrossing (MABC) along with marker-assisted selection (MAS) contributes immensely to overcome the main limitation of the conventional breeding and accelerates recurrent parent genome (RPG) recovery. The MABC approach was employed to incorporate (a) blast resistance gene(s) from the donor parent Pongsu Seribu 1, the blast-resistant local variety in Malaysia, into the genetic background of MR219, a popular high-yielding rice variety that is blast susceptible, to develop a blast-resistant MR219 improved variety. In this perspective, the recurrent parent genome recovery was analyzed in early generations of backcrossing using simple sequence repeat (SSR) markers. Out of 375 SSR markers, 70 markers were found polymorphic between the parents, and these markers were used to evaluate the plants in subsequent generations. Background analysis revealed that the extent of RPG recovery ranged from 75.40% to 91.3% and from 80.40% to 96.70% in BC1F1 and BC2F1 generations, respectively. In this study, the recurrent parent genome content in the selected BC2F2 lines ranged from 92.7% to 97.7%. The average proportion of the recurrent parent in the selected improved line was 95.98%. MAS allowed identification of the plants that are more similar to the recurrent parent for the loci evaluated in backcross generations. The application of MAS with the MABC breeding program accelerated the recovery of the RP genome, reducing the number of generations and the time for incorporating resistance against rice blast. Copyright © 2014 Académie des sciences. Published by Elsevier SAS. All rights reserved.

  10. Inundation and erosion susceptibility in wave dominated beaches

    Directory of Open Access Journals (Sweden)

    Jorge Trindade

    2013-06-01

    Full Text Available Hydrodynamic forces over the beach sediments are the main driving factors affecting the frequency and magnitude of morphological changes in beach systems. Most of the time, these driving factors act in a foreseeable way and do not represent any danger either to the coastal systems or to their population. However, hydrodynamic forces are also capable of inducing high morphodynamic behaviour on the beach profiles and very often in a short period of time; this endangers people and property and leads to system retreat. The most common consequences of the occurrence of this type of phenomena over the landforms are costal inundation and erosion. Still, many coastal systems, especially beach systems, have recovery mechanisms. Resilience levels have a very important role in the beach morphodynamic status and exposure to potential damaging event assessments. The Portuguese West coast has a high wave energetic environment during winter, where waves with 5 year recurrence period can reach 9.2m and storms are frequent. This research aims to access beach hazard and susceptibility to inundation and erosion. Three beach systems were selected and monitored applying sequential profiling methodology over a four year period (2004 -2007. Sta. Rita, Azul and Foz do Lizandro beaches are representative systems of the coastal stretch between Peniche and Cascais, which is a cliff dominated coast. Results from the monitoring campaigns are presented, including volume budgets, beach face slope changes, berm occurrence and heights and planimetric coastline dynamics. A hazard and susceptibility assessment diagram and zonation are proposed, including the parameterization of local flood (i.e. mean sea level, maximum spring tides, and surge and run -up levels and erosion potentials (i.e. volume budget and beach planimetric dynamics.

  11. Recurrent aphthous stomatitis. An update.

    Science.gov (United States)

    Ship, J A

    1996-02-01

    Recurrent aphthous ulceration or recurrent aphthous stomatitis is the most common oral mucosal disease known to human beings. Despite much clinical and research attention, the causes remain poorly understood, the ulcers are not preventable, and treatment is symptomatic. The most common presentation is minor recurrent aphthous stomatitis: recurrent, round, clearly defined, small, painful ulcers that heal in 10 to 14 days without scarring. Major recurrent aphthous stomatitis lesions are larger (greater than 5 mm), can last for 6 weeks or longer, and frequently scar. The third variety of recurrent aphthous stomatitis is herpetiform ulcers, which present as multiple small clusters of pinpoint lesions that can coalesce to form large irregular ulcers and last 7 to 10 days. Diagnosis of all varieties is usually made after clinical examination. Many local and systemic factors have been associated with these conditions, and there is evidence that there may be a genetic and immunopathogenic basis for recurrent aphthous ulceration. Management of this condition depends on the clinical presentation and symptoms and includes analgesic, antimicrobial, and immunomodulatory drugs. As dental clinicians and researchers become better trained in oral medicine and stomatology, it is anticipated that the pathophysiology, prevention, and treatment of recurrent aphthous ulceration will improve in the future.

  12. Susceptibility and reactivity in polysensitized individuals following controlled induction

    DEFF Research Database (Denmark)

    Bangsgaard, Nannie; Carlsen, Berit C; Johansen, Jeanne Duus

    2010-01-01

    It is uncertain whether polysensitized patients acquire multiple allergies only because of a high degree of exposure to environmental allergens, or because of being highly susceptible to developing contact allergy.......It is uncertain whether polysensitized patients acquire multiple allergies only because of a high degree of exposure to environmental allergens, or because of being highly susceptible to developing contact allergy....

  13. Persistent and recurrent Trichomonas vaginalis infections: epidemiology, treatment and management considerations.

    Science.gov (United States)

    Seña, Arlene C; Bachmann, Laura H; Hobbs, Marcia M

    2014-06-01

    Trichomonas vaginalis (TV) is a common sexually transmitted infection that can cause vaginitis, cervicitis and urethritis. Persistent and recurrent TV infections are frequent in women, potentially due to the lack of routine screening recommendations for this pathogen, the chronic nature of some infections, and drug resistance. Metronidazole and tinidazole are two oral drugs that are effective against trichomoniasis. There are few alternative treatment options for persons with a metronidazole allergy or treatment failure. Most TV isolates from women with treatment failures that have been analyzed for susceptibility testing in the United States have exhibited low-level metronidazole resistance, supporting the initial use of tinidazole for patients who fail metronidazole therapy. Several non-nitroimidazole drugs and other agents have demonstrated acceptable in vitro activity or cure rates in case reports for metronidazole-resistant trichomoniasis; however, clinical trials are imperative to evaluate their efficacy as alternative therapeutic regimens for this highly prevalent infection.

  14. Recurrent Aphthous Stomatitis: A Review.

    Science.gov (United States)

    Edgar, Natalie Rose; Saleh, Dahlia; Miller, Richard A

    2017-03-01

    Aphthous stomatitis is a painful and often recurrent inflammatory process of the oral mucosa that can appear secondary to various well-defined disease processes. Idiopathic recurrent aphthous stomatitis is referred to as recurrent aphthous stomatitis. The differential diagnosis for recurrent aphthous ulcerations is extensive and ranges from idiopathic benign causes to inherited fever syndromes, to connective tissue disease, or even inflammatory bowel diseases. A thorough history and review of systems can assist the clinician in determining whether it is related to a systemic inflammatory process or truly idiopathic. Management of aphthous stomatitis is challenging. For recurrent aphthous stomatitis or recalcitrant aphthous stomatitis from underlying disease, first-line treatment consists of topical medications with use of systemic medications as necessary. Herein, the authors discuss the differential diagnosis and treatment ladder of aphthous stomatitis as described in the literature.

  15. Risk factors for recurrence after acute colonic diverticulitis

    DEFF Research Database (Denmark)

    Hupfeld, Line; Burcharth, Jakob; Pommergaard, Hans-Christian

    2017-01-01

    PURPOSE: Several factors may influence the risk of recurrence after an episode of acute colonic diverticulitis. Until now, a comprehensive systematic overview and evaluation of relevant risk factors have not been presented. This review aimed at assembling and evaluating current evidence on risk...... factors for recurrence after conservatively treated acute colonic diverticulitis. METHODS: PubMed, Embase, and Cochrane databases were searched for studies evaluating risk factors for recurrence after acute diverticulitis treated non-surgically defined as antibiotic treatment, percutaneous abscess....../low, medium, high). RESULTS: Of 1153 screened records, 35 studies were included, enrolling 396,676 patients with acute diverticulitis. A total of 50,555 patients experienced recurrences. Primary diverticulitis with abscess formation and young age increased the risk of recurrence. Readmission risk was higher...

  16. Antimycotics susceptibility testing of dermatophytes

    Directory of Open Access Journals (Sweden)

    Arsić-Arsenijević Valentina

    2010-01-01

    Full Text Available Dermatophytes are moulds that produce infections of the skin, hair and nails of humans and animals. The most common forms among these infections are onychomycosis and tinea pedis affecting 20% of world population. These infections are usually chronic. The treatment of dermatophytoses tends to be prolonged partly because available treatments are not very effective. Antifungal drug consumption and public health expenditure are high worldwide, as well as in Serbia. For adequate therapy, it is necessary to prove infection by isolation of dermatophytes and to test the antifungal susceptibility of isolates. Susceptibility testing is important for the resistance monitoring, epidemiological research and to compare in vitro activities of new antifungal agents. The diffusion and dilution methods of susceptibility tests are used, and technical issues of importance for the proper performance and interpretation of test results are published in the document E.DEF 9.1 (EUCAST and M38-A2 (CLSI. The aim of our paper is to promptly inform the public about technical achievements in this area, as well as the new organization of laboratory for medical mycology in our country. The formation of laboratory networks coordinated by the National Reference Laboratory for the cause of mycosis need to enable interlaboratory studies and further standardization of methods for antifungal susceptibility testing of dermatophytes, reproducibility of tests and clinical correlation monitoring (MIK values and clinical outcome of dermatophytosis. The importance of the new organization is expected efficient improvement in the dermatophytosis therapy at home, better quality of patient's life and the reduction of the cost of treatment.

  17. Penatalaksanaan infeksi herpes simpleks oral rekuren Management of recurrent oral herpes simplex infection

    OpenAIRE

    Erni Marlina; Bagus Soebadi

    2013-01-01

    Recurrent oral herpes simplex infection was the secondary or recurrent form of primary herpes simpex infection. In human, herpes simplex virus was latent or dormant and could reactivate. Recurrency due to virus reactivation induced by emotional stress, high fever, ultraviolet exposed, oral tissue or neuron tissue trauma, immunosuppresion condition, and hormonal disturbance. The aim of this paper was to report and discuss management of recurrent oral herpes simplex infection which ...

  18. Genetic susceptibility of periodontitis

    NARCIS (Netherlands)

    Laine, M.L.; Crielaard, W.; Loos, B.G.

    2012-01-01

    In this systematic review, we explore and summarize the peer-reviewed literature on putative genetic risk factors for susceptibility to aggressive and chronic periodontitis. A comprehensive literature search on the PubMed database was performed using the keywords ‘periodontitis’ or ‘periodontal

  19. Fourie susceptible.pmd

    African Journals Online (AJOL)

    Prof. Adipala Ekwamu

    a number of cultivars exhibited field resistance to halo blight and bacterial brown spot, all cultivars were more or less susceptible to .... Cerillos. Alubia. I. 91. 57. Kranskop. Red speckled sugar. II. 97. 63. OPS-RS1. Red speckled sugar. II. 96. 63. OPS-RS2. Red speckled sugar. I. 100. 61. OPS-RS3. Red speckled sugar. II. 97.

  20. Recurrent aphthous stomatitis.

    Science.gov (United States)

    Cui, Ricky Z; Bruce, Alison J; Rogers, Roy S

    2016-01-01

    Recurrent aphthous stomatitis (RAS) is the most common acute oral ulcerative condition in North America. RAS is divided into a mild, common form, simple aphthosis, and a severe, less common form, complex aphthosis. Aphthosis is a reactive condition. The lesions of RAS can represent the mucosal manifestation of a variety of conditions. These include conditions with oral and genital aphthae such as ulcus vulvae acutum, reactive nonsexually related acute genital ulcers, and Behçet disease. The mouth is the beginning of the gastrointestinal (GI) tract, and the lesions of RAS can be a manifestation of GI diseases such as gluten-sensitive enteropathy, ulcerative colitis, and Crohn disease. Complex aphthosis may also have correctable causes. The clinician should seek these in a careful evaluation. Successful management of both simple and complex aphthosis depends on accurate diagnosis, proper classification, recognition of provocative factors, and the identification of associated diseases. The outlook for patients with both simple and complex aphthosis is positive. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Radiotherapeutic alternatives for previously irradiated recurrent gliomas

    Directory of Open Access Journals (Sweden)

    Schulz-Ertner Daniela

    2007-08-01

    Full Text Available Abstract Re-irradiation for recurrent gliomas has been discussed controversially in the past. This was mainly due to only marginal palliation while being associated with a high risk for side effects using conventional radiotherapy. With modern high-precision radiotherapy re-irradiation has become a more wide-spread, effective and well-tolerated treatment option. Besides external beam radiotherapy, a number of invasive and/or intraoperative radiation techniques have been evaluated in patients with recurrent gliomas. The present article is a review on the available methods in radiation oncology and summarizes results with respect to outcome and side effects in comparison to clinical results after neurosurgical resection or different chemotherapeutic approaches.

  2. STDP in recurrent neuronal networks

    Directory of Open Access Journals (Sweden)

    Matthieu Gilson

    2010-09-01

    Full Text Available Recent results about spike-timing-dependent plasticity (STDP in recurrently connected neurons are reviewed, with a focus on the relationship between the weight dynamics and the emergence of network structure. In particular, the evolution of synaptic weights in the two cases of incoming connections for a single neuron and recurrent connections are compared and contrasted. A theoretical framework is used that is based upon Poisson neurons with a temporally inhomogeneous firing rate and the asymptotic distribution of weights generated by the learning dynamics. Different network configurations examined in recent studies are discussed and an overview of the current understanding of STDP in recurrently connected neuronal networks is presented.

  3. [Recurrent aphthous stomatitis in Rheumatology].

    Science.gov (United States)

    Riera Matute, Gabriel; Riera Alonso, Elena

    2011-01-01

    Recurrent aphthous stomatitis consists on recurring oral ulcers of unknown etiology. Oral ulcers may be different in number and size depending on the clinical presentation, which also determines the time needed for healing. Moreover, there are factors associated to outbreaks but not implicated in its etiopathogenesis. When oral aphthosis has a known etiology, it is not considered as recurrent aphthous stomatitis. The severity and the clinical presentation helps in the differential diagnosis. Treatment is symptomatic in recurrent aphthous stomatitis while, if there is an underlying systemic disease, the treatment of such disease is need in addition to topical treatment. Copyright © 2011 Elsevier España, S.L. All rights reserved.

  4. Villitis of unknown aetiology: correlation of recurrence with clinical outcome.

    LENUS (Irish Health Repository)

    Feeley, L

    2010-01-01

    Villitis of unknown aetiology (VUA) is associated with adverse pregnancy outcome. Consequently, an ability to predict recurrence could be clinically relevant. We examined placentas where villitis was diagnosed in a previous pregnancy to establish the risk of recurrence and outcome. A total of 304 cases of VUA were diagnosed in our laboratory over a 4-year period. Subsequently, 19 of this cohort had a second placenta examined histologically. Recurrence and clinical outcome were recorded. Villitis recurred in 7 of 19 cases (37